¼±Åà - È­»ìǥŰ/¿£ÅÍŰ ´Ý±â - ESC

 

Part 23. Nephrology

³Ú½¼ Á¤¸®

Part 23.  Nephrology

Section 1. Structure And Function Of The Kidney     

Chapter 462. Anatomy of the glomerulus

1) *from 6cm, 24gm in fullterm to 12cm or more, 150gm in adults

2) cortex ; glomeruli, prox. & distal conv.tubules & collecting ducts

   medulla ; straight portions of the tubules, loops of Henle, vasa recta, terminal collecting ducts         

3) blood supply (COÀÇ 10% Â÷Áö)

    ; aorta-> renal a. -> segmental br.-> interlobar a. -> arcuate a. -> interlobular a. -> aff. arterioles -> glo. capillary network -> eff. arterioles

4) juxtaglomerular apparatus

  ; controls the secretion of renin             

  ; consists of ¨çspeciallized m. cells in the walls of aff.a. ¨è lacis cell ¨é macular densa of distal tubule

5) Glomerulus

    ; 1 million nephron in kidneys

    ; complete at birth but functional immature

    ;     ¨ç endothelium

                   - fenestrations

        ¨è GBM

               i) lamina lara interna ( subendoth.)

               ii) central electron dense lamina densa

                iii) lamina lara externa ( subepith.)         

        ¨é epithelial cells

            - filtration slit(space between the foot process)

    ; mesangium

        - ¢¾±â´É

                   ¨ç supporting structure of glomerular capillary

                ¨è play a role in regulation of glomerular blood flow, filtration

                ¨é play a role in removal of macromolecules(i.e. immune complex) frome glomerulus

                           by intracellular phagocytosis

                                   transport through intercellular channels to JG region

6) Bowman capsule

462.1. Glomerular filtration

; ultrafiltrate all substance except proteins(like albumin, globulins) exceeding *68,000 MW

; Forces for ultrafiltration

    ¨ç glo.cap.hydrostatic pr. <- systemic art.pr.

    ¨è glo.cap.oncotic pr.

    ¨é glo.plasma flow rate

    ¨ê hydrostatic pr. within Bowman space

    ¨ë permeability of glo.cap.wall

; adult values at *3yr

; *standardized to surf. area(1.73m2) of a 70kg adult to comparison

; ¡Úfiltration rate°¡ 70% ÀÌÇÏ·Î ¶³¾îÁ®¾ß serum creatinine »ó½Â

; *GFRÀÌ °¨¼ÒÇϸé tubular secretion of creatinine Áõ°¡ÇϹǷΠfiltration rate°¡ ½ÇÁ¦º¸´Ù overestimate µÉ¼ö ÀÖ´Ù.

; *serum CrÀÌ 2.0mg/dl(180umol/L) ÀÌ»óÀ̸é GFRÀº little merit

    --> *renal functionÀº secrum creatinineÀ¸·Î F/UÇØ¾ß ÇÑ´Ù.

¢¾ TRP

    = (1- Cpi/Ccr) x 100

    = (1- Upi*Scr/Spi*Ucr) x 100

         (nl ; 78-93%)

Section 2. Conditions particulary associated with hematuria

¡Ø81ÁÖ Table XXIII-1 & Ç¥17-1(p694)

 

¡ÚTable XXIII-2

; microscopic hematuria

    - *> 5 RBC/HPF in the sediment from 10ml of centrifuged freshly voided urine

    - asymptomatic microscopic hematuria : 0.5-2.0% of school aged children

; persistent microscopic hematuria

    - further outpatient evaluation

    - ¡Ú> 5 RBC/HPF on 3 UA at monthly intervals

Chapter 463. Glomerular Disease

Pathogenesis

# mechanism of glomerular injury

    ; immunologic

  ; inherited (presumably biochemical)

  ; coagulation disorders

# Immunologic injury

  ; *¡ãcommon causes

    ; Áõ°Å

         ¨ç experimental immune mediated GN ¿Í morphologic & immunopathologic similarity

           ¨è immune reactants(Ig & C')À» glo.¿¡¼­ ¹ß°ß

       ¨é serum C' abn. ¿Í autoAb.(ex.Anti GBM) ÃâÇö

      2) 2 major mechanism of immunologic injury

        ¨ç localization of circulating Ag-Ab immune complex

        ¨è local Ag in situ¿Í AbÀÇ interaction

            ex) non-collagenous domain [NC-1] of type IV

               collagen : putative Ag in human antiGBM nephritis

      

         A. immune complex mediated ds.

             immune complex -> accumulate in glo. -> injury

          ½ÇÇè) acute serum sickness in rabbit iv of bovine albumin

                -> acute proliferative GN

           cf. glo.localization¿¡ °ü¿©ÀÎÀÚ

          +-¨ç complex : conc, charge, size

          | ¨è glo.ÀÇ Æ¯Â¡ : mesangial trapping, negatively charged capillary wall

          | ¨é hydrodynamic forces

          +-¨ê various mediatorsÀÇ influence : angiotensin II, PG

       B. Anti-GBM antbody dsease : in situ Ag-Ab interaction

          : IF»ó linear deposition of Ig. & C' on GBM

             À̴  i) Goodpasture disease -+ °ú ºñ½Á

                  ii) RPGNÀÇ certain type -+

     2. Biochemical mediation

      * Complement system

        +-Classic pathway : activated by Ag-Ab immune complex

        +-Alternative pathway : activated by polysaccharides & endotoxin

     3. Coagulation system

     activated +- drectly by endoth.injury->thrombogenic subendoth.³ëÃâ->coagulation                |    cascade

              +--  indirectly by C' activation

Pathology

      different ds. state¿¡¼­ similar microscoic change º¸ÀÌ´Â °æ¿ìµµ ÀÖ´Ù.

    1. Proliferation of glomerular cells

     ¨ç +-generalized : all glo.

        +-focal : only some glo.

     ¨è +-diffuse : single glo.ÀÇ all part

        + segmental :     ¡¨    some part

     ¨é  ÁÖ·Î +-endoth. & mesangial cell prolif. ¸¹À½

              +-mesangial matrixµµ Áõ°¡

           -> glo.size Áõ°¡, glo.cap.lumen °¨¼Ò -> renal insuff. 

   2. Crescent formation in Bowman space

     ¨ç proliferation of parietal epith.cells of B space - esp. RPGN

     ¨è in response to fibrin deposit in B space

      1) new crescent ( fibrin, prolif.epith.cell, BM like material, macrophage )

       -> fibroepithelial crescent

       -> glomerular cell death (necrosis)

      2) generalized mesangial proliferationÀÌ µ¿¹ÝµÇ°í immune complex &

          antiGBM Ab°¡ µ¿¹Ý

      3) Glomerular exudation of blood cells

          neutrophils : m.c.

          eos, baso, mono

      4) thickened appearance of GBM

         ¿øÀÎ

       +- ¨ç true increase in width of memb. : membranous glomeruloathy

       |  ¨è memb.°ú ºñ½ÁÇÏ°Ô ¿°»öµÇ´Â immune comlexÀÇ massive Ä§Âø : SLE

       +- ¨é subendothelial space¿¡ mesangial cell°ú matrixÀÇ interposition (split app.)

                                                       : type I MPGN, others

      5) Sclerosis

         scar tssue in glomerulus

         ¶§·Î increase in mesangial matrix ÀǹÌ

Chapter 464. Recurrent Gross Hematuria

¡ÚTable 464-1

Ig A Nephropathy (= Berger Nephropathy)

Pathology & Pathogenesis

# LM

    ; focal & segmental mesangial proliferation

    ; increased matrix

  ; some gerneralized mesangial proliferation

    ; occasionally crescent formation

# IF

    ; IgA deposition in mesangirum

    ; lesser amount of Ig M, Ig G, C3, properdin deposition

# recurrence in transplanted kidney

    --> suggest systemic disorders

Clinical & Laboratory Manifestation

    ; ³²:¿© - 2:1

    ; episode of gross hematuria or microscopic hematuria on routine exam

    ; renal function

           - relatively normal

         - proteinuria : < 1gm/day (minimal)

    ; C3 normal

Prognosis & Treatment

      ¨ç ´ë°³ no kidney damage

      ¨è 30%¿¡¼­ progressive ds.·Î develop.

         no Tx. - activity Á¦ÇÑÀº ÇÊ¿ä ¾ø´Ù.

      ¨é number of gross hematuria, persistent microscopic hematuria between

         episode´Â  Px.¿Í ¹«°ü

# ¡ØPoor Prognosis Factor

    ; hypertension

  ; diminished renal function

  ; proteinuria > 1g/day between episodes of gross hematuria

  ; histologic evidence of diffuse GN with crescent, scarring

# ¡ØIg A deposition diseases

  ¨ç Berger ds.  

  ¨è H-S nephritis

  ¨é SLE

  ¨ê Liver cirrhosis

    ¨ë rarely MCLS

Idiopathic Hematuria (=Benign Familial Hematuria)

     ; Á¤ÀÇ : LM & IF »ó normal histologic finding & recurrent episode of gross

             hematuria

          EM »ó some case - marked thinning of GBM

     ; excellent Px.

     ; F/up to DDx. Alport synd.

Alport Syndrome

     : m.c. of hereditary nephritis

       marked variability                                

       X chrosome¿¡ Á¸ÀçÇÏ´Â Á¦ IVÇü collagenÀÇ a5 »ç½½ À¯ÀüÀÚÀÇ µ¹¿¬º¯ÀÌ

    1) Pathology

      ¨ç ³ªÁß¿¡ mesangial proliferation & cap. wall thickening->progressive glo.

         sclerosis  -> tubular atrophy, interstitial infl. & fibrosis, foam cell

      ¨è EM»ó thickening, thinning, splitting & layering of GBM & tubule

                  (not specific to Alport synd.)

      ¨é immunopathologic study (-)

    2) Clinical sx.

      ¨ç renal involvement

          m.c.+- Asymptomatic microscopic hematuria

              +- recurrent gross hematuria

      ¨è sensorineural hearing loss (¼Ò¼ö)

          -esp, high frequency range -> Á¡Â÷ ÁøÇàµÇ¾î deafness

      ¨é eye abnormality (10%)

         i) cataracts

         ii) Keratoconus ( anterior lenticonus )

         iii) spherophakia ( macular lesion )

    3) Genetics

      : ¨ç X-linked dominant => male¿¡¼­ severe course

               ( autosomal dominant µµ ÀÖ´Ù.)

        ¨è 20%¿¡¼­´Â No family Hx. of renal ds.

    4) Complication

       ¨ç hypertension       ¨è UTI       ¨é CRF

    5) Px. & Tx.

       ¨ç male:10-20´ë¿¡ end stage RF with hearing loss->dialysis & kidney                          transplantation

       ¨è female:normal life span & subclinical hearing loss

Idiopathic Hypercalciuria

; present as     ¨ç RGH

           ¨è persistent microscopic hematuria

               ¨é dysuria in the absence of stone formation

Etiology

    ; excessive GI absorption of normal dietary Ca. intake  

    ; defect in renal tub. Ca. reabsop.

Diagnosis

    ; ¡Ú24hr U ca. excretion  > 4mg/kg

    ; screening test

           - ¡Ørandom Uca/Ucr > 0.2

Differential Diagnosis

    ; normal infants

    ; hypercalcemic hypercalciuria due to hyperparathyroidism or Vit. D intoxication

Complication

    ; ¡ØNephrolithiasis

Treatment

    ; Oral thiazide

           - controversal

           - Indication

                   / persistent gross hematuria or dysuria

           - *Chlorothiazide 10-20mg/kg/24hr single morning dose

                   --> Uca. excretion < 4mg/kg/24hr.µÇ°í Cl/M. resolve µÉ¶§±îÁö Áõ·®

                   --> 1³â ÈÄ Áß´Ü

           - S/E : *Hypokalemia

Chapter 465. Gross or Microscopic Hematuria

465.1 Acute Poststreptococcal Glomerulonephritis

# acute nephritic syndrome

    ; sudden onset of gross hematuria, edema, hypertension, renal insuff.

Etiology & Epidemiology

; nephritogenic groupA ¥â-hemolytic streptococcus

    - throat infection : *serotype 12, cold weather

  - skin inf. or pyoderma : *serotype 49, warm weather

Pathology

    ; symmetrical enlarged Kidney

  ; LM

        - diffuse mesangial cell proliferation with an increase in mesangial matrix

           - PMNL infiltration in glomeruli

           - maybe crescent and interstitial inflammation

    ; IF

           - *lumpy-bumpy deposit of Ig & C' on GBM & mesangium

    ; EM

           - *humps on epithelial side of GBM (=subepithelial hump)

Pathogenesis

    ¨ç immune complexÀÎÇÑ mech.À¸·Î »ý°¢.

        - ÀÌÀ¯+-morphologic study

              +-serum C3 depression

          but not clear yet    

    ¨è acute serum sickness in rabbit°ú ºñ½Á

    ¨é C'activationÀº alternative rather than classic immune-comp. med. pathway

Clinical Manifestation

    ¨ç child but 3yr ÀÌÀüÀº rare

    ¨è streptococcal infectionÈÄ 1-2wk°æ°úÈÄ

       latent period

             +- pharyngitis : 9-11ÀÏ

             +- pyoderma : 3ÁÖ or ÀÌ»ó

    ¨é Sx. :

       i) asymptomatic microscopic hematuria - ARF±îÁö ´Ù¾ç.

       ii) edema, hypertension, oliguria, encephalopathy, CHF

        * edema : due to +-water & salt retention

                         +-nephrotic syndrome

       iii) nonspecific symptom

    malaise, lethargy, abd. & flank pain, fever

    - acute phase´Â ´ë°³ 1mo. ³» È£Àü.

      urinary abn.´Â 1yr.ÀÌ»ó  Áö¼Ó°¡´É.

    - acute phase :4-10ÀÏ

      Gross hematuria : ´ë°³ 1wk.

      Microscopic hematuria : 1-2mo.

Diagnosis

    ¨ç UA»ó

          : i) RBC with   ii) RBC casts   iii) proteinuria  iv) PMNL ; common

    ¨è mild normochromic anemia due to hemodilution and hemolysis

    ¨é C3 °¨¼Ò (90%)

    complement +-low for 10ds

                | normalize within 4-5wk

                    +-5-10%´Â S-C3 not reduced

    ¨ê evidence of streptococcal inf.

      i)throat culture : Dx. of carrier state or support Dx.

      ii) ASO (not helpful : skin inf.ÈÄ´Â Áõ°¡µÇÁö ¾ÊÀ½.)

    : Àεο°ÈÄ 1-2ÁÖÈÄ »ó½Â, 3-5ÁÖ peak, 2-3 mo. °ÉÃÄ ¼­¼­È÷ °¨¼Ò.

      iii) DNase B antigen : best single Ab titer

        * alternative ¨Í Streptozyme test ¨Î Streptolysin ¨Ï DNaseB ¨Ð hyaluronidase

                     ¨Ñ Streptokinase    ¨Ò NADase

        µû¶ó¼­ +-acute nephritis

               | evidence of recent streptococcal inf.

               +-low C3

         -> À̷μ­ clinical Dx. of PSGN °¡´É

         -> renal biopsy´Â not Ix.

           but, ¨çSLE                       -------+ rule out Çϴ°ÍÀÌ Áß¿ä.

               ¨èacute exacerbation of chronic GN  -

# ¢¾Renal biopsy indication for PSGN

  ¨ç development of ARF or nephrotic synd

  ¨è absence of evidence of streptococcal inf.

  ¨é absence of hypocomplementemia

  ¨ê persistent of marked hematuria or proteinuria

  ¨ë diminished renal function

  ¨ì low C3 level > 3 mo. after onset

Complication

    ; *complication of ARF

           - volume overload, circulatory congestion, hypertension, hyperkalemia, hyperphosphatemia, hypocalcemia, acidosis, seizures, uremia

Prevention

    ; early systemic antibiotic therapy of streptococcal throat and skin infections

           - *not eliminate the risk of GN

    ; *culture of family member

           - if culture(+), treated

 Treatment

    ; No specific Tx.       

    ; 10-day systemic antibiotics course

           - Penicillin recommended

    ; *restricted activity

           - *only acute phase of diseases

Prognosis

; complete recovery

    - *95% ÀÌ»ó

; no evidence of progression to chronic GN

; if severe acute phase, glo. hyalinization and then progression to chronic renal insufficiency

; *recurrence : extremely rare.

Chapter 466. Membranous Glomerulopathy

; *¡ãcommon cause of nephrotic syndrome in adult

Pathology

# LM

    ; *diffuse thickening of GBM without significant proliferative change

        - due to memb. like material production by visceral epi.cell in response to immune comlex        - deposited on the epithelial side of membrane

           - spike on the epithelial side of GBM

# IF

    ; granular deposit of IgG & C3

# EM

    ; *EDM deposits on epithelial side of GBM

Pathogenesis

    - immune complex mediated ds.

    - experimental Heymenn nephritis ºñ½Á

Clinical Manifestation

    - 2nd decade of life¿¡ m.c.

    - Nephrotic syndrome ¼Ò°ß

       with microscopic hematuria

            occasionally gross hematuria

    - B.P & C3 : normal

Diagnosis

    - renal biopsy => confirm

       Ix.  ¨ç presentation of nephrotic syndrome over 8yr.old

           ¨è unexplained hematuria & proteinuria

# associated diseases

    ; SLE, cancer, gold or penicillamine therapy, syphilis, HB viral inf.

Complication

    ; ¡Úincreased risk of renal v. thrombosis

Treatment

    ¨ç spontaneous resolution in majority of children

    ¨è salt restriction & diuretics for nephrotic state

    ¨é immunosuppressive therapy : ÀϺΠȯÀÚ¿¡¼­ progressive renal insuff. ¸¦ ´ÊÃá´Ù.

Chapter 467. Systemic Lupus Erythematosus

      ¨ç fever  ¨è wt. loss  ¨é rash  ¨ê hematologic abn.

      ¨ë arthritis  ¨ì heart, lung, CNS, kidney ħ¹üÇÏ´Â systemic ds.

  - kidney involvement : m.c. manifestation in child

                         occasionally only manifestation

Pathogenesis & pathology

    - immune complex mediated ds.

    - aberration in both B & T cell function

# ¢ÞClassification by WHO by EM, IF, LM

  WHO class I nephritis

           ; no histologic abnormality

  WHO Class II (= mesangial lupus nephritis)

           ; *mesangial deposits containing immunoglobulin and complements in some glomeruli

        class IIA

                   - normal LM

       class IIB

                   - focal & segmental mesangial hypercellularity & increased matrix

  WHO Class III (= focal proliferative LN)

       ; *mesangial deposit in almost all glomerulus

       ; subendothelial deposit in some

        ; *focal & segmental mesangial proliferation

           ; occasionally capillary wall necrosis & crescent formation

  WHO Class IV (= diffuse proliferative LN)

           ; *¡ãcommon & severe form

           ; *massive mesangial & subendothelial deposit in all glomeruli

           ; mesangial proliferation in all glomeruli

           ; ¡Úwire loop lesion

                   - thickened cap.wall (= subendoth. deposit)

           ; commonly necrosis, crescent formation, scarring

  WHO Class V (= membranous LN)

           ; ¡ãleast common

# common transformation

Clinical manifestation

      ´ë°³ adolescent girl

    ¨ç milder form (all class II, some class III) : hematuria, normal renal function,

                                                   proteinuria ( < 1gm/day )

    ¨è some class III & all class IV : hematuria & proteinuria

         reduced renal function

         nephrotic synd. or ARF

    ¨é some prolif.LN½Ã normal UA º¸Àϼöµµ ÀÖ´Ù.

    ¨ê Class V : nephrotic synd.

Diagnosis

    ¨ç ÀÇ½É : crculating ANA

    ¨è È®Áø : anti DNA Ab ( native double stranded )

    ¨é C3 & C4 °¨¼Ò in active ds.

    ¨ê renal biopsy´Â ¹Ýµå½Ã ½ÃÇà.

Treatment

# immunosuppressive therapy

    ; aims

           - clinical & serologic remission

       - *normalization of anti DNA Ab & C3, C4

    ; initiation in all patients

     - Pds 60mg/m2/day div. 3 or 4 doses

    ; some class III, all class IV Áï more severe case

     - azathioprine 2-3mg/kg once daily Ãß°¡

   ¨é 1-2mo.ÈÄ serologic remission µÇ¸é Pds 60mg/m2/day - ADT, single dose

                                           -> 5mg¾¿ taperingÇØ 30mg/m2±îÁö.

   ¨ê azathioprineµµ °¨·®ÇÏ¿© 1yr.ÈÄ discontinue.

                 - À̶§ serologic study, renal monitoring ÇÊ¿ä.

Prognosis

   : dramatically improved

     ds. is controlled, not cured

   : relapse & side effect ÁÖÀÇ

Chapter 468. Membranoproliferative Glomerulonephritis  (=Mesangiocapillary GN )

; *¡ãcommon cause of chronic GN in older child & young adults

Pathology & Pathogenesis

; *hypocomplementemia

    - DDx from other form of chronic GN

; some C3 nephritic factor

# ¡ÚThree Histologic Types

    1) Type I MPGN

         ; *¡ãcommon form

    ; LM.

             - accentuation of lobular pattern by generalized increased mesangial cell & matrix

                   - glomerular capilary wall thickening & duplicated or split due to interposition of mesangial cytoplasm and matrix

                           / ¡Údouble tract or tram-tract app. of GBM

             - *crescent : high relation to poor Px.

           ; IF

            - C3 & lesser amount of Ig in mesangium & along the pph. capillary wall

    ; EM

            - immune complex deposit in *mesangium & subendothelium

    2) Type II MPGN

    ; LM

            - *less prominent mesangial change

         - capilary wall

                           / *ribbon-like thickening due to dense deposit at GBM in EM

                           / *rare splitting of membrane

         - *crescent : common

           ; IF

                   - *Ig in Bowman capsule, mesangium, tubular BM

                   - *C3 with minimal Ig along the margin of the dense deposits on GBM

           ; EM

                   - *immune complex deposit in region of but distinct from lamina densa with GBM thickening

    3) Type III MPGN

           ; LM, IF

                   - resemble in type I

           ; EM

                   - *contiguous subepith. & subendoth. deposits

                   - *disruption & layering of lamina densa of BM

Clinical Manifestation

    ; *¡ãcommon in 2nd decade

    ; mostly nephrotic syndrome

    ; some gross hematuria, asymptomatic mcroscopic hematuria, proteinuria

    ; *HT - common

    ; *decreased C3

Diagnosis & Differential Diagnosis

# ¡Úonset of nephrotic syndrome in child more than 8yr

    --> *renal biopsys ÇØ¾ß ÇÑ´Ù.

# D/Dx with APGN

  ; °øÅëÁ¡

           ¨ç gross hematuria

           ¨è C3 °¨¼Ò

        ¨é ASO Áõ°¡ (coincidental)

    ; ´Ù¸¥Á¡

           - APGN : 2mo. ³» dramatically improve

           - MPGN

                   / persistent clin. Sx. -> Renal biopsyÇÊ¿ä

          / 6ÁÖ ÀÌ»ó C3 °¨¼Ò

Prognosis & Treatment

    ; all type is poor prognosis

           - *esp. type II

    ; I,II´Â kidney transplantationÈÄ¿¡µµ Àç¹ß

    ¨ë No difinite therapy    -+

       long term alternate Pds-+·Î clinical courseÀÇ stabilization.

Chapter 469. GN Of Chronic Infection

¡ÚEtiology

    ¨ç subacute bacterial endocarditis ( Str. viridans or other organisms )

    ¨è infected ventriculoatrial shunt for hydrocephalus ( staphylococcus epidermidis )

    ¨é syphilis

    ¨ê hepatitis B, hepatitis C

    ¨ë Candidiasis

    ¨ì malaria

Pathogenesis

     infecting organismÀÌ foreign AgÀ¸·Î ÀÛ¿ë.

       -> high level of circulating AgÁ¸Àç¿¡ ´ëÇÑ host Ab response·Î

           immune complexÇü¼º.

       -> Kidney¿¡ deposition

       -> GN ÃÊ·¡

  3) histopathologic findings may resembles

     +- PSGN

     |  Membranous GN

     +- MPGN

       Sx : acute nephritic or nephotic syndrome

      C3 °¨¼Ò : common

  4) Tx.

    ¨ç eradication of inf. -> usually resolution

    ¨è progression to end-stage RF °¡´É.

Chapter470. Rapidly Progressive (Crescentric) GN

; *presence of crescents in majority of glomeruli

; *rapidly progressive clinical course

Classification

# idiopathic

# ¡Ø87 2ndary group RPGN (with underlying ds.)

    ; PSGN

    ; Lupus

    ; MPGN

    ; GN of Goodpasture ds.

    ; GN of anaphylactoid purpura

Pathology & Pathogenesis

# Crescents

  ; inside of Bowman capsule

    ; *consists of proliferating epithelial cells of capsule, fibrin, BM-like material, macrophages

    ; mechanism of crescents formation

           - necrosis or disruption of glomerular capillary wall

                   --> *deposition of fibrin in bowman capsule

                   --> crescents formations

# pathogenesis

  ; *no evidence for immunologic mechanism

    ; some Ab against GBM

    ; others immune complexs on capillary wall

    ; ¡Únormal C3 level

Clinical Manifestation

    ¨ç ARF : ´ë°³

    ¨è end-stage RF within wks to mos.(after onset )

Diagnosis & Differential Diagnosis

    ¨ç ANA, C3, anti DNase B titer ÃøÁ¤À¸·Î ŸÁúȯ R/O

    ¨è confirm : Kidney biopsy

Prognosis & Treatment

    ; PSGN associated RPGN

           - spontaneously recovery

    ; Lupus or Anaphylactoid purpura associated RPGN

           - PRS + Azathioprine

                   --> success

    ; ¡ÚRPGN associated with remaining types

           - *poor prognosis

           - ¡Ø94 some effective reports

                   / *pulse methylprednisolone + oral cyclophosphamide

                   / *plasmapheresis

Chapter 471. Goodpasture Disease

; pulmoonary hemorrhage, GN associated Ab against lung & GBM

# Goodpasture syndrome

    ; clinical picture of pulmonary hemorrhage with GN in several ds

    ¨ç SLE

    ¨è Ana. purpura

    ¨é polyarteritis nodosa

    ¨ê Wegener granulomatosis

Pathology

; *resemble RPGN in LM

; IF

    - *continuous linear pattern of IgG along the GBM (antiGBM Ab)

Clinical Manifestation

      extremely rare in child

     ¨ç hemoptysis : usually presenting complaints, pulmonary hemorrhage

                    ¼öÀÏ ¶Ç´Â ¼öÁÖÈÄ

     ¨è hematuria

     ¨é proteinuria develop

     ¨ê Progressive RF ¹ß»ý

    ; *C3 : normal

Prognosis

     »ýÁ¸Çϸé commonly end stage RF ÁøÇà

     No definite therapy

        +- pulse met0hylprednisone

        |  oral cyclophosphamide

        +- plasmpheresis

     cause of death : pulmonary hemrrhage

Chapter 472. Hemolytic Uremic Syndrome

; *¡ãcommon cause of ARF in young children

Etiology

    ; bacterial

           - ¢ÞE. coli (O157:H7) : ¡ãcommon

           - shigella, salmonella, campylobacter, s.pneumonia

    - Bartonella

    ; viral

           - *coxsackie, ECHO, influenza, variecella, EBV

    ; oral contraceptive

  ; pyran copolymer(inducer of interferon)

    ; *SLE

    ; malignant hypertension

    ; pre-eclampsia

  ; postpartum RF

    ; radiation nephritis

Pathology

     ¨ç Ãʱâ glo. change

       i) cap.wall thickening   ii) cap.lumen narrowing   iii) mesangial widening

     ¨è fibrin thrombi -> cortical necrosis

     ¨é severely -> partial or total sclerosis

¡Ø92 Pathogenesis

    ; endothelial cell injury : primary event

           --> localized clotting

           --> microangiopathic anemia due to altered vasculature

           --> thrombocytopenia due to intrarenal plt. adhesion or damage

    ; *no evidence of DIC

Clinical Manifestation

    ; *¡ãcommon under 4yr

     ¨ç ¼±ÇàÁõ»ó

         ´ë°³ gastroenteritis ( fever, vomiting, diarrhea, abd. pain )

              URI, less commonly

     ¨è 5-10ÀÏÈÄ

         sudden onset of pallor, irritability, weakness, lethargy, oliguria

     ¨é P/Ex»ó

         dehydration, edema, petechiae, hepatosplenomegaly, marked irritability

Diagnosis & Differential Diagnosis

; syndrome

    - *microangiopathic hemolytic anemia, thrombocytopenia, ARF

; Laboratory Finding

  - Hb 5-9 g/dl

  - PBS

           / helmet cells, burr cells, fragmented RBCs

  - diminished Haptoglobin

  - moderate increased reticulocyte

    - Coombs (-)

  - *leukocytosis > 30,000/mm3

    - thromocytopenia 20,000-100,000/mm3

    - normali PT, PTT

    - UA

           / surprisingly mild low grade microscopic hematuria, proteinuria

; vary from mild renal insufficiency to ARF

; barium enema

    - colonic spasma and transient early filling defects

           --> subsequential intestinal stenosis

# Differential Diagnosis

  ; Lupus, malignant hypertension

    ; ¡Úbilateral renal v. thrombosis

           - *¡ãdifficult

           - °øÅëÁ¡

                   / preceding AGE

         / dehydration, pallor

                   / microangiopathic hemolytic anemia, thrombocytopenia, ARF

    - Â÷ÀÌÁ¡

                   / *marked enlarged kidney in renal vein thrombosis

# ¢¾Renal Bipsy Ix.

  ; prolonged renal failure > 2wks

    ; thrombocytopenia(-)

Complication

    ; anemia, acidosis, hyperkalemia, fluid overload, CHF, hypertension, Uremia

  ; ¢¾Extrarenal Complication

           - CNS manifestation : irrtability, seizure, coma

           - colitis : melena, perforation

    - *diabetes mellitus

    - *rhabdomyolysis

Prognosis & Treatment

    ; more than 90% normal renal function recovery

    ; corticosteroid

           - *no value

    ; anticoagulants

           - heparin

                   / no beneficial effects

    ; *fibrinolytic therapy

           - *theoretical

           - risks to outweigh the pontential gains

    ; plasmapheresis,

    ; FFP

    ; ¡Úearly & frequent peritoneal dialysis

           - *¡ãgood treatment

           - *control of uremic state and promote recovery by removing an inhibitor of fibrinolysis

Chapter 473.  Infection As A Cause Of Hematuria

    ; Gross or microscopic hematuria

     - UT  ÀÇ bacterial, micobacterial, viral infectin °ú

       °ü·ÃÀÖ´Ù.

    1) cystitis: bacterial, micobacterial, viral

    2) urethritis:

      . gross or microscopic hematuria, urgency, urethral discomfort

      . UA ß¾ RBC, pyuria

      . urine culture: usually negative

        bacterial, ureaplasma, chlamydia ʦ

      . spontaneous relieve ʦ

      . Tx. : 10 day tetracycline

             + urinary analgesics(phenazopyridine hydrochloride)

      . conservative Tx. ·Î ¾ÈµÇ¸é cystoscopy ½ÃÇà

        --> underlying Abn. detect

Chapter 474. Hematologic Disease Causing Hematuria

474.1 Coagulopathies & Thrombocytopenia

 inherited acquired disorders of coagulation

     hemophilia

     DIC

     thrombocytpenia

but usually hematuria is not a presenting sign. usually after other

  manifestations

474.2 Sickle Cell Nephropathy

            gross or microscopic hematuria

             ; sickling in hypoxic acidic, hypertonic medulla --> vascular stasis-->                   bl. flow 

               --> ischemia --> papillary necrosis --> interstitial fibrosis

            clinical manifestation

             ; urinary concentrating defect, RTA

              nephrotic syndrome (rarely) - focal sclerosis or MPGN °ú ºñ½Á

              ´ëºÎºÐÀÇ hematuria °¡ spontaneousely recover µÈ´Ù.

474.3 Renal Vein Thrombosis

Epidemiology

# ¡Ú2 Distinct Patterns

    ; new born & infant

        - asso. with *asphyxia, dehydration, shock, sepsis, infant of DM mother

    ; after infancy

       - asso. with *NS(¡ãfrequently membranous nephropathy), cyanotic heart ds, use of angiographic contrast agent

Pathogenesis

; intrarenal venous radicle ¿¡¼­ ½ÃÀÛÇÏ¿© antegrade & retrograde spread

  --> renal v. involve ´Â ¾ÊµÊ

; thrombus formation

      endoth. cell injury

          by i) hypoxia, ii) endotoxin, iii) contrast media

          ; conjunction /c hypercoagulable state (nephrotic syndrome)

      diminished vs. blood flow

          hypovolemia: shock, dehydraton, NS

          intravascular sludging of blood(polycythemia)

Clinical manifestaions

in infant

i) sudden onset of gross hematuria

ii) unilat or bilat. flank mass

in old children

i) gross & microscopic hematuria  ii) flank pain

   unilat. > bilat.

   bilat. ½Ã ARF

Diagnosis

Hx. : predisposing clinical factor ÀÖ´Â pt. ¿¡¼­ hematuria & flank

      mass êó

Lab/F : i) microangiopathic hemolytic anemia

         ii) thrombocytopenia

U/S ß¾: marked enlargement

radionuclide study : little or no renal function in involved kidney

venacarvogram & doppler flow study  to confirmed the diagnosis

  in occult case --> µÉ¼öÀÖÀ¸¸é ÇÇÇÑ´Ù.

Differential Diagnosis

hematuria : esp. hemorrlytic uremic syndrome

renal enlargement

i) hydronephrosis, ii) cystic ds, iii) Wilms tumor, iv) abscess

v) hematoma

Treatment

 unilat. renal v. thrombosis

 supportive tx.

 i) fluid & electrolyte correction

 ii) Tx. of infection

 iii) prophylactic anticoagulation to prevent thrombosis

     - ȯÀÚ°¡ DIC ¿¡ ºüÁø°æ¿ì¸¦ Á¦¿ÜÇϰí´Â ÀÇ¹Ì ¾ø´Ù.

 bilat. renal v. thrombosis

 : CRF ·Î °¡´Â °æ¿ì°¡ ¸¹´Ù.

 i) thrombectomy

 ii) systemic fibrolytic agents

Prognosis

 in infant

 progressive atrophy --> small scared kidney

 nephrectomy ; if, hypertension or chr. infection ( + )

             -> acute phase ¿¡¼­´Â ½Ç½ÃÇÏÁö¾ÊÀ½

  in old children

  involved kidney may recover

  ( ƯÈ÷ nephrotic SD À̳ª CHD¿Í ¿¬°üµÈ thrombosisÀÇ °æ¿ì)

Chapter 475 Anatomic Abnormalities associated with Hematuria

Congenital Abnormalities

; gross or microscopic hematuria ´Â UT. malformation ÀÇ ´ëºÎºÐÀÇ ÇüÅ¿¡¼­ ³ªÅ¸³¯¼ö ÀÖ´Ù.

; flank ¿¡ minor trauma ÈÄ sudden onset of usually painless grosshematuria½Ã ÀǽÉ

--> ureteropelvic junctional obstruction

cystic kidney °¡ ÀÚÁÖ µ¿¹ÝµÊ

Trauma

; gross or microscopic hematuria, flank pain, abdominal regidity

-- may occur

475.1 Autosomal Recessive PCK( Polycystic Kidney)

(=infantile polycystic diseases)

; may not detected until after infancy

; *hepatic cysts with significant liver disease

Patholgy

    ; markedly both enlarged kidney

    ; grossly innumerable cysts throughout cortex & medulla

    ; LM

           - *¡°cyst¡± is collecting duct dilatation

           - normal interstitium & remainder of the tubules

                   --> progressing to interstitial fibrosis & tubular atropy

                   --> renal failure

    ; hepatic cyst

           - cirrhosis, portal hypertension, eso. varix rupture

           - *when severity of hepatic manifestation exceeds renal involvements

                   --> called ¡Ú¡° congenital hepatic fibrosis¡±

Clinical Manifestation

          bilat. flank mass at birth

          oligo hydroamnios µ¿¹Ý Òý

        --> Potter synd. ÃÊ·¡

          : flat nose, recessed chin, epicanthal fold,

           low set ear, limb abn. ( due to compression of fetus)

           pul. hypoplasia --> neonatal resp. destress -->spont. pneumothorax

                   cf) spont. pneumothorax ½Ã kidney U/S é© (in neonate)

          gross & microscopic hematuria , hypertension ÀÌ ÈçÇÏ´Ù.

          renal function Àº Á¤»ó ȤÀº °¨¼Ò ( renal malformation ÀÇ severity¿¡ ÀÇÁ¸)

Diagnosis

    ; Hx. & P/Ex.

  ; U/S finding

           - marked enlarged & uniformly hyper echogenic kidney

  ; IVP

           - opacification of dilated collecting duct

           - *radial stresks similar to spokes of wheel

    ; open surgical bx. of the Liver & Rt. kidney toward the end of the 1st year

           - confirm of Diagnosis

Differential Diagnosis

. ( bilat. renal enlargement)

         multicystic dysplasia

         hydronephrosis

         wilm`s tumor

         renal v. thrombosis 

Treatment

         supportive ( includiing careful management of HT.)

Prognosis

         severe renal involve ½Ã neonatal period ¿¡ pul. & renal insuff. ·Î ÞÝ

         »ýÁ¸ÀÚ´Â renal insuff. ¹ß»ýÀü ¼ö³âµ¿¾È »ì¼öµµ ÀÖ´Ù. À̶§ Kid. size ´Â ÁÙ°í

          HT. Àº less severeÇÏ´Ù.

         renal failure ¹ß»ý½Ã -- dialysis , kid. transplantation

         hepatic fibrosis, or cirrhosis ½Ã portal hypertensionÃÊ·¡µÇ¸ç poor Px.

475.2  Autosomal Dominant PCK

; also known as Adult polycystic kidney

  A.D.

  enlarged kid. /c cortical & medullary cysts ( dilated tubule)

  sx. : 4th or 5th decade ¿¡

     i) gross or microscopic hematuria

     ii) flank pain & mass bilat.

     iii) Hypertension

 µ¿¹ÝÁúȯ

     i) hepatic cyst of no clinical importance

     ii) aneurysm of cerebral circulaton -- ICH ÃÊ·¡

 Supportive Tx.

 Px.

   end stage renal failure at 6th or 7th decade

475.3 Vascular Abnormalities

       hematoma    -----+ of kid. & lower UT. -- extremly rare cause of hematuria

       AV malformation -+

       usually present /c gross hematuria & the passage of blood clots

       renal colic -- upper UT. involve ½Ã ¹ß»ý °¡´É

       Dx. -- confirmed by angiography

Chapter 476. Miscellaneous Etiologies Of Hematuria

476.1 Exercise Hematuria

        gross or microscopic hematuria °¡ vigorous exercise ÈÄ¿¡ ¿Ã¼ö ÀÖ´Ù.

        benign, rare in female, /ass. c  dysuria

        color of urine -- red to black

        urine ¿¡¼­  blood clot ÀÌ º¸Àϼö ÀÖ´Ù.

        RBC cast ¾ø°í renal ds. evidence ¾ø´Ù.

        ¿îµ¿¸ØÃß°í 48½Ã°£³» ¼Ò½Ç

        lower UT. origine À¸·Î »ý°¢

        DDx. Rhabdomyolysis, march hemoglobinuria

476.2 Drugs

# alteration in coagulation system

    ; heparin , waparin, aspirin

# tubular damage

    ; PC, sulfonamide

# hemorrhagic cystitis

    ; cyclophosphamide

Chapter 477. Evaluation Of The Child With Hematuria

Hx. & P/Ex.

    ; ÃÖ±Ù URI, skin & GI infection --> AGN or hemolytic uremic synd.

  ; frequency, dysuria, unexplained fever --> UTI

  ; ¡ØFlank Mass

           - hydronephrosis, cystic ds., renal v. thrombosis or tumor

    ; gross hematuria ÀÇ ÃÖ±Ù Hx. --> IgA nephropathy, idiopathic hematuria

                                       Alport SD. hypercalciuria

       rash & joint pain µ¿¹Ý½Ã --> HSP, Lupus

       ±×¿Ü trauma Hx. bleeding difficulties, drug usage, °¡Á·ÀÇ Kid. Ds. Hx. HT Hx.

Laboratory Finding

       anemia

         - dilutional ; ARF ¶§ fluid over load ¶§¹®

         - blood loss ; pul. hemorrhage in Goos pasture ds.

                       melena in HSP, HUS

          - hemolytic ; HUS, SLE

                    ----    hemorrlytic state ÀÇ confirm - reti. count Áõ°¡

                                                          plasma Hb level Áõ°¡

                                                          plasma haptoglobin °¨¼Ò

       PBS ( microangiopathic process in HUS, renal v. thrombosis, vasculitis, SLE

       autoantibody °¡ ( Coomb`s test (+), ANA, leukpenia, multisystem. ds. )

       sickle Hb for black child --> anemia ¾øÀ»¶§µµ

       urine culture ; UTI °¡´É¼º Æò°¡

       CCr, protein & Ca excretion -- À̰ÍÀÌ ºÒ°¡´É Çϸé S-Cr., urine protein by                                     dipstick ,  ca. to cr. ratio in random urine

       urinary RBC morph. °¡ lower tr. À̸é normal, glomerular À̸é dysmorphic.

       -- ¹Ýµå½Ã hematuria ÀÇ À§Ä¡¿Í ÀÏÄ¡ÇÏÁö´Â ¾ÊÀ½

# decreased C3

    ; PSGN

    ; MPGN

    ; Lupus GN

    ; chr. infection GN

# thrombocytopenia

         : plt. »ý»ê ¡é (mal.)

         : plt. ÆÄ±« ¡è ( ITP, HUS, RVT)

Imaging Studies

    3)    IVP, U/S --> str. Abn ¸¦ R/o ÇÔ

          cytogram --> infection À» °¡ÁøÈ¯ÀÚ, lower tr. ÀÇ lesionÀÌ ÀǽɵǴ ȯÀÚ

Renal Biopsy

         persistent microscopic hematuria /ass, c

         i) decreased renal function

         ii) proteinuria

         iii) hypertension

         one or more episode of unexplained gross hematuria

         persistent high grade microscopic hematuria

    5) cystoscopy ; hematuria ¸¦ °¡ÁøÈ¯¾Æ¿¡¼­ routine evaluationÀº ¾Æ´Ï´Ù.

         more helpful - i) bright red hematuria

                        ii) dysuria

                        iii) sterile urine culture

                        iv) ³²¾Æ¿¡¼­ ÁÖ·Î trauma¿¡ ÀÇÇÑ urethral lesionÀ» È®ÀÎÇÔ

                        v) lower UT. ÀÇ neoplasm È®ÀÎ

   * hematuria °¡ 6 mo ÀÌÀüµ¿¾È ÀÖÀ»½Ã

                    - streptococcal inf. ÀÇ serologic evidence ¸¦ È®ÀÎ ÇØ¾ß ÇÑ´Ù.

                       ; throat. & skin inf. culture

                       ; ANA for Lupus

  ** »ó±â study ¿¡¼­ ¸ðµÎ Á¤»óÀÌ ³ª¿À¸é ´õÀÌ»óÀÇ study´Â ÇÊ¿ä¾ø´Ù.

       ÇÏÁö¸¸ IgA nephropathy or Alport SD. Àº ÀÖÀ»¼ö ÀÖ´Ù.

       --> long term f/u ÀÌ ÇÊ¿äÇÔ.

Section 3. Condition Particularly Associated with Proteinuria

; upper limit of normal protein excretion in healthy person

    - 150mg/24hr

    - half

           : plasma origin - mostly Albumin ( 30mg/24hr)

    - the others

           : Tamm-Horsfall protein (mucoprotein produced in distal tubule)

# ÃøÁ¤ ¹æ¹ý

    1) dipstick test

           ; -, ¡¾, +(30mg/dl), ++(100mg/dl), +++(300mg/dl), ++++( 2000mg/dl ¡è)

           ; primarily detection of Albumin

           ; *less sensitive other form protein

                   - *Bence Jones protein, gamma globulin

    2) Sulfosalicylic method

# ¢¾False Positive

  1) dipstick

           ; highly concentrated urine

    ; gross hematuria

    ; contamination with chlorhexidine or benzalkonium

           ; pH over 8.0

    ; phenazopyridine therapy

    2) Sulfosalicylic acid method

    ; radiographic contrast media

    ; PC or cephalosporin therapy  

    ; tolbutamide

    ; sulfonamide

# semiquantitative fashion

    ; U-protein/U-Cr in a random specimen (ÇÑ±ÛÆÇ:¾ÆÄ§ ù¼Òº¯)

           - 2¼¼ÀÌÇÏ¿¡¼­ 0.5 ¡é

         - older child ¿¡¼­ 0.2 ¡é

    - ¡Úmore than 3

                   --> *suggest nephrotic range proteinuria

Chapter 478  Non-Pathologic Proteinuria

¡ÚTable 478-1

# proteinuria ÀÇ Á¤ÀÇ (ÇÑ±ÛÆÇ)

    ; qualitative

        - 1ÁÖÀÌ»óÀÇ °£°ÝÀ¸·Î 3ȸÀÌ»ó °Ë»ç½Ã

       ¿äºñÁß ¡Â 1.015 À϶§ :  1+ ¡è

       ¿äºñÁß ¡Ã 1.015 À϶§ :  2+ ¡è

    ; semiquantitative

     ¾ÆÄ§ ù ¼Òº¯¿¡¼­ ´Ü¹é/Cr.(mg.dl) ºñ°¡ 0.2 ¡è

    ; quantitative

     i) Á¤»ó ¡´ 4mg/m2/hr

     ii) ´Ü¹é´¢ : 4 - 40mg/m2/hr

    iii) N S  ¡µ40mg/m2/hr

# non-pathologic proteinuria

  ; *less than 1000mg/24hr and never associated with edema

478.1 Postural(Orthstatic) Proteinuria

Clinical Manifestation     

    ; may increase 10-fold time or more

    ; unknown etiology

  ; normal laboratory finding & renal bx.

Diagnosis

# urine collection

    ; supine collection 

        - ¹ã¿¡ 30ºÐ°£ ´©¾îÀÖÀºÈÄ ÀÌ»óÅ¿¡¼­ ¹è´¢ÇÏ¿© ÀÌ uriine Àº discard ( time check)

         --> large glass liquid  ¸ÔÀÎÈÄ Àç¿ò --> ¾ÆÄ§¿¡ ´©¿îä collection

    ; upright collection

       - normal daily activity Çϸ鼭 2¹øcollection

# *supine collectionÀº Á¤»óÀ̰í, upright collectionÀÌ proteinuriaÀ» º¸¿©¾ß ÇÑ´Ù.

Treatment

    ; *ÃßÀû°üÂûÀÌ ¿äÇÑ´Ù.

478.2 Febrile Proteinuria

       38.3¡É ¡è ½Ã õó( 101¢µ)

       ±âÀü : unknown

       2+ ´Â ³ÑÁö¾Ê´Â´Ù.

       fever »ç¶óÁú¶§ resolve µÇ¸é benign À¸·Î »ý°¢

478.3 Exercise Proteinuria

       48 hr rest ÈÄ normal À̸é benign

       2+ ÀÌ»ó ³ÑÁö¾Ê´Â´Ù.

    ; marked prteinuria

       glomerular ds.

       CHF

       constrictive pericarditis

Chapter 479. Pathlogic Proteinuria

479.1 Tubular Proteinuria

; loss of low molecular weight protein than albumin

    - *lysozyme, light chains of Ig, ¥â2 -microglobulin, insulin, growth hormone

; *rarely exceeds 1g/24hr

; *not asso. with edema

; *asso. with other defects of tubular function

    - glucosuria, phosphaturia, bicarbonate wasting, aminoaciduria

; Dx. by electroporesis of urine

479.2 Glomerular Proteinuria

; *¡ãcommon cause of proteinuria

; variable range from less than 1g to more than 30g/24hr

; index of protein selectivity

    - C IgG/ C transferrine or albumin

  £¼ 0.1 highly selective

  £¾ 0.2 poorly selective

    - selective

           / *loss of plasma protein up to albumin including albumin

           / *MCGN

    - nonselective

           / alb. & largest MW protein loss ( IgG)

           / mostly GN

Chapter 480. Persistent Asymptomatic Proteinuria

# ¢¾Definition

    ; apparently healthy child

    ; *persist hematuria for 3mo without hematuria

    ; amount of proteinuria - less than 2g/24hr

    ; *never associated with edema

# prevalence

    ; 6% in school age children

# ¡Ú¿øÀÎ

  ; postural proteinuria, membranous, MPGN, pyelonephritis, hereditary nephritis, develpmental anormaly, benign proteinuria

# ¡ØEvaluation Of Persistent Asymptomatic Proteinuria

    ; urine culture, Ccr, 24hr protein excretion, s-alb., C3, renal U/S

    ; ¡ØAnnual Evaluation

        - UA, Ccr, BP, P/Ex, 24hr protein excretion

# renal bx. Ix.

  ; persistent asymptomatic proteinuria ¡µ1g/24hr

  ; hematuria, HT., or diminished renal function µ¿¹Ý½Ã

Chapter 481. Nephrotic Syndrome ( Nephrosis )

Etiology  

# clinical

    ; 90% idiopathic NS

    ; 10% glomerulonephritis

           - membranous GN, MPGN

# pathologic

    ; 85% minimal change

  ; 5% mesangeal proliferation

    ; *10% focal sclerosis

Pathphysiology

 ºÎºÐÀûÀ¸·Î Cap. wall³»ÀÇ negative charged glycoprotein ÀÇ loss·Î

 capillary permeability Áõ°¡ --> proteinuria

* nephrosis ¶§

  . proteinuria > 2g/day ÀÌ»ó ÁÖ·Î alb.

  . alb. 2.5g/dl in serum ÀÌÇϽà edema ¹ß»ý

# ¡ÚMechanism Of Edema Formation In Nephrosis

    ; urinary protein loss

           --> hypoalbuminemia

           --> decreased plasma oncotic pr.  

           --> transudatoin of fluid into interstitial space 

       --> decreased intravascular volume

           --> decreased renal perfusion pr.  

           --> renin-angiotensin- aldosterone system activation & release of ADH

    --> stimulation distal tubular reabsorption of sodium & collecting duct reabsorption of water

           --> reabsorped Na & water shift to interstitial space due to decreased plasma oncotic pr.

Na. & water excretion ¿¡ÀÖ¾î intrarenal defect

        Cap. wall permeability ¸¦ Áõ°¡½ÃŰ´Â circulating agent

# ¢¾Hyperlipidemia Mechanism

    ; hypoproteinemia

           - stimulation of generalized protein synthesis in the liver including the lipoprotein

    ; diminished lipid catabolism

           - due to decreased level of lipoprotein lipase

481.1 Idiopathic Nephrotic Syndrome

; 90%

; has been transformed into another type

Etiology

; unknown

; immunologic mechanism ¿¡ ÀÇÇØ mediate

; IgE mediation in some

; ̧̿: abn. in thymus-derive T-cell lymphocyte function

  --> vascular permeability Áõ°¡ÀÎÀÚ °ü¿©

Pathology

# ¡Ú3 Morphologic Pattern

  1) MCNS (85%)

        ; normal or minimal increased in mesangial cell & matrix

        ; *EM - retraction of epith. foot process

        ; IF - typically negative

           ; *95%À̻󿡼­ corticosteroid ¿¡ responce

    2) Mesangial proliferative group(5%)

        ; diffuse increase in mesangial cell & matrix

        ; IgM, C3 µîÀÌ ÁÖ·Î Ä§ÂøµÊ

       ; *50 - 60% ¿¡¼­ corticosteroid¿¡ ¹ÝÀÀ 

  3) *Focal Sclerosis (10%)

         ; mostly glomerulus - normal or mesangeal proliferation

         ; *juxtamedullary glomerulus - segmental scarring in one or more lobules

         ; *progressive course

                   --> ultimately involvement of all glomeruli

                   --> *end stage RF

         ; *20% response to prednisolone or cytotoxic therapy

         ; transplanted kid. ¿¡µµ Àç¹ßʦ

Clinical Manifestation

    ; *male:female = 2 : 1                          

           - MCNS or FS : 66% male

         - MPGN : 65% female

    ; *¡ãcommon between 2-6yr

        . URI °¡ ¼±ÇàµÇ¾î ³ªÅ¸³ª´Â °æ¿ì°¡ Òý 

           pitting edema ( periorbital, lower ext.)

             --> generalized edema, wt. loss, ascites, pleural effusion, UO ¡é.

           anorexia, abd. pain, diarrhea; common

           hypertension ; uncommon

Diagnosis

 UA: proteinuria 3+ or 4+

  Microscopic hematuria (+). Gross hematuria : rare

 Renal func. : normal or diminished

 lower Ccr. ; vol. ¡é ÀÎÇØ , renal perfusion ¡é

 --> intravascular vol. dl restore µÇ¸é normal ·Î µ¹¾Æ¿Â´Ù.

 protein excretion ; 2g/24hr ¡è (40mg/m2/day¡è)

 s- Alb. ¡´ 2g/dl

 s- Ca. ¡é ( owing to alb. bounding fraction ¡é)

 C3 ; normal

 8¼¼ÀÌÀü (1-8¼¼) onset; renal bx. ¾øÀÌ corticosteroid tx.

 8¼¼ÀÌÈÄ MCNS °¡ ¸¹Áö¸¸ membrain or MPGN ÀÌ increasingly common

    --> renal bx. ¸ÕÀú½ÃÇàÇϰí Ä¡·á

Complication

# Intection

    ; major Cx

    ; ¢ÞWhy Susceptable ?

           - decreased Ig level

       - edema fluid acting as a culture media

           - protein deficency

       - decreased bactericidal activity of leukocyte

           - immunosuppressive therapy

           - decreased perfusion of the spleen due to hypovolemia

           - loss of complement factor (properdin factor B) in urine

    ; type

           - peritonitis

                   / *¡ãcommon

           - sepsis, pneumonia, cellulitis, UTI

    ; organism

           - ¡ÚStreptococcus pneumoniae

                   / *¡ãcommon for peritonitis

           - G(-) bacteriae

    ; prevention

          - *all patients ´Â remission ½Ã polyvalent pneumococcal vaccination

# Tendency To Arterial & Venous Thrombosis Tendency

    ; ¢Þwhy ?

           - *elevated plasma levels of coagulation factor in plasma (1, 5, 7, 8, 10)

           - elevated levels of inhibitors of fibrinolysis

           - decreased levels of anti-thrombin III

           - increased platelet aggragation

    ; site

           - renal v. & IVC 

    - thrombosis, pul. embolism, cerebrocortical thrombosis

# deficiency of coagulation factors (9, 11, 12)

# reduced serum vitamin D

Treatment

# salt restriction: edema ¾ø¾îÁö¸é ÇØÁ¦

fluid intake: edema ½ÉÇÏÁö¾ÊÀ¸¸é not restrict

tolerable physical activity

# Tx of generalized edema

    ; diuretics

  i) chlorothiazide 10-40mg/kg/day #2

  ii) spironolactone 3-5mg/kg/day qid : hypokalemia Àִ°æ¿ì »ç¿ë

                                            oral kcl supplement

hospitalization

   severe edema -->respiratory destress(pleural effusion)

                 --> scrotal swelling, ascites

    ; ¡ÚSevere Edema

           - °ú°Å) iv albumin and then iv furosemide

           - ÇöÀç) ¢Àoral furosemide 1-2mg/kg every 4hr + metolazone 0.2-0.4mg/kg/day #2

         / should be monitoring of electrolyte & renal function

           - maybe 25% albumin 1g/kg24hr

                   / transient, vol. overload with hypertension & heart failure

# Corticosteroids

    ; ¡ÚPrednisone 60mg/m2/day (max. 60mg/day) #3-4

    ; usually reponse *within 2wks

           - *if not response 1mo after continuous steroid therapy

                   --> *steroid resistant ·Î »ý°¢Çϰí renal biopsy¸¦ ½Ç½ÃÇÑ´Ù.

    ; 5days after urine becomes free( -, ¡¾, + on dipstick)

           --> PRS every other day as a single dose with breakfast

           --> continued for 3-6mo

                   / ¢¾why?

                           : maintain the remission using nontoxic dose of PRS

                           : avoiding frequent relapse

                           : avoiding cumulative toxicity of frequent courses of daily administration of PRS

           - *abruptly discontinued

                   / *Ä¡·áÁß´ÜÈÄ 1³â±îÁö´Â severe illnes, surgery°¡ ÀÖÀ»¶§ corticosteroid supplementationÀÌ ÇÊ¿äÇÔ

# ¡Ú¡°relapse¡±

           - *recurrence of edema not simply of proteinuria

# steroid dependent

  ; relapses shortly after switching to or after terminating alternative-day therapy

# Tx of relapse

    ; treated in similar manner

    ; *if frequently relapse or severe toxicity of steroids, considered cyclophosphamide

           - prolongation of duration of remission

           - 3mg/kg/24hr as a single dose for 12wks

           - renal bx. recommanded before trial

           - S/E

                   / leukopenia, disseminated varicellar infection, hemorrhagic cystitis, alopecia, sterility

           - WBC count weekly

                   / if WBC < 5000/mm3, discontinued

# Tx of steroid resistent

    ; 3-6mo cyclophosphamide + methylprednisolone

    ; cyclosporine

# renal transplantation

    ; end stage renal failure due to steroid resistent focal & segmental glomerulosclerosis

# recurrent nephrotic syndrome

   ; 15 - 55% of pt.

Prognosis

       repeated relapse µÇ¸é steroid responsive nephrotic syndrome ÀÇ °æ¿ì

            2nd decade ¸»¿¡ spontaneous resolution µÊ

         +-residual renal dysfunctionÀ̾ø°í

         | generally not hereditary

         +-fertile ( unless cyclophosphamide or chorambucil tx. )

             --> reassurance é©

        remission ½Ã´Â normal & unrestricted diet & activity

            --> ´õÀÌ»ó urine protein check ÇÊ¿ä¾øÀ½

481.2 Glomerulonephritis

: 2ndary nephrotic syndrome /ass,c Glomerulonephritis    

-- nephrotic syndrome may develop during the course of any type of  GN.

   /mc in ass.    membranous

                  MPGN

                  PSGN

                  Lupus

                  Chr. infection( malaria, Schistosomiasis)

                  H S P nephritis

              ; secere Glo. ds. ÀǹÌÇϳª nephritis ÁÁ¾ÆÁö¸é¼­ resolve ʦ

481.3 Tumors

# solid tumor such as carcinoma

    ; membranous glomerulopathy

             immune complex ds.( tumor Ag. °ú tumor specific Ab. ·Î ±¸¼ºµÈ  

                                     immune complex ¿¡ ÀÇÇØ mediate µÊ )

# Lymphoma ( esp. Hodgkin ds.)

  ; ¡Øminimal change ds.

           - *¡ãcommon

    ; proliferative change

               ; lymphokine by tumor --> Glo. cap. permeability 

481.4 Drugs

# membranous glomerulonephropathy

    ; penicillamine, gold, mercury compounds, captopril

# minimal change ds

  ; probenecid, ethosuximide, methimazole, lithium

# proliferative GN

  ; procainamide, chlorpropamide, phenytoin, trimetadione, paramethadione    

481.5  Congenital Nephrotic Syndrome

# ¢¾Causes Of Nephrotic Syndrome In 1st 6mo Of Life

    ; congenital nephrotic syndrome

    ; congenital infection

           - syphilis, toxoplasmosis, CMV

  ; diffuse mesangial sclerosis of unknown origin

           - Drash synd. : nephropathy, Wilms tumor, genital abnormalities

# causes of nephrotic syndrome between 6-12mo

    ; idiopathic nephrotic syndrome

    ; drugs

Congenital Nephrotic Syndrome (= Infantile Microcystic Ds., Finnish Type)

    ; A.R.

  ; common in scandinavian descent

Pathology

   ; proximal convoluted tubule ÀÇ dilatation ( microcystic ds.)

   ; glomeruli -- mesangial prolif. & sclerosis

Pathgenesis

    ; unknown

Clinical Manifestation

 ; proteinuria ( birth or ´ë°³ 3mo À̳»)

 ; ass. sx.

   i) prematurity

   ii) enlarged placenta

   iii) resp. destress

   iv) separation of cranial suture

Prognosis

 course: persistent edema

   recurrent infection

    death by 5yr of age (¡ñ infection or renal failure ·Î »ç¸ÁÇÑ´Ù.)

Treatment

  ; supportive

  ; kidney transplantation--> ±Ã±ØÀûÀ¸·Î

  corticosteroid & immunesuppressive agent : no value

  AFP: prerenal Dx. °¡´É (20ÁÖÀÌÀü¿¡)

Section 4. Tubular Disorders

Chapter 482. Tubular Function

Sodium

         1) reabsorption

          +-65% of filtered Na+ : proximal tubule

          |      glucose & aminoacid °¡ ÇÔ²² reaborption

          |      --> isotonically absorbed

          +-25% : ascending liimb of loop of Henle

          |       active transport of Cl  ¿Í ÇÔ²²

          +-10% : distal tubule & collecting duct

                  mediated by aldosterone

                  ÀÌ¿Í °°Àº reabsorptionÀ¸·Î »ýÈÄ 1¼¼ÀÌÈĺÎÅÍ

                  urinary Na concentration ÀÌ 1mEq/L À¯Áö

         2) excretion

            ECF vol.°ü¿© ¡ç ECF vol. regulating factor¿¡ ¿µÇâ ¹ÞÀ½

Potasium

        1) absorption

           all of the filtered potasium, reaborbed in proximal tubule

       2) excretion

         distal tubular & collecting duct secretion

            modified by    ECF pH

                          aldosterone

                          urine flow rate & Na + conc.

Calcium

         98% Èí¼ö at tubule

         65% °¡ prox. tubule ¿¡¼­ Na Èí¼ö¿Í °ü·Ãêó

         . Èí¼öÀÇ Áõ°¡    PTH

                          reduction of ECF

                          thiazide diuretics

       . Excretion Áõ°¡    saline infusion

                          furosemide

Phosphate

: ´ëºÎºÐ prox. tubule

                   reabsoption inhibited by PTH

Magnesium

: prox. tubule ¿¡¼­ 25%Èí¼ö( 1/4)

                    ´ë°³ Èí¼ö ¹× moderation of Mg excretion ÀÇ ÁÖ¿äÀå¼Ò:

                    thick ascending limb of Henle

Maturation Of Tubular Function

       ; at birth & ±×ÈÄ ¸î°³¿ù±îÁö´Â tubular functional capabilities °¡ ¼ºÀκ¸´Ù ³·´Ù.

          healthy newborn ÀÇ maximal urinary conc. capacity  °¡ ³·´Ù.

          ( 600 - 700mOsm/kgH2O )

         # ³·ÀºÀÌÀ¯

               reduced GFR

               tubular cell immaturity

               reduced nephron length

               reduced medullary solute gradient

               due to +-increased medullary blood flow

                         +-low urea production

               ADH ¿¡ diminished tubular responsiveness

          newborn ÀÇ diluting capacity´Â adult ¿Í À¯»ç

          water load excretion °¨¼Ò  in NB ( low GFR ¶§¹®)

          newborn Àº Na+ , K+ , H+ , phosphate excretion °¨¼Ò

           --> due to  +-low GFR

                        +-immaturity of tubular function

      #  Tubular Ds.

         1) functonal

              defect in the function of tubular cell

              relatively rare

              inherited or acquired

              initially normal renal function

              ÀϺδ progressive renal damage

        2) anatomic disorder

           structure of tubule ÀÇ ÀÌ»ó

            ex) cystic ds.

Chapter 483. Renal Tubular Acidosis

         : impaired urinary acidification ¿¡ÀÇÇÑ systemic hyperchloremic acidosis ÀÇ

           clinical state.

        . Type

             type I : distal RTA

             type II : proximal RTA

             type IV : mineralocorticosteroid deficiency        

               cf) type III : variant type I

Normal Urinay Acidification

       filtered HCO3 ÀÇ 85% ´Â prox. tubule ¿¡¼­ reabsorption µÈ´Ù.

       ³ª¸ÓÁö 15%´Â distal tubule ¿¡¼­ reabsorption. --> premature ¿Í neonate ¿¡´Â         ÀϽÃÀûÀ¸·Î ¾à°£ °¨¼ÒµÊ

       acidification mediated by

         i) distal tubular secretion of H+

            (ÀϺδ mineralocortocoid - dependent)

         ii) distal tubular secretion of ammonia

            ( acidic urine ¿¡¼­ ammonium ion Çü¼º )

       ¡¤ normal kid. ´Â filter µÈ ¸ðµç bicarbonate¸¦ Èí¼öÇÑ´Ù.

       ¡¤ bicarbonate ÀÇ prox. tubular reabsorptionÀº Na+ ¿Í ±³È¯ÇÏ¿© tubular umen            ³»·Î H+ ÀÇ ºÐºñ¸¦ À¯¹ßÇÑ´Ù.

       ¡¤ H+ Àº carbonic acid ¸¦ Çü¼ºÇϱâ À§ÇÏ¿© carbonic anhydrase ¿¡ ÀÇÇØfiltered

          bicarbonate ¿Í °áÇÕÇÑ´Ù. --> ÀÌ´Â water ¿Í carbon dioxide ·Î ÇØ¸®µÈ´Ù.

       ¡¤ carbon dioxide ´Â proximal tubular cell ·Î diffusion µÈ´Ù.

       ¡¤ ¿©±â¼­ carbonic anhydrase ÀÇ ¿µÇâÀ¸·Î ´Ù½Ã carbonic acid ·Î change µÈ´Ù.

       ¡¤ carbonic acid ´Â H+¸¦ »ý¼ºÇϱâ À§Çؼ­ ÇØ¸®µÇ°í ÀÌ´Â ´Ù½Ã bicarbonate ¸¦

          Èí¼öÇϱâÀ§ÇØ ºÐºñµÈ´Ù. ±×¸®°í À̶§ bicarbonate ´Â ´Ù½Ã peritubular cap. ·Î

          µé¾î°£´Ù.

¢ÞTable 483-1

Proximal RTA ( Type II)

Pathgenesis

     1) reduced prox. tubular reabsorption of bicarbonate  

       presumably due to deficient carbonic anhydrase production --> prox. tubule           ¿¡¼­ 60%¸¸  reabsorption ( distal tubuleÀº 15% ¸¸ Èí¼ö )

       25% ±îÁö urinary loss

      ; prox. RTA more severe than distal RTA

     2) Lab/f

          s-bicarbonate ¡é: 15 - 18mEq/L (bicarbonate threshold )

          urine Àº acidified( pH¡´ 5.5) ¡ñ distal tubule ÀÇ acidification mechaniam Àº

                      intact Çϱ⠶§¹®¿¡ filtered bicarbonate °¡ °¨¼Ò

          hypokalemia

          distal tubule ¿¡¼­ NaHCO3 ´Ù·® --> Na  reabsorption in exchange for k+

          Hyperchloremia

           ECF vol. °¨¼Ò·Î ÀÎÇØ +- chloride  reabsorption ÀÚ±Ø

                                +- aldosterone secretion ¡è --> k+ loss¡è  

   3) classification of prox. RTA

     a) isolated prox. RTA

          transient or persistent

          sporadic or inherited ( ´ë°³ A.D. )

     b) Fanconi synd.

       ; generalized defect in prox. tubular transport   

       Ư¡ : glucosuria

             phosphaturia

             aminoaciduria

             prox. RTA

      * primary Fanconi synd. : A.D. or recessive

      * secondary  Fanconi synd. : inherited form , acquired form

 Inherited Form

Cystinosis

: AR

          i) nephropathic form: 3¼¼ÀÌÇÏ õó

               Sx.: polyuria, polydipsia(conc. defect), Fever (dehydration), growth                          retardation

                     rickets, hotophobia, blond hair & fair skin(diminished pigment) 

               Dx.: cystine crystal in cornea by slit lamp

                    elevated cystine contents of leukocytes

               course : progressive renal damage ¡ç intracellular cystine accum.

                     end stage RF at end of 1st decade

               Tx. : none, cysteamine À¸·Î ÀÓ»ó½Ãµµ

         ii) Juvenile form: later in life, less severe

Lowe Syndrome

         i) X-linked

         ii) mental retardation

         iii) Hypotonia

         iv) cataract, glaucoma

         v) generalized prox. tubular dysfunc.

            unknown metabolic defect

Galactosemia

        prox. tubule ¿¡¼­ prolonged ÇÑgalactose acc. À¸·Î ÀÎÇØ¼­ renal manifestationÀÌ

        ³ªÅ¸³²

        Hereditary fructose intolerance

          AR

          fructose 1-phosphate aldolase def.

        tyrosinemia

        Wilson ds.

        medullary cystic ds.

      AD

       cf) ºñ½ÁÇÑ ÁúȯÀÎ nephronophthisis ´Â AR

        children Àº recessive °¡ Òý

        adult ´Â dominant  °¡ Òý

       .Pathology

        cyst in the medulla: dilatation of the distal tubule & collecting duct

        progressive interstitial inflammation & fibrosis ·Î ÀÎÇØ

        --> glomerular sclerosis, cortical atropy, renal insufficiency

        cause of acquired Fanconi synd.

           heavy metals( lead, mercury, cadmium, uranium)

           out-dated tetracycline

           proteinuric states ( myeloma, nephrotic syndrome )

           interstitial nephritis

           hyperparathyroidism -+

                                | carbonic anhydrase inhibition ¿¡ÀÇÇØ prox. RTA

                                | ÀÇ ¿øÀÎ

           vit-D def. reckets ---+ 

Distal RTA (Type I)

            distal tubule °ú cdllecting duct ¿¡¼­ H+ secertion deficiency

            urinary HCO3 ÀÇ loss´Â ´ë°³ (5 - -15%)

            severe systemic acidosis Áö¸¸ urine pH ´Â 5.8 ÀÌÇÏ´Â µÇÁö¾ÊÀ½

            hyperchloremia, hypokalemia

            nephrocalcinosis ʦ

          +-isolated

          |     sporadic

          |     inherited: AD or AR

          +-2ndary i) interstitial nephritis

                  ii) toxin, amphotericin B, lithium, toluene

Medullary Sponge Kidmey

            non-inherited ds.

            º´¸® : cystic dilatation of the terminal portion of the collecting duct

                          ( renal pyramid µé¾î°¡´ÂºÎºÐ)

            renal func. & life span : normal

            µ¿¹Ý

             pyelonephritis, hypercalciuria, nephrocalcinosis

             nephrolithiasis, distal RTA , impaired concentrating capacity

Mineralocorticoid Deficiency ( Type IV)

         1) ±âÀü :    aldosterone ÀÇ inadequate production

                     aldosterone ¿¡ distal tubule ÀÇ responsiveness °¨¼Ò

           --> tubular cell mb. ¿¡ electrochemical gradient Çü¼º ¾ÊµÊ

                tubular lumen ÀÌ negative µÇ¾î H+ ion secretion °¨¼Ò ÀߵǰÔÇÏ´Â

                gradientÇü¼º¾ÊµÊ

           --> Aldosterone mediated Na+ resorption °¨¼Ò

           --> hyperkalemic , hyperchlooremic acidosis (-> renal ammonia

            production °¨¼Ò-> ammonium ion excretion °¨¼Ò -> urine pH 5.5 ÀÌÇÏ )

         2) ¿øÀÎ

              adrenal gl. ds. ( aldosterone ¡é, renin ¡è)

             i) addison ds.

             ii) cong. adrenal hyperplasia

             iii) primary hyper aldosteronism

              : ald. production °¨¼Ò

                normal renal fx.

               urinary Na+ wasting, plasma renin level ¡è

              Hyoreninemic hypoaldosteronism ( renin & aldo. ¡é)

              i) kid. ds. /c interstitial damage &

                   juxtaglomerular apparatus destruction

              ii) vol. expansion --+°úµµ °ü¿©

                 PG inhibition ---+

                   : renal function °¨¼Ò

             pseudohypoaldosteronism ( renin & ald. ¡è)

             i) distal tubular responsiveness to ald.

                 : normal renal function

                   salt wasting

            ii) renal insufficiency & medllary ds. °¡ÀÖ´Â adult ¿¡¼­ º¼¼öÀÖÀ½

Clinical Management Of RTA

Clinical Manifestation

# isolated form of prox. & distal RTA

    ; *growth failure toward the end of 1yr of life

    ; GI symptoms

# secondary

  ; similar to isolated form

    ; underlying ds features

# Mineralocorticoid deficiency

  ; underlying ds feature

# distal RTA

    ; hypercalciuria

       - nephrocalcinosis

      nephrolithiasis

      renalparenchymal destruction

(2) ¿øÀÎ :unknown

    °¡´É    calcium carbonate release À§ÇØ bone destruction

             ( acidosis ±³Á¤À§ÇØ carbonate --> bicarbonate )

            urinary citrate °¨¼Ò --> calcium chelation

Diagnosis

1) systemic acidosis ÀÏÀ¸Å°´Â ÁúȯÀ» ¸ÕÀú R/o

   diarrhea, lactic acidosis, DM, renal failure

2) Lab.

    prox. & distal RTA : s- bicarbonate ¡é, s- k+¡é, hyperchloremia

    Mineralocorticoid deficiency, RTA, systemic acidosis, hyperkalemia

 3) 1st morning urine pH ¿Í µ¿½Ã ¿¡ s- electrolyte ÃøÁ¤ ; prox. & distal RTA             ÀǽɽÃ

  s- HCO3 < 16mEq/L

  pH < 5.5: proximal RTA

  pH > 5.5: distal RTA 

  s- HCO3 ( 17 - 20mEq/L)

  i) ammonium chloride loading ÈÄ °¨º°Ê¦

  ii) fractional excretion of bicarbonate

        4) prox. RTA ½Ã glucosuria, phosphaturia, aminoaciduria ã±â

        5) RTA confirm ½Ã  underlying cause ã±â

Treatment

 Goal +--   correction of acidosis

      +--   maintenance of normal HCO3, k+

  Shohl solution

   : normal alkalinizing solution for oral use containing

    1,mEq/L of sodium as sodium citrate

  potassium citrate ÷°¡ ( 1mEq/L of Na, K & 2mEq/L HCO3)

  NaHCO3 tablet (325 - 650mg) in order pt.

  diuretics & kayexalate for Mineralocorticoid deficiency   

Prognosis

       1) isolated prox. RTA

          óÀ½¿£ distal º¸´Ù ½ÉÇϳª resolution ʦ

       2) isolated distal RTA

            life long ds. ( renal failure ´Â ¹ß»ýÇÒ¼ö ÀÖÁö¸¸)

            early detection & treatment before nephrocalcinosis ½Ã excellent Px.

            continuing alkali therapy & life long monitoring of clinical status

     3) Mineralocorticoid RTA

       ´ë°³ obstructive uropathyÈÄ õó ÇϹǷΠ obstruction correction ÈÄ 12mo ³» ¼Ò½Ç

483.1 Rickets Associated with RTA

     rickets may be present type II RTA or proximal RTA

     hypophosphatemia & phosphauria

     hyperchloremia, metabolic acidosis, bicarbonuria, hyperkaliuria

     bone demineralization - Type I & distal RTA

       type I - ÀûÀýÇÑ acid urine Çü¼ººÒ°¡

       type II - lowered renal threthold for bicarbonate

                impaired urinary acidification

     metabolic bone ds. - occured in both type

   ¢¹ Ư¡ : bone pain, growth retardation, osteopenia, pathologic fracture

     RTA pt. ¿¡¼­ 1,25(OH)2D ´Â normal

     RTA pt. ¿¡¼­ azotemia ³ª renal mass ÀÇ loss °¡ ÀÖ´Â °æ¿ì

      -- serum 1,25(OH)2D ´Â Á¾Á¾ °¨¼ÒÇÑ´Ù.

     distal RTA ¿¡¼­ bone dimineralization

          - dessolution of bone

          - because -- CaHCO3 °¡ metabolic acidosis ¿¡´ëÇÑ buffer·Î ÁÖ¾îÁö±â¶§¹®

    acidosis ¸¦ ¿ªÀü½Ã۱â À§ÇÑ bicarbonate ÀÇ Åõ¿©´Â

          bone dissolution & hypercalciuria ¸¦ ¸ØÃß°Ô ÇÔ.

   ¢¹Treatment.

   proximal RTA - bone ds. ÀÇ Ä¡·á¸¦ À§ÇØ bicarbonate ¿Í oral phosphate¸¦ Åõ¿©

   vit-D : secondary hyperparathyroidism¿¹¹æ

483.2 Fanconi Syndrome

(rickets associated with multiple defect of the proximal renal tubule)

   1) °³¿ä

     1. Ư¡ : generalized aminoaciduria, renal glycosuria. & phosphaturia resulting in

               hypophosphatemia

     2. ass. but inconstant renal tubular abn.

          a. excessive bicarbonaturia leading to RTA

          b. hyperkaliuria leading to hypokalemia

          c. rmdhl sodium wasting, uricosuria, proteinuria & hyposthenuria

     3. clinical hallmarks

           a. linear growth failure

           b. rickets resistant to dose of vit.-D that are ordinarily adequate for tx. of

              nutritional deficiency

  2) Etiology

     1. genetically transmitted inborn error of metabolism

       ; cystinosis, fructose intolerance, galactosemia, glycogenosis, Lowe synd.

         tyrosinemia, & wilson ds.)

     2. some acquired ds.

       : including exposure to environmental toxins      

       a. heavy metals; Cd, Pb, Hg.

       b. drugs; tetracycline, gentamicine, azathiopurine

     3. Idiopathic : /mc

        sporadic or inherited as a mendelian dominant or recessive

  3) Pathogenesis

     1. abn. in some final common pathway for normal mb. trnsport in the prox.               renal tubule

       : deficient energy production, abnormalities in mb. str. or both°¡ impaired

         tubular uptake or back-leak of solutes À» ÃÊ·¡ÇÔ

     2. renal potassium wasting Àº bicarbonate & glucose ÀÇ excessive urinary loss

        ¿¡ÀÇÇØ ÃÊ·¡µÊ

     3. urinary sodium loss´Â large excretin of urinary anion ¿¡ ÀÇÇÔ

     4. normal to low serum calcium, varable urinary calcium

     5. vasopressin - resistant urinary concentrating defect °¡ Á¾Á¾ ³ªÅ¸³².

     6. rickets´Â  combined effects of metabolic acidosis & hypophosphatemia

        or  hypophosphatemia alone ¿¡ ÀÇÇØ ÃÊ·¡µÊ

     7. vitamin D resistance ´Â metabolic acidosis Á¸Àç½Ã ³ªÅ¸³ª´Â abn. prox. tubular          cells ¿¡ ÀÇÇØ¼­ conversion of vitamin D to 1.25(OH)2 D2 ÀÇ Àå¾Ö¿¡ ÀÇÇÔ  

     8. nonspecific microscopic findings

        a. dilatated renal tubules, with variation in size & shape, swelling of epithelial             cells, & atropy

        b. common foci of interstitial fibrosis

        c. enlarged mitochondria on EM

        d. Ư¡ÀûÀ¸·Î glomerular architecture´Â ¸»±â±îÁö º¸Á¸µÊ

   4) Clinical manifestations

     1. primary Fancony synd. Àº Ư¡ÀûÀ¸·Î first 6mo of life ȤÀº 3rd or 4th decade

       ¿¡ ³ªÅ¸³².

     2. ¿µ¾Æ±â¿¡´Â vomiting , polydipsia, polyuria, contipationÀÌ ¹ß»ýÇÔ

     3. episode og weakness, fever /c dehydration, & metabolic acidosis

     4. failure to thrive, especially in linear growth

     5. adquate vit-D intake & the absence of glomerular insufficiency ¿¡µµ ºÒ±¸Çϰí

      ¹æ»ç¼±ÇÐÀûÀ¸·Î rickets , steopenia ³ªÅ¸³². À̼ҰßÀº renal tubular cause ¸¦

      ³ªÅ¸³½´Ù.

   5) Lab.

      1. hyperchloremic metabolic acidosis /c normal "anion gap", hypokalemia,

         hypophosphatemia, & hypouricemia

      2. elevated fractional excretion of phosphate

      3. elevated ALP activity if rickets is present

      4. glycosuria at normal serum glucose concentrations

      5. generalized nonspecific aminoaciduria

      6. inappropriatly elevated urinary pH , /c low levels of urinary ammonia &

         titratable acid

      7. ¸»±â¿¡ GFR ÀÌ °¨¼ÒÇϸé s-electrolyte ¿Í aminaciduria, glycosuria.&

          phosphaturia ÀÇ "paradoxic" improvement ¸¦ º¸ÀÓ

    6) Dx.

      1. no definite diagnosis test for idiopathic Fanconi syndrome

      2. aminoaciduria, diminished tubular reabsorption of phosphate, & elevated ALP

        activity

      3. child /c stunted growth. rickets refractory to ordinary doses of vit-D , renal

         glycosuria ´Â multiple tubular dysfunctionÀ» ÀÏÀ¸Å´

      4. metabolic acidosis, hypokalemia : È®ÁõÀû

      5. fluid deprivative to test urinary concentrating ability

         : risky in the face of obligatory hyposthenuria

      6. glucose loading : profound symptomatic hypokalemia by shifting potassium

         into cells À» ¾ß±â

  7) Treatment

    1. 2ndary Fanconi syndrome ȯÀÚ´Â underlying cause ¸¦ ã¾Æ¾ß ÇÑ´Ù.

    2. primary Fanconi syndrome Àº mineral & electrolyte balance µîÀÇ                     symptomatic therapy ¸¦ ½ÃÇàÇϸé, »ý¸íÀ» ¿¬ÀåÇϰí Á¾Á¾ normal life ¸¦ ¿µÀ§ÇÑ´Ù. 

    3. ricketsÀÇ Ä¡·á, skeletal deformities ¿¹¹æ

    4. rickets or osteopenia ÀÇ Ä¡·á

      a. i) large dose of vit.-D : usual starting dose 5000u/24hr

                                maximal dose 2000 - 4000 u/kg/day

        ii) dihydrotachisterol : starting dose 0.05 - 0.1 mg/24hr

            ( 1mg is equivalent to 120000 u of vit-D)

        iii) 1,25(OH)2D : greater potency, shorter half-life, hypercalcemia ÃÊ·¡°¡ ÀåÁ¡

      b. vit-D over dose ¿¡ÀÇÇÑ hypercalcemia ¸¦ ¹æÁöÇϱâ À§Çؼ­ s-Ca. level À»

         ÁÖ±âÀûÀ¸·Î ( weekly at first, then monthly) À¸·Î ÃøÁ¤

      c. hypophosphatemia ÀÇ Ä¡·á

       i) oral supplementation /c 1 - 3g for neutral phosphate/24hr given in

             4 - 5 equally spaced dose  

       ii) abdominal pain, diarrhea °¡ Ä¡·áÁß ³ªÅ¸³ª¸é ÀϽÃÀûÀ¸·Î Áß´ÜÈÄ lower dose

           ·Î ´Ù½Ã ½ÃÀÛ

       iii) phosphate ´Â hypocalcemia, 2ndary hyperparathyroidism À» ¹æÁöÇϱâ À§ÇØ              ¼­ ¹Ýµå½Ã vit.-D ¿Í µ¿½Ã¿¡ Åõ¿© 

    5. metabolic acidosis due to excessive bicarbonaturia ±³Á¤Àº ¸¹Àº ¾çÀÇ alkali

          ( 2 - 15 mEq/ kg/24hr of alkali ) °¡ ÇÊ¿äÇÔ

      a. i) sodium bicarbonate : 1 mEq of base = 1ml

        ii) shohl solution :   1 mEq of base = 1ml

             ( 140 g of citric acid, 90 g of sodium citrate qs to 1L with water)

        iii) polycitra : 2 mEq of base = 1ml

          ( 5ml = 550mg of potasium citrate, 500mg of sodium citrate, 334mg of

            citric acid )

      b. serum bicarbonate level À» °ÅÀÇ normal level (18-20mEq/L)±îÁö

           ±³Á¤ÇÏ¿©¾ßÇÔ

      c. alkali´Â 1-1¨ö hr after meals in 3-4 divided dose/day ¿¡ º¹¿ë

      d. extra salt & water should be provided to counter excessive losses

483.3 Cystinosis ( Lignac Synd., Fanconi Syndrome With Cystinosis )

  1) Ư¡

     1. the clinical & lab. features of  Fanconi syndrome

     2. the additional distinctive finding of abn. accumulation of cystine in

        various tissues

  2) Pathgenesis

    1. unknown cause

    2. increased uptake of cystine ´Â  lysosomes ¿¡ ÃàÀûÀ» ÃÊ·¡ÇÔ

       ÀÌ´Â ÀÌ amino acide ÀÇ lysosomal release ÀÇ failure ¿¡ ÀÇÇÔ

        specific enzyme defect ´Â ¹ß°ßµÇÁö ¾Ê¾ÒÀ½

    3. cystine deposition ÀÇ ºÎÀ§

       i) RES system : esp. in spleen, liver, lymph node & BM

       ii) renal tubular cells, cornea & conjunctiva

       iii) periperal blood leukocyte & fibroblasts

       iv) but not in muscle & brain

  3) Á¶Á÷ ¼Ò°ß

     1. early renal change ´Â primary  Fanconi syndrome °ú À¯»ç

       Ư¡ÀûÀÎ "swan neck" lesion : atropy & shortening of the proxiomal tubule

       just beneath the glomerulus

    2. birefringent cystine cristals in interstitial tissue, but rare in tubular cells

    3. renal failure °¡ ÁøÇàÇÔ¿¡ µû¶ó kid. ´Â shrunken & contracted ,

       with glomerular sclerosis & interstitial fibrosis

  4) ÀÓ»ó¼Ò°ß

     1. AR rait

     2. three clinical patterns

       a. infantile or nephropathic form

         i) 3 -12 mo°æ  Fanconi syndrome À¸·Î ³ªÅ¸³²

         ii) generalized aminoaciduria /s predominance of cystine

         iii) GFR ÀÌ Á¡Â÷ °¨¼ÒÇÏ¿© CRF °¡ 1st decade À̳»¿¡ ¹ß»ý

         iv) severe growth failure, hypothyroidism

         v) distinctive clinical features

           ;brond hair & fair complexion, owing to defect inb melanin synthesis

            photophobia 2ndary to deposite  of cystine crystals on the cunjunctiva

        b. adolescent or intermediate form

          i) mild renal involvement with onset in the 2nd decade & slow progression

          ii) growth failure is not a feature of this form

        c. adult type

          i) benign, no renal ds.

          ii) cystine crystals in the cornea, BM, & leukocytes

   5) °Ë»ç¼Ò°ß

     1. deposition of cystine crystals ¿Ü¿¡´Â Fanconi syndrome °ú À¯»ç.

     2. tubular proteinuria °¡ nephropathic cystinosis ÀÇ early phase Ư¡À̳ª

        renal failure °¡ ÁøÇàÇÔ¿¡ µû¶ó glomerular proteinuria °¡ ÀÕµû¶ó ³ªÅ¸³­´Ù.

   6) Áø´Ü

     1. in the asymptomatic NB infant from an affected family

        : cystine content of leukocytes or fibroblasts (Á¤»óÀÇ 80 - 100¹è)

     2. later, granular & circinate irreguralities in the peripheral pigmentation of the           retina

     3. cystine crystals in the BM, lymph nodes, conjunctivae, and rectal mucosa

     4. slit lamp examination»ó cornea¿¡ crystal

     5. prenatal diagnosis´Â amniotic fluid cells¿¡ increased cystine concentration

     6. cystine depositionµµ Fanconi syndromeµµ ³ªÅ¸³ªÁö ¾Ê´Â cystinuria¿Í È¥µ¿ÇÏ¿©         ¼­ ´Â ¾ÈµÇ¸ç, ÀÌ´Â an inborn error of specific amino acid transportÀÌ´Ù.

  7) Ä¡·á

    1. Ãʱ⿡ tubular dysfunction¿¡ ´ëÇÑ symptomatic therapy´Â primary Fanconi              syndrome³ö À¯»çÇÏ´Ù.

    2. cysteamine(sulfhydryl binder) : in vivo¿¡¼­ intracellular cystineÀ» °¨¼Ò½Ã۸ç,            ¸î¸î ¼Ò¾Æ¿¡¼­´Â renal failure ÁøÇà¼Óµµ¸¦ ¿ÏÈ­½ÃŲ´Ù.

    3. hemodialysis and renal transplantation for end-stage renal failure

    4. renal transplantation ÈÄ¿¡´Â ȯ¾Æ´Â Àß Áö³»³ª long-term survivors´Â

      a. progressive photophobia or retinopathy¸¦ °æÇèÇÑ´Ù. ÀÌ °æ¿ì cystiamine eye            dropsÀÌ È¿°úÀÖÀ½

      b. associated with long-term extrarenal manifestations

      : swallowing dysfunction, myopathy, pancreatic endocrine and exocrine                     insufficiency, and various CNS problems(Áï seizure, cerebral atrophy)

483.4 Oculocerebrorenal Dystrophy (=Lowe Syndrome)

 1)°³¿ä

    1. rare disorder, X-linked recessive trait

    2. in addition to Fanconi syndrome, organic aciduria, decreased production of                 urinary ammonia, an occasionally heavy proteinuria               

    3. distinctive clinical features

      : congenital cataract, glaucoma, and buphthalmos

    4. ±×¿Ü Ư¡À¸·Î

      a. severe hypotonia and hyporeflexia in the lst year

      b. severe and often progressive mental retardation

      c. rickets, marked osteopenia, and pathologic fracture as a result of metabolic             acidosis and phosphate depletion

 2)PATHOGENESIS

   1. unknown pathogenesis, ±×·¯³ª ÃÖ±Ù in vitro studies¿¡¼­ collagen metabolismÀÇ

     ÀÌ»óÀ» ÀǽÉÇÔ

   2. pathologic studies´Â splitting of the glomerular basement membrane, with

      marked variation in their thickness¸¦ º¸ÀÓ

 3)ÀÓ»ó¼Ò°ß

    1. early life : eye findings and mental retardation

      later : Fanconi syndromeÀÌ ÀÓ»óÀûÀ¸·Î ºÐ¸íÇØÁü

    2. childhood½Ã±â¸¦ »ì¾Æ³²À¸¸é Fanconi syndromeÀº spontaneouslyȸº¹µÇ³ª, CRF°¡         µÉ ¼ö ÀÖÀ½

  4)Ä¡·á

    1. no specific therapy

    2. supportive, as in primary Fanconi syndrome

483.5 Renal Osteodystrophy

  1)°³¿ä

   1. renal osteodystophyÀÇ Àǹ̴ chronic renal disease¸¦ °¡Áø ȯ¾Æ¿¡¼­ mineral°ú         bone metabolismÀÇ ÀÌ»óÀ¸·Î ³ªÅ¸³ª´Â skeletal growth¿Í remodelingÀÇ º¯È­ÀÌ´Ù.

   2. these abnormalities include

     a. malabsorption of calcicum, phosphaste retention, hyperfuncion of the                          parathyroid glands

      b. cutaneous, vascular, and visceral calcifications

      c. impairment in the renal production of biologiclally active vitamin D

   3. GFRÀÌ Á¤»óÀÎ tubular dysfunction½Ã¿¡µµ ³ªÅ¸³¯ ¼ö ÀÖÀ¸³ª, glomerular                      insufficiency³ª uremia¸¦ °¡Áø ȯ¾Æº¸´Ù´Â ÈçÇÏÁö ¾Ê´Ù.

   4. ÀÌÀü¿¡´Â renal (uremic) rickets ȤÀº renal dwarfismÀ̶ó ºÒ·È´Âµ¥, ÀÌ´Â severe         linear growth failure°¡ rickets¿Í °°Àº X-ray change¸¦ º¸¿´±â ¶§¹®

     a. ÀÌ ¼Ò°ßÀº ÀÏÂ÷ÀûÀ¸·Î vitamin D deficiency¿¡ ´ëÇÑ mineralization defect¿¡ ±âÀΠ        ÇÑ´Ù°í ¸ÕÀú »ý°¢µÇ¾úÁö¸¸,

     b. ÀÌÂ÷ÀûÀÎ hyperparathyroidismµµ ÀÓ»óÀû, ¹æ»ç¼±ÇÐÀûÀ¸·Î ¶È°°ÀÌ Áß¿äÇÑ ¿ªÇÒÇÔ

   5. pediatric dialysis, kidney transplantationÀ» ½ÃÇàÇÔ¿¡ µû¶ó renal osteodystrophy°¡       CRFÀÇ ÁÖ¿äÇÕº´Áõ(acidosis, anemia, calororic deficiency µî°ú ÇÔ²²)À¸·Î ¶°¿Ã¶ú´Ù.

 

  2)PATHOGENESIS

    1. normal dietary intake of phosphorus¸¦ °¡Áø early in the course of chronic renal         insufficiency(GFR 25  50§¢/min/1.73m2)¿¡´Â

     a. renal tubular synthesis of 1,25(OH)2D3°¡ phosphate-mediated suppressionµÇ¾î

       a) malabsorption of calcium and phsphorus

       b) unknown mechanismÀÇ defective mineralization of osteoid(osteomalacia)ÃÊ·¡

     b.Áõ°¡µÈ PTHÀÇ °á°ú, increased bone resorption°ú increased renal phophate              excretionÀ» ÃÊ·¡Çϸç, serum calcuimÀº À¯ÁöµÇ¸ç serum phophorus´Â ½ÇÁ¦ÀûÀ¸·Î

        normal¿¡¼­ lowÀÌ´Ù.

     c. dietary phophate restrictionÀº serum 1,25(OH)2D3 levelÀÇ Áõ°¡¿Í, 2ndary                       hyperparathyroidismÀÌ improveµÊ

   2. critical renal threshold(¿¹¸¦ µé¾î GFRÀÌ Á¤»óÀÇ ¾à 25  30%)ÀÏ ¶§´Â

       a. Áõ°¡µÈ PTH¿¡ ´ëÇÑ phophaturic renal responseÀÇ ¼Ò½Ç

       b. compensatory hyperparathyroidismÀÌ serum calciumÀ» Á¤»óÀ¸·Î ȸº¹½Ã۱⠠          À§Çؼ­ ÀÕ´Þ¾Æ ÀϾ´Ù.

       c. roentgenographic and histologic evidende of exaggerated osteoclast mediated                 resorption of bone(osteitis fibrosa)

       d. endosteal fibrosis, increased bone turnover and replacement of regularly

       textured lamellar bone with disorganized and structurally deficient woven bone

   3. chronic metabolic acidosisµµ ¾Æ¸¶µµ bone¿¡¼­ calcium resorption°ú renal                 excretionÀ» Áõ°¡½ÃÅ´À¸·Î½á bony change¸¦ ¾ß±â½ÃÅ´

   

  3)Á¶Á÷¼Ò°ß

    1. variable

    2. trabecular boneÀº predominant osteomalacia, predominant osteitis fibrosa ȤÀº          most commonly, a mixed patternÀ» ³ªÅ¸³¿

    3. ÀϺΠȯÀÚ¿¡¼­´Â fracturing osteomalacia¿Í low bone turnover´Â mineralization          front¿¡ aluminumÀÇ ÃàÀûÀ» ÃÊ·¡Çϴµ¥, ÀÌ´Â orally administered aluminum              binders ȤÀº aluminum-containing dialysis solutions¿¡ ³ëÃâµÇ¾ú±â ¶§¹®ÀÌ´Ù.

 

  4)¹æ»ç¼±ÇÐÀû ¼Ò°ß

     1. abnormalities at the epiphyseal growth plate

       : °¡²û nutritional ricketsÀ» ´àÀ¸³ª Á¾Á¾ ÇöÀúÈ÷ ±¸º°µÊ

    2. growth plateÀÇ longitudinal width°¡ ½ÇÁ¦·Î´Â Áõ°¡µÇ¾î ÀÖÁö ¾ÊÁö¸¸, ±×·¸°Ô º¸ÀÌ        ´Â °ÍÀº dysplastic trabeculasÀ» °¡Áø metaphyseal fibrosisÀÇ bar Çü¼º ¶§¹®ÀÌ´Ù.

    3. concomitant defect in mineralizationÀº ´ÙÀ½À» ÃÊ·¡ÇÔ

      a. a failure in modeling, with persistence of cartilage

      b. an expanded epiphyseal diameter

      c. frequent overriding of the lateral border of the metaphysis

 

  5)ÀÓ»ó ¼Ò°ß

    1. CRFÀÇ ¹ßº´½Ã±â°¡ younger child, ±×¸®°í renal failureÀÇ longer durationÀº              osteodystrophyÀÇ incidence¿Í severityÀ» Å©°Ô ÇÑ´Ù.

    2. congenital diseases of the kidney¸¦ °¡Áø ¼Ò¾Æ(5¼¼ ÀÌÇÏ¿¡¼­ ¿ì¼¼)´Â ¼Ò¾Æ ÈĹݱ⠠      ¿¡ ³ªÅ¸³ª´Â glomerulonephritides º¸´Ù disease onset°ú end-stage renal failure          »çÀÌÀÇ intervalÀÌ ´õ ±æ´Ù.

    3 ±×·¯³ª, congenital nephropathies ȯÀÚ´Â bone disease°¡ °¡¼ÓµÇ´Âµ¥ ÀÌ´Â maximal              growth, bone modeling and remodeling ½Ã±âÀ̱⠶§¹®ÀÌ´Ù.

    4. the earliest sign of renal osteodystrophy

       : usually growth failure

     ±×¿Ü CRF¿¡ µ¿¹ÝµÈ anemia, metabolic acidosis, protein-calorie malnutrition,                 hormonal disorders, and trace mineral deficiencies

    5. advancing diseaseÀÇ additional clinical manifestations

      : muscle weakness, bone pain, bone deformities, slipped epiphyses, metaphyseal              fractures, metastatic calcification, and pruritus

    6. genu varum, frontal bossing ±×¸®°í dentgal abnormalities´Â young children¿¡¼­         ÇöÀúÇÔ

    7. hypocalcemia¿¡µµ ºÒ±¸Çϰí tetany´Â µå¹®µ¥, ÀÌ´Â metabolic acidosis¿Í                                    hyperparathyroidismÀÇ combined protective effects ¶§¹®ÀÌ´Ù.

 

 6)°Ë»ç½Ç ¼Ò°ß

   1. mild hypocalcemia, but usually elevated Ca  P product by increased levels of              serum phosphorus

   2. Áõ°¡µÈ ALP activity´Â Áõ°¡µÈ bone turnover¸¦ ³ªÅ¸³»³ª, ¼Ò¾Æ¿¡¼­´Â ¼ºÀθ¸Å­             reliasble signÀº ¾Æ´Ï´Ù.

 

   3. sensitive early indicator of osteitis fibrosa : hand¿Í wristÀÇ X-ray¿¡¼­                     subperiosteal erosions of the middle and distal phalanges, ±×¸®°í erosionsÀº           distal clavicle, inner aspects of the distal femur and proximal tibia¿¡µµ ³ªÅ¸³².

   4. the earliest indication of bone disease : elevated serum levels of PTH

      GFRÀÌ 50  75§¢/min/1.73m2 À϶§µµ ³ªÅ¸³².

   5. PTHÀÇ degree of elevationÀº osteitis fibrosaÀÇ ¹æ»ç¼±ÇÐÀû, Á¶Á÷ÇÐÀû ¼Ò°ß°ú ÀÏÄ¡       Çϳª, histologic osteomalaciaÀÇ degree´Â serum³» chemical abnormalities               ȤÀº coarsening of trabeculasÀÇ ¹æ»ç¼±ÇÐÀû ¼Ò°ß°ú ÀÏÄ¡ÇÏÁö ¾Ê´Â´Ù.

 

  7)Ä¡·á

    1. renal osteodystrophy can usually be successfully managed by

      a. controlling hyperphosphatemia

      b. supplying adquate oral calcium intake

      c. providing extra vitamin D

    2. hyperphosphatemiaÀÇ Ä¡·á

      a. dietary phophate restriction : ½ÃÀÛÇÏ´Â indicationÀº raised PTH level

      b. aluminum-containing phosphate bindersÀÇ oral administration

      a) risks of aluminum intoxication ¶§¹®¿¡ °¡´ÉÇϸé ÇÇÇØ¾ß Çϸç, dietary                            restrictionÀÌ ÃæºÐÇÏÁö ¾ÊÀ¸¸é »ç¿ëÇÔ

        b) aluminum hydoxide or aluminum carbonate gel

            : a starting dose of 20  30mg/kg/24hr in divided doses with meals

             ÀÌÈÄ ¿ë·®À» Á¶ÀýÇÏ¿© serum phosphorus¸¦ 4  5mg/dl·Î À¯Áö½ÃÅ´

        c) long-term treatment with high-dose aluminum-containing bindersÀÇ ÇÕº´Áõ

            : osteomalacic osteodystrophy and a progressive, irreversible                                          encephalopathy

    3. calcium supplementation

      a. calcium carbonate ÇüÅ·ΠÇÏ·ç¿¡ 1  1.5g of elemental calciumÀ» diet¿¡ ÷°¡

      b. calcium carbonateÀÇ ÀåÁ¡

        a) the highest percentage of elemental calcium

        b) some degree of phosphate binding, particularly when given with meals

    4. acidosis controlÀº sodium bicarbonate¸¦ »ç¿ë

        : usually 1  2mEq/kg/24hr, divided into thirds and given 1hr after meals

    5. providing extra vitamin D

      a. 1,25(OH)2D3

        a) preferred form

        b) indicationÀº symptomatic bone disease with hypocalcemia

              secondary hypoparathyroidism

              evidence of osteitis fibrosa on X-ray or bone biopsy

       c) starting dose´Â 15  40ng/kg/24hrÀ̸ç, À̸¦ hypercalcemia risk¸¦ ¹æÁöÇϱ⠠                 À§Çؼ­ 8  12½Ã°£ °£°ÝÀ¸·Î Åõ¿©Çϰí, ¿ë·®ÀÇ stepwise adjustment¿Í                     biochemical monitoringÀÌ ÇÊ¿äÇÔ

      b. dihydrotachysterol(DHT)

        a) ÀåÁ¡ : better ratio of therapeutic to toxic effects

          shorter half-life´Â hypercalcemiaÀÇ ÇÕº´ÁõÀ» °¨¼Ò½ÃÅ´

        b) starting dose´Â 0.1  0.2mg/24hrÀ̸ç, serum calciumÀ» Á¤»óÈ­½Ã۰í, X-ray            »ó bone abnormalities¸¦ healing½Ã۵µ·Ï ¿ë·®À» weekly or biweekly·Î Á¶Àý             ÇÑ´Ù.

      c. frequent measurements of serum calcium and phosphorus

      d. CRF¿¡¼­´Â serum calciumÀÇ "set point"°¡ Áõ°¡ÇϹǷÎ, vitamin D therapyÀÇ            therapeutic goalÀº serum calciumÀ» 10.5  11.0mg/dl±îÁö ¿Ã¸®´Â °ÍÀÌ´Ù.

    6. hemodialysis or chronic peritoneal dialysis

    7. autotransplantation of the parathyroid gland

     a. medical therapy¿¡ ¹ÝÀÀÀÌ ¾ø´Â severe secondary hyperparathyroidism ȯÀÚ¿¡          ¼­ ½ÃÇà

       b. indication : severe bone pain, mental aberrations, severe pruritus, fractures,                                chronic  hypercalcemia, and metastatic calcification

Chapter 484.Nephrogenic Diabetes Inspidus

Etiology

# primary NDI

  ; *rare, inherited ds, X-linked recessive ds

    ; ³² : complete unresponsive to ADH

  ; ¿© : partial

# 2ndary NDI

    ; medullary concentrating gradient lossÃÊ·¡ Áúȯ

       a)acute or chronic renal failure

       b)obstructive & p ostobstructive uropathy

       c)vesicoureteral reflux

       d)cystec ds. : interstitial nephritis

       e)osmotic diuresis, nephrocalcinosis

  ; tubule¿¡ ADH effect °¨¼ÒµÈ °æ¿ì

       a)hypokalemia b)hypercalcemia c) lithium d) democlocycline therapy

Pathogenesis

   cf.concentration of urine

   (1)hypertonic renal medulla<countercurrent mech.

   (2)permeability of distal tubule & collecting duct to water <ADH

Clinical Manifestation

# male with primary NDI

    ; polyuria, polydipsia in infancy

    ; hypernatremic dehydration episode

# female in primary NDI

    ; milder

    ; not detected until later life

Diagnosis

# primary NDI

  ; clinical Hx.

  ; male with family Hx

# Laboratory Finding

  ; hypernatremia, diluted urine

    ; ¡Ús-osmolality > 295mosm/kg H2O & concurrent urine osmolality < s-osmolality

           - diagnosis

           - *dehydration test ºÒÇÊ¿ä

# confirm diagnosis

    ; aqueous vasopressin 0.1-0.2u/kg im ÈÄ 4h °£°ÝÀ¸·Î serum & urine osmolarity ÃøÁ¤.

     -> urine / plasma osmolality

         ratio < 1.0 ; nephrogenic D.I

         ratio > 1.0 ; central D.I

                     psychogenic polydipsia

# s-osmol < 295 mOsm / Kg ÀÌÇÏÀ̸é fast½ÃÄÑ 295ÀÌ»óµÇ¸é dehydration test

        cf. B.W 3%ÀÌ»ó loss ->fluid Åõ¿©

# biochemical & radiographic study½Ç½ÃÇÏ¿© ÀÌÂ÷Àû ¿øÀÎ ¹èÁ¦

Complication

   (1) mental retardation by repeated hypertonic dehydration

   (2) growth retardation

       male¿¡ ³ªÅ¸³² ; intrinsic

   (3) collecting system dilatation->¼ö³â¸¶´Ù renal scan À¸·Î hydronephrosis°üÂû

Treatment

# ¸ñÇ¥

    ; provision of adequate fluid & caloric intake

    ; reduction of urinary solute load

# diuretics therapy

    ; sodium depletion

           --> enhancement of Na & water reabsorption in proximal tubules

           --> paradoxical response

    ; *chlorthiazide(20-40mg/kg/day in divided dose) with moderate salt restriction

           - significant reduce need for fluid intake & frequency of voiding

           - *hypokalemia monitoring

    ; *no effect on 2ndary NDI

# inhibitors of PG synthesis

    ; indomethacin

    ; *diuretic therapy ½ÇÆÐ½Ã ½Ãµµ

Prognosis

     pri.NDI: life long. good Px. if hypernatremic dehy. is avoided genetic counselling

      2nd.   : underlying ds. nature¿¡ µû¸§

Chapter 485. Bartter Syndrome

   Ư¡:  hypokalemia

         normal BP

         vascular insensitivity to pressure agents

         elevated plasma renin & aldosterone

   AR·Î inherited°æ¿ìµµ ÀÖÀ½

Pathology

    IG apparatus hyperplasia < renin »ý»ê Àå¼Ò

    renal parenchyme

    ´ë´Ù¼ö´Â Á¤»ó

    ¼Ò¼ö¿¡¼­ nonspecific glo. ds or interstitial ds. or both

Pathogenesis

; *primary defect in chloride reabsorption in ascending limb of loop of Henle

    --> reduced medullary hypertonicity (concentrating defect)

    --> extra NaCl in distal tubule

    --> reabsorption of sodium exchange for potassium

    --> urinary potassium wasting

    --> hypokalemia

    --> stimulating prostaglandins systhesis

    --> vascular insensitivity to pressure agents

    --> activation of Renin-Angiotensin-Aldosterone

    --> aggregation of renal potassium wasting

Clinical Manifestation

; young children

    - *growth failure, muscle weakness, constipation, polyuria, dehydration

; older children

    - *muscle weakness or cramps, carpopedal spasm

Diagnosis

   a)hypokalemia(<2.5mEq/L) 

   b)normal blood pressure

   c)defective platelet aggregation

   d)hypochloremia

   e)metabolic alkalosis

   f)plasma renin, aldosterone, PGE2 Áõ°¡

   g)urinary K+, Cl Áõ°¡

    ¶§·Î hypercalciuria, hyperuricemia, hypomagnesemia,urinary sodium wasting

     confirm by histologic demonstration of hyperplasia of JG cell

# DDx

    ; licorice abuse

    ; laxative or diuretic use

  ; persistent vomiting or diarrhea

    ; Pyelonephritis

    ; D.I

# DDx point

    ; laxative use,vomiting diarrhea, D.I½Ã hypovolemiaµ¿¹Ý

        --> low urinary Cl level (cf. Bartter SD½Ã Áõ°¡)

Treatment

  5)The goal of Tx; to maintain s-potasium level>3.5meq/l

                   and adequate nutriton

    a)potassium chloride(K-Lyte/ cl;25-50mEq of KCl);S-K35mEq/lÀÌ»ó

                                                  250mg/24/hr½Ã±îÁö Áõ·®

    b)sodium chloride supplementation

    c)-fail-->triamterene 5-10mg/kg/day in div.

    d)-fail-->indomethacine 3-5mg/kg/day Sig1/3

Prognosis

; uncertain

; *¸¹Àº ȯÀÚ´Â remain well

; ÀϺο¡¼­ renal insuff.

; growh failure À־ normal stature

Chapter 486. Interstitial Nephritis

 

  ´ë°³ tubular damage µ¿¹Ý

  glome.change´Â minimal

   - Common cause of interstitial nephritis

  1.Acute interstitial nephritis

   1)pathology

       interstitial infiltrate

      a)lymphocytes b)plasma cells c)eosinophils ¶§·Î d)neutrophils

        edema: tubular degeneration & necrosis

    2)pathogenesis

      unknown

       a)hypersensitivity reaction; drug

       b)tubular BM¿¡ immune complexÀÇ deposition; Lupus.MPGN

       c)anti BM Ab ; Goodpasture, membranous

       d)cell mediated mechanism ; sarcoidosis, transplant rejection

    3)C/M

      a)drug°¡ hospitalized pt.½Ã m/c cause

        1ÁÖÀÌ»ó drug»ç¿ë½Ã i)fever & rash¹ß°ß

                           ii)eosinophil Áõ°¡ in blood urine or both

      b)others; ARF or acute GN¿Í À¯»çÇÑ clinical picture

      c)onsetÀº ant. uveitis¿¡ ÀÇÇØ ¼±ÇàµÉ¼ö ÀÖ´Ù.

   4)Dx.

     renal biopsy·Î confirm

      ¼Òº¯³» È£»ê±¸ Áõ°¡      

   5)Tx. & Px                      

     a)ARF Tx.                   ---+

     b)inciting agent withhold         |  ·Î complete resolve

     c)precipitating inf. Tx.        ---+

     d)severe histologic injury & renal failure½Ã

        --->high dose corticosteroid·Î dramatic improve.

  2.Chronic interstitial nephritis

   1)patholoty

     a)infiltrates; lymphocytes plasma cells

     b)tnterstitial fibrosis

     c)tubular dilatation & atrophy

     d)partial or total glom. sclerosis

  2)clinical manifestation

     ´ë°³ occult structural abnormality of Kidney & Urinary tract µ¿¹Ý

       (cystic ds. obstruction, reflux)

      ÃÊÁõ»ó;a) CRF

              i)N &V ii)pallor iii)headache iv)fatigue v)HT vi)growth failure

             b)underlying ds ÀÇ Áõ»ó: (UTI, flank mass)

  3)Dx.; renal biopsy not indicated

       ´ë°³ underlying ds¿Í ¿¬°üµÈ chronic renal insufficiencyÀÇ ¾ç»óÀ¸·Î Áø´Ü

  4)Cx. & Px

  progression to end-stage RF

  avoidance of phenacetin(analgesics) & lithium -> adult¿¡¼­

    renal Fc improvement ÀÖÀ½

section 5. toxic nephropathy - renal failure

Chapter 487. Toxic Nephropathy

 

 . medication

  diagnostic agents(iodinated radiographic contrast media)

  chemicals

 . directly damage

    renal bl.flow °¨¼Ò , ATN , intratubular obs.

   indirectly

    allergic or hypersensitivity in vessels & interstitium

 

  ** Preventive measures may reduce the risk of nephrotoxicity

     a)pre-existing renal ds½Ã c.m´ë½Å US or scan

     b)non-nephrotoxic agent·Î ġȯ

     c)lowest effective dose of agent with bl. level monitoring

     d)renal insuff. ½Ã dose reduction

     e)µ¿½Ã¿¡ several nephrotoxic agentÇÔ²² »ç¿ë±ÝÁö

   table 487-1

Chapter 488.Cortical Necrosis

 

   a) renal cortical(frequently medullary)necrosis´Â several typeÀÇ renal injuryÀÇ

     final common result

   b) ´ë°³ both kidney involve

   c) pathy or entire cortex involve

 

1) Etiology

    NB¿¡¼­ÀÇ ¿øÀÎ: a)dehydration

                   b)asphyxia

                   c)shock

                   d)DIC

                   e)renal vein thrombosis

    NBÈÄ:      Hemolytic uremic syndromeÀÌ m/c cause

 

2) pathology

    cortical infarction, congestion of glo.

    thrombosis of arterioles, tubular necrosis

 

3) pathogenesis

    toxin  ->  endoth. cell injury(endotoxin)

              intrarenal coagulation ->thrombosis, cortical necrosis

    diminished renal cortical blood flow --> endothelial cell injury

 

4) clinical manifestation

  a) ARF, b) enlarged Kid., c) U/O °¨¼Ò,  d) gross hematuria

 

5) Dx.

  US»ó enlarged but non - obstructed kidney

  scan»ó °¨¼Ò or no renal bl. flow & no function

 

6) Tx. & Px

  supportive care

    --> correction of dehydration, asphyxia shock sepsis Tx.

 

3.UTI in newborn

  chapter. 101 & 492

Chapter 489. Renal Failure

489.1 Acute Renal Failure

# oliguria

    ; daily U.O <400mL/m2

    ; < 0.5ml/kg/hr in infancy

Etiology

¡ÚTable 489-1

¡ÚTable 489-2

Pathogenesis

# prerenal cause

    ; decreased renal perfusion->GFR°¨¼Ò

  ; ÀÏÁ¤½Ã°£³» hypoperfusion ±³Á¤½Ã¿¡´Â reversible

# renal causes

  ; hemolytic uremic syndrome

           - ¡ãcommon cause in toddlers

    ; ATN

           - no arterial or glomerular lesion

           - ¡ÚProposed Mechanisms

                   / alterations in intrarenal hemodyanmics

                   / tubular obstruction

                   / passive backflow of glomerular filtrate across injured tubular cells into peritubular capillary

    ; GN

# postrenal causes

    ; upper collecting systemÀÇ dilatationÀº acute ureteral obstruction¼öÀÏ ÈÄ¿¡¾ß ÃÊ·¡

Clinical Manifestation

  .precipitating ds.µû¶ó variable

  .Áõ»ó & sign related to RF

     a) pallor(anemia)

     b) U.O °¨¼Ò

     c) edema(salt & water overload)

     d) hypertension ,vomiting, lethargy(uremic encephalopathy)

Diagnosis

# careful Hx.

    cf. flank mass½Ã »ý°¢

    a)renal vein thrombosis,  b) tumor,  c) cystic ds.,  d) obstruction

# Laboratory Finding

    a) anemia

     +-dilutional

     +-hemolytic ; lupus, renal v. thrombosis, HUS

   b) leukopenia ; lupus

   c) thrombocytopenia ; lupus, renal v. thrombosis, HUS

   d) hypoNa+ ; dilutional

   e) hyperK+

   f) acidosis

   g) BUN,Cr,uric acid, phosphate Áõ°¡; diminished RF

   h) hypocalcemia(hyperphosphatemia)

   i) C3 °¨¼Ò : i) PSGN   ii) lupus  iii) MPGN

   j) Ab; antistreptococcal ; PSGN

          nuclear ; lupus

          neutrophilic cytoplasmic antigens(ANCA;Wegener granulomatosis,microscopic

                                                 polyarteritis)

          BM antigen ; Goodpasture ds.

   k) chest X-ray ; cardiomegaly, pul congestion -> fluid overload

   l) ¸ðµç ARF pt. ½Ã obstruction°¡´É¼º ¹ß°ßÀ§ÇØ

     i) plain abd. X-ray

     ii) U/S ; CRF , obst. uropathy DDx

     iii) renal scan é©

     iv) RGP ; ¶§·Î

        <-- obst½Ã percut. nephrostomy½ÃÇàÀ¸·Î reverse ʦ

Treatment

 1) children /c hypovolemia

  ; volemic replacement

 

 

   Uosm

   UNa

  Fr.Na excret.

   hypovolemia

 impending ATN

 >500mOsm/kgH2O    <350

 <20mEq/L            >40mEq/L

 <1%                 >1%

 

                           UNa/PNa

 Fractional Na excretion =  ---------   * 100

                           Ucr/Pcr

 

 .Ä¡·á : isotonic saline iv 20mL/kg over 30 min

        ´ë°³ 2hr. ³» voiding

        bladder cath. CVP ÇÊ¿ä ʦ

        hydration ÈÄ diureticsʦ

 2) Impending RF

  diuretics on prevention of anuria ; controversy

  established anuria¿¡´Â no value

  furosemide  --   urine  production ¡è  by altering tub. func

  mannitol     --      

  ±×·¯³ª urine ¡è ÀÌ renal func. È£ÀüÀ̳ª natural ds. È£Àü

  Àǹ̾øÀ¸³ª, a) hyperkalemia,  b) fluid overload ±³Á¤¿¡´Â È¿°ú.

   < furosemide >

     : hypovolemia¾øÀ» °æ¿ì

     a) initial single dose of 2mg/kg(rate 4mg/min to avoid ototoxicity)

     b) 10mg/kg of furosemide, if no response

        b)¿¡µµ response¾øÀ¸¸é CIx.

     c) single iv of 0.5g/kg of mannitol over 30min in addition or in place

        of furosimide

       ;È¿°ú ÀÖµç ¾øµç ´õÀÌ»ó »ç¿ë¸øÇÔ

 3) Fluid restriction

   volume expansionÀ̳ª diuretics¿¡ È¿°ú¾ø´Â °æ¿ì´Â essential

   a) 400mL/m2/24h(insensible loss) + urine ¾ç ; Á¤»ó intravascular volume½Ã

   b) 10-30% glucose containing solution without electrolytes

   c) blood. GI loss´Â ±³Á¤

 4) hyperkalemia

    serum level 6mEq/L½Ã cardiac arrythmia, cardiac arrest ʦ

      a) adequate renal f. µÇ±âÀü¿¡´Â K+ restriction

      b) EKG changes

        i) tall, peaked T waves ; earliest

        ii)ST seg. depression

        iii) P-R prolongation

        iv) QRS widening  

        v) cardiac arrest

     c) s-K+ ÀÌ 5.5mEq/L·Î ¿À¸£¸é Tx½ÃÀÛ

        i) ¸ðµç solution¿¡ high conc. of glucoseÆ÷ÇÔ

        ii) Kayexalate(sodium polystyrene sulfonate resin) exchange Na for K

           1g/kg p.o or retention enema

           20% 10ml/kg sorbitol ; enema½Ã

           orally, suspended in 2mL/kg of 70% of sorbitol½Ã best results

           (¡ñ sorbitolÀº osmotic diarrheaÀÏÀ¸Å´) every 2hr. À¸·Î repeat

   d) s-K+ÀÌ 7mEq/LÀÌ»ó ¿À¸£¸é

      -->sequentially following emergency step½ÃÀÛ

      i) 10% calcium gluconate ; 0.5 mL/kg iv over 10min

        H.R monitoringÇϸç 20beat/minÀÌ»ó H.R¡èµÇ¸é ½¬¾ú´Ù°¡ °è¼Ó

      ii) 7.5 % NaHCO3   3mEq/kg iv

         cx. ; vol. expansion, hypertension, tetany

     iii) 50% glucose 1mL/kg with R.I 1u/5g of glucose iv over 1hr.

         hypoglycemia monitor é©

     iv)kayexalate

     ¡¤i)Àº K+¡é½ÃŰÁö´Â ¾ÊÀ¸³ª (K+ induced myocardial irritability¿¡ counteract

        effect´Â ÀÖÀ½)

     ¡¤ii)Àº K+ shifting into intracellular compartment from ECF ÀÌ

          measurementÀÇ duration of actionÀº ´ÜÁö ¼ö½Ã°£ Áö¼ÓµÇ¹Ç·Î

          persistent hyperkalemia½Ã dialysis é©

 5) acidosis

   a)inadequate excretion of H+ & ammonia´ë°³ Ä¡·á é©

   b)Ä¡·á ÇÊ¿äÇÑ °æ¿ì

     severe acidosis  -- arterial pH < 7.15

                        s-HCO3 < 8mEq/L

       --> ÀÌ ¶§´Â resp. drive ¡é , myocardial irritability ¡è

  c) partial correction by iv route

     ¸ñÇ¥ pH=7.20,  HCO3=12mEq/L

     ¡ÅmEq  NaHCO3 required = 0.3 ¡¿ BW ¡¿ (12-sHCO3)

     ³ª¸ÓÁö´Â s-Ca. phosphatemia /c reciprocal  , hypocalcemia

     acidosis¶§ total calcium ionized fraction ¡è·Î tetany¹ß»ýÀÌ ¹æÁöµÇ¾ú´Ù°¡

     acidosis rapid correctionÀ¸·Î ionized Ca ¡é ->tetany

Hypocalcemia

    ; Tx by lowering serum phosphorus

    ; *no calcium iv if not tetany

           - *calcium(mg/dl)xphosphorus(mg/dl)ÀÌ 70ÀÌ»óÀ̸é calcium salt deposition in tissue

    ; ¡Úphosphate-binding calcium carbonate antacids

           - Titralac Liquid (3M Company, St. Paul, MN)

                   / starting dose 5-15ml with meal and before bed

           - Os-Cal 500 tablets (Marion Laboratories, Kansas City, MO)

                   / 1-3 tablets with meals and before bed

           - regular strength TUMS (SmithKline Beecham, Pittsburgh, PA)

                   / 1-3 tablets with meals and before bed

           - Á¤»óÀÌ µÉ¶§±îÁö Á¡Â÷ Áõ·®ÇÑ´Ù.

Hyponatremia

    ;due to excessive amount of hypotonic sol.

      a) Tx. by fluid restriction

      b) s-Na ÀÌ 120ÀÌÇÏÀ̸é cbr. edema & Hemorrhage ʦ

        mEq Nacl required = 0.6 ¡¿ B.W ¡¿ (125 - sNa)

      c) risk of hypertonic sodium

         i)vol. expansion

         ii)HT

         iii)CHF  -->¹ß»ýÇϸé peritoneal dialysis ½Ç½Ã

 8) Hypertension

    1¡£ ds. process

    ECF vol expansion µî¿¡ ÀÇÇØ »ý±è

     a) salt & water restriction ; critical

     b) severe acute symptomatic HT

        i) diazoxide ; DOC

          1-3mg/kg(max 150mg) rapidly iv (10ÃÊ À̳») --> 10-20ºÐ³» BP ¡é

          ¸¸ÀÏ È¿°ú ºÒÃæºÐ½Ã 30ºÐÈÄ 2nd inject or nifedipine 0.25-0.5mg/kg p.o

          HT crisis½Ã sodium nitroprusside,  labetalol continuous iv infusion

       ii) furosemide concomitantly

   c) less severe hypertension

      i) ECF vol. expansion ¹æÁö

        +-> salt & water restriction

        +-> furosemide

     ii) beta blocker(propranolol) ; 1-3 mg/kg/12hr p.o

     iii) vasodilator(apresoline) ; 0.5-1.5 mg/kg/6hr iv

 9)Seizure

   a)¿øÀÎ ; i)primary ds process ; SLE

           ii)hyponaremia ; water intoxication

           iii)hypocalcemia ; tetany

           iv)HT

           v)uremic state itself

           vi)hypoglycemia

  b)Tx.

      i)underlying cause

     ii)diazepam; most effective but metabolite °¡ renal insuff. ½Ã ÃàÀû

 10)Anemia

    a)´ë°³ hemodilution; Hb 9-10 g/dl   -->  no transfusion

    b) blood loss by active bleedingÀº º¸Ãæ é©

    c) hemolytic anemia(SLE,HUS )

        -- prolong RF ½Ã 

       Hb < 7g/dl½Ã transfusion

       vol. overload, CHF , pul, edema , HT À§Çè ÀÖÀ¸¹Ç·Î 4-6hr µ¿¾È transfusion

       /c fresh packed RBCÀÇ slow transfusion  10ml/kg

11) diet ; 400cal/m2/day ¡è

    a) healthy & well-nourished À̰í ARF°¡ ªÀ» °æ¿ì´Â

       diet´Â restricted to fat & carbohydrate¸¸ ÁØ´Ù(gum drops or jelly beans)

    b) Na,K ,water restriction

    c) 3ÀÏ ÀÌ»ó Áö¼Ó½Ã expanded oral diet or TPN /c a.a

 12) dialysis

   Ix ; a) acidosis

       b) electrolyte abn.

       c) CNS disturbance

       d) HT

       e) fluid overload

       f) CHF

 14) continuous hemofiltraton

   is useful -  a)acute renal failure

               (ƯÈ÷, i. wnstable cardiopulmonary dynamics

                     ii.severe coagulopathies

                     iii.unavailablity of the peritoneal cavity due to

                        surgery or trauma

               b)fluid overload

               c)severe electrolyte or acid-base disturbances

     ¡Ø performed by two basic configurations

         a) continuous arteriovenous hemofiltration (CAVH)

         b) continuous venovenous hemofiltration (CVVH)

    15) life threatening Cx. of uremia 

        a)hermorrhage  b)pericarditis  c)CNS dysfuction

        risk of Cx.Àº Cr.º¸´Ù BUNÄ¡¿Í ´õ °ü·Ã

Prognosis

    underlying causeµû¶ó

      1)normalized ʦ

         a) prerenal causes

         b) hemolytic uremic syndrome

         c) acute tubular necrosis

         d) acute interstitial nephritis

         e)uric acid nephropathy

     2) recovery of renal function ÀÌ unusualÇÑ °æ¿ì

        a)RPGN, b)bilat. renal v. thrombosis, c) bilat. cortical necrosis

      ¡Ø ARF & CRF ÀÇ dialysis Ix.

         a) BUN >100 mg/dl

         b) uncontrollable hyperkalemia

         c) intractable severe met. acidosis or acidemia which cannot safely

            corrected by NaHCO3

         d) fluid overload /c circulatory congestion & pul. edema

489.2 Chronic Renal Failure

¡ÚEtiology

# under the age of 5yr

    ; *anatomic abnormalities

        - hypoplaia, dysplasia, obstruction, malformation

# after 5yr of age

  ; acquired glomerular ds.

  ; hereditary disorders - Alport synd. cystic ds

Pathogenesis

     ¾î¶² Á¾·ùÀÇ Kid. damageµç renal functional deteriorationÀÇ critical levelµµ´Þ½Ã         end-stage RF ·Î progressive renal function deterioration °ü·Ã factors

      a)ongoing immunologic injury

      b)hemodynamically mediated hyperfiltration in surviving glomeruli

      c)dietary protein & phosphorus intake

      d)persistent proteinuria --  Á÷Á¢ glomerular cap.wall damage

      e)systemic hypertension -->glomerular sclerosis -->HE filtrate injury

# *20% of GFRµÇ¾î¾ß uremia ³ªÅ¸³­´Ù.

¡ÚTable 489-4

Clinical Manifestation

   anatomic abnnormality½Ã

   non specific presenting complaints

         ; headache , fatigue ,lethargy, anorexia, vomiting

           polydipsia, ployuria, growth failure

  P/E

    ¡¤unrewarding

    ¡¤pale & weak. BP ¡è

    ¡¤anatomic abn. ·Î ÀÎÇØ ¼ö³â¿¡ °Éó  renal failure °¡ slowly develop ÇÒ¼öÀÖÀ¸¸ç

       À̶§ growth retardation &  rickets °¡ µ¿¹ÝµÉ¼ö ÀÖ´Ù.

 

Treatment

   management of pt. with CRF

     a) clinical status

        P/E, blood pr. close monitoring

     b) Lab. status

       i) routine exam. /q 1mo

          .Hb(anemia)

          .electrolyte -- hyponatremia

                        hyperkalemia

                        acidosis

          .BUN,Cr   -- nitrogen accumulation

                       level of renal function

          .calcium¡é,  phosphorus¡è

          .ALP ¡è --hypocalcemia

                     hypophosphatemia

                     osteodystrophy

       ii) periodic exam /q 6mo.

           .PTH     --        osteodystrophy early evidence

           .bone X-ray  --     detect ʦ

      iii) ÀÌ¿Ü

          .chest X-ray      --   assess cardiac function

          .echocardiogram   --

      iv) nutritional status

         a)s-albumin, b) zinc, c) trasfusion,  d) folic acid, e) iron level

Diet In CRF

     a) GFR <50% ½Ã growth rate ¡é

     b) ÁÖ ¿øÀÎÀÌ inadequate caloric intakeÀ̹ǷΠ-->unrestricted amount of

        +-> Carbohydrate (sugar, jam, honey, glucose polymer)

        +-> fat(medium chain TG)

           --> intermittent or overnight N-G or gastrostomy tube feeding

                 recumbiniant human GH therapy /c optimal days

           --> linear growth Á¶Àý

     c) BUN = 80mg/dl¡è½Ã dietary protein restriction

         ; 1.5 g/kg/24h·Î proteinÀÌ high biologic value(egg>milk>meat>fish>fowl)

     d) cow's milk¿¡ phosphate ¡è¹Ç·Î

       i) moderate restriction

       ii) use of a formular containing a reduced amount of  phosphate

          ( Similac PM 60/40, Loss laboratories, columbus, OH)

          ¶§¶§·Î oral phosphate binder ¿Í conjunction µÈ´Ù.

     e) water soluble Vit. deficiency (owing to inadequate intake or dialysis loss)

         ; Nephrocap(Fleming, fenton, MO) --> routinely supplyÇØ¾ßÇÔ. 

     f) Zinc & iron --> deficient È®ÀÎÈÄ °ø±Þ

     g) fat soluble vit. A, E, K  supplementation ; not required

Water & Electrolyte Management

      a) water; dialysisÇÊ¿äÇÑ Á¤µµ ¾Æ´Ï¸é no restriction

      b) Na+; edema, hypertension, CHF µîÀÌ ÀÖÀ¸¸é salt restriciton /c furosemide                                                                       (1-4mg/kg/day)

             ; salt wasting form; Na supplementation

      c) K+

Acidosis In CRF

      s-HCO3°¡ 20ÀÌÇÏÀ̸é Ä¡·á; ¼ºÀå¿¡ µµ¿ò.

      Bicitra

      NaHCO3 tablet

Renal Osteodystrophy

    ; develops in asso. with hyperphosphatemia, hypocalcemia, s-ALP ¡è, PTH ¡è

  b) hyperphosphatemia

      i) GFRÀÌ moramalÀÇ 30%¡é ½Ã phosphorus level ¡è

      ii) reciprocal solubility relationshipÀ¸·Î hypocalcemia ->2ndary

         hyperparathyroidism(+)

      iii) Tx.

          ¡¤aluminum hydroxide

            cf. aluminum poisoning

             ; dementia osteomalacia->rarely

          ¡¤ calcium carbonate suspension

               phosphate binder

               low phosphate formula(Similac PM 60/40)

               enhancing fecal excretion by orl calcium carbonate

     c)hypocalcemia

       i)±âÀü

             . reciprocally by hyperphosphatemia

             . inadequate dietary intake

             . decreased intestinal Ca absorption caused by a deficiency

                in the active form of Vit. D

      ii)Tx.

            . hyperphospatemia±³Á¤

            . ¾ÈµÇ¸é oral calcium supplement(Neo Calgulucon Syrup, Os-cal         

               tablets);500-2000mg/day

    d) Vit D.

        severe kidney dysfuncton½Ã 1-hydroxylation¾ÈµÇ¾î Vit.D def.

         i) Ix. for Vit. D therapy

             . s-phosphorus < 6.0mg/dl ÀÌÇÏ·Î ±³Á¤Çϰí calcium supplementationÇÏ

               ¿©µµ persistent hypocalcemia

             . elevated s-ALP¿Í X-ray ß¾ ricketÀǽɵǴ osteodystrophy pt.¿¡

        ii) Tx.

          ½ÃÀÛ    . 1 capsule(0.25ug)/d of active dihydroxy Vit D

                  . 0.05-0.20mg/day of dihydrotachysterol solution

       ¡¤normal s-ca. ALP, X-rayß¾ healing½Ã±îÁö dose ¡èÈÄ initial level

            ·Î Á¡Â÷ °¨¼Ò.

       ¡¤subperiosteal erosion of edge distal phalanges of index & middle finger

            ; hyperparathyroidism

Anemia In CRF

 ; ´ë°³ Hb 6-9g/dl

     ¡¤transfusion; not indicated

     ¡¤suppression of erythropoietin production

     ¡¤ Hb < 6 ½Ã 10mL/kg of packed RBC  ,

     ¡¤ recombinant erythropoietin therapy

Hypertension In CRF

    a) Diazoxide 1-3mg/kg iv or sublingual nifedipine ; emergency½Ã 0.025-0.5 mg/kg

    b) furosemide 2-4mg/kg iv (rate; 4mg/min);circ. overload µ¿¹ÝµÈ severe HT½Ã

    c) sodium nitroprusside´Â renal insuff.½Ã ÁÖÀÇ toxic thiocyanateÃàÀû

    d) Tx. of sustainde hypertension½Ã

        i) salt restriction(2-3g/day)

       ii) furosemide (1-4mg/kg/day)

       iii) propranolol(1-4mg/kg/day)

       iv) hydralazine(1-5mg/kg/day)

       v) combination

     e)  d)·Î inadequately control½Ã minoxidil, captopril»ç¿ë

Drug Dosage In CRF

    RF½Ã dosage modificationÇÊ¿ä¾ø´Â drug

     antibiotics; a) CM,  b) clindamycin,  c) cloxacillin,  d) EM,  e) rifampin

489.3 End-Stage Renal Failure

 

  1) successful kidney transplant

     ; ultimate goal -->living-ralated donor½Ã creatinineÀÌ 5-6mg/dl½Ã

       HLA typingºÎÅÍ ½ÃÀÛ

 2) Dialysis

    creatinineÀÌ 10mg/dl¿¡ µµ´Þ½Ã

    pt's clinical status

    Lab/F

    availability of kidney donor µû¶ó ½ÃÇà

     a) hemodialysis

     b) CAPD(continuous ambulatory peritoneal D)

       ; standard technique for majority of children requiring chr. dialysis

         not as effficient as hemodialysis

    table 489-6

Chapter 490.  Renal Transplantation

# *Optimal Tx For Children With ESRD

    ; living related donor renal transplantation (LRD-RT)

¢¾Table 490-1 Criteria For Performing Living Related Donor Or Cadaveric Renal Transplantaion In Pediatric Patients

# ESRDÀÇ ¿øÀÎ

    ; ³ªÀÌ¿¡ µû¶ó ´Ù¸£´Ù.

           - *13-17¼¼ : glomerulopathy

    - 5¼¼¹Ì¸¸ : congenital & obstructive process

    1) *congenital renal disease(53%)

  2) glomerulonephritides(20%)

  3) focal segmental glomerular sclerosis(12%)

  4) metabolic disease(10%)

  5) mescellaneous(5%)

¡ÚTable 490-2 Most Frequent Hereditary Metabolic Disease Of Childhood That Lead To End-Stage Renal Disease

Table 490-3

Treatment

 1. RT procedure

  1) 15¡­20Kg ¹Ì¸¸ : midline incisionÈÄ transperitoneal graft

  2) 20Kg ÀÌ»ó : right iliac fossa¿¡ retroperitoneal location

                 ¡æ renal vessel : external iliac vessel°ú anastomosis

                    ureter¸¦ bladder¿¡ reimplantation(ureteroneocystostomy)

                    lower pole : intestine»çÀÌ¿¡ freeÇÏ°Ô µÒ

 2. TABLE 490-4

 3. survival rate

 

 

 LRD-RT

 CAD-RT

 1³â

 ¾à 90%

   72%

 3³â

  80%

   65%

 4. TABEL490-5

Histocompatibility

 1. major histocompatibility complex(MHC) gene

  1) locus : chromosome 6 ÀÇ short arm

  2) ±â´É : human leukocyte antigen(HLA)¸¦ encode

  3) À¯Àü : Mendelian fashion inheritance

   Figure 490-3

4) ±¸¼º

   ¨ç class I protein(tissue transplantation antigen) : HLA-A,-B,-C

      cell-mediated immunotoxicity

   ¨è class II protein : immune responce À¯µµ

                       HLA-DP,-DQ,-DR

   ¨é class III protein : tumor necrosis factor(TNF)

                       complement component (C2 & C4)

  5) HLA-A,-B &-DR : clinical transplantation¿¡¼­ °¡Àå Áß¿ä

     : good HLA match¡æ graft loss °¨¼Ò

  6) class I & II antigenÀÇ cellular expression

   ¨ç B & T lymphocyte & macrophage¿¡ ±¹ÇÑ

   ¨è inflammation¿¡¼­ T cell¿¡ ÀÇÇØ ºÐºñµÇ´Â lymphokine(IL-2,4 & 5)¿¡

      ÀÇÇØ  multiplication

  7) CD4(T-helper) & CD8(T-suppressor) cell surface marker

     : MHC (HLA) I (histocompatibility) Ag°ú high affinity°¡Áü

       ¡æ class I Ag°¡Áø cell¿¡ attach

       ¡æ cytokine»ý¼º signal Àü´Þ or cell lysis

Rejection Reaction

# Clinical Manifestation

    ; *swelling & tenderness of grafts, fever, oliguria, hypertension, progressive elevation of serum creatinine

# Classification

    ; acute & chronic rejection reaction

        - *cellular & humoral mechanism¿¡ ÀÇÇÑ graft damage

    ; accelerated(hyperacute) rejection reaction

           -

# Diagnosis

  ; renal ultrasound - enlarged graft & echogenic cortex

  ; renal scan : blood flow °¨¼Ò

  ; ¡Úgraft biopsy

           - *definite diagnosis

    ; glomerular immunofluorescence (-)

# Differential Diagnosis

   ¨ç acute tubular necrosis

   ¨è cyclosporine-A toxicity

   ¨é graftÀÇ original renal diseaseÀÇ de novo occurrence

# ¹ß»ýºóµµ

   ¨ç LRD-RT : 50%

   ¨è CRD-RT : 65%

# histocompatibility testÀÇ ÀÇÀÇ

    : LRD & CAD RTÀÇ survival ¿¬Àå¿¡ °¡Àå Áß¿ä

  1) best survival result

     : MLC nonstimulatory sibling donor¿Í °°Àº HLA-A, -B, -C & -D/DR °¡Áø °æ¿ì

  2) second best : haplotye matchÀÖ´Â sibling or parent donor

Principles Of Immunosuppression And Therapy Of Rejection Reations

 1. RRÀÇ ±âÀü (Fig 490-3)

    : foreign bodyÀÎ renal graft

      ¡æ immune systemÀÇ stimulation

      ¡æ cell-mediated & humoral-mediated immune inflammationÀÇ activation

      ¡æ cell destruction & RR

¡ÚTable 490-6 Immunosuppressive Agent

# °¡Àå ÈçÈ÷ »ç¿ëµÇ´Â protocol

  ; *azathioprine, cyclosporine, & low dose corticosteroid sequential immunosuppression

  2) antithymocyte globulin(ATGAM) »ç¿ë

     : prophylaxis·Î »ç¿ë or postoperative period¿¡ »ç¿ë

       ¡æ 50%¿¡¼­ short-term graft outcome Çâ»ó

       ¡æ ÀÌ½Ä 6°³¿ù ÈÄ mean serum creatinine level °¨¼Ò

       ¡æ transplant ÈÄ first RR »çÀÌ interval Áõ°¡

       ¡æ 1 year graft survival Áõ°¡

Grwoth And Renal Transplantation

1. chronic renal failure & ESRD-dialysisÀÇ complication

  1) stunted linear growth

     overt malnutrition : less often

 

  2) Ä¡·á

   ¨ç supportive care : stamina Çâ»ó °¡´É

                       well-being sense

   ¨è successful transplant¸¸ÀÌ À̵é abnormalityÀÇ ÀûÀýÇÑ ±³Á¤ °¡´É

 2. growth retardation

  1) RT ½Ç½Ã ÀÌÀü : 5¼¼ ÀÌÀü¿¡ -2.8 SD(standard deviation)

     1¹øÀÌ»ó RT ½Ç½Ã : -3.2 SD

  2) transplant-related accelerated growth

   ¨ç 6¡­12°³¿ù Áö¼Ó

   ¨è younger children¿¡¼­ °üÂû

   ¨é adolescent¿¡¼± Ùí

   ¨ê weight gain : 2¡­3³â µ¿¾È normal adolescent¿Í À¯»çÇÑ Æò±ÕÄ¡ º¸ÀÓ

  3) daily corticosteroid

   ¨ç growth retardationÀ¯¹ß °¡´É

   ¨è »ç¿ë ¹æ¹ý

      : daily steroid¸¦ 6°³¿ù°£ ¿ë·® °¨¼Ò½ÃŰ¸ç »ç¿ë

       ¡æ every-other-day steroid »ç¿ëÇϸç 0.5¡­0.2mg/KgÀ¸·Î tapering

       ¡æ single-dose every-other day

  4) recombinant human growth hormone(Nuprin)

     : ÀÌ½Ä ÀüÈÄ¿¡ »ç¿ë

       ¡æ linear growth Çâ»ó

          graft functionÀº °¨¼Ò °¡´É

Complication

¡ÚTable 490-7

# Infection

    ; *¡ãcommon cause of death during 1yr after transplantation

    ; CMV infection

           - *¡ãcommon

           - °ø¿©ÀÚ or À̽ÄÀÚÀÇ CMV Ab titer ¹Ýµå½Ã ÃøÁ¤

        - ¡ÚTable 490-8

           - reactivation state

                   / *apparent 1-3mo

                   / 90% : asymptomatic & self-limited

            / 5¡­10% : death

                   / Treatment

                           : low-dose immunosuppressive agents with antiviral agent

                           : *gancyclovir & anti-CMV immunoglobulin IV

                   / kidney biopsy

                           : rejectionÀÇ monitoring

        - *direct tissue damage or triggering of rejection reaction

           - systemic CMV infection(lung, brain, liver ħ¹ü)

           / immunosuppressionÁß´Ü

       - unresponsive rejection : kidney Á¦°Å

           - concomitant viral infection

             / varicella-zoster, Epstein-Barr, herpes simplex, hepatitis

  ; Pneumocystis carinii

        - trimethoprim-sulfamethoxazoleÀÇ prophylactic use½Ã¿¡¸¸ ¹æÁö

     (bacterial urinary tract infectionµµ ¹æÁö)

# mortality

  ; 4-4.5%

      ¡æ ÀÌÁß 40¡­45%°¡ infection ¶§¹®

# tumor

    ; ÁÖ·Î lymphoma, sarcoma & carcinoma ¹ß»ý

    ; high death rate