Part 23. Nephrology

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 (CO의 10% 차지)

    ; 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 ①speciallized m. cells in the walls of aff.a. ② lacis cell ③ macular densa of distal tubule

5) Glomerulus

    ; 1 million nephron in kidneys

    ; complete at birth but functional immature

    ;     ① endothelium

                   - fenestrations

        ② GBM

               i) lamina lara interna ( subendoth.)

               ii) central electron dense lamina densa

                iii) lamina lara externa ( subepith.)         

        ③ epithelial cells

            - filtration slit(space between the foot process)

    ; mesangium

        - ♥기능

                   ① supporting structure of glomerular capillary

                ② play a role in regulation of glomerular blood flow, filtration

                ③ 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

    ① glo.cap.hydrostatic pr. <- systemic art.pr.

    ② glo.cap.oncotic pr.

    ③ glo.plasma flow rate

    ④ hydrostatic pr. within Bowman space

    ⑤ permeability of glo.cap.wall

; adult values at *3yr

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

; ★filtration rate가 70% 이하로 떨어져야 serum creatinine 상승

; *GFR이 감소하면 tubular secretion of creatinine 증가하므로 filtration rate가 실제보다 overestimate 될수 있다.

; *serum Cr이 2.0mg/dl(180umol/L) 이상이면 GFR은 little merit

    --> *renal function은 secrum creatinine으로 F/U해야 한다.

♥ TRP

    = (1- Cpi/Ccr) x 100

    = (1- Upi*Scr/Spi*Ucr) x 100

         (nl ; 78-93%)

Section 2. Conditions particulary associated with hematuria

※81주 Table XXIII-1 & 표17-1(p694)

 

★Table 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

    - ★> 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

  ; *▲common causes

    ; 증거

         ① experimental immune mediated GN 와 morphologic & immunopathologic similarity

           ② immune reactants(Ig & C')을 glo.에서 발견

       ③ serum C' abn. 와 autoAb.(ex.Anti GBM) 출현

      2) 2 major mechanism of immunologic injury

        ① localization of circulating Ag-Ab immune complex

        ② local Ag in situ와 Ab의 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

          실험) acute serum sickness in rabbit iv of bovine albumin

                -> acute proliferative GN

           cf. glo.localization에 관여인자

          +-① complex : conc, charge, size

          | ② glo.의 특징 : mesangial trapping, negatively charged capillary wall

          | ③ hydrodynamic forces

          +-④ various mediators의 influence : angiotensin II, PG

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

          : IF상 linear deposition of Ig. & C' on GBM

             이는  i) Goodpasture disease -+ 과 비슷

                  ii) RPGN의 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.노출->coagulation                |    cascade

              +--  indirectly by C' activation

Pathology

      different ds. state에서 similar microscoic change 보이는 경우도 있다.

    1. Proliferation of glomerular cells

     ① +-generalized : all glo.

        +-focal : only some glo.

     ② +-diffuse : single glo.의 all part

        + segmental :     〃    some part

     ③  주로 +-endoth. & mesangial cell prolif. 많음

              +-mesangial matrix도 증가

           -> glo.size 증가, glo.cap.lumen 감소 -> renal insuff. 

   2. Crescent formation in Bowman space

     ① proliferation of parietal epith.cells of B space - esp. RPGN

     ② 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 proliferation이 동반되고 immune complex &

          antiGBM Ab가 동반

      3) Glomerular exudation of blood cells

          neutrophils : m.c.

          eos, baso, mono

      4) thickened appearance of GBM

         원인

       +- ① true increase in width of memb. : membranous glomeruloathy

       |  ② memb.과 비슷하게 염색되는 immune comlex의 massive 침착 : SLE

       +- ③ subendothelial space에 mesangial cell과 matrix의 interposition (split app.)

                                                       : type I MPGN, others

      5) Sclerosis

         scar tssue in glomerulus

         때로 increase in mesangial matrix 의미

Chapter 464. Recurrent Gross Hematuria

★Table 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

    ; 남:여 - 2:1

    ; episode of gross hematuria or microscopic hematuria on routine exam

    ; renal function

           - relatively normal

         - proteinuria : < 1gm/day (minimal)

    ; C3 normal

Prognosis & Treatment

      ① 대개 no kidney damage

      ② 30%에서 progressive ds.로 develop.

         no Tx. - activity 제한은 필요 없다.

      ③ number of gross hematuria, persistent microscopic hematuria between

         episode는  Px.와 무관

# ※Poor Prognosis Factor

    ; hypertension

  ; diminished renal function

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

  ; histologic evidence of diffuse GN with crescent, scarring

# ※Ig A deposition diseases

  ① Berger ds.  

  ② H-S nephritis

  ③ SLE

  ④ Liver cirrhosis

    ⑤ rarely MCLS

Idiopathic Hematuria (=Benign Familial Hematuria)

     ; 정의 : LM & IF 상 normal histologic finding & recurrent episode of gross

             hematuria

          EM 상 some case - marked thinning of GBM

     ; excellent Px.

     ; F/up to DDx. Alport synd.

Alport Syndrome

     : m.c. of hereditary nephritis

       marked variability                                

       X chrosome에 존재하는 제 IV형 collagen의 a⁵ 사슬 유전자의 돌연변이

    1) Pathology

      ① 나중에 mesangial proliferation & cap. wall thickening->progressive glo.

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

      ② EM상 thickening, thinning, splitting & layering of GBM & tubule

                  (not specific to Alport synd.)

      ③ immunopathologic study (-)

    2) Clinical sx.

      ① renal involvement

          m.c.+- Asymptomatic microscopic hematuria

              +- recurrent gross hematuria

      ② sensorineural hearing loss (소수)

          -esp, high frequency range -> 점차 진행되어 deafness

      ③ eye abnormality (10%)

         i) cataracts

         ii) Keratoconus ( anterior lenticonus )

         iii) spherophakia ( macular lesion )

    3) Genetics

      : ① X-linked dominant => male에서 severe course

               ( autosomal dominant 도 있다.)

        ② 20%에서는 No family Hx. of renal ds.

    4) Complication

       ① hypertension       ② UTI       ③ CRF

    5) Px. & Tx.

       ① male:10-20대에 end stage RF with hearing loss->dialysis & kidney                          transplantation

       ② female:normal life span & subclinical hearing loss

Idiopathic Hypercalciuria

; present as     ① RGH

           ② persistent microscopic hematuria

               ③ dysuria in the absence of stone formation

Etiology

    ; excessive GI absorption of normal dietary Ca. intake  

    ; defect in renal tub. Ca. reabsop.

Diagnosis

    ; ★24hr U ca. excretion  > 4mg/kg

    ; screening test

           - ※random Uca/Ucr > 0.2

Differential Diagnosis

    ; normal infants

    ; hypercalcemic hypercalciuria due to hyperparathyroidism or Vit. D intoxication

Complication

    ; ※Nephrolithiasis

Treatment

    ; Oral thiazide

           - controversal

           - Indication

                   / persistent gross hematuria or dysuria

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

                   --> Uca. excretion < 4mg/kg/24hr.되고 Cl/M. resolve 될때까지 증량

                   --> 1년 후 중단

           - 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 β-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

    ① immune complex인한 mech.으로 생각.

        - 이유+-morphologic study

              +-serum C3 depression

          but not clear yet    

    ② acute serum sickness in rabbit과 비슷

    ③ C'activation은 alternative rather than classic immune-comp. med. pathway

Clinical Manifestation

    ① child but 3yr 이전은 rare

    ② streptococcal infection후 1-2wk경과후

       latent period

             +- pharyngitis : 9-11일

             +- pyoderma : 3주 or 이상

    ③ Sx. :

       i) asymptomatic microscopic hematuria - ARF까지 다양.

       ii) edema, hypertension, oliguria, encephalopathy, CHF

        * edema : due to +-water & salt retention

                         +-nephrotic syndrome

       iii) nonspecific symptom

    malaise, lethargy, abd. & flank pain, fever

    - acute phase는 대개 1mo. 내 호전.

      urinary abn.는 1yr.이상  지속가능.

    - acute phase :4-10일

      Gross hematuria : 대개 1wk.

      Microscopic hematuria : 1-2mo.

Diagnosis

    ① UA상

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

    ② mild normochromic anemia due to hemodilution and hemolysis

    ③ C3 감소 (90%)

    complement +-low for 10ds

                | normalize within 4-5wk

                    +-5-10%는 S-C3 not reduced

    ④ evidence of streptococcal inf.

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

      ii) ASO (not helpful : skin inf.후는 증가되지 않음.)

    : 인두염후 1-2주후 상승, 3-5주 peak, 2-3 mo. 걸쳐 서서히 감소.

      iii) DNase B antigen : best single Ab titer

        * alternative ⓐ Streptozyme test ⓑ Streptolysin ⓒ DNaseB ⓓ hyaluronidase

                     ⓔ Streptokinase    ⓕ NADase

        따라서 +-acute nephritis

               | evidence of recent streptococcal inf.

               +-low C3

         -> 이로서 clinical Dx. of PSGN 가능

         -> renal biopsy는 not Ix.

           but, ①SLE                       -------+ rule out 하는것이 중요.

               ②acute exacerbation of chronic GN  -

# ♥Renal biopsy indication for PSGN

  ① development of ARF or nephrotic synd

  ② absence of evidence of streptococcal inf.

  ③ absence of hypocomplementemia

  ④ persistent of marked hematuria or proteinuria

  ⑤ diminished renal function

  ⑥ 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% 이상

; 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

; *▲common 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 비슷

Clinical Manifestation

    - 2nd decade of life에 m.c.

    - Nephrotic syndrome 소견

       with microscopic hematuria

            occasionally gross hematuria

    - B.P & C3 : normal

Diagnosis

    - renal biopsy => confirm

       Ix.  ① presentation of nephrotic syndrome over 8yr.old

           ② unexplained hematuria & proteinuria

# associated diseases

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

Complication

    ; ★increased risk of renal v. thrombosis

Treatment

    ① spontaneous resolution in majority of children

    ② salt restriction & diuretics for nephrotic state

    ③ immunosuppressive therapy : 일부 환자에서 progressive renal insuff. 를 늦춘다.

Chapter 467. Systemic Lupus Erythematosus

      ① fever  ② wt. loss  ③ rash  ④ hematologic abn.

      ⑤ arthritis  ⑥ heart, lung, CNS, kidney 침범하는 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

# ㉿Classification 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)

           ; *▲common & severe form

           ; *massive mesangial & subendothelial deposit in all glomeruli

           ; mesangial proliferation in all glomeruli

           ; ★wire loop lesion

                   - thickened cap.wall (= subendoth. deposit)

           ; commonly necrosis, crescent formation, scarring

  WHO Class V (= membranous LN)

           ; ▲least common

# common transformation

Clinical manifestation

      대개 adolescent girl

    ① milder form (all class II, some class III) : hematuria, normal renal function,

                                                   proteinuria ( < 1gm/day )

    ② some class III & all class IV : hematuria & proteinuria

         reduced renal function

         nephrotic synd. or ARF

    ③ some prolif.LN시 normal UA 보일수도 있다.

    ④ Class V : nephrotic synd.

Diagnosis

    ① 의심 : crculating ANA

    ② 확진 : anti DNA Ab ( native double stranded )

    ③ C3 & C4 감소 in active ds.

    ④ renal biopsy는 반드시 시행.

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 즉 more severe case

     - azathioprine 2-3mg/kg once daily 추가

   ③ 1-2mo.후 serologic remission 되면 Pds 60mg/m²/day - ADT, single dose

                                           -> 5mg씩 tapering해 30mg/m²까지.

   ④ azathioprine도 감량하여 1yr.후 discontinue.

                 - 이때 serologic study, renal monitoring 필요.

Prognosis

   : dramatically improved

     ds. is controlled, not cured

   : relapse & side effect 주의

Chapter 468. Membranoproliferative Glomerulonephritis  (=Mesangiocapillary GN )

; *▲common cause of chronic GN in older child & young adults

Pathology & Pathogenesis

; *hypocomplementemia

    - DDx from other form of chronic GN

; some C3 nephritic factor

# ★Three Histologic Types

    1) Type I MPGN

         ; *▲common 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

                           / ★double 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

    ; *▲common in 2nd decade

    ; mostly nephrotic syndrome

    ; some gross hematuria, asymptomatic mcroscopic hematuria, proteinuria

    ; *HT - common

    ; *decreased C3

Diagnosis & Differential Diagnosis

# ★onset of nephrotic syndrome in child more than 8yr

    --> *renal biopsys 해야 한다.

# D/Dx with APGN

  ; 공통점

           ① gross hematuria

           ② C3 감소

        ③ ASO 증가 (coincidental)

    ; 다른점

           - APGN : 2mo. 내 dramatically improve

           - MPGN

                   / persistent clin. Sx. -> Renal biopsy필요

          / 6주 이상 C3 감소

Prognosis & Treatment

    ; all type is poor prognosis

           - *esp. type II

    ; I,II는 kidney transplantation후에도 재발

    ⑤ No difinite therapy    -+

       long term alternate Pds-+로 clinical course의 stabilization.

Chapter 469. GN Of Chronic Infection

★Etiology

    ① subacute bacterial endocarditis ( Str. viridans or other organisms )

    ② infected ventriculoatrial shunt for hydrocephalus ( staphylococcus epidermidis )

    ③ syphilis

    ④ hepatitis B, hepatitis C

    ⑤ Candidiasis

    ⑥ malaria

Pathogenesis

     infecting organism이 foreign Ag으로 작용.

       -> high level of circulating Ag존재에 대한 host Ab response로

           immune complex형성.

       -> Kidney에 deposition

       -> GN 초래

  3) histopathologic findings may resembles

     +- PSGN

     |  Membranous GN

     +- MPGN

       Sx : acute nephritic or nephotic syndrome

      C3 감소 : common

  4) Tx.

    ① eradication of inf. -> usually resolution

    ② progression to end-stage RF 가능.

Chapter470. Rapidly Progressive (Crescentric) GN

; *presence of crescents in majority of glomeruli

; *rapidly progressive clinical course

Classification

# idiopathic

# ※87 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

    ; ★normal C₃ level

Clinical Manifestation

    ① ARF : 대개

    ② end-stage RF within wks to mos.(after onset )

Diagnosis & Differential Diagnosis

    ① ANA, C3, anti DNase B titer 측정으로 타질환 R/O

    ② confirm : Kidney biopsy

Prognosis & Treatment

    ; PSGN associated RPGN

           - spontaneously recovery

    ; Lupus or Anaphylactoid purpura associated RPGN

           - PRS + Azathioprine

                   --> success

    ; ★RPGN associated with remaining types

           - *poor prognosis

           - ※94 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

    ① SLE

    ② Ana. purpura

    ③ polyarteritis nodosa

    ④ Wegener granulomatosis

Pathology

; *resemble RPGN in LM

; IF

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

Clinical Manifestation

      extremely rare in child

     ① hemoptysis : usually presenting complaints, pulmonary hemorrhage

                    수일 또는 수주후

     ② hematuria

     ③ proteinuria develop

     ④ Progressive RF 발생

    ; *C3 : normal

Prognosis

     생존하면 commonly end stage RF 진행

     No definite therapy

        +- pulse met0hylprednisone

        |  oral cyclophosphamide

        +- plasmpheresis

     cause of death : pulmonary hemrrhage

Chapter 472. Hemolytic Uremic Syndrome

; *▲common cause of ARF in young children

Etiology

    ; bacterial

           - ㉿E. coli (O157:H7) : ▲common

           - 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

     ① 초기 glo. change

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

     ② fibrin thrombi -> cortical necrosis

     ③ severely -> partial or total sclerosis

※92 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

    ; *▲common under 4yr

     ① 선행증상

         대개 gastroenteritis ( fever, vomiting, diarrhea, abd. pain )

              URI, less commonly

     ② 5-10일후

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

     ③ P/Ex상

         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

    ; ★bilateral renal v. thrombosis

           - *▲difficult

           - 공통점

                   / preceding AGE

         / dehydration, pallor

                   / microangiopathic hemolytic anemia, thrombocytopenia, ARF

    - 차이점

                   / *marked enlarged kidney in renal vein thrombosis

# ♥Renal Bipsy Ix.

  ; prolonged renal failure > 2wks

    ; thrombocytopenia(-)

Complication

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

  ; ♥Extrarenal 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

    ; ★early & frequent peritoneal dialysis

           - *▲good 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  의 bacterial, micobacterial, viral infectin 과

       관련있다.

    1) cystitis: bacterial, micobacterial, viral

    2) urethritis:

      . gross or microscopic hematuria, urgency, urethral discomfort

      . UA 上 RBC, pyuria

      . urine culture: usually negative

        bacterial, ureaplasma, chlamydia 可

      . spontaneous relieve 可

      . Tx. : 10 day tetracycline

             + urinary analgesics(phenazopyridine hydrochloride)

      . conservative Tx. 로 안되면 cystoscopy 시행

        --> 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 과 비슷

              대부분의 hematuria 가 spontaneousely recover 된다.

474.3 Renal Vein Thrombosis

Epidemiology

# ★2 Distinct Patterns

    ; new born & infant

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

    ; after infancy

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

Pathogenesis

; intrarenal venous radicle 에서 시작하여 antegrade & retrograde spread

  --> renal v. involve 는 않됨

; 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. 시 ARF

Diagnosis

Hx. : predisposing clinical factor 있는 pt. 에서 hematuria & flank

      mass 有

Lab/F : i) microangiopathic hemolytic anemia

         ii) thrombocytopenia

U/S 上: marked enlargement

radionuclide study : little or no renal function in involved kidney

venacarvogram & doppler flow study  to confirmed the diagnosis

  in occult case --> 될수있으면 피한다.

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

     - 환자가 DIC 에 빠진경우를 제외하고는 의미 없다.

 bilat. renal v. thrombosis

 : CRF 로 가는 경우가 많다.

 i) thrombectomy

 ii) systemic fibrolytic agents

Prognosis

 in infant

 progressive atrophy --> small scared kidney

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

             -> acute phase 에서는 실시하지않음

  in old children

  involved kidney may recover

  ( 특히 nephrotic SD 이나 CHD와 연관된 thrombosis의 경우)

Chapter 475 Anatomic Abnormalities associated with Hematuria

Congenital Abnormalities

; gross or microscopic hematuria 는 UT. malformation 의 대부분의 형태에서 나타날수 있다.

; flank 에 minor trauma 후 sudden onset of usually painless grosshematuria시 의심

--> ureteropelvic junctional obstruction

cystic kidney 가 자주 동반됨

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 ★“ congenital hepatic fibrosis”

Clinical Manifestation

          bilat. flank mass at birth

          oligo hydroamnios 동반 多

        --> Potter synd. 초래

          : 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 시 kidney U/S 要 (in neonate)

          gross & microscopic hematuria , hypertension 이 흔하다.

          renal function 은 정상 혹은 감소 ( renal malformation 의 severity에 의존)

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 시 neonatal period 에 pul. & renal insuff. 로 死

         생존자는 renal insuff. 발생전 수년동안 살수도 있다. 이때 Kid. size 는 줄고

          HT. 은 less severe하다.

         renal failure 발생시 -- dialysis , kid. transplantation

         hepatic fibrosis, or cirrhosis 시 portal hypertension초래되며 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 에

     i) gross or microscopic hematuria

     ii) flank pain & mass bilat.

     iii) Hypertension

 동반질환

     i) hepatic cyst of no clinical importance

     ii) aneurysm of cerebral circulaton -- ICH 초래

 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 시 발생 가능

       Dx. -- confirmed by angiography

Chapter 476. Miscellaneous Etiologies Of Hematuria

476.1 Exercise Hematuria

        gross or microscopic hematuria 가 vigorous exercise 후에 올수 있다.

        benign, rare in female, /ass. c  dysuria

        color of urine -- red to black

        urine 에서  blood clot 이 보일수 있다.

        RBC cast 없고 renal ds. evidence 없다.

        운동멈추고 48시간내 소실

        lower UT. origine 으로 생각

        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.

    ; 최근 URI, skin & GI infection --> AGN or hemolytic uremic synd.

  ; frequency, dysuria, unexplained fever --> UTI

  ; ※Flank Mass

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

    ; gross hematuria 의 최근 Hx. --> IgA nephropathy, idiopathic hematuria

                                       Alport SD. hypercalciuria

       rash & joint pain 동반시 --> HSP, Lupus

       그외 trauma Hx. bleeding difficulties, drug usage, 가족의 Kid. Ds. Hx. HT Hx.

Laboratory Finding

       anemia

         - dilutional ; ARF 때 fluid over load 때문

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

                       melena in HSP, HUS

          - hemolytic ; HUS, SLE

                    ----    hemorrlytic state 의 confirm - reti. count 증가

                                                          plasma Hb level 증가

                                                          plasma haptoglobin 감소

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

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

       sickle Hb for black child --> anemia 없을때도

       urine culture ; UTI 가능성 평가

       CCr, protein & Ca excretion -- 이것이 불가능 하면 S-Cr., urine protein by                                     dipstick ,  ca. to cr. ratio in random urine

       urinary RBC morph. 가 lower tr. 이면 normal, glomerular 이면 dysmorphic.

       -- 반드시 hematuria 의 위치와 일치하지는 않음

# decreased C3

    ; PSGN

    ; MPGN

    ; Lupus GN

    ; chr. infection GN

# thrombocytopenia

         : plt. 생산 ↓ (mal.)

         : plt. 파괴 ↑ ( ITP, HUS, RVT)

Imaging Studies

    3)    IVP, U/S --> str. Abn 를 R/o 함

          cytogram --> infection 을 가진환자, lower tr. 의 lesion이 의심되는 환자

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 를 가진환아에서 routine evaluation은 아니다.

         more helpful - i) bright red hematuria

                        ii) dysuria

                        iii) sterile urine culture

                        iv) 남아에서 주로 trauma에 의한 urethral lesion을 확인함

                        v) lower UT. 의 neoplasm 확인

   * hematuria 가 6 mo 이전동안 있을시

                    - streptococcal inf. 의 serologic evidence 를 확인 해야 한다.

                       ; throat. & skin inf. culture

                       ; ANA for Lupus

  ** 상기 study 에서 모두 정상이 나오면 더이상의 study는 필요없다.

       하지만 IgA nephropathy or Alport SD. 은 있을수 있다.

       --> long term f/u 이 필요함.

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)

# 측정 방법

    1) dipstick test

           ; -, ±, +(30mg/dl), ++(100mg/dl), +++(300mg/dl), ++++( 2000mg/dl ↑)

           ; primarily detection of Albumin

           ; *less sensitive other form protein

                   - *Bence Jones protein, gamma globulin

    2) Sulfosalicylic method

# ♥False 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 (한글판:아침 첫소변)

           - 2세이하에서 0.5 ↓

         - older child 에서 0.2 ↓

    - ★more than 3

                   --> *suggest nephrotic range proteinuria

Chapter 478  Non-Pathologic Proteinuria

★Table 478-1

# proteinuria 의 정의 (한글판)

    ; qualitative

        - 1주이상의 간격으로 3회이상 검사시

       요비중 ≤ 1.015 일때 :  1+ ↑

       요비중 ≥ 1.015 일때 :  2+ ↑

    ; semiquantitative

     아침 첫 소변에서 단백/Cr.(mg.dl) 비가 0.2 ↑

    ; quantitative

     i) 정상 〈 4mg/m2/hr

     ii) 단백뇨 : 4 - 40mg/m2/hr

    iii) N S  〉40mg/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 

        - 밤에 30분간 누어있은후 이상태에서 배뇨하여 이 uriine 은 discard ( time check)

         --> large glass liquid  먹인후 재움 --> 아침에 누운채 collection

    ; upright collection

       - normal daily activity 하면서 2번collection

# *supine collection은 정상이고, upright collection이 proteinuria을 보여야 한다.

Treatment

    ; *추적관찰이 요한다.

478.2 Febrile Proteinuria

       38.3℃ ↑ 시 出( 101℉)

       기전 : unknown

       2+ 는 넘지않는다.

       fever 사라질때 resolve 되면 benign 으로 생각

478.3 Exercise Proteinuria

       48 hr rest 후 normal 이면 benign

       2+ 이상 넘지않는다.

    ; 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, β2 -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

; *▲common cause of proteinuria

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

; index of protein selectivity

    - C IgG/ C transferrine or albumin

  ＜ 0.1 highly selective

  ＞ 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

# ♥Definition

    ; 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

# ★원인

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

# ※Evaluation Of Persistent Asymptomatic Proteinuria

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

    ; ※Annual Evaluation

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

# renal bx. Ix.

  ; persistent asymptomatic proteinuria 〉1g/24hr

  ; hematuria, HT., or diminished renal function 동반시

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

 부분적으로 Cap. wall내의 negative charged glycoprotein 의 loss로

 capillary permeability 증가 --> proteinuria

* nephrosis 때

  . proteinuria > 2g/day 이상 주로 alb.

  . alb. 2.5g/dl in serum 이하시 edema 발생

# ★Mechanism 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 에있어 intrarenal defect

        Cap. wall permeability 를 증가시키는 circulating agent

# ♥Hyperlipidemia 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 에 의해 mediate

; IgE mediation in some

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

  --> vascular permeability 증가인자 관여

Pathology

# ★3 Morphologic Pattern

  1) MCNS (85%)

        ; normal or minimal increased in mesangial cell & matrix

        ; *EM - retraction of epith. foot process

        ; IF - typically negative

           ; *95%이상에서 corticosteroid 에 responce

    2) Mesangial proliferative group(5%)

        ; diffuse increase in mesangial cell & matrix

        ; IgM, C3 등이 주로 침착됨

       ; *50 - 60% 에서 corticosteroid에 반응 

  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. 에도 재발可

Clinical Manifestation

    ; *male:female = 2 : 1                          

           - MCNS or FS : 66% male

         - MPGN : 65% female

    ; *▲common between 2-6yr

        . URI 가 선행되어 나타나는 경우가 多 

           pitting edema ( periorbital, lower ext.)

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

           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. ↓ 인해 , renal perfusion ↓

 --> intravascular vol. dl restore 되면 normal 로 돌아온다.

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

 s- Alb. 〈 2g/dl

 s- Ca. ↓ ( owing to alb. bounding fraction ↓)

 C3 ; normal

 8세이전 (1-8세) onset; renal bx. 없이 corticosteroid tx.

 8세이후 MCNS 가 많지만 membrain or MPGN 이 increasingly common

    --> renal bx. 먼저시행하고 치료

Complication

# Intection

    ; major Cx

    ; ㉿Why 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

                   / *▲common

           - sepsis, pneumonia, cellulitis, UTI

    ; organism

           - ★Streptococcus pneumoniae

                   / *▲common for peritonitis

           - G(-) bacteriae

    ; prevention

          - *all patients 는 remission 시 polyvalent pneumococcal vaccination

# Tendency To Arterial & Venous Thrombosis Tendency

    ; ㉿why ?

           - *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 없어지면 해제

fluid intake: edema 심하지않으면 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 있는경우 사용

                                            oral kcl supplement

hospitalization

   severe edema -->respiratory destress(pleural effusion)

                 --> scrotal swelling, ascites

    ; ★Severe Edema

           - 과거) iv albumin and then iv furosemide

           - 현재) ♣oral 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

    ; ★Prednisone 60mg/m²/day (max. 60mg/day) #3-4

    ; usually reponse *within 2wks

           - *if not response 1mo after continuous steroid therapy

                   --> *steroid resistant 로 생각하고 renal biopsy를 실시한다.

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

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

           --> continued for 3-6mo

                   / ♥why?

                           : maintain the remission using nontoxic dose of PRS

                           : avoiding frequent relapse

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

           - *abruptly discontinued

                   / *치료중단후 1년까지는 severe illnes, surgery가 있을때 corticosteroid supplementation이 필요함

# ★“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 되면 steroid responsive nephrotic syndrome 의 경우

            2nd decade 말에 spontaneous resolution 됨

         +-residual renal dysfunction이없고

         | generally not hereditary

         +-fertile ( unless cyclophosphamide or chorambucil tx. )

             --> reassurance 要

        remission 시는 normal & unrestricted diet & activity

            --> 더이상 urine protein check 필요없음

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. 의미하나 nephritis 좋아지면서 resolve 可

481.3 Tumors

# solid tumor such as carcinoma

    ; membranous glomerulopathy

             immune complex ds.( tumor Ag. 과 tumor specific Ab. 로 구성된  

                                     immune complex 에 의해 mediate 됨 )

# Lymphoma ( esp. Hodgkin ds.)

  ; ※minimal change ds.

           - *▲common

    ; 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

# ♥Causes 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 의 dilatation ( microcystic ds.)

   ; glomeruli -- mesangial prolif. & sclerosis

Pathgenesis

    ; unknown

Clinical Manifestation

 ; proteinuria ( birth or 대개 3mo 이내)

 ; 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 (∵ infection or renal failure 로 사망한다.)

Treatment

  ; supportive

  ; kidney transplantation--> 궁극적으로

  corticosteroid & immunesuppressive agent : no value

  AFP: prerenal Dx. 가능 (20주이전에)

Section 4. Tubular Disorders

Chapter 482. Tubular Function

Sodium

         1) reabsorption

          +-65% of filtered Na+ : proximal tubule

          |      glucose & aminoacid 가 함께 reaborption

          |      --> isotonically absorbed

          +-25% : ascending liimb of loop of Henle

          |       active transport of Cl  와 함께

          +-10% : distal tubule & collecting duct

                  mediated by aldosterone

                  이와 같은 reabsorption으로 생후 1세이후부터

                  urinary Na concentration 이 1mEq/L 유지

         2) excretion

            ECF vol.관여 ← ECF vol. regulating factor에 영향 받음

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% 흡수 at tubule

         65% 가 prox. tubule 에서 Na 흡수와 관련有

         . 흡수의 증가    PTH

                          reduction of ECF

                          thiazide diuretics

       . Excretion 증가    saline infusion

                          furosemide

Phosphate

: 대부분 prox. tubule

                   reabsoption inhibited by PTH

Magnesium

: prox. tubule 에서 25%흡수( 1/4)

                    대개 흡수 및 moderation of Mg excretion 의 주요장소:

                    thick ascending limb of Henle

Maturation Of Tubular Function

       ; at birth & 그후 몇개월까지는 tubular functional capabilities 가 성인보다 낮다.

          healthy newborn 의 maximal urinary conc. capacity  가 낮다.

          ( 600 - 700mOsm/kgH2O )

         # 낮은이유

               reduced GFR

               tubular cell immaturity

               reduced nephron length

               reduced medullary solute gradient

               due to +-increased medullary blood flow

                         +-low urea production

               ADH 에 diminished tubular responsiveness

          newborn 의 diluting capacity는 adult 와 유사

          water load excretion 감소  in NB ( low GFR 때문)

          newborn 은 Na+ , K+ , H+ , phosphate excretion 감소

           --> 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

              일부는 progressive renal damage

        2) anatomic disorder

           structure of tubule 의 이상

            ex) cystic ds.

Chapter 483. Renal Tubular Acidosis

         : impaired urinary acidification 에의한 systemic hyperchloremic acidosis 의

           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 의 85% 는 prox. tubule 에서 reabsorption 된다.

       나머지 15%는 distal tubule 에서 reabsorption. --> premature 와 neonate 에는         일시적으로 약간 감소됨

       acidification mediated by

         i) distal tubular secretion of H+

            (일부는 mineralocortocoid - dependent)

         ii) distal tubular secretion of ammonia

            ( acidic urine 에서 ammonium ion 형성 )

       · normal kid. 는 filter 된 모든 bicarbonate를 흡수한다.

       · bicarbonate 의 prox. tubular reabsorption은 Na+ 와 교환하여 tubular umen            내로 H+ 의 분비를 유발한다.

       · H+ 은 carbonic acid 를 형성하기 위하여 carbonic anhydrase 에 의해filtered

          bicarbonate 와 결합한다. --> 이는 water 와 carbon dioxide 로 해리된다.

       · carbon dioxide 는 proximal tubular cell 로 diffusion 된다.

       · 여기서 carbonic anhydrase 의 영향으로 다시 carbonic acid 로 change 된다.

       · carbonic acid 는 H+를 생성하기 위해서 해리되고 이는 다시 bicarbonate 를

          흡수하기위해 분비된다. 그리고 이때 bicarbonate 는 다시 peritubular cap. 로

          들어간다.

㉿Table 483-1

Proximal RTA ( Type II)

Pathgenesis

     1) reduced prox. tubular reabsorption of bicarbonate  

       presumably due to deficient carbonic anhydrase production --> prox. tubule           에서 60%만  reabsorption ( distal tubule은 15% 만 흡수 )

       25% 까지 urinary loss

      ; prox. RTA more severe than distal RTA

     2) Lab/f

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

          urine 은 acidified( pH〈 5.5) ∵ distal tubule 의 acidification mechaniam 은

                      intact 하기 때문에 filtered bicarbonate 가 감소

          hypokalemia

          distal tubule 에서 NaHCO3 다량 --> Na  reabsorption in exchange for k+

          Hyperchloremia

           ECF vol. 감소로 인해 +- chloride  reabsorption 자극

                                +- aldosterone secretion ↑ --> k+ loss↑  

   3) classification of prox. RTA

     a) isolated prox. RTA

          transient or persistent

          sporadic or inherited ( 대개 A.D. )

     b) Fanconi synd.

       ; generalized defect in prox. tubular transport   

       특징 : 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: 3세이하 出

               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 ← intracellular cystine accum.

                     end stage RF at end of 1st decade

               Tx. : none, cysteamine 으로 임상시도

         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 에서 prolonged 한galactose acc. 으로 인해서 renal manifestation이

        나타남

        Hereditary fructose intolerance

          AR

          fructose 1-phosphate aldolase def.

        tyrosinemia

        Wilson ds.

        medullary cystic ds.

      AD

       cf) 비슷한 질환인 nephronophthisis 는 AR

        children 은 recessive 가 多

        adult 는 dominant  가 多

       .Pathology

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

        progressive interstitial inflammation & fibrosis 로 인해

        --> 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 에의해 prox. RTA

                                | 의 원인

           vit-D def. reckets ---+ 

Distal RTA (Type I)

            distal tubule 과 cdllecting duct 에서 H+ secertion deficiency

            urinary HCO3 의 loss는 대개 (5 - -15%)

            severe systemic acidosis 지만 urine pH 는 5.8 이하는 되지않음

            hyperchloremia, hypokalemia

            nephrocalcinosis 可

          +-isolated

          |     sporadic

          |     inherited: AD or AR

          +-2ndary i) interstitial nephritis

                  ii) toxin, amphotericin B, lithium, toluene

Medullary Sponge Kidmey

            non-inherited ds.

            병리 : cystic dilatation of the terminal portion of the collecting duct

                          ( renal pyramid 들어가는부분)

            renal func. & life span : normal

            동반

             pyelonephritis, hypercalciuria, nephrocalcinosis

             nephrolithiasis, distal RTA , impaired concentrating capacity

Mineralocorticoid Deficiency ( Type IV)

         1) 기전 :    aldosterone 의 inadequate production

                     aldosterone 에 distal tubule 의 responsiveness 감소

           --> tubular cell mb. 에 electrochemical gradient 형성 않됨

                tubular lumen 이 negative 되어 H+ ion secretion 감소 잘되게하는

                gradient형성않됨

           --> Aldosterone mediated Na+ resorption 감소

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

            production 감소-> ammonium ion excretion 감소 -> urine pH 5.5 이하 )

         2) 원인

              adrenal gl. ds. ( aldosterone ↓, renin ↑)

             i) addison ds.

             ii) cong. adrenal hyperplasia

             iii) primary hyper aldosteronism

              : ald. production 감소

                normal renal fx.

               urinary Na+ wasting, plasma renin level ↑

              Hyoreninemic hypoaldosteronism ( renin & aldo. ↓)

              i) kid. ds. /c interstitial damage &

                   juxtaglomerular apparatus destruction

              ii) vol. expansion --+과도 관여

                 PG inhibition ---+

                   : renal function 감소

             pseudohypoaldosteronism ( renin & ald. ↑)

             i) distal tubular responsiveness to ald.

                 : normal renal function

                   salt wasting

            ii) renal insufficiency & medllary ds. 가있는 adult 에서 볼수있음

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) 원인 :unknown

    가능    calcium carbonate release 위해 bone destruction

             ( acidosis 교정위해 carbonate --> bicarbonate )

            urinary citrate 감소 --> calcium chelation

Diagnosis

1) systemic acidosis 일으키는 질환을 먼저 R/o

   diarrhea, lactic acidosis, DM, renal failure

2) Lab.

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

    Mineralocorticoid deficiency, RTA, systemic acidosis, hyperkalemia

 3) 1st morning urine pH 와 동시 에 s- electrolyte 측정 ; prox. & distal RTA             의심시

  s- HCO3 < 16mEq/L

  pH < 5.5: proximal RTA

  pH > 5.5: distal RTA 

  s- HCO3 ( 17 - 20mEq/L)

  i) ammonium chloride loading 후 감별可

  ii) fractional excretion of bicarbonate

        4) prox. RTA 시 glucosuria, phosphaturia, aminoaciduria 찾기

        5) RTA confirm 시  underlying cause 찾기

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 첨가 ( 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

          처음엔 distal 보다 심하나 resolution 可

       2) isolated distal RTA

            life long ds. ( renal failure 는 발생할수 있지만)

            early detection & treatment before nephrocalcinosis 시 excellent Px.

            continuing alkali therapy & life long monitoring of clinical status

     3) Mineralocorticoid RTA

       대개 obstructive uropathy후 出 하므로  obstruction correction 후 12mo 내 소실

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 - 적절한 acid urine 형성불가

       type II - lowered renal threthold for bicarbonate

                impaired urinary acidification

     metabolic bone ds. - occured in both type

   ▷ 특징 : bone pain, growth retardation, osteopenia, pathologic fracture

     RTA pt. 에서 1,25(OH)2D 는 normal

     RTA pt. 에서 azotemia 나 renal mass 의 loss 가 있는 경우

      -- serum 1,25(OH)2D 는 종종 감소한다.

     distal RTA 에서 bone dimineralization

          - dessolution of bone

          - because -- CaHCO3 가 metabolic acidosis 에대한 buffer로 주어지기때문

    acidosis 를 역전시키기 위한 bicarbonate 의 투여는

          bone dissolution & hypercalciuria 를 멈추게 함.

   ▷Treatment.

   proximal RTA - bone ds. 의 치료를 위해 bicarbonate 와 oral phosphate를 투여

   vit-D : secondary hyperparathyroidism예방

483.2 Fanconi Syndrome

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

   1) 개요

     1. 특징 : 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 both가 impaired

         tubular uptake or back-leak of solutes 을 초래함

     2. renal potassium wasting 은 bicarbonate & glucose 의 excessive urinary loss

        에의해 초래됨

     3. urinary sodium loss는 large excretin of urinary anion 에 의함

     4. normal to low serum calcium, varable urinary calcium

     5. vasopressin - resistant urinary concentrating defect 가 종종 나타남.

     6. rickets는  combined effects of metabolic acidosis & hypophosphatemia

        or  hypophosphatemia alone 에 의해 초래됨

     7. vitamin D resistance 는 metabolic acidosis 존재시 나타나는 abn. prox. tubular          cells 에 의해서 conversion of vitamin D to 1.25(OH)2 D2 의 장애에 의함  

     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. 특징적으로 glomerular architecture는 말기까지 보존됨

   4) Clinical manifestations

     1. primary Fancony synd. 은 특징적으로 first 6mo of life 혹은 3rd or 4th decade

       에 나타남.

     2. 영아기에는 vomiting , polydipsia, polyuria, contipation이 발생함

     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 에도 불구하고

      방사선학적으로 rickets , steopenia 나타남. 이소견은 renal tubular cause 를

      나타낸다.

   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. 말기에 GFR 이 감소하면 s-electrolyte 와 aminaciduria, glycosuria.&

          phosphaturia 의 "paradoxic" improvement 를 보임

    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 는 multiple tubular dysfunction을 일으킴

      4. metabolic acidosis, hypokalemia : 확증적

      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 을 야기

  7) Treatment

    1. 2ndary Fanconi syndrome 환자는 underlying cause 를 찾아야 한다.

    2. primary Fanconi syndrome 은 mineral & electrolyte balance 등의                     symptomatic therapy 를 시행하면, 생명을 연장하고 종종 normal life 를 영위한다. 

    3. rickets의 치료, skeletal deformities 예방

    4. rickets or osteopenia 의 치료

      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 초래가 장점

      b. vit-D over dose 에의한 hypercalcemia 를 방지하기 위해서 s-Ca. level 을

         주기적으로 ( weekly at first, then monthly) 으로 측정

      c. hypophosphatemia 의 치료

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

             4 - 5 equally spaced dose  

       ii) abdominal pain, diarrhea 가 치료중 나타나면 일시적으로 중단후 lower dose

           로 다시 시작

       iii) phosphate 는 hypocalcemia, 2ndary hyperparathyroidism 을 방지하기 위해              서 반드시 vit.-D 와 동시에 투여 

    5. metabolic acidosis due to excessive bicarbonaturia 교정은 많은 양의 alkali

          ( 2 - 15 mEq/ kg/24hr of alkali ) 가 필요함

      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 을 거의 normal level (18-20mEq/L)까지

           교정하여야함

      c. alkali는 1-1½ hr after meals in 3-4 divided dose/day 에 복용

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

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

  1) 특징

     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 는  lysosomes 에 축적을 초래함

       이는 이 amino acide 의 lysosomal release 의 failure 에 의함

        specific enzyme defect 는 발견되지 않았음

    3. cystine deposition 의 부위

       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) 조직 소견

     1. early renal change 는 primary  Fanconi syndrome 과 유사

       특징적인 "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 가 진행함에 따라 kid. 는 shrunken & contracted ,

       with glomerular sclerosis & interstitial fibrosis

  4) 임상소견

     1. AR rait

     2. three clinical patterns

       a. infantile or nephropathic form

         i) 3 -12 mo경  Fanconi syndrome 으로 나타남

         ii) generalized aminoaciduria /s predominance of cystine

         iii) GFR 이 점차 감소하여 CRF 가 1st decade 이내에 발생

         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) 검사소견

     1. deposition of cystine crystals 외에는 Fanconi syndrome 과 유사.

     2. tubular proteinuria 가 nephropathic cystinosis 의 early phase 특징이나

        renal failure 가 진행함에 따라 glomerular proteinuria 가 잇따라 나타난다.

   6) 진단

     1. in the asymptomatic NB infant from an affected family

        : cystine content of leukocytes or fibroblasts (정상의 80 - 100배)

     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 examination상 cornea에 crystal

     5. prenatal diagnosis는 amniotic fluid cells에 increased cystine concentration

     6. cystine deposition도 Fanconi syndrome도 나타나지 않는 cystinuria와 혼동하여         서 는 안되며, 이는 an inborn error of specific amino acid transport이다.

  7) 치료

    1. 초기에 tubular dysfunction에 대한 symptomatic therapy는 primary Fanconi              syndrome놔 유사하다.

    2. cysteamine(sulfhydryl binder) : in vivo에서 intracellular cystine을 감소시키며,            몇몇 소아에서는 renal failure 진행속도를 완화시킨다.

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

    4. renal transplantation 후에는 환아는 잘 지내나 long-term survivors는

      a. progressive photophobia or retinopathy를 경험한다. 이 경우 cystiamine eye            drops이 효과있음

      b. associated with long-term extrarenal manifestations

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

483.4 Oculocerebrorenal Dystrophy (=Lowe Syndrome)

 1)개요

    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. 그외 특징으로

      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, 그러나 최근 in vitro studies에서 collagen metabolism의

     이상을 의심함

   2. pathologic studies는 splitting of the glomerular basement membrane, with

      marked variation in their thickness를 보임

 3)임상소견

    1. early life : eye findings and mental retardation

      later : Fanconi syndrome이 임상적으로 분명해짐

    2. childhood시기를 살아남으면 Fanconi syndrome은 spontaneously회복되나, CRF가         될 수 있음

  4)치료

    1. no specific therapy

    2. supportive, as in primary Fanconi syndrome

483.5 Renal Osteodystrophy

  1)개요

   1. renal osteodystophy의 의미는 chronic renal disease를 가진 환아에서 mineral과         bone metabolism의 이상으로 나타나는 skeletal growth와 remodeling의 변화이다.

   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. GFR이 정상인 tubular dysfunction시에도 나타날 수 있으나, glomerular                      insufficiency나 uremia를 가진 환아보다는 흔하지 않다.

   4. 이전에는 renal (uremic) rickets 혹은 renal dwarfism이라 불렸는데, 이는 severe         linear growth failure가 rickets와 같은 X-ray change를 보였기 때문

     a. 이 소견은 일차적으로 vitamin D deficiency에 대한 mineralization defect에 기인         한다고 먼저 생각되었지만,

     b. 이차적인 hyperparathyroidism도 임상적, 방사선학적으로 똑같이 중요한 역할함

   5. pediatric dialysis, kidney transplantation을 시행함에 따라 renal osteodystrophy가       CRF의 주요합병증(acidosis, anemia, calororic deficiency 등과 함께)으로 떠올랐다.

 

  2)PATHOGENESIS

    1. normal dietary intake of phosphorus를 가진 early in the course of chronic renal         insufficiency(GFR 25  50㎖/min/1.73m²)에는

     a. renal tubular synthesis of 1,25(OH)2D3가 phosphate-mediated suppression되어

       a) malabsorption of calcium and phsphorus

       b) unknown mechanism의 defective mineralization of osteoid(osteomalacia)초래

     b.증가된 PTH의 결과, increased bone resorption과 increased renal phophate              excretion을 초래하며, serum calcuim은 유지되며 serum phophorus는 실제적으로

        normal에서 low이다.

     c. dietary phophate restriction은 serum 1,25(OH)2D3 level의 증가와, 2ndary                       hyperparathyroidism이 improve됨

   2. critical renal threshold(예를 들어 GFR이 정상의 약 25  30%)일 때는

       a. 증가된 PTH에 대한 phophaturic renal response의 소실

       b. compensatory hyperparathyroidism이 serum calcium을 정상으로 회복시키기            위해서 잇달아 일어난다.

       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 acidosis도 아마도 bone에서 calcium resorption과 renal                 excretion을 증가시킴으로써 bony change를 야기시킴

   

  3)조직소견

    1. variable

    2. trabecular bone은 predominant osteomalacia, predominant osteitis fibrosa 혹은          most commonly, a mixed pattern을 나타냄

    3. 일부 환자에서는 fracturing osteomalacia와 low bone turnover는 mineralization          front에 aluminum의 축적을 초래하는데, 이는 orally administered aluminum              binders 혹은 aluminum-containing dialysis solutions에 노출되었기 때문이다.

 

  4)방사선학적 소견

     1. abnormalities at the epiphyseal growth plate

       : 가끔 nutritional rickets을 닮으나 종종 현저히 구별됨

    2. growth plate의 longitudinal width가 실제로는 증가되어 있지 않지만, 그렇게 보이        는 것은 dysplastic trabeculas을 가진 metaphyseal fibrosis의 bar 형성 때문이다.

    3. concomitant defect in mineralization은 다음을 초래함

      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)임상 소견

    1. CRF의 발병시기가 younger child, 그리고 renal failure의 longer duration은              osteodystrophy의 incidence와 severity을 크게 한다.

    2. congenital diseases of the kidney를 가진 소아(5세 이하에서 우세)는 소아 후반기        에 나타나는 glomerulonephritides 보다 disease onset과 end-stage renal failure          사이의 interval이 더 길다.

    3 그러나, congenital nephropathies 환자는 bone disease가 가속되는데 이는 maximal              growth, bone modeling and remodeling 시기이기 때문이다.

    4. the earliest sign of renal osteodystrophy

       : usually growth failure

     그외 CRF에 동반된 anemia, metabolic acidosis, protein-calorie malnutrition,                 hormonal disorders, and trace mineral deficiencies

    5. advancing disease의 additional clinical manifestations

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

    6. genu varum, frontal bossing 그리고 dentgal abnormalities는 young children에서         현저함

    7. hypocalcemia에도 불구하고 tetany는 드문데, 이는 metabolic acidosis와                                    hyperparathyroidism의 combined protective effects 때문이다.

 

 6)검사실 소견

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

   2. 증가된 ALP activity는 증가된 bone turnover를 나타내나, 소아에서는 성인만큼             reliasble sign은 아니다.

 

   3. sensitive early indicator of osteitis fibrosa : hand와 wrist의 X-ray에서                     subperiosteal erosions of the middle and distal phalanges, 그리고 erosions은           distal clavicle, inner aspects of the distal femur and proximal tibia에도 나타남.

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

      GFR이 50  75㎖/min/1.73m² 일때도 나타남.

   5. PTH의 degree of elevation은 osteitis fibrosa의 방사선학적, 조직학적 소견과 일치       하나, histologic osteomalacia의 degree는 serum내 chemical abnormalities               혹은 coarsening of trabeculas의 방사선학적 소견과 일치하지 않는다.

 

  7)치료

    1. renal osteodystrophy can usually be successfully managed by

      a. controlling hyperphosphatemia

      b. supplying adquate oral calcium intake

      c. providing extra vitamin D

    2. hyperphosphatemia의 치료

      a. dietary phophate restriction : 시작하는 indication은 raised PTH level

      b. aluminum-containing phosphate binders의 oral administration

      a) risks of aluminum intoxication 때문에 가능하면 피해야 하며, dietary                            restriction이 충분하지 않으면 사용함

        b) aluminum hydoxide or aluminum carbonate gel

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

             이후 용량을 조절하여 serum phosphorus를 4  5mg/dl로 유지시킴

        c) long-term treatment with high-dose aluminum-containing binders의 합병증

            : osteomalacic osteodystrophy and a progressive, irreversible                                          encephalopathy

    3. calcium supplementation

      a. calcium carbonate 형태로 하루에 1  1.5g of elemental calcium을 diet에 첨가

      b. calcium carbonate의 장점

        a) the highest percentage of elemental calcium

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

    4. acidosis control은 sodium bicarbonate를 사용

        : 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) indication은 symptomatic bone disease with hypocalcemia

              secondary hypoparathyroidism

              evidence of osteitis fibrosa on X-ray or bone biopsy

       c) starting dose는 15  40ng/kg/24hr이며, 이를 hypercalcemia risk를 방지하기                   위해서 8  12시간 간격으로 투여하고, 용량의 stepwise adjustment와                     biochemical monitoring이 필요함

      b. dihydrotachysterol(DHT)

        a) 장점 : better ratio of therapeutic to toxic effects

          shorter half-life는 hypercalcemia의 합병증을 감소시킴

        b) starting dose는 0.1  0.2mg/24hr이며, serum calcium을 정상화시키고, X-ray            상 bone abnormalities를 healing시키도록 용량을 weekly or biweekly로 조절             한다.

      c. frequent measurements of serum calcium and phosphorus

      d. CRF에서는 serum calcium의 "set point"가 증가하므로, vitamin D therapy의            therapeutic goal은 serum calcium을 10.5  11.0mg/dl까지 올리는 것이다.

    6. hemodialysis or chronic peritoneal dialysis

    7. autotransplantation of the parathyroid gland

     a. medical therapy에 반응이 없는 severe secondary hyperparathyroidism 환자에          서 시행

       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

    ; 남 : complete unresponsive to ADH

  ; 여 : partial

# 2ndary NDI

    ; medullary concentrating gradient loss초래 질환

       a)acute or chronic renal failure

       b)obstructive & p ostobstructive uropathy

       c)vesicoureteral reflux

       d)cystec ds. : interstitial nephritis

       e)osmotic diuresis, nephrocalcinosis

  ; tubule에 ADH effect 감소된 경우

       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

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

           - diagnosis

           - *dehydration test 불필요

# confirm diagnosis

    ; aqueous vasopressin 0.1-0.2u/kg im 후 4h 간격으로 serum & urine osmolarity 측정.

     -> urine / plasma osmolality

         ratio < 1.0 ; nephrogenic D.I

         ratio > 1.0 ; central D.I

                     psychogenic polydipsia

# s-osmol < 295 mOsm / Kg 이하이면 fast시켜 295이상되면 dehydration test

        cf. B.W 3%이상 loss ->fluid 투여

# biochemical & radiographic study실시하여 이차적 원인 배제

Complication

   (1) mental retardation by repeated hypertonic dehydration

   (2) growth retardation

       male에 나타남 ; intrinsic

   (3) collecting system dilatation->수년마다 renal scan 으로 hydronephrosis관찰

Treatment

# 목표

    ; 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 실패시 시도

Prognosis

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

      2nd.   : underlying ds. nature에 따름

Chapter 485. Bartter Syndrome

   특징:  hypokalemia

         normal BP

         vascular insensitivity to pressure agents

         elevated plasma renin & aldosterone

   AR로 inherited경우도 있음

Pathology

    IG apparatus hyperplasia < renin 생산 장소

    renal parenchyme

    대다수는 정상

    소수에서 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 증가

   g)urinary K+, Cl 증가

    때로 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.I시 hypovolemia동반

        --> low urinary Cl level (cf. Bartter SD시 증가)

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/l이상

                                                  250mg/24/hr시까지 증량

    b)sodium chloride supplementation

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

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

Prognosis

; uncertain

; *많은 환자는 remain well

; 일부에서 renal insuff.

; growh failure 있어도 normal stature

Chapter 486. Interstitial Nephritis

 

  대개 tubular damage 동반

  glome.change는 minimal

   - Common cause of interstitial nephritis

  1.Acute interstitial nephritis

   1)pathology

       interstitial infiltrate

      a)lymphocytes b)plasma cells c)eosinophils 때로 d)neutrophils

        edema: tubular degeneration & necrosis

    2)pathogenesis

      unknown

       a)hypersensitivity reaction; drug

       b)tubular BM에 immune complex의 deposition; Lupus.MPGN

       c)anti BM Ab ; Goodpasture, membranous

       d)cell mediated mechanism ; sarcoidosis, transplant rejection

    3)C/M

      a)drug가 hospitalized pt.시 m/c cause

        1주이상 drug사용시 i)fever & rash발견

                           ii)eosinophil 증가 in blood urine or both

      b)others; ARF or acute GN와 유사한 clinical picture

      c)onset은 ant. uveitis에 의해 선행될수 있다.

   4)Dx.

     renal biopsy로 confirm

      소변내 호산구 증가      

   5)Tx. & Px                      

     a)ARF Tx.                   ---+

     b)inciting agent withhold         |  로 complete resolve

     c)precipitating inf. Tx.        ---+

     d)severe histologic injury & renal failure시

        --->high dose corticosteroid로 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

     대개 occult structural abnormality of Kidney & Urinary tract 동반

       (cystic ds. obstruction, reflux)

      초증상;a) CRF

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

             b)underlying ds 의 증상: (UTI, flank mass)

  3)Dx.; renal biopsy not indicated

       대개 underlying ds와 연관된 chronic renal insufficiency의 양상으로 진단

  4)Cx. & Px

  progression to end-stage RF

  avoidance of phenacetin(analgesics) & lithium -> adult에서

    renal Fc improvement 있음

section 5. toxic nephropathy - renal failure

Chapter 487. Toxic Nephropathy

 

 . medication

  diagnostic agents(iodinated radiographic contrast media)

  chemicals

 . directly damage

    renal bl.flow 감소 , ATN , intratubular obs.

   indirectly

    allergic or hypersensitivity in vessels & interstitium

 

  ** Preventive measures may reduce the risk of nephrotoxicity

     a)pre-existing renal ds시 c.m대신 US or scan

     b)non-nephrotoxic agent로 치환

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

     d)renal insuff. 시 dose reduction

     e)동시에 several nephrotoxic agent함께 사용금지

   table 487-1

Chapter 488.Cortical Necrosis

 

   a) renal cortical(frequently medullary)necrosis는 several type의 renal injury의

     final common result

   b) 대개 both kidney involve

   c) pathy or entire cortex involve

 

1) Etiology

    NB에서의 원인: a)dehydration

                   b)asphyxia

                   c)shock

                   d)DIC

                   e)renal vein thrombosis

    NB후:      Hemolytic uremic syndrome이 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 감소,  d) gross hematuria

 

5) Dx.

  US상 enlarged but non - obstructed kidney

  scan상 감소 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

★Table 489-1

★Table 489-2

Pathogenesis

# prerenal cause

    ; decreased renal perfusion->GFR감소

  ; 일정시간내 hypoperfusion 교정시에는 reversible

# renal causes

  ; hemolytic uremic syndrome

           - ▲common cause in toddlers

    ; ATN

           - no arterial or glomerular lesion

           - ★Proposed Mechanisms

                   / alterations in intrarenal hemodyanmics

                   / tubular obstruction

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

    ; GN

# postrenal causes

    ; upper collecting system의 dilatation은 acute ureteral obstruction수일 후에야 초래

Clinical Manifestation

  .precipitating ds.따라 variable

  .증상 & sign related to RF

     a) pallor(anemia)

     b) U.O 감소

     c) edema(salt & water overload)

     d) hypertension ,vomiting, lethargy(uremic encephalopathy)

Diagnosis

# careful Hx.

    cf. flank mass시 생각

    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 증가; diminished RF

   h) hypocalcemia(hyperphosphatemia)

   i) C3 감소 : 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) 모든 ARF pt. 시 obstruction가능성 발견위해

     i) plain abd. X-ray

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

     iii) renal scan 要

     iv) RGP ; 때로

        <-- obst시 percut. nephrostomy시행으로 reverse 可

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

 

 .치료 : isotonic saline iv 20mL/kg over 30 min

        대개 2hr. 내 voiding

        bladder cath. CVP 필요 可

        hydration 후 diuretics可

 2) Impending RF

  diuretics on prevention of anuria ; controversy

  established anuria에는 no value

  furosemide  --   urine  production ↑  by altering tub. func

  mannitol     --      

  그러나 urine ↑ 이 renal func. 호전이나 natural ds. 호전

  의미없으나, a) hyperkalemia,  b) fluid overload 교정에는 효과.

   < furosemide >

     : hypovolemia없을 경우

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

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

        b)에도 response없으면 CIx.

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

        of furosimide

       ;효과 있든 없든 더이상 사용못함

 3) Fluid restriction

   volume expansion이나 diuretics에 효과없는 경우는 essential

   a) 400mL/m2/24h(insensible loss) + urine 양 ; 정상 intravascular volume시

   b) 10-30% glucose containing solution without electrolytes

   c) blood. GI loss는 교정

 4) hyperkalemia

    serum level 6mEq/L시 cardiac arrythmia, cardiac arrest 可

      a) adequate renal f. 되기전에는 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+ 이 5.5mEq/L로 오르면 Tx시작

        i) 모든 solution에 high conc. of glucose포함

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

           1g/kg p.o or retention enema

           20% 10ml/kg sorbitol ; enema시

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

           (∵ sorbitol은 osmotic diarrhea일으킴) every 2hr. 으로 repeat

   d) s-K+이 7mEq/L이상 오르면

      -->sequentially following emergency step시작

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

        H.R monitoring하며 20beat/min이상 H.R↑되면 쉬었다가 계속

      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 要

     iv)kayexalate

     ·i)은 K+↓시키지는 않으나 (K+ induced myocardial irritability에 counteract

        effect는 있음)

     ·ii)은 K+ shifting into intracellular compartment from ECF 이

          measurement의 duration of action은 단지 수시간 지속되므로

          persistent hyperkalemia시 dialysis 要

 5) acidosis

   a)inadequate excretion of H+ & ammonia대개 치료 要

   b)치료 필요한 경우

     severe acidosis  -- arterial pH < 7.15

                        s-HCO3 < 8mEq/L

       --> 이 때는 resp. drive ↓ , myocardial irritability ↑

  c) partial correction by iv route

     목표 pH=7.20,  HCO3=12mEq/L

     ∴mEq  NaHCO3 required = 0.3 × BW × (12-sHCO3)

     나머지는 s-Ca. phosphatemia /c reciprocal  , hypocalcemia

     acidosis때 total calcium ionized fraction ↑로 tetany발생이 방지되었다가

     acidosis rapid correction으로 ionized Ca ↓ ->tetany

Hypocalcemia

    ; Tx by lowering serum phosphorus

    ; *no calcium iv if not tetany

           - *calcium(mg/dl)xphosphorus(mg/dl)이 70이상이면 calcium salt deposition in tissue

    ; ★phosphate-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

           - 정상이 될때까지 점차 증량한다.

Hyponatremia

    ;due to excessive amount of hypotonic sol.

      a) Tx. by fluid restriction

      b) s-Na 이 120이하이면 cbr. edema & Hemorrhage 可

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

      c) risk of hypertonic sodium

         i)vol. expansion

         ii)HT

         iii)CHF  -->발생하면 peritoneal dialysis 실시

 8) Hypertension

    1。 ds. process

    ECF vol expansion 등에 의해 생김

     a) salt & water restriction ; critical

     b) severe acute symptomatic HT

        i) diazoxide ; DOC

          1-3mg/kg(max 150mg) rapidly iv (10초 이내) --> 10-20분내 BP ↓

          만일 효과 불충분시 30분후 2nd inject or nifedipine 0.25-0.5mg/kg p.o

          HT crisis시 sodium nitroprusside,  labetalol continuous iv infusion

       ii) furosemide concomitantly

   c) less severe hypertension

      i) ECF vol. expansion 방지

        +-> 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)원인 ; 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 가 renal insuff. 시 축적

 10)Anemia

    a)대개 hemodilution; Hb 9-10 g/dl   -->  no transfusion

    b) blood loss by active bleeding은 보충 要

    c) hemolytic anemia(SLE,HUS )

        -- prolong RF 시 

       Hb < 7g/dl시 transfusion

       vol. overload, CHF , pul, edema , HT 위험 있으므로 4-6hr 동안 transfusion

       /c fresh packed RBC의 slow transfusion  10ml/kg

11) diet ; 400cal/m2/day ↑

    a) healthy & well-nourished 이고 ARF가 짧을 경우는

       diet는 restricted to fat & carbohydrate만 준다(gum drops or jelly beans)

    b) Na,K ,water restriction

    c) 3일 이상 지속시 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

               (특히, 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

     ※ 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.은 Cr.보다 BUN치와 더 관련

Prognosis

    underlying cause따라

      1)normalized 可

         a) prerenal causes

         b) hemolytic uremic syndrome

         c) acute tubular necrosis

         d) acute interstitial nephritis

         e)uric acid nephropathy

     2) recovery of renal function 이 unusual한 경우

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

      ※ ARF & CRF 의 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

★Etiology

# 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

     어떤 종류의 Kid. damage든 renal functional deterioration의 critical level도달시         end-stage RF 로 progressive renal function deterioration 관련 factors

      a)ongoing immunologic injury

      b)hemodynamically mediated hyperfiltration in surviving glomeruli

      c)dietary protein & phosphorus intake

      d)persistent proteinuria --  직접 glomerular cap.wall damage

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

# *20% of GFR되어야 uremia 나타난다.

★Table 489-4

Clinical Manifestation

   anatomic abnnormality시

   non specific presenting complaints

         ; headache , fatigue ,lethargy, anorexia, vomiting

           polydipsia, ployuria, growth failure

  P/E

    ·unrewarding

    ·pale & weak. BP ↑

    ·anatomic abn. 로 인해 수년에 걸처  renal failure 가 slowly develop 할수있으며

       이때 growth retardation &  rickets 가 동반될수 있다.

 

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↓,  phosphorus↑

          .ALP ↑ --hypocalcemia

                     hypophosphatemia

                     osteodystrophy

       ii) periodic exam /q 6mo.

           .PTH     --        osteodystrophy early evidence

           .bone X-ray  --     detect 可

      iii) 이외

          .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% 시 growth rate ↓

     b) 주 원인이 inadequate caloric intake이므로 -->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 조절

     c) BUN = 80mg/dl↑시 dietary protein restriction

         ; 1.5 g/kg/24h로 protein이 high biologic value(egg>milk>meat>fish>fowl)

     d) cow's milk에 phosphate ↑므로

       i) moderate restriction

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

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

          때때로 oral phosphate binder 와 conjunction 된다.

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

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

     f) Zinc & iron --> deficient 확인후 공급

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

Water & Electrolyte Management

      a) water; dialysis필요한 정도 아니면 no restriction

      b) Na+; edema, hypertension, CHF 등이 있으면 salt restriciton /c furosemide                                                                       (1-4mg/kg/day)

             ; salt wasting form; Na supplementation

      c) K+

Acidosis In CRF

      s-HCO3가 20이하이면 치료; 성장에 도움.

      Bicitra

      NaHCO3 tablet

Renal Osteodystrophy

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

  b) hyperphosphatemia

      i) GFR이 moramal의 30%↓ 시 phosphorus level ↑

      ii) reciprocal solubility relationship으로 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)기전

             . reciprocally by hyperphosphatemia

             . inadequate dietary intake

             . decreased intestinal Ca absorption caused by a deficiency

                in the active form of Vit. D

      ii)Tx.

            . hyperphospatemia교정

            . 안되면 oral calcium supplement(Neo Calgulucon Syrup, Os-cal         

               tablets);500-2000mg/day

    d) Vit D.

        severe kidney dysfuncton시 1-hydroxylation안되어 Vit.D def.

         i) Ix. for Vit. D therapy

             . s-phosphorus < 6.0mg/dl 이하로 교정하고 calcium supplementation하

               여도 persistent hypocalcemia

             . elevated s-ALP와 X-ray 上 ricket의심되는 osteodystrophy pt.에

        ii) Tx.

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

                  . 0.05-0.20mg/day of dihydrotachysterol solution

       ·normal s-ca. ALP, X-ray上 healing시까지 dose ↑후 initial level

            로 점차 감소.

       ·subperiosteal erosion of edge distal phalanges of index & middle finger

            ; hyperparathyroidism

Anemia In CRF

 ; 대개 Hb 6-9g/dl

     ·transfusion; not indicated

     ·suppression of erythropoietin production

     · Hb < 6 시 10mL/kg of packed RBC  ,

     · recombinant erythropoietin therapy

Hypertension In CRF

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

    b) furosemide 2-4mg/kg iv (rate; 4mg/min);circ. overload 동반된 severe HT시

    c) sodium nitroprusside는 renal insuff.시 주의 toxic thiocyanate축적

    d) Tx. of sustainde hypertension시

        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)로 inadequately control시 minoxidil, captopril사용

Drug Dosage In CRF

    RF시 dosage modification필요없는 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 donor시 creatinine이 5-6mg/dl시

       HLA typing부터 시작

 2) Dialysis

    creatinine이 10mg/dl에 도달시

    pt's clinical status

    Lab/F

    availability of kidney donor 따라 시행

     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)

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

# ESRD의 원인

    ; 나이에 따라 다르다.

           - *13-17세 : glomerulopathy

    - 5세미만 : congenital & obstructive process

    1) *congenital renal disease(53%)

  2) glomerulonephritides(20%)

  3) focal segmental glomerular sclerosis(12%)

  4) metabolic disease(10%)

  5) mescellaneous(5%)

★Table 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 미만 : midline incision후 transperitoneal graft

  2) 20Kg 이상 : right iliac fossa에 retroperitoneal location

                 → renal vessel : external iliac vessel과 anastomosis

                    ureter를 bladder에 reimplantation(ureteroneocystostomy)

                    lower pole : intestine사이에 free하게 둠

 2. TABLE 490-4

 3. survival rate

 

	LRD-RT	CAD-RT
1년	약 90%	72%
3년	80%	65%

 4. TABEL490-5

Histocompatibility

 1. major histocompatibility complex(MHC) gene

  1) locus : chromosome 6 의 short arm

  2) 기능 : human leukocyte antigen(HLA)를 encode

  3) 유전 : Mendelian fashion inheritance

   Figure 490-3

4) 구성

   ① class I protein(tissue transplantation antigen) : HLA-A,-B,-C

      cell-mediated immunotoxicity

   ② class II protein : immune responce 유도

                       HLA-DP,-DQ,-DR

   ③ class III protein : tumor necrosis factor(TNF)

                       complement component (C2 & C4)

  5) HLA-A,-B &-DR : clinical transplantation에서 가장 중요

     : good HLA match→ graft loss 감소

  6) class I & II antigen의 cellular expression

   ① B & T lymphocyte & macrophage에 국한

   ② inflammation에서 T cell에 의해 분비되는 lymphokine(IL-2,4 & 5)에

      의해  multiplication

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

     : MHC (HLA) I (histocompatibility) Ag과 high affinity가짐

       → class I Ag가진 cell에 attach

       → cytokine생성 signal 전달 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 mechanism에 의한 graft damage

    ; accelerated(hyperacute) rejection reaction

           -

# Diagnosis

  ; renal ultrasound - enlarged graft & echogenic cortex

  ; renal scan : blood flow 감소

  ; ★graft biopsy

           - *definite diagnosis

    ; glomerular immunofluorescence (-)

# Differential Diagnosis

   ① acute tubular necrosis

   ② cyclosporine-A toxicity

   ③ graft의 original renal disease의 de novo occurrence

# 발생빈도

   ① LRD-RT : 50%

   ② CRD-RT : 65%

# histocompatibility test의 의의

    : LRD & CAD RT의 survival 연장에 가장 중요

  1) best survival result

     : MLC nonstimulatory sibling donor와 같은 HLA-A, -B, -C & -D/DR 가진 경우

  2) second best : haplotye match있는 sibling or parent donor

Principles Of Immunosuppression And Therapy Of Rejection Reations

 1. RR의 기전 (Fig 490-3)

    : foreign body인 renal graft

      → immune system의 stimulation

      → cell-mediated & humoral-mediated immune inflammation의 activation

      → cell destruction & RR

★Table 490-6 Immunosuppressive Agent

# 가장 흔히 사용되는 protocol

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

  2) antithymocyte globulin(ATGAM) 사용

     : prophylaxis로 사용 or postoperative period에 사용

       → 50%에서 short-term graft outcome 향상

       → 이식 6개월 후 mean serum creatinine level 감소

       → transplant 후 first RR 사이 interval 증가

       → 1 year graft survival 증가

Grwoth And Renal Transplantation

1. chronic renal failure & ESRD-dialysis의 complication

  1) stunted linear growth

     overt malnutrition : less often

 

  2) 치료

   ① supportive care : stamina 향상 가능

                       well-being sense

   ② successful transplant만이 이들 abnormality의 적절한 교정 가능

 2. growth retardation

  1) RT 실시 이전 : 5세 이전에 -2.8 SD(standard deviation)

     1번이상 RT 실시 : -3.2 SD

  2) transplant-related accelerated growth

   ① 6∼12개월 지속

   ② younger children에서 관찰

   ③ adolescent에선 無

   ④ weight gain : 2∼3년 동안 normal adolescent와 유사한 평균치 보임

  3) daily corticosteroid

   ① growth retardation유발 가능

   ② 사용 방법

      : daily steroid를 6개월간 용량 감소시키며 사용

       → every-other-day steroid 사용하며 0.5∼0.2mg/Kg으로 tapering

       → single-dose every-other day

  4) recombinant human growth hormone(Nuprin)

     : 이식 전후에 사용

       → linear growth 향상

          graft function은 감소 가능

Complication

★Table 490-7

# Infection

    ; *▲common cause of death during 1yr after transplantation

    ; CMV infection

           - *▲common

           - 공여자 or 이식자의 CMV Ab titer 반드시 측정

        - ★Table 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

                           : rejection의 monitoring

        - *direct tissue damage or triggering of rejection reaction

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

           / immunosuppression중단

       - unresponsive rejection : kidney 제거

           - concomitant viral infection

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

  ; Pneumocystis carinii

        - trimethoprim-sulfamethoxazole의 prophylactic use시에만 방지

     (bacterial urinary tract infection도 방지)

# mortality

  ; 4-4.5%

      → 이중 40∼45%가 infection 때문

# tumor

    ; 주로 lymphoma, sarcoma & carcinoma 발생

    ; high death rate