Part 23. Nephrology

넬슨 정리

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 (CO 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 speciallized m. cells in the walls of aff.a. lacis cell macular densa of distal tubule

5) Glomerulus

    ; 1 million nephron in kidneys

    ; complete at birth but functional immature

    ;     endothelium

                   - fenestrations

        GBM

               i) lamina lara interna ( subendoth.)

               ii) central electron dense lamina densa

                iii) lamina lara externa ( subepith.)         

        epithelial cells

            - filtration slit(space between the foot process)

    ; mesangium

        - ♥기능

                   supporting structure of glomerular capillary

                play a role in regulation of glomerular blood flow, filtration

                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

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

    glo.cap.oncotic pr.

    glo.plasma flow rate

    hydrostatic pr. within Bowman space

    permeability of glo.cap.wall

; adult values at *3yr

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

; filtration rate 70% 이하로 떨어져야 serum creatinine 상승

; *GFR 감소하면 tubular secretion of creatinine 증가하므로 filtration rate 실제보다 overestimate 될수 있다.

; *serum Cr 2.0mg/dl(180umol/L) 이상이면 GFR little merit

    --> *renal function 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

81 Table XXIII-1 & 17-1(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

         experimental immune mediated GN morphologic & immunopathologic similarity

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

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

      2) 2 major mechanism of immunologic injury

        localization of circulating Ag-Ab immune complex

        local Ag in situ Ab 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.localization 관여인자

          +- complex : conc, charge, size

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

          | hydrodynamic forces

          +- various mediators influence : angiotensin II, PG

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

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

             이는  i) Goodpasture disease -+ 비슷

                  ii) RPGN 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

     +-generalized : all glo.

        +-focal : only some glo.

     +-diffuse : single glo. all part

        + segmental :         some part

       주로 +-endoth. & mesangial cell prolif. 많음

              +-mesangial matrix 증가

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

   2. Crescent formation in Bowman space

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

     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 proliferation 동반되고 immune complex &

          antiGBM Ab 동반

      3) Glomerular exudation of blood cells

          neutrophils : m.c.

          eos, baso, mono

      4) thickened appearance of GBM

         원인

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

       |  memb. 비슷하게 염색되는 immune comlex massive 침착 : SLE

       +- subendothelial space mesangial cell matrix 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

    ; : - 2:1

    ; episode of gross hematuria or microscopic hematuria on routine exam

    ; renal function

           - relatively normal

         - proteinuria : < 1gm/day (minimal)

    ; C3 normal

Prognosis & Treatment

      대개 no kidney damage

      30%에서 progressive ds. develop.

         no Tx. - activity 제한은 필요 없다.

      number of gross hematuria, persistent microscopic hematuria between

         episode  Px. 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

  Berger ds.  

  H-S nephritis

  SLE

  Liver cirrhosis

    rarely MCLS

Idiopathic Hematuria (=Benign Familial Hematuria)

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

             hematuria

          EM some case - marked thinning of GBM

     ; excellent Px.

     ; F/up to DDx. Alport synd.

Alport Syndrome

     : m.c. of hereditary nephritis

       marked variability                                

       X chrosome 존재하는 IV collagen a5 사슬 유전자의 돌연변이

    1) Pathology

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

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

      EM thickening, thinning, splitting & layering of GBM & tubule

                  (not specific to Alport synd.)

      immunopathologic study (-)

    2) Clinical sx.

      renal involvement

          m.c.+- Asymptomatic microscopic hematuria

              +- recurrent gross hematuria

      sensorineural hearing loss (소수)

          -esp, high frequency range -> 점차 진행되어 deafness

      eye abnormality (10%)

         i) cataracts

         ii) Keratoconus ( anterior lenticonus )

         iii) spherophakia ( macular lesion )

    3) Genetics

      : X-linked dominant => male에서 severe course

               ( autosomal dominant 있다.)

         20%에서는 No family Hx. of renal ds.

    4) Complication

       hypertension       UTI       CRF

    5) Px. & Tx.

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

       female:normal life span & subclinical hearing loss

Idiopathic Hypercalciuria

; present as     RGH

           persistent microscopic hematuria

               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

                   --> 1 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

    immune complex인한 mech.으로 생각.

        - 이유+-morphologic study

              +-serum C3 depression

          but not clear yet    

    acute serum sickness in rabbit 비슷

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

Clinical Manifestation

    child but 3yr 이전은 rare

    streptococcal infection 1-2wk경과후

       latent period

             +- pharyngitis : 9-11

             +- pyoderma : 3 or 이상

    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 phase 대개 1mo. 호전.

      urinary abn. 1yr.이상  지속가능.

    - acute phase :4-10

      Gross hematuria : 대개 1wk.

      Microscopic hematuria : 1-2mo.

Diagnosis

    UA

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

    mild normochromic anemia due to hemodilution and hemolysis

    C3 감소 (90%)

    complement +-low for 10ds

                | normalize within 4-5wk

                    +-5-10% S-C3 not reduced

    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, 3-5 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 biopsy not Ix.

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

               acute exacerbation of chronic GN  -

# Renal biopsy indication for PSGN

  development of ARF or nephrotic synd

  absence of evidence of streptococcal inf.

  absence of hypocomplementemia

  persistent of marked hematuria or proteinuria

  diminished renal function

  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 life m.c.

    - Nephrotic syndrome 소견

       with microscopic hematuria

            occasionally gross hematuria

    - B.P & C3 : normal

Diagnosis

    - renal biopsy => confirm

       Ix.  presentation of nephrotic syndrome over 8yr.old

           unexplained hematuria & proteinuria

# associated diseases

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

Complication

    ; increased risk of renal v. thrombosis

Treatment

    spontaneous resolution in majority of children

    salt restriction & diuretics for nephrotic state

    immunosuppressive therapy : 일부 환자에서 progressive renal insuff. 늦춘다.

Chapter 467. Systemic Lupus Erythematosus

      fever  wt. loss  rash  hematologic abn.

      arthritis  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

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

                                                   proteinuria ( < 1gm/day )

    some class III & all class IV : hematuria & proteinuria

         reduced renal function

         nephrotic synd. or ARF

    some prolif.LN normal UA 보일수도 있다.

    Class V : nephrotic synd.

Diagnosis

    의심 : crculating ANA

    확진 : anti DNA Ab ( native double stranded )

    C3 & C4 감소 in active ds.

    renal biopsy 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 more severe case

     - azathioprine 2-3mg/kg once daily 추가

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

                                           -> 5mg tapering 30mg/m2까지.

   azathioprine 감량하여 1yr. 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

           gross hematuria

           C3 감소

        ASO 증가 (coincidental)

    ; 다른점

           - APGN : 2mo. dramatically improve

           - MPGN

                   / persistent clin. Sx. -> Renal biopsy필요

          / 6 이상 C3 감소

Prognosis & Treatment

    ; all type is poor prognosis

           - *esp. type II

    ; I,II kidney transplantation후에도 재발

    No difinite therapy    -+

       long term alternate Pds-+ clinical course stabilization.

Chapter 469. GN Of Chronic Infection

Etiology

     subacute bacterial endocarditis ( Str. viridans or other organisms )

    infected ventriculoatrial shunt for hydrocephalus ( staphylococcus epidermidis )

    syphilis

    hepatitis B, hepatitis C

    Candidiasis

    malaria

Pathogenesis

     infecting organism foreign Ag으로 작용.

       -> high level of circulating Ag존재에 대한 host Ab response

           immune complex형성.

       -> Kidney deposition

       -> GN 초래

  3) histopathologic findings may resembles

     +- PSGN

     |  Membranous GN

     +- MPGN

       Sx : acute nephritic or nephotic syndrome

      C3 감소 : common

  4) Tx.

    eradication of inf. -> usually resolution

    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

    ARF : 대개

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

Diagnosis & Differential Diagnosis

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

    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

    SLE

    Ana. purpura

    polyarteritis nodosa

    Wegener granulomatosis

Pathology

; *resemble RPGN in LM

; IF

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

Clinical Manifestation

      extremely rare in child

     hemoptysis : usually presenting complaints, pulmonary hemorrhage

                    수일 또는 수주후

     hematuria

     proteinuria develop

      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

     초기 glo. change

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

     fibrin thrombi -> cortical necrosis

     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

     선행증상

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

              URI, less commonly

     5-10일후

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

     P/Ex

         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  bacterial, micobacterial, viral infectin

       관련있다.

    1) cystitis: bacterial, micobacterial, viral

    2) urethritis:

      . gross or microscopic hematuria, urgency, urethral discomfort

      . UA RBC, pyuria

      . urine culture: usually negative

        bacterial, ureaplasma, chlamydia

      . spontaneous relieve

      . Tx. : 10 day tetracycline

             + urinary analgesics(phenazopyridine hydrochloride)

      . conservative Tx. 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 비슷

              대부분의 hematuria 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 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. ARF

Diagnosis

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

      mass

Lab/F : i) microangiopathic hemolytic anemia

         ii) thrombocytopenia

U/S : 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 빠진경우를 제외하고는 의미 없다.

 bilat. renal v. thrombosis

 : CRF 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 CHD 연관된 thrombosis 경우)

Chapter 475 Anatomic Abnormalities associated with Hematuria

Congenital Abnormalities

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

; flank minor trauma sudden onset of usually painless grosshematuria 의심

--> ureteropelvic junctional obstruction

cystic kidney 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

        --> 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 kidney U/S (in neonate)

          gross & microscopic hematuria , hypertension 흔하다.

          renal function 정상 혹은 감소 ( renal malformation severity 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 neonatal period pul. & renal insuff.

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

          HT. less severe하다.

         renal failure 발생시 -- dialysis , kid. transplantation

         hepatic fibrosis, or cirrhosis 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

     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 발생 가능

       Dx. -- confirmed by angiography

Chapter 476. Miscellaneous Etiologies Of Hematuria

476.1 Exercise Hematuria

        gross or microscopic hematuria vigorous exercise 후에 올수 있다.

        benign, rare in female, /ass. c  dysuria

        color of urine -- red to black

        urine 에서  blood clot 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 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 fluid over load 때문

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

                       melena in HSP, HUS

          - hemolytic ; HUS, SLE

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

                                                          plasma Hb level 증가

                                                          plasma haptoglobin 감소

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

       autoantibody ( 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. lower tr. 이면 normal, glomerular 이면 dysmorphic.

       -- 반드시 hematuria 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 R/o

          cytogram --> infection 가진환자, lower tr. lesion 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 가진환아에서 routine evaluation 아니다.

         more helpful - i) bright red hematuria

                        ii) dysuria

                        iii) sterile urine culture

                        iv) 남아에서 주로 trauma 의한 urethral lesion 확인함

                        v) lower UT. neoplasm 확인

   * hematuria 6 mo 이전동안 있을시

                    - streptococcal inf. serologic evidence 확인 해야 한다.

                       ; throat. & skin inf. culture

                       ; ANA for Lupus

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

       하지만 IgA nephropathy or Alport SD. 있을수 있다.

       --> long term f/u 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 정의 (한글판)

    ; qualitative

        - 1주이상의 간격으로 3회이상 검사시

       요비중 1.015 일때 :  1+

       요비중 1.015 일때 :  2+

    ; semiquantitative

     아침 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 uriine discard ( time check)

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

    ; upright collection

       - normal daily activity 하면서 2collection

# *supine collection 정상이고, upright collection proteinuria 보여야 한다.

Treatment

    ; *추적관찰이 요한다.

478.2 Febrile Proteinuria

       38.3 ( 101)

       기전 : unknown

       2+ 넘지않는다.

       fever 사라질때 resolve 되면 benign 으로 생각

478.3 Exercise Proteinuria

       48 hr rest 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 loss

 capillary permeability 증가 --> proteinuria

* nephrosis

  . 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 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 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 responce

    2) Mesangial proliferative group(5%)

        ; diffuse increase in mesangial cell & matrix

        ; IgM, C3 등이 주로 침착됨

       ; *50 - 60% 에서 corticosteroid 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 선행되어 나타나는 경우가  

           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 돌아온다.

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

 s- Alb. 2g/dl

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

 C3 ; normal

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

 8세이후 MCNS 많지만 membrain or MPGN 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 remission 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 생각하고 renal biopsy 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, surgery 있을때 corticosteroid supplementation 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 경우

            2nd decade 말에 spontaneous resolution

         +-residual renal dysfunction이없고

         | generally not hereditary

         +-fertile ( unless cyclophosphamide or chorambucil tx. )

             --> reassurance

        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

481.3 Tumors

# solid tumor such as carcinoma

    ; membranous glomerulopathy

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

                                     immune complex 의해 mediate )

# 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 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 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 함께 reaborption

          |      --> isotonically absorbed

          +-25% : ascending liimb of loop of Henle

          |       active transport of Cl  함께

          +-10% : distal tubule & collecting duct

                  mediated by aldosterone

                  이와 같은 reabsorption으로 생후 1세이후부터

                  urinary Na concentration 1mEq/L 유지

         2) excretion

            ECF vol.관여 ECF vol. regulating factor 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% 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 moderation of Mg excretion 주요장소:

                    thick ascending limb of Henle

Maturation Of Tubular Function

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

          healthy newborn maximal urinary conc. capacity  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 diminished tubular responsiveness

          newborn diluting capacity adult 유사

          water load excretion 감소  in NB ( low GFR 때문)

          newborn 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 이상

            ex) cystic ds.

Chapter 483. Renal Tubular Acidosis

         : impaired urinary acidification 에의한 systemic hyperchloremic acidosis

           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 85% prox. tubule 에서 reabsorption 된다.

       나머지 15% distal tubule 에서 reabsorption. --> premature 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. filter 모든 bicarbonate 흡수한다.

       · bicarbonate prox. tubular reabsorption Na+ 교환하여 tubular umen            내로 H+ 분비를 유발한다.

       · H+ carbonic acid 형성하기 위하여 carbonic anhydrase 의해filtered

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

       · carbon dioxide proximal tubular cell diffusion 된다.

       · 여기서 carbonic anhydrase 영향으로 다시 carbonic acid change 된다.

       · carbonic acid H+ 생성하기 위해서 해리되고 이는 다시 bicarbonate

          흡수하기위해 분비된다. 그리고 이때 bicarbonate 다시 peritubular cap.

          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%  reabsorption ( distal tubule 15% 흡수 )

       25% 까지 urinary loss

      ; prox. RTA more severe than distal RTA

     2) Lab/f

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

          urine acidified( pH 5.5) distal tubule acidification mechaniam

                      intact 하기 때문에 filtered bicarbonate 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

               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 galactose acc. 으로 인해서 renal manifestation

        나타남

        Hereditary fructose intolerance

          AR

          fructose 1-phosphate aldolase def.

        tyrosinemia

        Wilson ds.

        medullary cystic ds.

      AD

       cf) 비슷한 질환인 nephronophthisis AR

        children recessive

        adult dominant 

       .Pathology

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

        progressive interstitial inflammation & fibrosis 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

                                | 원인

           vit-D def. reckets ---+ 

Distal RTA (Type I)

            distal tubule cdllecting duct 에서 H+ secertion deficiency

            urinary HCO3 loss 대개 (5 - -15%)

            severe systemic acidosis 지만 urine pH 5.8 이하는 되지않음

            hyperchloremia, hypokalemia

            nephrocalcinosis

          +-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 inadequate production

                     aldosterone distal tubule responsiveness 감소

           --> tubular cell mb. electrochemical gradient 형성 않됨

                tubular lumen 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 동시 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 감별可

  ii) fractional excretion of bicarbonate

        4) prox. RTA glucosuria, phosphaturia, aminoaciduria 찾기

        5) RTA confirm   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

       2) isolated distal RTA

            life long ds. ( renal failure 발생할수 있지만)

            early detection & treatment before nephrocalcinosis excellent Px.

            continuing alkali therapy & life long monitoring of clinical status

     3) Mineralocorticoid RTA

       대개 obstructive uropathy 하므로  obstruction correction 12mo 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 normal

     RTA pt. 에서 azotemia renal mass loss 있는 경우

      -- serum 1,25(OH)2D 종종 감소한다.

     distal RTA 에서 bone dimineralization

          - dessolution of bone

          - because -- CaHCO3 metabolic acidosis 에대한 buffer 주어지기때문

    acidosis 역전시키기 위한 bicarbonate 투여는

          bone dissolution & hypercalciuria 멈추게 .

   Treatment.

   proximal RTA - bone ds. 치료를 위해 bicarbonate oral phosphate 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 both impaired

         tubular uptake or back-leak of solutes 초래함

     2. renal potassium wasting bicarbonate & glucose excessive urinary loss

        에의해 초래됨

     3. urinary sodium loss large excretin of urinary anion 의함

     4. normal to low serum calcium, varable urinary calcium

     5. vasopressin - resistant urinary concentrating defect 종종 나타남.

     6. rickets  combined effects of metabolic acidosis & hypophosphatemia

        or  hypophosphatemia alone 의해 초래됨

     7. vitamin D resistance metabolic acidosis 존재시 나타나는 abn. prox. tubular          cells 의해서 conversion of vitamin D to 1.25(OH)2 D2 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 architecture 말기까지 보존됨

   4) Clinical manifestations

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

       나타남.

     2. 영아기에는 vomiting , polydipsia, polyuria, contipation 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

      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 감소하면 s-electrolyte aminaciduria, glycosuria.&

          phosphaturia "paradoxic" improvement 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 multiple tubular dysfunction 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 야기

  7) Treatment

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

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

    3. rickets 치료, skeletal deformities 예방

    4. rickets or osteopenia 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 방지하기 위해서 s-Ca. level

         주기적으로 ( weekly at first, then monthly) 으로 측정

      c. hypophosphatemia 치료

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

             4 - 5 equally spaced dose  

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

           다시 시작

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

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

          ( 2 - 15 mEq/ kg/24hr of alkali ) 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 거의 normal level (18-20mEq/L)까지

           교정하여야함

      c. alkali 1-1½ hr after meals in 3-4 divided dose/day 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   lysosomes 축적을 초래함

       이는 amino acide lysosomal release failure 의함

        specific enzyme defect 발견되지 않았음

    3. cystine deposition 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 primary  Fanconi syndrome 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 진행함에 따라 kid. shrunken & contracted ,

       with glomerular sclerosis & interstitial fibrosis

  4) 임상소견

     1. AR rait

     2. three clinical patterns

       a. infantile or nephropathic form

         i) 3 -12 mo  Fanconi syndrome 으로 나타남

         ii) generalized aminoaciduria /s predominance of cystine

         iii) GFR 점차 감소하여 CRF 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 유사.

     2. tubular proteinuria nephropathic cystinosis early phase 특징이나

        renal failure 진행함에 따라 glomerular proteinuria 잇따라 나타난다.

   6) 진단

     1. in the asymptomatic NB infant from an affected family

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

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

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

     4. slit lamp examination cornea crystal

     5. prenatal diagnosis amniotic fluid cells increased cystine concentration

     6. cystine deposition Fanconi syndrome 나타나지 않는 cystinuria 혼동하여         안되며, 이는 an inborn error of specific amino acid transport이다.

  7) 치료

    1. 초기에 tubular dysfunction 대한 symptomatic therapy primary Fanconi              syndrome 유사하다.

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

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

    4. renal transplantation 후에는 환아는 지내나 long-term survivors

      a. progressive photophobia or retinopathy 경험한다. 경우 cystiamine eye            drops 효과있음

      b. associated with long-term extrarenal manifestations

      : swallowing dysfunction, myopathy, pancreatic endocrine and exocrine                     insufficiency, and various CNS problems( 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 metabolism

     이상을 의심함

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

      marked variation in their thickness 보임

 3)임상소견

    1. early life : eye findings and mental retardation

      later : Fanconi syndrome 임상적으로 분명해짐

    2. childhood시기를 살아남으면 Fanconi syndrome spontaneously회복되나, CRF         있음

  4)치료

    1. no specific therapy

    2. supportive, as in primary Fanconi syndrome

483.5 Renal Osteodystrophy

  1)개요

   1. renal osteodystophy 의미는 chronic renal disease 가진 환아에서 mineral         bone metabolism 이상으로 나타나는 skeletal growth remodeling 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. GFR 정상인 tubular dysfunction시에도 나타날 있으나, glomerular                      insufficiency uremia 가진 환아보다는 흔하지 않다.

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

     a. 소견은 일차적으로 vitamin D deficiency 대한 mineralization defect 기인         한다고 먼저 생각되었지만,

     b. 이차적인 hyperparathyroidism 임상적, 방사선학적으로 똑같이 중요한 역할함

   5. pediatric dialysis, kidney transplantation 시행함에 따라 renal osteodystrophy       CRF 주요합병증(acidosis, anemia, calororic deficiency 등과 함께)으로 떠올랐다.

 

  2)PATHOGENESIS

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

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

       a) malabsorption of calcium and phsphorus

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

     b.증가된 PTH 결과, increased bone resorption increased renal phophate              excretion 초래하며, serum calcuim 유지되며 serum phophorus 실제적으로

        normal에서 low이다.

     c. dietary phophate restriction serum 1,25(OH)2D3 level 증가와, 2ndary                       hyperparathyroidism improve

   2. critical renal threshold(예를 들어 GFR 정상의 25  30%) 때는

       a. 증가된 PTH 대한 phophaturic renal response 소실

       b. compensatory hyperparathyroidism serum calcium 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 acidosis 아마도 bone에서 calcium resorption renal                 excretion 증가시킴으로써 bony change 야기시킴

   

  3)조직소견

    1. variable

    2. trabecular bone predominant osteomalacia, predominant osteitis fibrosa 혹은          most commonly, a mixed pattern 나타냄

    3. 일부 환자에서는 fracturing osteomalacia low bone turnover mineralization          front aluminum 축적을 초래하는데, 이는 orally administered aluminum              binders 혹은 aluminum-containing dialysis solutions 노출되었기 때문이다.

 

  4)방사선학적 소견

     1. abnormalities at the epiphyseal growth plate

       : 가끔 nutritional rickets 닮으나 종종 현저히 구별됨

    2. growth plate longitudinal width 실제로는 증가되어 있지 않지만, 그렇게 보이        것은 dysplastic trabeculas 가진 metaphyseal fibrosis bar 형성 때문이다.

    3. concomitant defect in mineralization 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. CRF 발병시기가 younger child, 그리고 renal failure longer duration              osteodystrophy incidence severity 크게 한다.

    2. congenital diseases of the kidney 가진 소아(5 이하에서 우세) 소아 후반기        나타나는 glomerulonephritides 보다 disease onset end-stage renal failure          사이의 interval 길다.

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

    4. the earliest sign of renal osteodystrophy

       : usually growth failure

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

    5. advancing disease additional clinical manifestations

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

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

    7. hypocalcemia에도 불구하고 tetany 드문데, 이는 metabolic acidosis                                    hyperparathyroidism 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 activity 증가된 bone turnover 나타내나, 소아에서는 성인만큼             reliasble sign 아니다.

 

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

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

      GFR 50  75/min/1.73m2 일때도 나타남.

   5. PTH degree of elevation osteitis fibrosa 방사선학적, 조직학적 소견과 일치       하나, histologic osteomalacia degree serum chemical abnormalities               혹은 coarsening of trabeculas 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. hyperphosphatemia 치료

      a. dietary phophate restriction : 시작하는 indication raised PTH level

      b. aluminum-containing phosphate binders oral administration

      a) risks of aluminum intoxication 때문에 가능하면 피해야 하며, dietary                            restriction 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 phosphorus 4  5mg/dl 유지시킴

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

            : osteomalacic osteodystrophy and a progressive, irreversible                                          encephalopathy

    3. calcium supplementation

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

      b. calcium carbonate 장점

        a) the highest percentage of elemental calcium

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

    4. acidosis control sodium bicarbonate 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) indication symptomatic bone disease with hypocalcemia

              secondary hypoparathyroidism

              evidence of osteitis fibrosa on X-ray or bone biopsy

       c) starting dose 15  40ng/kg/24hr이며, 이를 hypercalcemia risk 방지하기                   위해서 8  12시간 간격으로 투여하고, 용량의 stepwise adjustment                     biochemical monitoring 필요함

      b. dihydrotachysterol(DHT)

        a) 장점 : better ratio of therapeutic to toxic effects

          shorter half-life hypercalcemia 합병증을 감소시킴

        b) starting dose 0.1  0.2mg/24hr이며, serum calcium 정상화시키고, X-ray            bone abnormalities healing시키도록 용량을 weekly or biweekly 조절             한다.

      c. frequent measurements of serum calcium and phosphorus

      d. CRF에서는 serum calcium "set point" 증가하므로, vitamin D therapy            therapeutic goal serum calcium 10.5  11.0mg/dl까지 올리는 것이다.

    6. hemodialysis or chronic peritoneal dialysis

    7. autotransplantation of the parathyroid gland

     a. medical therapy 반응이 없는 severe secondary hyperparathyroidism 환자에          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

    ; : complete unresponsive to ADH

  ; : 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

  ; tubule 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 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

       male 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. nature 따름

Chapter 485. Bartter Syndrome

   특징:  hypokalemia

         normal BP

         vascular insensitivity to pressure agents

         elevated plasma renin & aldosterone

   AR 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.I hypovolemia동반

        --> low urinary Cl level (cf. Bartter SD 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.change 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 BM immune complex deposition; Lupus.MPGN

       c)anti BM Ab ; Goodpasture, membranous

       d)cell mediated mechanism ; sarcoidosis, transplant rejection

    3)C/M

      a)drug hospitalized pt. m/c cause

        1주이상 drug사용시 i)fever & rash발견

                           ii)eosinophil 증가 in blood urine or both

      b)others; ARF or acute GN 유사한 clinical picture

      c)onset ant. uveitis 의해 선행될수 있다.

   4)Dx.

     renal biopsy confirm

      소변내 호산구 증가      

   5)Tx. & Px                      

     a)ARF Tx.                   ---+

     b)inciting agent withhold         |  complete resolve

     c)precipitating inf. Tx.        ---+

     d)severe histologic injury & renal failure

        --->high dose corticosteroid 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 증상: (UTI, flank mass)

  3)Dx.; renal biopsy not indicated

       대개 underlying ds 연관된 chronic renal insufficiency 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 ds c.m대신 US or scan

     b)non-nephrotoxic agent 치환

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

     d)renal insuff. dose reduction

     e)동시에 several nephrotoxic agent함께 사용금지

   table 487-1

Chapter 488.Cortical Necrosis

 

   a) renal cortical(frequently medullary)necrosis several type renal injury

     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

    NB:      Hemolytic uremic syndrome 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.

  US enlarged but non - obstructed kidney

  scan 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 system dilatation 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 mass 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. obstruction가능성 발견위해

     i) plain abd. X-ray

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

     iii) renal scan

     iv) RGP ; 때로

        <-- obst percut. nephrostomy시행으로 reverse

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. voiding

        bladder cath. CVP 필요

        hydration diuretics

 2) Impending RF

  diuretics on prevention of anuria ; controversy

  established anuria에는 no value

  furosemide  --   urine  production   by altering tub. func

  mannitol     --      

  그러나 urine 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 diuretics 효과없는 경우는 essential

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

   b) 10-30% glucose containing solution without electrolytes

   c) blood. GI loss 교정

 4) hyperkalemia

    serum level 6mEq/L cardiac arrythmia, cardiac arrest

      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+ 5.5mEq/L 오르면 Tx시작

        i) 모든 solution 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 ; enema

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

           ( sorbitol osmotic diarrhea일으킴) every 2hr. 으로 repeat

   d) s-K+ 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

     iv)kayexalate

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

        effect 있음)

     ·ii) K+ shifting into intracellular compartment from ECF

          measurement duration of action 단지 수시간 지속되므로

          persistent hyperkalemia dialysis

 5) acidosis

   a)inadequate excretion of H+ & ammonia대개 치료

   b)치료 필요한 경우

     severe acidosis  -- arterial pH < 7.15

                        s-HCO3 < 8mEq/L

       --> 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

     acidosis 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) 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 120이하이면 cbr. edema & Hemorrhage

        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 (10 이내) --> 10-20분내 BP

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

          HT crisis 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 renal insuff. 축적

 10)Anemia

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

    b) blood loss by active bleeding 보충

    c) hemolytic anemia(SLE,HUS )

        -- prolong RF  

       Hb < 7g/dl transfusion

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

       /c fresh packed RBC slow transfusion  10ml/kg

11) diet ; 400cal/m2/day

    a) healthy & well-nourished 이고 ARF 짧을 경우는

       diet restricted to fat & carbohydrate 준다(gum drops or jelly beans)

    b) Na,K ,water restriction

    c) 3 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. Cr.보다 BUN치와 관련

Prognosis

    underlying cause따라

      1)normalized

         a) prerenal causes

         b) hemolytic uremic syndrome

         c) acute tubular necrosis

         d) acute interstitial nephritis

         e)uric acid nephropathy

     2) recovery of renal function unusual 경우

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

      ARF & CRF 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. damage renal functional deterioration critical level도달시         end-stage RF 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 abnnormality

   non specific presenting complaints

         ; headache , fatigue ,lethargy, anorexia, vomiting

           polydipsia, ployuria, growth failure

  P/E

    ·unrewarding

    ·pale & weak. BP

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

       이때 growth retardation &  rickets 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

      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% growth rate

     b) 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/24h protein high biologic value(egg>milk>meat>fish>fowl)

     d) cow's milk 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 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-HCO3 20이하이면 치료; 성장에 도움.

      Bicitra

      NaHCO3 tablet

Renal Osteodystrophy

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

  b) hyperphosphatemia

      i) GFR moramal 30% 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 dysfuncton 1-hydroxylation안되어 Vit.D def.

         i) Ix. for Vit. D therapy

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

               여도 persistent hypocalcemia

             . elevated s-ALP X-ray ricket의심되는 osteodystrophy pt.

        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 healing시까지 dose ↑후 initial level

            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 10mL/kg of packed RBC  ,

     · recombinant erythropoietin therapy

Hypertension In CRF

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

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

    c) sodium nitroprusside renal insuff. 주의 toxic thiocyanate축적

    d) Tx. of sustainde hypertension

        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) inadequately control minoxidil, captopril사용

Drug Dosage In CRF

    RF 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 donor creatinine 5-6mg/dl

       HLA typing부터 시작

 2) Dialysis

    creatinine 10mg/dl 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

# ESRD 원인

    ; 나이에 따라 다르다.

           - *13-17 : 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) 1520Kg 미만 : midline incision transperitoneal graft

  2) 20Kg 이상 : right iliac fossa retroperitoneal location

                 renal vessel : external iliac vessel anastomosis

                    ureter bladder reimplantation(ureteroneocystostomy)

                    lower pole : intestine사이에 free하게

 2. TABLE 490-4

 3. survival rate

 

 

 LRD-RT

 CAD-RT

 1

  90%

   72%

 3

  80%

   65%

 4. TABEL490-5

Histocompatibility

 1. major histocompatibility complex(MHC) gene

  1) locus : chromosome 6 short arm

  2) 기능 : human leukocyte antigen(HLA) encode

  3) 유전 : Mendelian fashion inheritance

   Figure 490-3

4) 구성

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

      cell-mediated immunotoxicity

   class II protein : immune responce 유도

                       HLA-DP,-DQ,-DR

   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 antigen cellular expression

   B & T lymphocyte & macrophage 국한

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

      의해  multiplication

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

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

       class I Ag가진 cell 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 mechanism 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

   acute tubular necrosis

   cyclosporine-A toxicity

   graft original renal disease de novo occurrence

# 발생빈도

   LRD-RT : 50%

   CRD-RT : 65%

# histocompatibility test 의의

    : LRD & CAD RT survival 연장에 가장 중요

  1) best survival result

     : MLC nonstimulatory sibling donor 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. RR 기전 (Fig 490-3)

    : foreign body renal graft

      immune system stimulation

      cell-mediated & humoral-mediated immune inflammation 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

     : prophylaxis 사용 or postoperative period 사용

       50%에서 short-term graft outcome 향상

       이식 6개월 mean serum creatinine level 감소

       transplant first RR 사이 interval 증가

       1 year graft survival 증가

Grwoth And Renal Transplantation

1. chronic renal failure & ESRD-dialysis complication

  1) stunted linear growth

     overt malnutrition : less often

 

  2) 치료

   supportive care : stamina 향상 가능

                       well-being sense

   successful transplant만이 이들 abnormality 적절한 교정 가능

 2. growth retardation

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

     1번이상 RT 실시 : -3.2 SD

  2) transplant-related accelerated growth

   612개월 지속

   younger children에서 관찰

   adolescent에선

   weight gain : 23 동안 normal adolescent 유사한 평균치 보임

  3) daily corticosteroid

   growth retardation유발 가능

   사용 방법

      : daily steroid 6개월간 용량 감소시키며 사용

       every-other-day steroid 사용하며 0.50.2mg/Kg으로 tapering

       single-dose every-other day

  4) recombinant human growth hormone(Nuprin)

     : 이식 전후에 사용

       linear growth 향상

          graft function 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

            / 510% : death

                   / Treatment

                           : low-dose immunosuppressive agents with antiviral agent

                           : *gancyclovir & anti-CMV immunoglobulin IV

                   / kidney biopsy

 &nb