Part 23. Nephrology
Section 1. Structure And Function Of The Kidney
Chapter 462. Anatomy of the glomerulus
1)
*from 6cm, 24gm in fullterm to 12cm
or more, 150gm in adults
2)
cortex ; glomeruli, prox. & distal conv.tubules & collecting ducts
medulla ; straight portions of the
tubules, loops of Henle, vasa recta, terminal collecting ducts
3)
blood supply (CO의 10% 차지)
; aorta-> renal a. ->
segmental br.-> interlobar a. -> arcuate a. -> interlobular a. ->
aff. arterioles -> glo. capillary network -> eff. arterioles
4)
juxtaglomerular apparatus
;
controls the secretion of renin
;
consists of ①speciallized m. cells in the walls
of aff.a. ② lacis cell ③
macular densa of distal tubule
5)
Glomerulus
; 1 million nephron in
kidneys
; complete at birth but
functional immature
; ① endothelium
-
fenestrations
②
GBM
i)
lamina lara interna ( subendoth.)
ii)
central electron dense lamina densa
iii)
lamina lara externa ( subepith.)
③
epithelial cells
-
filtration slit(space between the foot process)
; mesangium
-
♥기능
①
supporting structure of glomerular capillary
②
play a role in regulation of glomerular blood flow, filtration
③
play a role in removal of macromolecules(i.e. immune complex) frome glomerulus
by
intracellular phagocytosis
transport
through intercellular channels to JG region
6)
Bowman capsule
462.1. Glomerular filtration
; ultrafiltrate all substance except proteins(like albumin, globulins) exceeding *68,000 MW
;
Forces for ultrafiltration
①
glo.cap.hydrostatic pr. <- systemic art.pr.
②
glo.cap.oncotic pr.
③
glo.plasma flow rate
④
hydrostatic pr. within Bowman space
⑤
permeability of glo.cap.wall
;
adult values at *3yr
;
*standardized to surf. area(1.73m2)
of a 70kg adult to comparison
;
★filtration rate가 70% 이하로
떨어져야 serum creatinine 상승
;
*GFR이
감소하면 tubular secretion of
creatinine 증가하므로 filtration rate가
실제보다 overestimate 될수
있다.
;
*serum Cr이 2.0mg/dl(180umol/L) 이상이면 GFR은 little merit
-->
*renal function은 secrum creatinine으로 F/U해야
한다.
♥ TRP
= (1- Cpi/Ccr) x 100
= (1- Upi*Scr/Spi*Ucr) x 100
(nl ; 78-93%)
Section 2. Conditions particulary associated with hematuria
※81주
Table XXIII-1 & 표17-1(p694)
★Table
XXIII-2
;
microscopic hematuria
- *> 5 RBC/HPF in the sediment from 10ml of centrifuged freshly
voided urine
- asymptomatic microscopic
hematuria : 0.5-2.0% of school aged children
;
persistent microscopic hematuria
- further outpatient
evaluation
- ★> 5
RBC/HPF on 3 UA at monthly intervals
Chapter 463. Glomerular Disease
Pathogenesis
#
mechanism of glomerular injury
; immunologic
;
inherited (presumably biochemical)
;
coagulation disorders
#
Immunologic injury
; *▲common
causes
; 증거
①
experimental immune mediated GN 와 morphologic &
immunopathologic similarity
②
immune reactants(Ig & C')을 glo.에서 발견
③
serum C' abn. 와 autoAb.(ex.Anti GBM) 출현
2) 2 major
mechanism of immunologic injury
①
localization of circulating Ag-Ab immune complex
②
local Ag in situ와 Ab의 interaction
ex) non-collagenous domain [NC-1] of type IV
collagen : putative Ag in human antiGBM nephritis
A. immune complex mediated ds.
immune complex -> accumulate in glo. -> injury
실험) acute serum sickness in rabbit
iv of bovine albumin
-> acute proliferative GN
cf. glo.localization에 관여인자
+-① complex : conc, charge, size
| ② glo.의 특징
: mesangial trapping, negatively charged capillary wall
| ③ hydrodynamic forces
+-④ various mediators의
influence : angiotensin II, PG
B.
Anti-GBM antbody dsease : in situ Ag-Ab interaction
: IF상 linear deposition of Ig. & C'
on GBM
이는 i) Goodpasture disease -+ 과 비슷
ii) RPGN의 certain type -+
2. Biochemical
mediation
* Complement
system
+-Classic pathway : activated by Ag-Ab immune complex
+-Alternative pathway : activated by polysaccharides & endotoxin
3. Coagulation system
activated +- drectly
by endoth.injury->thrombogenic subendoth.노출->coagulation
| cascade
+-- indirectly by C'
activation
Pathology
different ds.
state에서 similar microscoic change 보이는 경우도 있다.
1. Proliferation of
glomerular cells
①
+-generalized : all glo.
+-focal : only some glo.
②
+-diffuse : single glo.의 all part
+
segmental : 〃 some part
③ 주로 +-endoth. &
mesangial cell prolif. 많음
+-mesangial matrix도 증가
-> glo.size 증가, glo.cap.lumen 감소
-> renal insuff.
2. Crescent formation in Bowman
space
①
proliferation of parietal epith.cells of B space - esp. RPGN
②
in response to fibrin deposit in B space
1) new crescent
( fibrin, prolif.epith.cell, BM like material, macrophage )
->
fibroepithelial crescent
->
glomerular cell death (necrosis)
2) generalized
mesangial proliferation이 동반되고 immune complex &
antiGBM Ab가 동반
3) Glomerular
exudation of blood cells
neutrophils : m.c.
eos, baso, mono
4) thickened
appearance of GBM
원인
+- ① true increase in width
of memb. : membranous glomeruloathy
| ② memb.과 비슷하게 염색되는
immune comlex의 massive 침착
: SLE
+- ③
subendothelial space에 mesangial cell과
matrix의 interposition (split app.)
:
type I MPGN, others
5) Sclerosis
scar tssue in glomerulus
때로 increase in mesangial matrix 의미
Chapter 464. Recurrent Gross Hematuria
★Table
464-1
Ig A Nephropathy (= Berger Nephropathy)
Pathology & Pathogenesis
#
LM
; focal & segmental
mesangial proliferation
; increased matrix
;
some gerneralized mesangial proliferation
; occasionally crescent
formation
#
IF
; IgA deposition in
mesangirum
; lesser amount of Ig M, Ig
G, C3, properdin deposition
#
recurrence in transplanted kidney
--> suggest systemic
disorders
Clinical & Laboratory Manifestation
; 남:여
- 2:1
; episode of gross hematuria
or microscopic hematuria on routine exam
; renal function
-
relatively normal
-
proteinuria : < 1gm/day (minimal)
; C3 normal
Prognosis & Treatment
① 대개
no kidney damage
②
30%에서 progressive ds.로
develop.
no Tx. - activity 제한은 필요 없다.
③
number of gross hematuria, persistent microscopic hematuria between
episode는 Px.와 무관
#
※Poor
Prognosis Factor
; hypertension
;
diminished renal function
;
proteinuria > 1g/day between episodes of gross hematuria
;
histologic evidence of diffuse GN with crescent, scarring
#
※Ig A
deposition diseases
①
Berger ds.
②
H-S nephritis
③
SLE
④
Liver cirrhosis
⑤
rarely MCLS
Idiopathic Hematuria (=Benign Familial Hematuria)
; 정의
: LM & IF 상 normal histologic finding &
recurrent episode of gross
hematuria
EM 상 some case - marked thinning of
GBM
; excellent Px.
; F/up to DDx. Alport
synd.
Alport Syndrome
: m.c. of hereditary
nephritis
marked
variability
X chrosome에 존재하는 제
IV형 collagen의 a5 사슬 유전자의 돌연변이
1) Pathology
① 나중에
mesangial proliferation & cap. wall thickening->progressive glo.
sclerosis -> tubular
atrophy, interstitial infl. & fibrosis, foam cell
②
EM상 thickening, thinning, splitting
& layering of GBM & tubule
(not specific to Alport synd.)
③
immunopathologic study (-)
2) Clinical sx.
①
renal involvement
m.c.+- Asymptomatic microscopic hematuria
+- recurrent gross hematuria
②
sensorineural hearing loss (소수)
-esp, high frequency range -> 점차 진행되어 deafness
③
eye abnormality (10%)
i) cataracts
ii) Keratoconus ( anterior lenticonus )
iii) spherophakia ( macular lesion )
3) Genetics
: ①
X-linked dominant => male에서 severe course
( autosomal dominant 도 있다.)
②
20%에서는 No family Hx. of renal ds.
4) Complication
①
hypertension
② UTI ③
CRF
5) Px. & Tx.
①
male:10-20대에 end stage RF with hearing
loss->dialysis & kidney
transplantation
②
female:normal life span & subclinical hearing loss
Idiopathic Hypercalciuria
;
present as ①
RGH
② persistent microscopic
hematuria
③
dysuria in the absence of stone formation
Etiology
; excessive GI absorption of
normal dietary Ca. intake
; defect in renal tub. Ca.
reabsop.
Diagnosis
; ★24hr U
ca. excretion > 4mg/kg
; screening test
-
※random
Uca/Ucr > 0.2
Differential Diagnosis
; normal infants
; hypercalcemic
hypercalciuria due to hyperparathyroidism or Vit. D intoxication
Complication
; ※Nephrolithiasis
Treatment
; Oral thiazide
-
controversal
-
Indication
/
persistent gross hematuria or dysuria
-
*Chlorothiazide 10-20mg/kg/24hr
single morning dose
-->
Uca. excretion < 4mg/kg/24hr.되고 Cl/M. resolve 될때까지 증량
-->
1년 후 중단
-
S/E : *Hypokalemia
Chapter 465. Gross or Microscopic Hematuria
465.1 Acute Poststreptococcal Glomerulonephritis
#
acute nephritic syndrome
; sudden onset of gross
hematuria, edema, hypertension, renal insuff.
Etiology & Epidemiology
;
nephritogenic groupA β-hemolytic streptococcus
- throat infection : *serotype 12, cold weather
-
skin inf. or pyoderma : *serotype 49,
warm weather
Pathology
; symmetrical enlarged Kidney
;
LM
-
diffuse mesangial cell proliferation with an increase in mesangial matrix
-
PMNL infiltration in glomeruli
-
maybe crescent and interstitial inflammation
; IF
-
*lumpy-bumpy deposit of Ig & C'
on GBM & mesangium
; EM
-
*humps on epithelial side of GBM
(=subepithelial hump)
Pathogenesis
①
immune complex인한 mech.으로 생각.
-
이유+-morphologic study
+-serum C3
depression
but not clear yet
②
acute serum sickness in rabbit과 비슷
③
C'activation은 alternative rather than classic
immune-comp. med. pathway
Clinical Manifestation
①
child but 3yr 이전은 rare
②
streptococcal infection후 1-2wk경과후
latent
period
+- pharyngitis : 9-11일
+- pyoderma : 3주 or 이상
③
Sx. :
i)
asymptomatic microscopic hematuria - ARF까지 다양.
ii) edema,
hypertension, oliguria, encephalopathy, CHF
* edema : due to +-water
& salt retention
+-nephrotic syndrome
iii)
nonspecific symptom
malaise, lethargy, abd.
& flank pain, fever
- acute phase는 대개
1mo. 내 호전.
urinary abn.는
1yr.이상 지속가능.
- acute phase :4-10일
Gross hematuria : 대개
1wk.
Microscopic hematuria : 1-2mo.
Diagnosis
①
UA상
: i) RBC with ii) RBC
casts iii) proteinuria iv) PMNL ; common
②
mild normochromic anemia due to hemodilution and hemolysis
③
C3 감소 (90%)
complement +-low for 10ds
|
normalize within 4-5wk
+-5-10%는 S-C3 not reduced
④
evidence of streptococcal inf.
i)throat culture
: Dx. of carrier state or support Dx.
ii) ASO (not
helpful : skin inf.후는 증가되지 않음.)
: 인두염후 1-2주후 상승, 3-5주
peak, 2-3 mo. 걸쳐 서서히 감소.
iii) DNase B
antigen : best single Ab titer
*
alternative ⓐ Streptozyme test ⓑ
Streptolysin ⓒ DNaseB ⓓ
hyaluronidase
ⓔ Streptokinase ⓕ
NADase
따라서
+-acute nephritis
| evidence of recent streptococcal inf.
+-low C3
-> 이로서 clinical Dx. of PSGN 가능
-> renal biopsy는 not Ix.
but, ①SLE
-------+ rule out 하는것이 중요.
②acute
exacerbation of chronic GN -
#
♥Renal biopsy indication for PSGN
① development of ARF or
nephrotic synd
② absence of evidence of
streptococcal inf.
③ absence of
hypocomplementemia
④ persistent of marked
hematuria or proteinuria
⑤ diminished renal
function
⑥ low C3
level > 3 mo. after onset
Complication
; *complication of ARF
-
volume overload, circulatory congestion, hypertension, hyperkalemia,
hyperphosphatemia, hypocalcemia, acidosis, seizures, uremia
Prevention
; early systemic antibiotic
therapy of streptococcal throat and skin infections
-
*not eliminate the risk of GN
; *culture of family member
-
if culture(+), treated
Treatment
; No specific Tx.
; 10-day systemic antibiotics
course
-
Penicillin recommended
; *restricted activity
-
*only acute phase of diseases
Prognosis
;
complete recovery
- *95% 이상
;
no evidence of progression to chronic GN
;
if severe acute phase, glo. hyalinization and then progression to chronic renal
insufficiency
;
*recurrence : extremely rare.
Chapter 466. Membranous Glomerulopathy
;
*▲common
cause of nephrotic syndrome in adult
Pathology
#
LM
; *diffuse thickening of GBM without significant proliferative change
-
due to memb. like material production by visceral epi.cell in response to
immune comlex -
deposited on the epithelial side of membrane
-
spike on the epithelial side of GBM
#
IF
; granular deposit of IgG
& C3
#
EM
; *EDM deposits on epithelial side of GBM
Pathogenesis
- immune complex mediated
ds.
- experimental Heymenn
nephritis 비슷
Clinical Manifestation
- 2nd decade of life에
m.c.
- Nephrotic syndrome 소견
with
microscopic hematuria
occasionally gross hematuria
- B.P & C3 : normal
Diagnosis
- renal biopsy => confirm
Ix.
① presentation of nephrotic
syndrome over 8yr.old
② unexplained hematuria &
proteinuria
#
associated diseases
; SLE, cancer, gold or
penicillamine therapy, syphilis, HB viral inf.
Complication
; ★increased
risk of renal v. thrombosis
Treatment
①
spontaneous resolution in majority of children
②
salt restriction & diuretics for nephrotic state
③
immunosuppressive therapy : 일부 환자에서 progressive renal
insuff. 를 늦춘다.
Chapter 467. Systemic Lupus Erythematosus
①
fever ②
wt. loss ③
rash ④ hematologic abn.
⑤
arthritis ⑥
heart, lung, CNS, kidney 침범하는 systemic ds.
- kidney involvement : m.c.
manifestation in child
occasionally only manifestation
Pathogenesis & pathology
- immune complex mediated
ds.
- aberration in both B &
T cell function
#
㉿Classification
by WHO by EM, IF, LM
WHO
class I nephritis
;
no histologic abnormality
WHO
Class II (= mesangial lupus nephritis)
;
*mesangial deposits containing
immunoglobulin and complements in some glomeruli
class
IIA
-
normal LM
class
IIB
-
focal & segmental mesangial hypercellularity & increased matrix
WHO
Class III (= focal proliferative LN)
;
*mesangial deposit in almost all
glomerulus
;
subendothelial deposit in some
;
*focal & segmental mesangial
proliferation
;
occasionally capillary wall necrosis & crescent formation
WHO
Class IV (= diffuse proliferative LN)
;
*▲common
& severe form
;
*massive mesangial &
subendothelial deposit in all glomeruli
;
mesangial proliferation in all glomeruli
;
★wire loop lesion
-
thickened cap.wall (= subendoth. deposit)
;
commonly necrosis, crescent formation, scarring
WHO
Class V (= membranous LN)
;
▲least common
#
common transformation
Clinical manifestation
대개
adolescent girl
①
milder form (all class II, some class III) : hematuria, normal renal function,
proteinuria ( < 1gm/day )
②
some class III & all class IV : hematuria & proteinuria
reduced
renal function
nephrotic synd. or ARF
③
some prolif.LN시 normal UA 보일수도 있다.
④
Class V : nephrotic synd.
Diagnosis
① 의심
: crculating ANA
② 확진
: anti DNA Ab ( native double stranded )
③
C3 & C4 감소
in active ds.
④
renal biopsy는 반드시 시행.
Treatment
#
immunosuppressive therapy
; aims
-
clinical & serologic remission
-
*normalization of anti DNA Ab & C3, C4
; initiation in all patients
- Pds 60mg/m2/day div. 3 or 4 doses
; some class III, all class
IV 즉 more severe case
- azathioprine
2-3mg/kg once daily 추가
③ 1-2mo.후
serologic remission 되면 Pds 60mg/m2/day - ADT, single dose
-> 5mg씩 tapering해
30mg/m2까지.
④ azathioprine도 감량하여
1yr.후 discontinue.
- 이때
serologic study, renal monitoring 필요.
Prognosis
: dramatically improved
ds. is controlled, not
cured
: relapse & side effect 주의
Chapter 468. Membranoproliferative Glomerulonephritis (=Mesangiocapillary GN )
;
*▲common
cause of chronic GN in older child & young adults
Pathology & Pathogenesis
;
*hypocomplementemia
- DDx from other form of
chronic GN
;
some C3 nephritic factor
#
★Three Histologic Types
1) Type I MPGN
;
*▲common
form
; LM.
- accentuation of
lobular pattern by generalized increased mesangial cell & matrix
-
glomerular capilary wall thickening & duplicated or split due to
interposition of mesangial cytoplasm and matrix
/
★double tract or tram-tract app. of GBM
- *crescent : high relation to poor Px.
;
IF
- C3
& lesser amount of Ig in mesangium & along the pph. capillary wall
; EM
- immune
complex deposit in *mesangium &
subendothelium
2) Type II MPGN
; LM
- *less prominent mesangial change
- capilary wall
/
*ribbon-like thickening due to dense
deposit at GBM in EM
/
*rare splitting of membrane
- *crescent
: common
;
IF
-
*Ig in Bowman capsule, mesangium,
tubular BM
-
*C3 with
minimal Ig along the margin of the dense deposits on GBM
;
EM
-
*immune complex deposit in region of
but distinct from lamina densa with GBM thickening
3) Type III MPGN
;
LM, IF
-
resemble in type I
;
EM
-
*contiguous subepith. &
subendoth. deposits
-
*disruption & layering of lamina
densa of BM
Clinical Manifestation
; *▲common in 2nd decade
; mostly nephrotic syndrome
; some gross hematuria,
asymptomatic mcroscopic hematuria, proteinuria
; *HT - common
; *decreased C3
Diagnosis & Differential Diagnosis
#
★onset of nephrotic syndrome in child more than 8yr
--> *renal biopsys 해야 한다.
#
D/Dx with APGN
; 공통점
①
gross hematuria
②
C3 감소
③
ASO 증가 (coincidental)
; 다른점
-
APGN : 2mo. 내 dramatically improve
-
MPGN
/
persistent clin. Sx. -> Renal biopsy필요
/ 6주 이상 C3
감소
Prognosis & Treatment
; all type is poor prognosis
-
*esp. type II
; I,II는
kidney transplantation후에도 재발
⑤
No difinite therapy -+
long term
alternate Pds-+로 clinical course의
stabilization.
Chapter 469. GN Of Chronic Infection
★Etiology
① subacute bacterial
endocarditis ( Str. viridans or other organisms )
②
infected ventriculoatrial shunt for hydrocephalus ( staphylococcus epidermidis
)
③
syphilis
④
hepatitis B, hepatitis C
⑤
Candidiasis
⑥
malaria
Pathogenesis
infecting organism이
foreign Ag으로 작용.
-> high
level of circulating Ag존재에 대한 host Ab response로
immune complex형성.
->
Kidney에 deposition
-> GN 초래
3) histopathologic findings may
resembles
+- PSGN
| Membranous GN
+- MPGN
Sx : acute
nephritic or nephotic syndrome
C3
감소 : common
4) Tx.
①
eradication of inf. -> usually resolution
②
progression to end-stage RF 가능.
Chapter470. Rapidly Progressive (Crescentric) GN
;
*presence of crescents in majority of
glomeruli
;
*rapidly progressive clinical course
Classification
#
idiopathic
#
※87
2ndary group RPGN (with underlying ds.)
; PSGN
; Lupus
; MPGN
; GN of Goodpasture ds.
; GN of anaphylactoid purpura
Pathology & Pathogenesis
#
Crescents
;
inside of Bowman capsule
; *consists of proliferating epithelial cells of capsule, fibrin,
BM-like material, macrophages
; mechanism of crescents
formation
-
necrosis or disruption of glomerular capillary wall
-->
*deposition of fibrin in bowman
capsule
-->
crescents formations
#
pathogenesis
; *no evidence for immunologic mechanism
; some Ab against GBM
; others immune complexs on
capillary wall
; ★normal
C3 level
Clinical Manifestation
①
ARF : 대개
②
end-stage RF within wks to mos.(after onset )
Diagnosis & Differential Diagnosis
①
ANA, C3, anti DNase B titer 측정으로 타질환
R/O
②
confirm : Kidney biopsy
Prognosis & Treatment
; PSGN associated RPGN
-
spontaneously recovery
; Lupus or Anaphylactoid
purpura associated RPGN
-
PRS + Azathioprine
-->
success
; ★RPGN
associated with remaining types
-
*poor prognosis
-
※94
some effective reports
/
*pulse methylprednisolone + oral
cyclophosphamide
/
*plasmapheresis
Chapter 471. Goodpasture Disease
;
pulmoonary hemorrhage, GN associated Ab against lung & GBM
#
Goodpasture syndrome
; clinical picture of
pulmonary hemorrhage with GN in several ds
①
SLE
②
Ana. purpura
③
polyarteritis nodosa
④
Wegener granulomatosis
Pathology
;
*resemble RPGN in LM
;
IF
- *continuous linear pattern of IgG along the GBM (antiGBM Ab)
Clinical Manifestation
extremely rare
in child
①
hemoptysis : usually presenting complaints, pulmonary hemorrhage
수일 또는 수주후
②
hematuria
③
proteinuria develop
④ Progressive RF 발생
; *C3 : normal
Prognosis
생존하면
commonly end stage RF 진행
No definite therapy
+-
pulse met0hylprednisone
| oral cyclophosphamide
+-
plasmpheresis
cause of death :
pulmonary hemrrhage
Chapter 472. Hemolytic Uremic Syndrome
;
*▲common
cause of ARF in young children
Etiology
; bacterial
-
㉿E.
coli (O157:H7) : ▲common
-
shigella, salmonella, campylobacter, s.pneumonia
- Bartonella
; viral
-
*coxsackie, ECHO, influenza,
variecella, EBV
; oral contraceptive
;
pyran copolymer(inducer of interferon)
; *SLE
; malignant hypertension
; pre-eclampsia
;
postpartum RF
; radiation nephritis
Pathology
① 초기
glo. change
i)
cap.wall thickening ii)
cap.lumen narrowing iii)
mesangial widening
②
fibrin thrombi -> cortical necrosis
③
severely -> partial or total sclerosis
※92 Pathogenesis
; endothelial cell injury :
primary event
-->
localized clotting
-->
microangiopathic anemia due to altered vasculature
-->
thrombocytopenia due to intrarenal plt. adhesion or damage
; *no evidence of DIC
Clinical Manifestation
; *▲common under 4yr
① 선행증상
대개 gastroenteritis ( fever,
vomiting, diarrhea, abd. pain )
URI, less commonly
②
5-10일후
sudden onset of pallor,
irritability, weakness, lethargy, oliguria
③
P/Ex상
dehydration, edema, petechiae, hepatosplenomegaly, marked irritability
Diagnosis & Differential Diagnosis
;
syndrome
- *microangiopathic hemolytic anemia, thrombocytopenia, ARF
;
Laboratory Finding
-
Hb 5-9 g/dl
-
PBS
/
helmet cells, burr cells, fragmented RBCs
-
diminished Haptoglobin
-
moderate increased reticulocyte
- Coombs (-)
- *leukocytosis > 30,000/mm3
- thromocytopenia
20,000-100,000/mm3
- normali PT, PTT
- UA
/
surprisingly mild low grade microscopic hematuria, proteinuria
;
vary from mild renal insufficiency to ARF
;
barium enema
- colonic spasma and
transient early filling defects
-->
subsequential intestinal stenosis
#
Differential Diagnosis
;
Lupus, malignant hypertension
; ★bilateral
renal v. thrombosis
-
*▲difficult
-
공통점
/
preceding AGE
/ dehydration, pallor
/
microangiopathic hemolytic anemia, thrombocytopenia, ARF
- 차이점
/
*marked enlarged kidney in renal vein
thrombosis
#
♥Renal Bipsy Ix.
;
prolonged renal failure > 2wks
; thrombocytopenia(-)
Complication
; anemia, acidosis,
hyperkalemia, fluid overload, CHF, hypertension, Uremia
; ♥Extrarenal Complication
-
CNS manifestation : irrtability, seizure, coma
-
colitis : melena, perforation
- *diabetes mellitus
- *rhabdomyolysis
Prognosis & Treatment
; more than 90% normal renal
function recovery
; corticosteroid
-
*no value
; anticoagulants
-
heparin
/
no beneficial effects
; *fibrinolytic therapy
-
*theoretical
-
risks to outweigh the pontential gains
; plasmapheresis,
; FFP
; ★early
& frequent peritoneal dialysis
-
*▲good
treatment
-
*control of uremic state and promote
recovery by removing an inhibitor of fibrinolysis
Chapter 473. Infection As A Cause Of Hematuria
; Gross or microscopic
hematuria
- UT 의 bacterial,
micobacterial, viral infectin 과
관련있다.
1) cystitis: bacterial,
micobacterial, viral
2) urethritis:
. gross or
microscopic hematuria, urgency, urethral discomfort
. UA 上
RBC, pyuria
. urine culture:
usually negative
bacterial, ureaplasma, chlamydia 可
. spontaneous
relieve 可
. Tx. : 10 day
tetracycline
+ urinary analgesics(phenazopyridine hydrochloride)
. conservative
Tx. 로 안되면 cystoscopy 시행
--> underlying Abn. detect
Chapter 474. Hematologic Disease Causing Hematuria
474.1 Coagulopathies & Thrombocytopenia
inherited acquired disorders of
coagulation
hemophilia
DIC
thrombocytpenia
but
usually hematuria is not a presenting sign. usually after other
manifestations
474.2 Sickle Cell Nephropathy
gross or microscopic hematuria
; sickling in hypoxic acidic, hypertonic medulla --> vascular
stasis-->
bl. flow
--> ischemia --> papillary necrosis --> interstitial fibrosis
clinical manifestation
; urinary concentrating defect, RTA
nephrotic syndrome (rarely) - focal sclerosis or MPGN 과 비슷
대부분의 hematuria 가
spontaneousely recover 된다.
474.3 Renal Vein Thrombosis
Epidemiology
#
★2 Distinct Patterns
; new born & infant
-
asso. with *asphyxia, dehydration,
shock, sepsis, infant of DM mother
; after infancy
-
asso. with *NS(▲frequently membranous nephropathy), cyanotic heart ds, use of
angiographic contrast agent
Pathogenesis
;
intrarenal venous radicle 에서 시작하여 antegrade &
retrograde spread
--> renal v. involve 는 않됨
;
thrombus formation
endoth. cell
injury
by i) hypoxia, ii) endotoxin, iii) contrast media
; conjunction /c hypercoagulable state (nephrotic syndrome)
diminished vs.
blood flow
hypovolemia: shock, dehydraton, NS
intravascular sludging of blood(polycythemia)
Clinical manifestaions
in
infant
i)
sudden onset of gross hematuria
ii)
unilat or bilat. flank mass
in
old children
i)
gross & microscopic hematuria
ii) flank pain
unilat. > bilat.
bilat. 시
ARF
Diagnosis
Hx.
: predisposing clinical factor 있는 pt. 에서
hematuria & flank
mass 有
Lab/F
: i) microangiopathic hemolytic anemia
ii) thrombocytopenia
U/S
上: marked enlargement
radionuclide
study : little or no renal function in involved kidney
venacarvogram
& doppler flow study to
confirmed the diagnosis
in occult case --> 될수있으면
피한다.
Differential Diagnosis
hematuria
: esp. hemorrlytic uremic syndrome
renal
enlargement
i)
hydronephrosis, ii) cystic ds, iii) Wilms tumor, iv) abscess
v)
hematoma
Treatment
unilat. renal v. thrombosis
supportive tx.
i) fluid & electrolyte correction
ii) Tx. of infection
iii) prophylactic anticoagulation to
prevent thrombosis
- 환자가
DIC 에 빠진경우를 제외하고는 의미 없다.
bilat. renal v. thrombosis
: CRF 로 가는 경우가 많다.
i) thrombectomy
ii) systemic fibrolytic agents
Prognosis
in infant
progressive atrophy --> small scared
kidney
nephrectomy ; if, hypertension or chr.
infection ( + )
-> acute phase 에서는 실시하지않음
in old children
involved kidney may recover
( 특히 nephrotic SD 이나
CHD와 연관된 thrombosis의 경우)
Chapter 475 Anatomic Abnormalities associated with Hematuria
Congenital Abnormalities
;
gross or microscopic hematuria 는 UT. malformation 의 대부분의 형태에서 나타날수 있다.
;
flank 에 minor trauma 후
sudden onset of usually painless grosshematuria시 의심
-->
ureteropelvic junctional obstruction
cystic
kidney 가 자주 동반됨
Trauma
;
gross or microscopic hematuria, flank pain, abdominal regidity
--
may occur
475.1 Autosomal Recessive PCK( Polycystic Kidney)
(=infantile
polycystic diseases)
;
may not detected until after infancy
;
*hepatic cysts with significant liver
disease
Patholgy
; markedly both enlarged
kidney
; grossly innumerable cysts
throughout cortex & medulla
; LM
-
*“cyst” is collecting duct dilatation
-
normal interstitium & remainder of the tubules
-->
progressing to interstitial fibrosis & tubular atropy
-->
renal failure
; hepatic cyst
-
cirrhosis, portal hypertension, eso. varix rupture
-
*when severity of hepatic
manifestation exceeds renal involvements
-->
called ★“ congenital hepatic fibrosis”
Clinical Manifestation
bilat. flank mass at birth
oligo hydroamnios 동반 多
--> Potter synd. 초래
: flat nose, recessed chin, epicanthal fold,
low set ear, limb abn. ( due to compression of fetus)
pul. hypoplasia --> neonatal resp. destress -->spont. pneumothorax
cf) spont. pneumothorax 시 kidney U/S 要
(in neonate)
gross & microscopic hematuria , hypertension 이 흔하다.
renal function 은 정상 혹은 감소 ( renal malformation 의
severity에 의존)
Diagnosis
; Hx. & P/Ex.
;
U/S finding
-
marked enlarged & uniformly hyper echogenic kidney
;
IVP
-
opacification of dilated collecting duct
-
*radial stresks similar to spokes of
wheel
; open surgical bx. of the
Liver & Rt. kidney toward the end of the 1st year
-
confirm of Diagnosis
Differential Diagnosis
.
( bilat. renal enlargement)
multicystic dysplasia
hydronephrosis
wilm`s tumor
renal v. thrombosis
Treatment
supportive ( includiing careful management of HT.)
Prognosis
severe renal involve 시 neonatal period 에
pul. & renal insuff. 로 死
생존자는 renal insuff. 발생전 수년동안 살수도 있다.
이때 Kid. size 는 줄고
HT. 은 less severe하다.
renal failure 발생시
-- dialysis , kid. transplantation
hepatic fibrosis, or cirrhosis 시 portal hypertension초래되며
poor Px.
475.2 Autosomal Dominant
PCK
;
also known as Adult polycystic kidney
A.D.
enlarged kid. /c cortical &
medullary cysts ( dilated tubule)
sx. : 4th or 5th decade 에
i) gross or
microscopic hematuria
ii) flank pain &
mass bilat.
iii) Hypertension
동반질환
i) hepatic cyst of no
clinical importance
ii) aneurysm of
cerebral circulaton -- ICH 초래
Supportive Tx.
Px.
end stage renal failure at 6th or
7th decade
475.3 Vascular Abnormalities
hematoma -----+
of kid. & lower UT. -- extremly rare cause of hematuria
AV
malformation -+
usually
present /c gross hematuria & the passage of blood clots
renal
colic -- upper UT. involve 시 발생 가능
Dx. --
confirmed by angiography
Chapter 476. Miscellaneous Etiologies Of Hematuria
476.1 Exercise Hematuria
gross or microscopic hematuria 가 vigorous exercise 후에 올수 있다.
benign,
rare in female, /ass. c dysuria
color of urine -- red to black
urine 에서 blood clot 이 보일수 있다.
RBC
cast 없고 renal ds. evidence 없다.
운동멈추고
48시간내 소실
lower UT. origine 으로 생각
DDx.
Rhabdomyolysis, march hemoglobinuria
476.2 Drugs
#
alteration in coagulation system
; heparin , waparin, aspirin
#
tubular damage
; PC, sulfonamide
#
hemorrhagic cystitis
; cyclophosphamide
Chapter 477. Evaluation Of The Child With Hematuria
Hx. & P/Ex.
; 최근
URI, skin & GI infection --> AGN or hemolytic uremic synd.
;
frequency, dysuria, unexplained fever --> UTI
; ※Flank Mass
-
hydronephrosis, cystic ds., renal v. thrombosis or tumor
; gross hematuria 의 최근
Hx. --> IgA nephropathy, idiopathic hematuria
Alport
SD. hypercalciuria
rash &
joint pain 동반시 --> HSP, Lupus
그외
trauma Hx. bleeding difficulties, drug usage, 가족의 Kid. Ds. Hx. HT Hx.
Laboratory Finding
anemia
- dilutional ; ARF 때 fluid over load 때문
- blood loss ; pul. hemorrhage in
Goos pasture ds.
melena in HSP, HUS
- hemolytic ; HUS, SLE
---- hemorrlytic
state 의 confirm - reti. count 증가
plasma Hb
level 증가
plasma haptoglobin 감소
PBS (
microangiopathic process in HUS, renal v. thrombosis, vasculitis, SLE
autoantibody 가 ( Coomb`s test (+), ANA,
leukpenia, multisystem. ds. )
sickle Hb
for black child --> anemia 없을때도
urine
culture ; UTI 가능성 평가
CCr,
protein & Ca excretion -- 이것이 불가능 하면 S-Cr., urine protein
by
dipstick , ca. to cr. ratio
in random urine
urinary
RBC morph. 가 lower tr. 이면
normal, glomerular 이면 dysmorphic.
-- 반드시
hematuria 의 위치와 일치하지는 않음
#
decreased C3
; PSGN
; MPGN
; Lupus GN
; chr. infection GN
#
thrombocytopenia
: plt. 생산 ↓ (mal.)
: plt. 파괴 ↑ ( ITP, HUS, RVT)
Imaging Studies
3) IVP, U/S --> str. Abn 를
R/o 함
cytogram --> infection 을 가진환자, lower tr. 의
lesion이 의심되는 환자
Renal Biopsy
persistent microscopic hematuria /ass, c
i) decreased renal function
ii) proteinuria
iii) hypertension
one or more episode of unexplained gross hematuria
persistent high grade microscopic hematuria
5) cystoscopy ; hematuria 를 가진환아에서 routine evaluation은 아니다.
more helpful - i) bright red hematuria
ii)
dysuria
iii) sterile urine culture
iv) 남아에서 주로 trauma에 의한
urethral lesion을 확인함
v) lower UT. 의 neoplasm 확인
* hematuria 가
6 mo 이전동안 있을시
- streptococcal inf. 의 serologic evidence 를 확인 해야 한다.
; throat. & skin inf. culture
; ANA for Lupus
** 상기 study 에서 모두 정상이 나오면 더이상의
study는 필요없다.
하지만
IgA nephropathy or Alport SD. 은 있을수 있다.
-->
long term f/u 이 필요함.
Section 3. Condition Particularly Associated with Proteinuria
;
upper limit of normal protein excretion in healthy person
- 150mg/24hr
- half
:
plasma origin - mostly Albumin ( 30mg/24hr)
- the others
:
Tamm-Horsfall protein (mucoprotein produced in distal tubule)
#
측정 방법
1) dipstick test
;
-, ±, +(30mg/dl), ++(100mg/dl),
+++(300mg/dl), ++++( 2000mg/dl ↑)
;
primarily detection of Albumin
;
*less sensitive other form protein
-
*Bence Jones protein, gamma globulin
2) Sulfosalicylic method
#
♥False Positive
1)
dipstick
;
highly concentrated urine
; gross hematuria
; contamination with chlorhexidine or benzalkonium
;
pH over 8.0
; phenazopyridine therapy
2) Sulfosalicylic acid method
; radiographic contrast media
; PC or cephalosporin therapy
; tolbutamide
; sulfonamide
#
semiquantitative fashion
; U-protein/U-Cr in a random
specimen (한글판:아침 첫소변)
-
2세이하에서 0.5 ↓
-
older child 에서 0.2 ↓
- ★more than 3
-->
*suggest nephrotic range proteinuria
Chapter 478 Non-Pathologic Proteinuria
★Table
478-1
#
proteinuria 의 정의 (한글판)
; qualitative
-
1주이상의 간격으로 3회이상 검사시
요비중 ≤
1.015 일때 : 1+ ↑
요비중 ≥
1.015 일때 : 2+ ↑
; semiquantitative
아침 첫 소변에서 단백/Cr.(mg.dl)
비가 0.2 ↑
; quantitative
i) 정상 〈
4mg/m2/hr
ii) 단백뇨
: 4 - 40mg/m2/hr
iii) N S 〉40mg/m2/hr
#
non-pathologic proteinuria
; *less than 1000mg/24hr and never
associated with edema
478.1 Postural(Orthstatic) Proteinuria
Clinical Manifestation
; may increase 10-fold time
or more
; unknown etiology
;
normal laboratory finding & renal bx.
Diagnosis
#
urine collection
; supine collection
-
밤에 30분간 누어있은후 이상태에서 배뇨하여 이 uriine 은
discard ( time check)
--> large glass liquid 먹인후 재움 --> 아침에 누운채
collection
; upright collection
-
normal daily activity 하면서 2번collection
#
*supine collection은
정상이고, upright collection이 proteinuria을 보여야
한다.
Treatment
; *추적관찰이 요한다.
478.2 Febrile Proteinuria
38.3℃ ↑ 시 出(
101℉)
기전
: unknown
2+ 는 넘지않는다.
fever 사라질때
resolve 되면 benign 으로 생각
478.3 Exercise Proteinuria
48 hr rest
후 normal 이면
benign
2+ 이상 넘지않는다.
; marked prteinuria
glomerular
ds.
CHF
constrictive pericarditis
Chapter 479. Pathlogic Proteinuria
479.1 Tubular Proteinuria
;
loss of low molecular weight protein than albumin
- *lysozyme, light chains of Ig, β2
-microglobulin, insulin, growth hormone
;
*rarely exceeds 1g/24hr
;
*not asso. with edema
;
*asso. with other defects of tubular
function
- glucosuria, phosphaturia,
bicarbonate wasting, aminoaciduria
;
Dx. by electroporesis of urine
479.2 Glomerular Proteinuria
;
*▲common
cause of proteinuria
;
variable range from less than 1g to more than 30g/24hr
;
index of protein selectivity
- C
IgG/ C transferrine or albumin
< 0.1 highly selective
> 0.2 poorly selective
- selective
/
*loss of plasma protein up to albumin
including albumin
/
*MCGN
- nonselective
/
alb. & largest MW protein loss ( IgG)
/
mostly GN
Chapter 480. Persistent Asymptomatic Proteinuria
#
♥Definition
; apparently healthy child
; *persist hematuria for 3mo without hematuria
; amount of proteinuria -
less than 2g/24hr
; *never associated with edema
#
prevalence
; 6% in school age children
#
★원인
;
postural proteinuria, membranous, MPGN, pyelonephritis, hereditary nephritis,
develpmental anormaly, benign proteinuria
#
※Evaluation
Of Persistent Asymptomatic Proteinuria
; urine culture, Ccr, 24hr
protein excretion, s-alb., C3, renal U/S
; ※Annual Evaluation
-
UA, Ccr, BP, P/Ex, 24hr protein excretion
#
renal bx. Ix.
;
persistent asymptomatic proteinuria 〉1g/24hr
;
hematuria, HT., or diminished renal function 동반시
Chapter 481. Nephrotic Syndrome ( Nephrosis )
Etiology
#
clinical
; 90% idiopathic NS
; 10% glomerulonephritis
-
membranous GN, MPGN
#
pathologic
; 85% minimal change
; 5% mesangeal proliferation
; *10% focal sclerosis
Pathphysiology
부분적으로 Cap. wall내의
negative charged glycoprotein 의 loss로
capillary permeability 증가
--> proteinuria
*
nephrosis 때
. proteinuria > 2g/day 이상 주로
alb.
. alb. 2.5g/dl in serum 이하시
edema 발생
#
★Mechanism Of Edema Formation In Nephrosis
; urinary protein loss
-->
hypoalbuminemia
-->
decreased plasma oncotic pr.
-->
transudatoin of fluid into interstitial space
-->
decreased intravascular volume
-->
decreased renal perfusion pr.
-->
renin-angiotensin- aldosterone system activation & release of ADH
--> stimulation distal tubular reabsorption of sodium &
collecting duct reabsorption of water
-->
reabsorped Na & water shift to interstitial space due to decreased plasma
oncotic pr.
Na.
& water excretion 에있어 intrarenal defect
Cap.
wall permeability 를 증가시키는 circulating agent
# ♥Hyperlipidemia Mechanism
; hypoproteinemia
-
stimulation of generalized protein synthesis in the liver including the
lipoprotein
; diminished lipid catabolism
-
due to decreased level of lipoprotein lipase
481.1 Idiopathic Nephrotic Syndrome
;
90%
;
has been transformed into another type
Etiology
;
unknown
;
immunologic mechanism 에 의해 mediate
;
IgE mediation in some
;
추측: abn. in thymus-derive T-cell
lymphocyte function
--> vascular permeability 증가인자 관여
Pathology
#
★3 Morphologic Pattern
1)
MCNS (85%)
;
normal or minimal increased in mesangial cell & matrix
;
*EM - retraction of epith. foot
process
;
IF - typically negative
;
*95%이상에서
corticosteroid 에 responce
2) Mesangial proliferative
group(5%)
;
diffuse increase in mesangial cell & matrix
;
IgM, C3 등이 주로 침착됨
;
*50 - 60% 에서
corticosteroid에 반응
3) *Focal Sclerosis (10%)
;
mostly glomerulus - normal or mesangeal proliferation
;
*juxtamedullary glomerulus -
segmental scarring in one or more lobules
;
*progressive course
-->
ultimately involvement of all glomeruli
-->
*end stage RF
;
*20% response to prednisolone or
cytotoxic therapy
;
transplanted kid. 에도 재발可
Clinical Manifestation
; *male:female = 2 : 1
-
MCNS or FS : 66% male
-
MPGN : 65% female
; *▲common between 2-6yr
.
URI 가 선행되어 나타나는 경우가 多
pitting edema ( periorbital, lower ext.)
--> generalized edema, wt. loss, ascites, pleural effusion, UO ↓.
anorexia, abd. pain, diarrhea; common
hypertension ; uncommon
Diagnosis
UA: proteinuria 3+ or 4+
Microscopic hematuria (+). Gross
hematuria : rare
Renal func. : normal or diminished
lower Ccr. ; vol. ↓ 인해
, renal perfusion ↓
--> intravascular vol. dl restore 되면
normal 로 돌아온다.
protein excretion ; 2g/24hr ↑
(40mg/m2/day↑)
s- Alb. 〈 2g/dl
s- Ca. ↓ ( owing to alb.
bounding fraction ↓)
C3 ; normal
8세이전 (1-8세)
onset; renal bx. 없이 corticosteroid tx.
8세이후 MCNS 가 많지만
membrain or MPGN 이 increasingly common
--> renal bx. 먼저시행하고
치료
Complication
#
Intection
; major Cx
; ㉿Why Susceptable ?
-
decreased Ig level
-
edema fluid acting as a culture media
-
protein deficency
-
decreased bactericidal activity of leukocyte
-
immunosuppressive therapy
-
decreased perfusion of the spleen due to hypovolemia
-
loss of complement factor (properdin factor B) in urine
; type
-
peritonitis
/
*▲common
-
sepsis, pneumonia, cellulitis, UTI
; organism
-
★Streptococcus pneumoniae
/
*▲common
for peritonitis
-
G(-) bacteriae
; prevention
-
*all patients 는 remission 시 polyvalent
pneumococcal vaccination
#
Tendency To Arterial & Venous Thrombosis Tendency
; ㉿why ?
-
*elevated plasma levels of
coagulation factor in plasma (1, 5, 7, 8, 10)
-
elevated levels of inhibitors of fibrinolysis
-
decreased levels of anti-thrombin III
-
increased platelet aggragation
; site
-
renal v. & IVC
- thrombosis, pul. embolism, cerebrocortical thrombosis
#
deficiency of coagulation factors (9, 11, 12)
#
reduced serum vitamin D
Treatment
#
salt restriction: edema 없어지면 해제
fluid
intake: edema 심하지않으면 not restrict
tolerable
physical activity
#
Tx of generalized edema
; diuretics
i) chlorothiazide 10-40mg/kg/day #2
ii) spironolactone 3-5mg/kg/day qid :
hypokalemia 있는경우 사용
oral
kcl supplement
hospitalization
severe edema -->respiratory
destress(pleural effusion)
--> scrotal swelling, ascites
; ★Severe
Edema
-
과거) iv albumin and then iv
furosemide
-
현재) ♣oral
furosemide 1-2mg/kg every 4hr + metolazone 0.2-0.4mg/kg/day #2
/ should be monitoring of electrolyte
& renal function
-
maybe 25% albumin 1g/kg24hr
/
transient, vol. overload with hypertension & heart failure
#
Corticosteroids
; ★Prednisone
60mg/m2/day (max. 60mg/day) #3-4
; usually reponse *within 2wks
-
*if not response 1mo after continuous
steroid therapy
-->
*steroid resistant 로
생각하고 renal biopsy를
실시한다.
; 5days after urine becomes
free( -, ±, + on dipstick)
-->
PRS every other day as a single dose with breakfast
-->
continued for 3-6mo
/
♥why?
:
maintain the remission using nontoxic dose of PRS
:
avoiding frequent relapse
:
avoiding cumulative toxicity of frequent courses of daily administration of PRS
-
*abruptly discontinued
/
*치료중단후 1년까지는 severe illnes, surgery가 있을때 corticosteroid supplementation이
필요함
#
★“relapse”
-
*recurrence of edema not simply of
proteinuria
#
steroid dependent
;
relapses shortly after switching to or after terminating alternative-day
therapy
#
Tx of relapse
; treated in similar manner
; *if frequently relapse or severe toxicity of steroids, considered
cyclophosphamide
-
prolongation of duration of remission
-
3mg/kg/24hr as a single dose for 12wks
-
renal bx. recommanded before trial
-
S/E
/
leukopenia, disseminated varicellar infection, hemorrhagic cystitis, alopecia,
sterility
-
WBC count weekly
/
if WBC < 5000/mm3, discontinued
#
Tx of steroid resistent
; 3-6mo cyclophosphamide +
methylprednisolone
; cyclosporine
#
renal transplantation
; end stage renal failure due
to steroid resistent focal & segmental glomerulosclerosis
#
recurrent nephrotic syndrome
; 15 - 55% of pt.
Prognosis
repeated
relapse 되면 steroid responsive nephrotic
syndrome 의 경우
2nd decade 말에 spontaneous resolution 됨
+-residual renal dysfunction이없고
| generally not hereditary
+-fertile ( unless cyclophosphamide or chorambucil tx. )
--> reassurance 要
remission 시는 normal & unrestricted diet
& activity
--> 더이상 urine protein check 필요없음
481.2 Glomerulonephritis
:
2ndary nephrotic syndrome /ass,c Glomerulonephritis
--
nephrotic syndrome may develop during the course of any type of GN.
/mc in ass. membranous
MPGN
PSGN
Lupus
Chr. infection( malaria, Schistosomiasis)
H S P nephritis
; secere Glo. ds. 의미하나 nephritis 좋아지면서
resolve 可
481.3 Tumors
#
solid tumor such as carcinoma
; membranous glomerulopathy
immune complex ds.( tumor Ag. 과 tumor specific Ab. 로 구성된
immune complex 에 의해 mediate 됨
)
#
Lymphoma ( esp. Hodgkin ds.)
; ※minimal change ds.
-
*▲common
; proliferative change
; lymphokine by tumor --> Glo. cap. permeability
481.4 Drugs
#
membranous glomerulonephropathy
; penicillamine, gold,
mercury compounds, captopril
#
minimal change ds
;
probenecid, ethosuximide, methimazole, lithium
#
proliferative GN
;
procainamide, chlorpropamide, phenytoin, trimetadione, paramethadione
481.5 Congenital
Nephrotic Syndrome
#
♥Causes Of Nephrotic Syndrome In 1st 6mo Of Life
; congenital nephrotic
syndrome
; congenital infection
-
syphilis, toxoplasmosis, CMV
;
diffuse mesangial sclerosis of unknown origin
-
Drash synd. : nephropathy, Wilms tumor, genital abnormalities
#
causes of nephrotic syndrome between 6-12mo
; idiopathic nephrotic
syndrome
; drugs
Congenital Nephrotic Syndrome (= Infantile
Microcystic Ds., Finnish Type)
; A.R.
; common in scandinavian descent
Pathology
; proximal convoluted tubule 의
dilatation ( microcystic ds.)
; glomeruli -- mesangial prolif.
& sclerosis
Pathgenesis
; unknown
Clinical Manifestation
; proteinuria ( birth or 대개
3mo 이내)
; ass. sx.
i) prematurity
ii) enlarged placenta
iii) resp. destress
iv) separation of cranial suture
Prognosis
course: persistent edema
recurrent infection
death by 5yr of age (∵
infection or renal failure 로 사망한다.)
Treatment
; supportive
; kidney transplantation--> 궁극적으로
corticosteroid & immunesuppressive
agent : no value
AFP: prerenal Dx. 가능
(20주이전에)
Section 4. Tubular Disorders
Chapter 482. Tubular Function
Sodium
1) reabsorption
+-65% of filtered Na+ : proximal
tubule
|
glucose & aminoacid 가 함께 reaborption
|
--> isotonically absorbed
+-25% : ascending liimb of loop of Henle
|
active transport of Cl 와 함께
+-10% : distal tubule & collecting duct
mediated by aldosterone
이와 같은 reabsorption으로 생후
1세이후부터
urinary Na concentration 이 1mEq/L 유지
2) excretion
ECF vol.관여 ← ECF vol. regulating factor에 영향 받음
Potasium
1)
absorption
all of the filtered potasium, reaborbed in proximal tubule
2)
excretion
distal tubular & collecting duct secretion
modified by ECF
pH
aldosterone
urine
flow rate & Na + conc.
Calcium
98% 흡수 at tubule
65% 가 prox. tubule 에서
Na 흡수와 관련有
. 흡수의 증가 PTH
reduction of ECF
thiazide diuretics
.
Excretion 증가 saline infusion
furosemide
Phosphate
:
대부분 prox. tubule
reabsoption inhibited by PTH
Magnesium
:
prox. tubule 에서 25%흡수( 1/4)
대개 흡수 및 moderation of Mg
excretion 의 주요장소:
thick ascending
limb of Henle
Maturation Of Tubular Function
; at birth
& 그후 몇개월까지는 tubular functional
capabilities 가 성인보다 낮다.
healthy newborn 의 maximal urinary conc.
capacity 가 낮다.
( 600 - 700mOsm/kgH2O )
# 낮은이유
reduced GFR
tubular cell immaturity
reduced nephron length
reduced medullary solute gradient
due to +-increased medullary blood flow
+-low urea production
ADH
에 diminished tubular responsiveness
newborn 의 diluting capacity는
adult 와 유사
water load excretion 감소 in NB ( low GFR 때문)
newborn 은 Na+ , K+ , H+ , phosphate
excretion 감소
--> due to +-low GFR
+-immaturity
of tubular function
# Tubular Ds.
1) functonal
defect in the function of tubular cell
relatively rare
inherited or acquired
initially normal renal function
일부는 progressive renal damage
2)
anatomic disorder
structure of tubule 의 이상
ex) cystic ds.
Chapter 483. Renal Tubular Acidosis
: impaired urinary acidification 에의한 systemic
hyperchloremic acidosis 의
clinical state.
.
Type
type I : distal RTA
type II : proximal RTA
type IV : mineralocorticosteroid deficiency
cf) type III : variant type I
Normal Urinay Acidification
filtered HCO3 의
85% 는 prox. tubule 에서
reabsorption 된다.
나머지
15%는 distal tubule 에서
reabsorption. --> premature 와 neonate 에는
일시적으로 약간 감소됨
acidification mediated by
i) distal tubular secretion of H+
(일부는 mineralocortocoid - dependent)
ii) distal tubular secretion of ammonia
( acidic urine 에서 ammonium ion 형성
)
·
normal kid. 는 filter 된 모든
bicarbonate를 흡수한다.
·
bicarbonate 의 prox. tubular reabsorption은
Na+ 와 교환하여 tubular umen
내로
H+ 의 분비를 유발한다.
·
H+ 은 carbonic acid 를 형성하기 위하여
carbonic anhydrase 에 의해filtered
bicarbonate 와 결합한다. --> 이는
water 와 carbon dioxide 로 해리된다.
·
carbon dioxide 는 proximal tubular cell 로
diffusion 된다.
· 여기서
carbonic anhydrase 의 영향으로 다시 carbonic acid 로
change 된다.
·
carbonic acid 는 H+를 생성하기 위해서 해리되고 이는 다시 bicarbonate 를
흡수하기위해 분비된다. 그리고 이때
bicarbonate 는 다시 peritubular cap. 로
들어간다.
㉿Table
483-1
Proximal RTA ( Type II)
Pathgenesis
1) reduced prox. tubular
reabsorption of bicarbonate
presumably
due to deficient carbonic anhydrase production --> prox. tubule
에서 60%만 reabsorption ( distal tubule은
15% 만 흡수 )
25% 까지
urinary loss
; prox. RTA more
severe than distal RTA
2) Lab/f
s-bicarbonate ↓: 15 - 18mEq/L (bicarbonate
threshold )
urine 은 acidified( pH〈
5.5) ∵ distal tubule 의
acidification mechaniam 은
intact 하기 때문에 filtered bicarbonate 가 감소
hypokalemia
distal tubule 에서 NaHCO3 다량
--> Na reabsorption in exchange
for k+
Hyperchloremia
ECF vol. 감소로 인해 +- chloride reabsorption 자극
+- aldosterone secretion ↑ --> k+ loss↑
3) classification of prox. RTA
a) isolated prox. RTA
transient or persistent
sporadic or inherited ( 대개 A.D. )
b) Fanconi synd.
;
generalized defect in prox. tubular transport
특징
: glucosuria
phosphaturia
aminoaciduria
prox. RTA
* primary
Fanconi synd. : A.D. or recessive
* secondary Fanconi synd. : inherited form ,
acquired form
Inherited
Form
Cystinosis
:
AR
i) nephropathic form: 3세이하 出
Sx.: polyuria, polydipsia(conc. defect), Fever (dehydration),
growth
retardation
rickets, hotophobia, blond hair & fair skin(diminished pigment)
Dx.: cystine crystal in cornea by slit lamp
elevated cystine contents of leukocytes
course : progressive renal damage ← intracellular cystine
accum.
end stage RF at end of 1st decade
Tx. : none, cysteamine 으로 임상시도
ii) Juvenile form: later in life, less severe
Lowe Syndrome
i) X-linked
ii) mental retardation
iii) Hypotonia
iv) cataract, glaucoma
v) generalized prox. tubular dysfunc.
unknown metabolic defect
Galactosemia
prox. tubule 에서 prolonged 한galactose
acc. 으로 인해서 renal manifestation이
나타남
Hereditary fructose intolerance
AR
fructose 1-phosphate aldolase def.
tyrosinemia
Wilson ds.
medullary cystic ds.
AD
cf) 비슷한 질환인
nephronophthisis 는 AR
children 은 recessive 가 多
adult 는 dominant 가 多
.Pathology
cyst
in the medulla: dilatation of the distal tubule & collecting duct
progressive interstitial inflammation & fibrosis 로 인해
-->
glomerular sclerosis, cortical atropy, renal insufficiency
cause of acquired Fanconi synd.
heavy metals( lead, mercury, cadmium, uranium)
out-dated tetracycline
proteinuric states ( myeloma, nephrotic syndrome )
interstitial nephritis
hyperparathyroidism -+
| carbonic anhydrase inhibition 에의해 prox. RTA
| 의 원인
vit-D def. reckets ---+
Distal RTA (Type I)
distal tubule 과
cdllecting duct 에서 H+ secertion deficiency
urinary HCO3 의 loss는 대개
(5 - -15%)
severe systemic acidosis 지만 urine pH 는
5.8 이하는 되지않음
hyperchloremia, hypokalemia
nephrocalcinosis 可
+-isolated
| sporadic
|
inherited: AD or AR
+-2ndary i) interstitial nephritis
ii) toxin, amphotericin B, lithium, toluene
Medullary Sponge Kidmey
non-inherited ds.
병리 : cystic dilatation of the
terminal portion of the collecting duct
( renal pyramid 들어가는부분)
renal func. & life span : normal
동반
pyelonephritis, hypercalciuria, nephrocalcinosis
nephrolithiasis, distal RTA , impaired concentrating capacity
Mineralocorticoid Deficiency ( Type IV)
1) 기전 : aldosterone 의
inadequate production
aldosterone 에 distal tubule 의
responsiveness 감소
--> tubular cell mb. 에 electrochemical gradient 형성 않됨
tubular lumen 이 negative 되어
H+ ion secretion 감소 잘되게하는
gradient형성않됨
--> Aldosterone mediated Na+ resorption 감소
--> hyperkalemic , hyperchlooremic acidosis (-> renal ammonia
production 감소->
ammonium ion excretion 감소 -> urine pH 5.5 이하
)
2) 원인
adrenal gl. ds. ( aldosterone ↓, renin ↑)
i) addison ds.
ii) cong. adrenal hyperplasia
iii) primary hyper aldosteronism
:
ald. production 감소
normal renal fx.
urinary Na+ wasting, plasma renin level ↑
Hyoreninemic hypoaldosteronism ( renin & aldo. ↓)
i) kid. ds. /c interstitial damage &
juxtaglomerular
apparatus destruction
ii) vol. expansion --+과도 관여
PG inhibition ---+
: renal function 감소
pseudohypoaldosteronism ( renin & ald. ↑)
i) distal tubular responsiveness to ald.
: normal renal function
salt wasting
ii) renal insufficiency & medllary ds. 가있는
adult 에서 볼수있음
Clinical Management Of RTA
Clinical Manifestation
#
isolated form of prox. & distal RTA
; *growth failure toward the end of 1yr of life
; GI symptoms
#
secondary
;
similar to isolated form
; underlying ds features
#
Mineralocorticoid deficiency
;
underlying ds feature
#
distal RTA
; hypercalciuria
-
nephrocalcinosis
nephrolithiasis
renalparenchymal
destruction
(2)
원인 :unknown
가능 calcium carbonate release 위해
bone destruction
( acidosis 교정위해 carbonate -->
bicarbonate )
urinary citrate 감소 --> calcium chelation
Diagnosis
1)
systemic acidosis 일으키는 질환을 먼저 R/o
diarrhea, lactic acidosis, DM,
renal failure
2)
Lab.
prox. & distal RTA : s-
bicarbonate ↓, s- k+↓,
hyperchloremia
Mineralocorticoid
deficiency, RTA, systemic acidosis, hyperkalemia
3) 1st morning urine pH 와 동시 에
s- electrolyte 측정 ; prox. & distal RTA
의심시
s- HCO3 < 16mEq/L
pH < 5.5: proximal RTA
pH > 5.5: distal RTA
s- HCO3 ( 17 - 20mEq/L)
i) ammonium chloride loading 후 감별可
ii) fractional excretion of bicarbonate
4)
prox. RTA 시 glucosuria, phosphaturia, aminoaciduria
찾기
5)
RTA confirm 시 underlying cause 찾기
Treatment
Goal +-- correction of acidosis
+-- maintenance of normal HCO3, k+
Shohl solution
: normal alkalinizing solution for
oral use containing
1,mEq/L of sodium as sodium
citrate
potassium citrate 첨가
( 1mEq/L of Na, K & 2mEq/L HCO3)
NaHCO3 tablet (325 - 650mg) in order pt.
diuretics & kayexalate for
Mineralocorticoid deficiency
Prognosis
1)
isolated prox. RTA
처음엔 distal 보다 심하나
resolution 可
2) isolated
distal RTA
life long ds. ( renal failure 는 발생할수 있지만)
early detection & treatment before nephrocalcinosis 시
excellent Px.
continuing alkali therapy & life long monitoring of clinical status
3) Mineralocorticoid
RTA
대개
obstructive uropathy후 出 하므로 obstruction correction 후
12mo 내 소실
483.1 Rickets Associated with RTA
rickets may be present
type II RTA or proximal RTA
hypophosphatemia &
phosphauria
hyperchloremia,
metabolic acidosis, bicarbonuria, hyperkaliuria
bone demineralization
- Type I & distal RTA
type I - 적절한
acid urine 형성불가
type II -
lowered renal threthold for bicarbonate
impaired urinary acidification
metabolic bone ds. -
occured in both type
▷ 특징 : bone pain, growth
retardation, osteopenia, pathologic fracture
RTA pt. 에서
1,25(OH)2D 는 normal
RTA pt. 에서
azotemia 나 renal mass 의
loss 가 있는 경우
-- serum
1,25(OH)2D 는 종종 감소한다.
distal RTA 에서
bone dimineralization
- dessolution of bone
- because -- CaHCO3 가 metabolic acidosis 에대한
buffer로 주어지기때문
acidosis 를 역전시키기
위한 bicarbonate 의 투여는
bone dissolution & hypercalciuria 를 멈추게 함.
▷Treatment.
proximal RTA - bone ds. 의 치료를 위해
bicarbonate 와 oral phosphate를 투여
vit-D : secondary
hyperparathyroidism예방
483.2 Fanconi Syndrome
(rickets
associated with multiple defect of the proximal renal tubule)
1) 개요
1. 특징
: generalized aminoaciduria, renal glycosuria. & phosphaturia resulting in
hypophosphatemia
2. ass. but inconstant
renal tubular abn.
a. excessive bicarbonaturia leading to RTA
b. hyperkaliuria leading to hypokalemia
c. rmdhl sodium wasting, uricosuria, proteinuria & hyposthenuria
3. clinical hallmarks
a. linear growth failure
b. rickets resistant to dose of vit.-D that are ordinarily adequate for
tx. of
nutritional deficiency
2) Etiology
1. genetically
transmitted inborn error of metabolism
; cystinosis,
fructose intolerance, galactosemia, glycogenosis, Lowe synd.
tyrosinemia, & wilson ds.)
2. some acquired ds.
:
including exposure to environmental toxins
a. heavy
metals; Cd, Pb, Hg.
b. drugs;
tetracycline, gentamicine, azathiopurine
3. Idiopathic : /mc
sporadic or inherited as a mendelian dominant or recessive
3) Pathogenesis
1. abn. in some final
common pathway for normal mb. trnsport in the prox.
renal tubule
:
deficient energy production, abnormalities in mb. str. or both가
impaired
tubular uptake or back-leak of solutes 을 초래함
2. renal potassium
wasting 은 bicarbonate & glucose 의
excessive urinary loss
에의해 초래됨
3. urinary sodium loss는
large excretin of urinary anion 에 의함
4. normal to low serum
calcium, varable urinary calcium
5. vasopressin -
resistant urinary concentrating defect 가 종종 나타남.
6. rickets는 combined effects of metabolic acidosis
& hypophosphatemia
or hypophosphatemia alone 에 의해 초래됨
7. vitamin D
resistance 는 metabolic acidosis 존재시 나타나는
abn. prox. tubular
cells 에 의해서 conversion of vitamin
D to 1.25(OH)2 D2 의 장애에 의함
8. nonspecific
microscopic findings
a.
dilatated renal tubules, with variation in size & shape, swelling of
epithelial
cells, & atropy
b.
common foci of interstitial fibrosis
c.
enlarged mitochondria on EM
d. 특징적으로
glomerular architecture는 말기까지 보존됨
4) Clinical manifestations
1. primary Fancony
synd. 은 특징적으로 first 6mo of life 혹은
3rd or 4th decade
에 나타남.
2. 영아기에는
vomiting , polydipsia, polyuria, contipation이 발생함
3. episode og
weakness, fever /c dehydration, & metabolic acidosis
4. failure to thrive,
especially in linear growth
5. adquate vit-D
intake & the absence of glomerular insufficiency 에도 불구하고
방사선학적으로 rickets , steopenia 나타남. 이소견은
renal tubular cause 를
나타낸다.
5) Lab.
1.
hyperchloremic metabolic acidosis /c normal "anion gap", hypokalemia,
hypophosphatemia, & hypouricemia
2. elevated
fractional excretion of phosphate
3. elevated ALP
activity if rickets is present
4. glycosuria at
normal serum glucose concentrations
5. generalized
nonspecific aminoaciduria
6.
inappropriatly elevated urinary pH , /c low levels of urinary ammonia &
titratable acid
7. 말기에
GFR 이 감소하면 s-electrolyte 와
aminaciduria, glycosuria.&
phosphaturia 의 "paradoxic" improvement
를 보임
6) Dx.
1. no definite
diagnosis test for idiopathic Fanconi syndrome
2.
aminoaciduria, diminished tubular reabsorption of phosphate, & elevated ALP
activity
3. child /c
stunted growth. rickets refractory to ordinary doses of vit-D , renal
glycosuria 는 multiple tubular dysfunction을 일으킴
4. metabolic
acidosis, hypokalemia : 확증적
5. fluid
deprivative to test urinary concentrating ability
: risky in the face of obligatory hyposthenuria
6. glucose loading
: profound symptomatic hypokalemia by shifting potassium
into cells 을 야기
7) Treatment
1. 2ndary Fanconi syndrome 환자는
underlying cause 를 찾아야 한다.
2. primary Fanconi syndrome 은
mineral & electrolyte balance 등의
symptomatic therapy 를 시행하면, 생명을 연장하고 종종
normal life 를 영위한다.
3. rickets의 치료,
skeletal deformities 예방
4. rickets or osteopenia 의 치료
a. i) large dose
of vit.-D : usual starting dose 5000u/24hr
maximal dose 2000 - 4000 u/kg/day
ii)
dihydrotachisterol : starting dose 0.05 - 0.1 mg/24hr
( 1mg is equivalent to 120000 u of vit-D)
iii)
1,25(OH)2D : greater potency, shorter half-life, hypercalcemia 초래가 장점
b. vit-D over
dose 에의한 hypercalcemia 를 방지하기 위해서
s-Ca. level 을
주기적으로 ( weekly at first, then monthly) 으로 측정
c.
hypophosphatemia 의 치료
i) oral
supplementation /c 1 - 3g for neutral phosphate/24hr given in
4 - 5 equally spaced dose
ii)
abdominal pain, diarrhea 가 치료중 나타나면 일시적으로 중단후 lower dose
로 다시 시작
iii)
phosphate 는 hypocalcemia, 2ndary
hyperparathyroidism 을 방지하기 위해
서 반드시 vit.-D 와 동시에 투여
5. metabolic acidosis due to
excessive bicarbonaturia 교정은 많은 양의 alkali
( 2 - 15 mEq/ kg/24hr of alkali ) 가 필요함
a. i) sodium
bicarbonate : 1 mEq of base = 1ml
ii)
shohl solution : 1 mEq of
base = 1ml
( 140 g of citric acid, 90 g of sodium citrate qs to 1L with water)
iii)
polycitra : 2 mEq of base = 1ml
( 5ml = 550mg of potasium citrate, 500mg of sodium citrate, 334mg of
citric acid )
b. serum
bicarbonate level 을 거의 normal level
(18-20mEq/L)까지
교정하여야함
c. alkali는
1-1½ hr after meals in 3-4 divided
dose/day 에 복용
d. extra salt
& water should be provided to counter excessive losses
483.3 Cystinosis ( Lignac Synd., Fanconi Syndrome With Cystinosis )
1) 특징
1. the clinical &
lab. features of Fanconi syndrome
2. the additional
distinctive finding of abn. accumulation of cystine in
various tissues
2) Pathgenesis
1. unknown cause
2. increased uptake of
cystine 는 lysosomes 에 축적을 초래함
이는 이
amino acide 의 lysosomal release 의
failure 에 의함
specific enzyme defect 는 발견되지 않았음
3. cystine deposition 의 부위
i) RES
system : esp. in spleen, liver, lymph node & BM
ii) renal
tubular cells, cornea & conjunctiva
iii)
periperal blood leukocyte & fibroblasts
iv) but
not in muscle & brain
3) 조직 소견
1. early renal change 는
primary Fanconi syndrome 과 유사
특징적인
"swan neck" lesion : atropy & shortening of the proxiomal tubule
just
beneath the glomerulus
2. birefringent cystine
cristals in interstitial tissue, but rare in tubular cells
3. renal failure 가 진행함에 따라
kid. 는 shrunken & contracted ,
with
glomerular sclerosis & interstitial fibrosis
4) 임상소견
1. AR rait
2. three clinical
patterns
a.
infantile or nephropathic form
i) 3 -12 mo경 Fanconi syndrome 으로 나타남
ii) generalized aminoaciduria /s predominance of cystine
iii) GFR 이 점차 감소하여 CRF 가
1st decade 이내에 발생
iv) severe growth failure, hypothyroidism
v) distinctive clinical features
;brond hair & fair complexion, owing to defect inb melanin synthesis
photophobia 2ndary to deposite
of cystine crystals on the cunjunctiva
b.
adolescent or intermediate form
i) mild renal involvement with onset in the 2nd decade & slow
progression
ii) growth failure is not a feature of this form
c.
adult type
i) benign, no renal ds.
ii) cystine crystals in the cornea, BM, & leukocytes
5) 검사소견
1. deposition of
cystine crystals 외에는 Fanconi syndrome 과 유사.
2. tubular proteinuria
가 nephropathic cystinosis 의
early phase 특징이나
renal failure 가 진행함에 따라 glomerular proteinuria
가 잇따라 나타난다.
6) 진단
1. in the asymptomatic
NB infant from an affected family
:
cystine content of leukocytes or fibroblasts (정상의 80 - 100배)
2. later, granular
& circinate irreguralities in the peripheral pigmentation of the
retina
3. cystine crystals in
the BM, lymph nodes, conjunctivae, and rectal mucosa
4. slit lamp
examination상 cornea에 crystal
5. prenatal diagnosis는
amniotic fluid cells에 increased cystine concentration
6. cystine deposition도
Fanconi syndrome도 나타나지 않는 cystinuria와 혼동하여
서 는 안되며, 이는
an inborn error of specific amino acid transport이다.
7) 치료
1. 초기에
tubular dysfunction에 대한 symptomatic therapy는
primary Fanconi
syndrome놔 유사하다.
2. cysteamine(sulfhydryl
binder) : in vivo에서 intracellular cystine을 감소시키며,
몇몇 소아에서는 renal failure 진행속도를
완화시킨다.
3. hemodialysis and renal
transplantation for end-stage renal failure
4. renal transplantation 후에는 환아는 잘 지내나
long-term survivors는
a. progressive
photophobia or retinopathy를 경험한다. 이 경우
cystiamine eye
drops이 효과있음
b. associated
with long-term extrarenal manifestations
: swallowing dysfunction, myopathy,
pancreatic endocrine and exocrine
insufficiency, and various CNS problems(즉 seizure, cerebral
atrophy)
483.4 Oculocerebrorenal Dystrophy (=Lowe Syndrome)
1)개요
1. rare disorder, X-linked
recessive trait
2. in addition to Fanconi
syndrome, organic aciduria, decreased production of
urinary ammonia, an occasionally heavy proteinuria
3. distinctive clinical
features
: congenital
cataract, glaucoma, and buphthalmos
4. 그외 특징으로
a. severe hypotonia and
hyporeflexia in the lst year
b. severe and
often progressive mental retardation
c. rickets,
marked osteopenia, and pathologic fracture as a result of metabolic
acidosis and phosphate depletion
2)PATHOGENESIS
1. unknown pathogenesis, 그러나 최근
in vitro studies에서 collagen metabolism의
이상을 의심함
2. pathologic studies는
splitting of the glomerular basement membrane, with
marked variation
in their thickness를 보임
3)임상소견
1. early life : eye findings
and mental retardation
later : Fanconi
syndrome이 임상적으로 분명해짐
2. childhood시기를 살아남으면
Fanconi syndrome은 spontaneously회복되나,
CRF가
될 수 있음
4)치료
1. no specific therapy
2. supportive, as in primary
Fanconi syndrome
483.5 Renal Osteodystrophy
1)개요
1. renal osteodystophy의 의미는
chronic renal disease를 가진 환아에서 mineral과
bone metabolism의 이상으로 나타나는 skeletal growth와
remodeling의 변화이다.
2. these abnormalities include
a. malabsorption of
calcicum, phosphaste retention, hyperfuncion of the
parathyroid glands
b. cutaneous, vascular, and visceral
calcifications
c. impairment in the renal production of
biologiclally active vitamin D
3. GFR이 정상인
tubular dysfunction시에도 나타날 수 있으나, glomerular
insufficiency나
uremia를 가진 환아보다는 흔하지 않다.
4. 이전에는 renal (uremic) rickets
혹은 renal dwarfism이라 불렸는데,
이는 severe
linear growth failure가 rickets와 같은
X-ray change를 보였기 때문
a. 이 소견은 일차적으로
vitamin D deficiency에 대한 mineralization defect에 기인 한다고 먼저 생각되었지만,
b. 이차적인
hyperparathyroidism도 임상적, 방사선학적으로
똑같이 중요한 역할함
5. pediatric dialysis, kidney
transplantation을 시행함에 따라 renal osteodystrophy가 CRF의 주요합병증(acidosis,
anemia, calororic deficiency 등과 함께)으로 떠올랐다.
2)PATHOGENESIS
1. normal dietary intake of
phosphorus를 가진 early in the course of chronic
renal
insufficiency(GFR 25 50㎖/min/1.73m2)에는
a. renal tubular
synthesis of 1,25(OH)2D3가
phosphate-mediated suppression되어
a) malabsorption of calcium and
phsphorus
b) unknown mechanism의
defective mineralization of osteoid(osteomalacia)초래
b.증가된
PTH의 결과, increased bone resorption과
increased renal phophate
excretion을 초래하며, serum calcuim은 유지되며
serum phophorus는 실제적으로
normal에서 low이다.
c. dietary phophate restriction은
serum 1,25(OH)2D3
level의 증가와,
2ndary
hyperparathyroidism이 improve됨
2. critical renal threshold(예를 들어
GFR이 정상의 약 25 30%)일 때는
a. 증가된
PTH에 대한 phophaturic renal response의 소실
b.
compensatory hyperparathyroidism이 serum calcium을 정상으로 회복시키기
위해서 잇달아 일어난다.
c.
roentgenographic and histologic evidende of exaggerated osteoclast
mediated
resorption of bone(osteitis fibrosa)
d.
endosteal fibrosis, increased bone turnover and replacement of regularly
textured
lamellar bone with disorganized and structurally deficient woven bone
3. chronic metabolic acidosis도 아마도
bone에서 calcium resorption과
renal
excretion을 증가시킴으로써 bony change를 야기시킴
3)조직소견
1. variable
2. trabecular bone은
predominant osteomalacia, predominant osteitis fibrosa 혹은
most commonly, a mixed pattern을 나타냄
3. 일부 환자에서는
fracturing osteomalacia와 low bone turnover는
mineralization
front에 aluminum의 축적을 초래하는데,
이는 orally administered aluminum
binders 혹은 aluminum-containing dialysis
solutions에 노출되었기 때문이다.
4)방사선학적 소견
1. abnormalities at
the epiphyseal growth plate
: 가끔
nutritional rickets을 닮으나 종종 현저히 구별됨
2. growth plate의
longitudinal width가 실제로는 증가되어 있지 않지만, 그렇게 보이 는 것은
dysplastic trabeculas을 가진 metaphyseal fibrosis의
bar 형성 때문이다.
3. concomitant defect in
mineralization은 다음을 초래함
a. a failure in
modeling, with persistence of cartilage
b. an expanded epiphyseal diameter
c. frequent overriding of the lateral
border of the metaphysis
5)임상 소견
1. CRF의 발병시기가
younger child, 그리고 renal failure의
longer duration은
osteodystrophy의 incidence와
severity을 크게 한다.
2. congenital diseases of the
kidney를 가진 소아(5세 이하에서 우세)는 소아 후반기 에 나타나는
glomerulonephritides 보다 disease onset과
end-stage renal failure
사이의 interval이 더 길다.
3 그러나,
congenital nephropathies 환자는 bone disease가 가속되는데
이는 maximal growth, bone modeling and
remodeling 시기이기 때문이다.
4. the earliest sign of renal
osteodystrophy
: usually growth failure
그외 CRF에 동반된
anemia, metabolic acidosis, protein-calorie malnutrition, hormonal disorders, and trace
mineral deficiencies
5. advancing disease의
additional clinical manifestations
: muscle weakness, bone pain, bone
deformities, slipped epiphyses, metaphyseal fractures, metastatic
calcification, and pruritus
6. genu varum, frontal
bossing 그리고 dentgal abnormalities는
young children에서
현저함
7. hypocalcemia에도 불구하고
tetany는 드문데, 이는
metabolic acidosis와 hyperparathyroidism의
combined protective effects 때문이다.
6)검사실 소견
1. mild hypocalcemia, but usually
elevated Ca P product by increased
levels of serum phosphorus
2. 증가된 ALP activity는 증가된
bone turnover를 나타내나, 소아에서는
성인만큼 reliasble sign은 아니다.
3. sensitive early indicator of
osteitis fibrosa : hand와 wrist의
X-ray에서 subperiosteal
erosions of the middle and distal phalanges, 그리고 erosions은
distal clavicle, inner aspects of the distal femur and proximal tibia에도 나타남.
4. the earliest indication of bone
disease : elevated serum levels of PTH
GFR이
50 75㎖/min/1.73m2 일때도 나타남.
5. PTH의
degree of elevation은 osteitis fibrosa의 방사선학적,
조직학적 소견과 일치 하나,
histologic osteomalacia의 degree는
serum내 chemical abnormalities
혹은 coarsening of trabeculas의 방사선학적
소견과 일치하지 않는다.
7)치료
1. renal osteodystrophy can
usually be successfully managed by
a. controlling
hyperphosphatemia
b. supplying adquate oral calcium intake
c. providing extra vitamin D
2. hyperphosphatemia의 치료
a. dietary phophate restriction : 시작하는
indication은 raised PTH level
b. aluminum-containing phosphate binders의
oral administration
a) risks of aluminum intoxication 때문에 가능하면 피해야 하며,
dietary
restriction이 충분하지 않으면 사용함
b) aluminum hydoxide or
aluminum carbonate gel
: a
starting dose of 20 30mg/kg/24hr in
divided doses with meals
이후 용량을 조절하여 serum phosphorus를
4 5mg/dl로 유지시킴
c) long-term treatment with
high-dose aluminum-containing binders의 합병증
:
osteomalacic osteodystrophy and a progressive, irreversible
encephalopathy
3. calcium supplementation
a. calcium carbonate 형태로 하루에
1 1.5g of elemental calcium을
diet에 첨가
b. calcium carbonate의 장점
a) the highest percentage of
elemental calcium
b) some degree of phosphate
binding, particularly when given with meals
4. acidosis control은
sodium bicarbonate를 사용
: usually 1 2mEq/kg/24hr, divided into thirds and
given 1hr after meals
5. providing extra vitamin D
a. 1,25(OH)2D3
a) preferred form
b) indication은
symptomatic bone disease with hypocalcemia
secondary hypoparathyroidism
evidence of osteitis fibrosa on
X-ray or bone biopsy
c) starting dose는
15 40ng/kg/24hr이며,
이를 hypercalcemia risk를 방지하기
위해서 8 12시간 간격으로 투여하고, 용량의
stepwise adjustment와
biochemical monitoring이 필요함
b. dihydrotachysterol(DHT)
a) 장점
: better ratio of therapeutic to toxic effects
shorter
half-life는 hypercalcemia의 합병증을 감소시킴
b) starting dose는
0.1 0.2mg/24hr이며,
serum calcium을 정상화시키고, X-ray
상 bone abnormalities를
healing시키도록 용량을 weekly or biweekly로 조절
한다.
c. frequent measurements of serum
calcium and phosphorus
d. CRF에서는 serum calcium의
"set point"가 증가하므로, vitamin D therapy의
therapeutic
goal은 serum calcium을
10.5 11.0mg/dl까지 올리는 것이다.
6. hemodialysis or chronic
peritoneal dialysis
7. autotransplantation of the
parathyroid gland
a. medical therapy에 반응이 없는
severe secondary hyperparathyroidism 환자에
서 시행
b. indication : severe bone pain,
mental aberrations, severe pruritus, fractures, chronic hypercalcemia, and metastatic
calcification
Chapter 484.Nephrogenic Diabetes Inspidus
Etiology
#
primary NDI
; *rare, inherited ds, X-linked recessive
ds
; 남
: complete unresponsive to ADH
; 여
: partial
#
2ndary NDI
; medullary concentrating
gradient loss초래 질환
a)acute or
chronic renal failure
b)obstructive
& p ostobstructive uropathy
c)vesicoureteral reflux
d)cystec
ds. : interstitial nephritis
e)osmotic
diuresis, nephrocalcinosis
;
tubule에 ADH effect 감소된 경우
a)hypokalemia b)hypercalcemia c) lithium d) democlocycline therapy
Pathogenesis
cf.concentration of urine
(1)hypertonic renal
medulla<countercurrent mech.
(2)permeability of distal tubule
& collecting duct to water <ADH
Clinical Manifestation
#
male with primary NDI
; polyuria, polydipsia in
infancy
; hypernatremic dehydration
episode
#
female in primary NDI
; milder
; not detected until later
life
Diagnosis
#
primary NDI
;
clinical Hx.
;
male with family Hx
#
Laboratory Finding
;
hypernatremia, diluted urine
; ★s-osmolality
> 295mosm/kg H2O & concurrent urine osmolality < s-osmolality
-
diagnosis
-
*dehydration test 불필요
#
confirm diagnosis
; aqueous vasopressin
0.1-0.2u/kg im 후 4h 간격으로 serum & urine
osmolarity 측정.
-> urine / plasma
osmolality
ratio < 1.0 ; nephrogenic D.I
ratio > 1.0 ; central D.I
psychogenic polydipsia
#
s-osmol < 295 mOsm / Kg 이하이면 fast시켜
295이상되면 dehydration test
cf.
B.W 3%이상 loss ->fluid 투여
#
biochemical & radiographic study실시하여 이차적 원인 배제
Complication
(1) mental retardation by repeated
hypertonic dehydration
(2) growth retardation
male에 나타남
; intrinsic
(3) collecting system
dilatation->수년마다 renal scan 으로
hydronephrosis관찰
Treatment
#
목표
; provision of adequate fluid
& caloric intake
; reduction of urinary solute
load
#
diuretics therapy
; sodium depletion
-->
enhancement of Na & water reabsorption in proximal tubules
-->
paradoxical response
; *chlorthiazide(20-40mg/kg/day in divided dose) with moderate salt
restriction
-
significant reduce need for fluid intake & frequency of voiding
-
*hypokalemia monitoring
; *no effect on 2ndary NDI
#
inhibitors of PG synthesis
; indomethacin
; *diuretic therapy 실패시 시도
Prognosis
pri.NDI: life long.
good Px. if hypernatremic dehy. is avoided genetic counselling
2nd. : underlying ds. nature에 따름
Chapter 485. Bartter Syndrome
특징: hypokalemia
normal BP
vascular insensitivity to pressure agents
elevated plasma renin & aldosterone
AR로 inherited경우도 있음
Pathology
IG apparatus hyperplasia
< renin 생산 장소
renal parenchyme
대다수는 정상
소수에서
nonspecific glo. ds or interstitial ds. or both
Pathogenesis
;
*primary defect in chloride
reabsorption in ascending limb of loop of Henle
--> reduced medullary hypertonicity
(concentrating defect)
--> extra NaCl in distal
tubule
--> reabsorption of sodium
exchange for potassium
--> urinary potassium
wasting
--> hypokalemia
--> stimulating
prostaglandins systhesis
--> vascular insensitivity
to pressure agents
--> activation of
Renin-Angiotensin-Aldosterone
--> aggregation of renal
potassium wasting
Clinical Manifestation
;
young children
- *growth failure, muscle weakness, constipation, polyuria,
dehydration
;
older children
- *muscle weakness or cramps, carpopedal spasm
Diagnosis
a)hypokalemia(<2.5mEq/L)
b)normal blood pressure
c)defective platelet aggregation
d)hypochloremia
e)metabolic alkalosis
f)plasma renin, aldosterone, PGE2 증가
g)urinary K+, Cl 증가
때로
hypercalciuria, hyperuricemia, hypomagnesemia,urinary sodium wasting
confirm by histologic
demonstration of hyperplasia of JG cell
#
DDx
; licorice abuse
; laxative or diuretic use
;
persistent vomiting or diarrhea
; Pyelonephritis
; D.I
#
DDx point
; laxative use,vomiting
diarrhea, D.I시 hypovolemia동반
-->
low urinary Cl level (cf. Bartter SD시 증가)
Treatment
5)The goal of Tx; to maintain s-potasium
level>3.5meq/l
and adequate nutriton
a)potassium chloride(K-Lyte/
cl;25-50mEq of KCl);S-K35mEq/l이상
250mg/24/hr시까지 증량
b)sodium chloride
supplementation
c)-fail-->triamterene
5-10mg/kg/day in div.
d)-fail-->indomethacine
3-5mg/kg/day Sig1/3
Prognosis
;
uncertain
;
*많은 환자는 remain well
;
일부에서 renal insuff.
;
growh failure 있어도 normal stature
Chapter 486. Interstitial Nephritis
대개 tubular damage 동반
glome.change는
minimal
- Common cause of interstitial
nephritis
1.Acute interstitial nephritis
1)pathology
interstitial infiltrate
a)lymphocytes
b)plasma cells c)eosinophils 때로 d)neutrophils
edema: tubular degeneration & necrosis
2)pathogenesis
unknown
a)hypersensitivity reaction; drug
b)tubular
BM에 immune complex의
deposition; Lupus.MPGN
c)anti BM Ab ; Goodpasture,
membranous
d)cell
mediated mechanism ; sarcoidosis, transplant rejection
3)C/M
a)drug가
hospitalized pt.시 m/c cause
1주이상
drug사용시 i)fever & rash발견
ii)eosinophil 증가 in blood urine or both
b)others; ARF or
acute GN와 유사한 clinical picture
c)onset은
ant. uveitis에 의해 선행될수 있다.
4)Dx.
renal biopsy로
confirm
소변내 호산구 증가
5)Tx. & Px
a)ARF Tx.
---+
b)inciting agent
withhold
| 로
complete resolve
c)precipitating inf.
Tx.
---+
d)severe histologic
injury & renal failure시
--->high dose corticosteroid로 dramatic improve.
2.Chronic interstitial nephritis
1)patholoty
a)infiltrates;
lymphocytes plasma cells
b)tnterstitial
fibrosis
c)tubular dilatation
& atrophy
d)partial or total
glom. sclerosis
2)clinical manifestation
대개
occult structural abnormality of Kidney & Urinary tract 동반
(cystic
ds. obstruction, reflux)
초증상;a)
CRF
i)N &V ii)pallor iii)headache iv)fatigue v)HT vi)growth failure
b)underlying ds 의 증상: (UTI, flank mass)
3)Dx.; renal biopsy not indicated
대개
underlying ds와 연관된 chronic renal
insufficiency의 양상으로 진단
4)Cx. & Px
progression to end-stage RF
avoidance of phenacetin(analgesics)
& lithium -> adult에서
renal Fc improvement 있음
section 5. toxic nephropathy - renal failure
Chapter 487. Toxic Nephropathy
. medication
diagnostic agents(iodinated radiographic
contrast media)
chemicals
. directly damage
renal bl.flow 감소
, ATN , intratubular obs.
indirectly
allergic or hypersensitivity
in vessels & interstitium
** Preventive measures may reduce the
risk of nephrotoxicity
a)pre-existing renal
ds시 c.m대신 US or scan
b)non-nephrotoxic
agent로 치환
c)lowest effective
dose of agent with bl. level monitoring
d)renal insuff. 시
dose reduction
e)동시에
several nephrotoxic agent함께 사용금지
table 487-1
Chapter 488.Cortical Necrosis
a) renal cortical(frequently
medullary)necrosis는 several type의
renal injury의
final common result
b) 대개 both kidney involve
c) pathy or entire cortex involve
1)
Etiology
NB에서의 원인:
a)dehydration
b)asphyxia
c)shock
d)DIC
e)renal vein thrombosis
NB후: Hemolytic uremic
syndrome이 m/c cause
2)
pathology
cortical infarction,
congestion of glo.
thrombosis of arterioles,
tubular necrosis
3)
pathogenesis
toxin -> endoth. cell injury(endotoxin)
intrarenal coagulation ->thrombosis, cortical necrosis
diminished renal cortical
blood flow --> endothelial cell injury
4)
clinical manifestation
a) ARF, b) enlarged Kid., c) U/O 감소, d) gross hematuria
5)
Dx.
US상 enlarged but non -
obstructed kidney
scan상 감소 or no renal bl. flow
& no function
6)
Tx. & Px
supportive care
--> correction of
dehydration, asphyxia shock sepsis Tx.
3.UTI
in newborn
chapter. 101 & 492
Chapter 489. Renal Failure
489.1 Acute Renal Failure
#
oliguria
; daily U.O <400mL/m2
; < 0.5ml/kg/hr in infancy
Etiology
★Table
489-1
★Table
489-2
Pathogenesis
#
prerenal cause
; decreased renal
perfusion->GFR감소
; 일정시간내
hypoperfusion 교정시에는 reversible
#
renal causes
;
hemolytic uremic syndrome
-
▲common cause in toddlers
; ATN
-
no arterial or glomerular lesion
-
★Proposed Mechanisms
/
alterations in intrarenal hemodyanmics
/
tubular obstruction
/
passive backflow of glomerular filtrate across injured tubular cells into
peritubular capillary
; GN
#
postrenal causes
; upper collecting system의
dilatation은 acute ureteral obstruction수일 후에야 초래
Clinical Manifestation
.precipitating ds.따라
variable
.증상 & sign related to
RF
a) pallor(anemia)
b) U.O 감소
c) edema(salt &
water overload)
d) hypertension
,vomiting, lethargy(uremic encephalopathy)
Diagnosis
#
careful Hx.
cf. flank mass시 생각
a)renal vein
thrombosis, b) tumor, c) cystic ds., d) obstruction
#
Laboratory Finding
a) anemia
+-dilutional
+-hemolytic ; lupus,
renal v. thrombosis, HUS
b) leukopenia ; lupus
c) thrombocytopenia ; lupus, renal
v. thrombosis, HUS
d) hypoNa+ ; dilutional
e) hyperK+
f) acidosis
g) BUN,Cr,uric acid, phosphate 증가;
diminished RF
h) hypocalcemia(hyperphosphatemia)
i) C3 감소
: i) PSGN ii) lupus iii) MPGN
j) Ab; antistreptococcal ; PSGN
nuclear ; lupus
neutrophilic cytoplasmic antigens(ANCA;Wegener
granulomatosis,microscopic
polyarteritis)
BM antigen ; Goodpasture ds.
k) chest X-ray ; cardiomegaly, pul
congestion -> fluid overload
l) 모든 ARF pt. 시
obstruction가능성 발견위해
i) plain abd. X-ray
ii) U/S ; CRF , obst. uropathy
DDx
iii) renal scan 要
iv) RGP ; 때로
<-- obst시 percut. nephrostomy시행으로
reverse 可
Treatment
1) children /c hypovolemia
; volemic replacement
|
Uosm |
UNa |
Fr.Na excret. |
hypovolemia impending ATN |
>500mOsm/kgH2O <350 |
<20mEq/L
>40mEq/L |
<1%
>1% |
UNa/PNa
Fractional Na excretion = --------- * 100
Ucr/Pcr
.치료 : isotonic saline iv
20mL/kg over 30 min
대개
2hr. 내 voiding
bladder
cath. CVP 필요 可
hydration 후 diuretics可
2) Impending RF
diuretics on prevention of anuria ;
controversy
established anuria에는
no value
furosemide -- urine production ↑ by altering tub. func
mannitol --
그러나 urine ↑ 이 renal func. 호전이나 natural ds. 호전
의미없으나, a) hyperkalemia, b) fluid overload 교정에는 효과.
< furosemide >
: hypovolemia없을 경우
a) initial single dose
of 2mg/kg(rate 4mg/min to avoid ototoxicity)
b) 10mg/kg of
furosemide, if no response
b)에도
response없으면 CIx.
c) single iv of
0.5g/kg of mannitol over 30min in addition or in place
of
furosimide
;효과 있든 없든 더이상 사용못함
3) Fluid restriction
volume expansion이나
diuretics에 효과없는 경우는 essential
a) 400mL/m2/24h(insensible loss) +
urine 양 ; 정상 intravascular volume시
b) 10-30% glucose containing
solution without electrolytes
c) blood. GI loss는 교정
4) hyperkalemia
serum level 6mEq/L시
cardiac arrythmia, cardiac arrest 可
a) adequate
renal f. 되기전에는 K+ restriction
b) EKG changes
i)
tall, peaked T waves ; earliest
ii)ST seg. depression
iii)
P-R prolongation
iv)
QRS widening
v)
cardiac arrest
c) s-K+ 이
5.5mEq/L로 오르면 Tx시작
i) 모든
solution에 high conc. of glucose포함
ii)
Kayexalate(sodium polystyrene sulfonate resin) exchange Na for K
1g/kg p.o or retention enema
20% 10ml/kg sorbitol ; enema시
orally, suspended in 2mL/kg of 70% of sorbitol시
best results
(∵ sorbitol은
osmotic diarrhea일으킴) every 2hr. 으로
repeat
d) s-K+이
7mEq/L이상 오르면
-->sequentially following emergency step시작
i) 10% calcium
gluconate ; 0.5 mL/kg iv over 10min
H.R
monitoring하며 20beat/min이상
H.R↑되면 쉬었다가 계속
ii) 7.5 %
NaHCO3 3mEq/kg iv
cx. ; vol. expansion, hypertension, tetany
iii) 50% glucose
1mL/kg with R.I 1u/5g of glucose iv over 1hr.
hypoglycemia monitor 要
iv)kayexalate
·i)은
K+↓시키지는 않으나 (K+ induced myocardial
irritability에 counteract
effect는 있음)
·ii)은
K+ shifting into intracellular compartment from ECF 이
measurement의 duration of action은 단지 수시간 지속되므로
persistent hyperkalemia시 dialysis 要
5) acidosis
a)inadequate excretion of H+ &
ammonia대개 치료 要
b)치료 필요한 경우
severe acidosis -- arterial pH < 7.15
s-HCO3 < 8mEq/L
--> 이 때는
resp. drive ↓ , myocardial irritability ↑
c) partial correction by iv route
목표
pH=7.20, HCO3=12mEq/L
∴mEq NaHCO3 required = 0.3 ×
BW × (12-sHCO3)
나머지는
s-Ca. phosphatemia /c reciprocal ,
hypocalcemia
acidosis때
total calcium ionized fraction ↑로 tetany발생이 방지되었다가
acidosis rapid
correction으로 ionized Ca ↓
->tetany
Hypocalcemia
; Tx by lowering serum
phosphorus
; *no calcium iv if not tetany
-
*calcium(mg/dl)xphosphorus(mg/dl)이 70이상이면 calcium salt
deposition in tissue
; ★phosphate-binding
calcium carbonate antacids
-
Titralac Liquid (3M Company, St. Paul, MN)
/
starting dose 5-15ml with meal and before bed
-
Os-Cal 500 tablets (Marion Laboratories, Kansas City, MO)
/
1-3 tablets with meals and before bed
-
regular strength TUMS (SmithKline Beecham, Pittsburgh, PA)
/
1-3 tablets with meals and before bed
-
정상이 될때까지 점차 증량한다.
Hyponatremia
;due to excessive amount of
hypotonic sol.
a) Tx. by fluid
restriction
b) s-Na 이
120이하이면 cbr. edema & Hemorrhage 可
mEq
Nacl required = 0.6 × B.W ×
(125 - sNa)
c) risk of
hypertonic sodium
i)vol. expansion
ii)HT
iii)CHF -->발생하면
peritoneal dialysis 실시
8) Hypertension
1。
ds. process
ECF vol expansion 등에 의해 생김
a) salt & water
restriction ; critical
b) severe acute
symptomatic HT
i)
diazoxide ; DOC
1-3mg/kg(max 150mg) rapidly iv (10초 이내) --> 10-20분내
BP ↓
만일 효과 불충분시 30분후
2nd inject or nifedipine 0.25-0.5mg/kg p.o
HT crisis시 sodium nitroprusside, labetalol continuous iv infusion
ii)
furosemide concomitantly
c) less severe hypertension
i) ECF vol.
expansion 방지
+->
salt & water restriction
+-> furosemide
ii) beta
blocker(propranolol) ; 1-3 mg/kg/12hr p.o
iii)
vasodilator(apresoline) ; 0.5-1.5 mg/kg/6hr iv
9)Seizure
a)원인 ; i)primary ds process
; SLE
ii)hyponaremia ; water intoxication
iii)hypocalcemia ; tetany
iv)HT
v)uremic state itself
vi)hypoglycemia
b)Tx.
i)underlying
cause
ii)diazepam; most
effective but metabolite 가 renal insuff. 시 축적
10)Anemia
a)대개
hemodilution; Hb 9-10 g/dl
--> no transfusion
b) blood loss by active
bleeding은 보충 要
c) hemolytic anemia(SLE,HUS
)
--
prolong RF 시
Hb <
7g/dl시 transfusion
vol.
overload, CHF , pul, edema , HT 위험 있으므로 4-6hr 동안
transfusion
/c fresh packed
RBC의 slow transfusion 10ml/kg
11)
diet ; 400cal/m2/day ↑
a) healthy &
well-nourished 이고 ARF가 짧을 경우는
diet는
restricted to fat & carbohydrate만 준다(gum drops or jelly
beans)
b) Na,K ,water restriction
c) 3일 이상 지속시
expanded oral diet or TPN /c a.a
12) dialysis
Ix ; a) acidosis
b)
electrolyte abn.
c) CNS
disturbance
d) HT
e) fluid
overload
f) CHF
14) continuous hemofiltraton
is useful - a)acute renal failure
(특히, i. wnstable cardiopulmonary
dynamics
ii.severe coagulopathies
iii.unavailablity of the peritoneal cavity due to
surgery or trauma
b)fluid overload
c)severe electrolyte or acid-base disturbances
※
performed by two basic configurations
a) continuous arteriovenous hemofiltration (CAVH)
b) continuous venovenous hemofiltration (CVVH)
15) life threatening Cx. of
uremia
a)hermorrhage b)pericarditis c)CNS dysfuction
risk
of Cx.은 Cr.보다 BUN치와 더 관련
Prognosis
underlying cause따라
1)normalized 可
a) prerenal causes
b) hemolytic uremic syndrome
c) acute tubular necrosis
d) acute interstitial nephritis
e)uric acid nephropathy
2) recovery of renal
function 이 unusual한 경우
a)RPGN, b)bilat. renal v. thrombosis, c) bilat. cortical necrosis
※
ARF & CRF 의 dialysis Ix.
a) BUN >100 mg/dl
b) uncontrollable hyperkalemia
c)
intractable severe met. acidosis or acidemia which cannot safely
corrected by NaHCO3
d) fluid overload /c circulatory congestion & pul. edema
489.2 Chronic Renal Failure
★Etiology
#
under the age of 5yr
; *anatomic abnormalities
-
hypoplaia, dysplasia, obstruction, malformation
#
after 5yr of age
;
acquired glomerular ds.
;
hereditary disorders - Alport synd. cystic ds
Pathogenesis
어떤 종류의
Kid. damage든 renal functional deterioration의
critical level도달시
end-stage RF 로 progressive renal function
deterioration 관련 factors
a)ongoing
immunologic injury
b)hemodynamically mediated hyperfiltration in surviving glomeruli
c)dietary
protein & phosphorus intake
d)persistent
proteinuria -- 직접
glomerular cap.wall damage
e)systemic
hypertension -->glomerular sclerosis -->HE filtrate injury
#
*20% of GFR되어야 uremia 나타난다.
★Table
489-4
Clinical Manifestation
anatomic abnnormality시
non specific presenting complaints
; headache , fatigue ,lethargy, anorexia, vomiting
polydipsia, ployuria, growth failure
P/E
·unrewarding
·pale
& weak. BP ↑
·anatomic
abn. 로 인해 수년에 걸처 renal failure 가
slowly develop 할수있으며
이때
growth retardation & rickets 가 동반될수 있다.
Treatment
management of pt. with CRF
a) clinical status
P/E,
blood pr. close monitoring
b) Lab. status
i) routine
exam. /q 1mo
.Hb(anemia)
.electrolyte -- hyponatremia
hyperkalemia
acidosis
.BUN,Cr -- nitrogen
accumulation
level of renal function
.calcium↓, phosphorus↑
.ALP ↑ --hypocalcemia
hypophosphatemia
osteodystrophy
ii)
periodic exam /q 6mo.
.PTH
--
osteodystrophy early evidence
.bone X-ray -- detect 可
iii) 이외
.chest X-ray -- assess cardiac function
.echocardiogram --
iv) nutritional
status
a)s-albumin, b) zinc, c) trasfusion, d) folic acid, e) iron level
Diet In CRF
a) GFR <50% 시
growth rate ↓
b) 주 원인이
inadequate caloric intake이므로 -->unrestricted
amount of
+-> Carbohydrate (sugar, jam, honey, glucose polymer)
+-> fat(medium chain TG)
--> intermittent or overnight N-G or gastrostomy tube feeding
recumbiniant human GH therapy /c optimal days
--> linear growth 조절
c) BUN = 80mg/dl↑시
dietary protein restriction
; 1.5 g/kg/24h로 protein이
high biologic value(egg>milk>meat>fish>fowl)
d) cow's milk에
phosphate ↑므로
i)
moderate restriction
ii) use of
a formular containing a reduced amount of
phosphate
( Similac PM 60/40, Loss laboratories, columbus, OH)
때때로 oral phosphate binder 와
conjunction 된다.
e) water soluble Vit.
deficiency (owing to inadequate intake or dialysis loss)
; Nephrocap(Fleming, fenton, MO) --> routinely supply해야함.
f) Zinc & iron
--> deficient 확인후 공급
g) fat soluble vit. A,
E, K supplementation ; not required
Water & Electrolyte Management
a) water;
dialysis필요한 정도 아니면 no restriction
b) Na+; edema,
hypertension, CHF 등이 있으면 salt restriciton /c
furosemide
(1-4mg/kg/day)
; salt wasting form; Na supplementation
c) K+
Acidosis In CRF
s-HCO3가
20이하이면 치료; 성장에 도움.
Bicitra
NaHCO3 tablet
Renal Osteodystrophy
; develops in asso. with
hyperphosphatemia, hypocalcemia, s-ALP ↑, PTH ↑
b) hyperphosphatemia
i) GFR이
moramal의 30%↓ 시 phosphorus level ↑
ii) reciprocal
solubility relationship으로 hypocalcemia ->2ndary
hyperparathyroidism(+)
iii) Tx.
·aluminum
hydroxide
cf. aluminum poisoning
; dementia osteomalacia->rarely
· calcium carbonate suspension
phosphate binder
low phosphate formula(Similac PM 60/40)
enhancing fecal excretion by orl calcium carbonate
c)hypocalcemia
i)기전
. reciprocally by hyperphosphatemia
. inadequate dietary intake
. decreased intestinal Ca absorption caused by a deficiency
in the active form of Vit. D
ii)Tx.
. hyperphospatemia교정
. 안되면 oral calcium supplement(Neo
Calgulucon Syrup, Os-cal
tablets);500-2000mg/day
d) Vit D.
severe kidney dysfuncton시 1-hydroxylation안되어
Vit.D def.
i) Ix. for Vit. D therapy
. s-phosphorus < 6.0mg/dl 이하로 교정하고 calcium
supplementation하
여도 persistent hypocalcemia
. elevated s-ALP와 X-ray 上
ricket의심되는 osteodystrophy pt.에
ii)
Tx.
시작 . 1 capsule(0.25ug)/d of
active dihydroxy Vit D
. 0.05-0.20mg/day of dihydrotachysterol solution
·normal
s-ca. ALP, X-ray上 healing시까지
dose ↑후 initial level
로 점차 감소.
·subperiosteal
erosion of edge distal phalanges of index & middle finger
; hyperparathyroidism
Anemia In CRF
; 대개 Hb 6-9g/dl
·transfusion;
not indicated
·suppression
of erythropoietin production
·
Hb < 6 시 10mL/kg of packed RBC ,
·
recombinant erythropoietin therapy
Hypertension In CRF
a) Diazoxide 1-3mg/kg iv or
sublingual nifedipine ; emergency시 0.025-0.5 mg/kg
b) furosemide 2-4mg/kg iv
(rate; 4mg/min);circ. overload 동반된 severe HT시
c) sodium nitroprusside는
renal insuff.시 주의 toxic thiocyanate축적
d) Tx. of sustainde
hypertension시
i)
salt restriction(2-3g/day)
ii)
furosemide (1-4mg/kg/day)
iii)
propranolol(1-4mg/kg/day)
iv)
hydralazine(1-5mg/kg/day)
v)
combination
e) d)로 inadequately control시
minoxidil, captopril사용
Drug Dosage In CRF
RF시
dosage modification필요없는 drug
antibiotics; a)
CM, b) clindamycin, c) cloxacillin, d) EM, e) rifampin
489.3 End-Stage Renal Failure
1) successful kidney transplant
; ultimate goal
-->living-ralated donor시 creatinine이
5-6mg/dl시
HLA typing부터 시작
2) Dialysis
creatinine이
10mg/dl에 도달시
pt's clinical status
Lab/F
availability of kidney donor
따라 시행
a) hemodialysis
b) CAPD(continuous
ambulatory peritoneal D)
; standard
technique for majority of children requiring chr. dialysis
not as effficient as hemodialysis
table 489-6
Chapter 490. Renal Transplantation
#
*Optimal Tx For Children With ESRD
; living related donor renal
transplantation (LRD-RT)
♥Table
490-1 Criteria For Performing Living Related Donor Or Cadaveric Renal
Transplantaion In Pediatric Patients
#
ESRD의 원인
; 나이에 따라 다르다.
-
*13-17세 : glomerulopathy
- 5세미만 : congenital & obstructive
process
1) *congenital renal disease(53%)
2)
glomerulonephritides(20%)
3)
focal segmental glomerular sclerosis(12%)
4)
metabolic disease(10%)
5)
mescellaneous(5%)
★Table
490-2 Most Frequent Hereditary Metabolic Disease Of Childhood That Lead To
End-Stage Renal Disease
Table 490-3
Treatment
1. RT procedure
1) 15∼20Kg 미만
: midline incision후 transperitoneal graft
2) 20Kg 이상 : right iliac fossa에
retroperitoneal location
→ renal vessel : external iliac
vessel과 anastomosis
ureter를 bladder에
reimplantation(ureteroneocystostomy)
lower pole : intestine사이에 free하게 둠
2. TABLE 490-4
3. survival rate
|
LRD-RT |
CAD-RT |
1년 |
약 90% |
72% |
3년 |
80% |
65% |
4. TABEL490-5
Histocompatibility
1. major histocompatibility complex(MHC)
gene
1) locus : chromosome 6 의
short arm
2) 기능 : human leukocyte
antigen(HLA)를 encode
3) 유전 : Mendelian fashion
inheritance
Figure 490-3
4)
구성
① class I protein(tissue
transplantation antigen) : HLA-A,-B,-C
cell-mediated
immunotoxicity
② class II protein :
immune responce 유도
HLA-DP,-DQ,-DR
③ class III protein :
tumor necrosis factor(TNF)
complement component (C2 & C4)
5) HLA-A,-B &-DR : clinical
transplantation에서 가장 중요
: good HLA match→
graft loss 감소
6) class I & II antigen의
cellular expression
① B & T lymphocyte
& macrophage에 국한
② inflammation에서
T cell에 의해 분비되는 lymphokine(IL-2,4
& 5)에
의해 multiplication
7) CD4(T-helper) & CD8(T-suppressor)
cell surface marker
: MHC (HLA) I
(histocompatibility) Ag과 high affinity가짐
→
class I Ag가진 cell에
attach
→
cytokine생성 signal 전달
or cell lysis
Rejection Reaction
#
Clinical Manifestation
; *swelling & tenderness of grafts, fever, oliguria, hypertension,
progressive elevation of serum creatinine
#
Classification
; acute & chronic
rejection reaction
-
*cellular & humoral mechanism에
의한 graft damage
; accelerated(hyperacute)
rejection reaction
-
#
Diagnosis
;
renal ultrasound - enlarged graft & echogenic cortex
;
renal scan : blood flow 감소
; ★graft biopsy
-
*definite diagnosis
; glomerular
immunofluorescence (-)
#
Differential Diagnosis
① acute tubular necrosis
② cyclosporine-A
toxicity
③ graft의
original renal disease의 de novo occurrence
#
발생빈도
① LRD-RT : 50%
② CRD-RT : 65%
#
histocompatibility test의 의의
: LRD & CAD RT의
survival 연장에 가장 중요
1) best survival result
: MLC nonstimulatory
sibling donor와 같은 HLA-A, -B, -C & -D/DR 가진 경우
2) second best : haplotye match있는
sibling or parent donor
Principles Of Immunosuppression And Therapy Of
Rejection Reations
1. RR의 기전 (Fig 490-3)
: foreign body인
renal graft
→
immune system의 stimulation
→
cell-mediated & humoral-mediated immune inflammation의
activation
→
cell destruction & RR
★Table
490-6 Immunosuppressive Agent
#
가장 흔히 사용되는 protocol
; *azathioprine, cyclosporine, & low
dose corticosteroid sequential immunosuppression
2) antithymocyte globulin(ATGAM) 사용
: prophylaxis로 사용
or postoperative period에 사용
→
50%에서 short-term graft outcome 향상
→ 이식
6개월 후 mean serum creatinine level 감소
→
transplant 후 first RR 사이
interval 증가
→
1 year graft survival 증가
Grwoth And Renal Transplantation
1.
chronic renal failure & ESRD-dialysis의 complication
1) stunted linear growth
overt malnutrition :
less often
2) 치료
① supportive care :
stamina 향상 가능
well-being sense
② successful transplant만이 이들
abnormality의 적절한 교정 가능
2. growth retardation
1) RT 실시 이전 : 5세 이전에
-2.8 SD(standard deviation)
1번이상
RT 실시 : -3.2 SD
2) transplant-related accelerated growth
① 6∼12개월 지속
② younger children에서 관찰
③ adolescent에선 無
④ weight gain : 2∼3년 동안
normal adolescent와 유사한 평균치 보임
3) daily corticosteroid
① growth retardation유발 가능
② 사용 방법
: daily steroid를
6개월간 용량 감소시키며 사용
→
every-other-day steroid 사용하며 0.5∼0.2mg/Kg으로
tapering
→
single-dose every-other day
4) recombinant human growth
hormone(Nuprin)
: 이식 전후에 사용
→
linear growth 향상
graft function은 감소 가능
Complication
★Table
490-7
#
Infection
; *▲common cause of death
during 1yr after transplantation
; CMV infection
-
*▲common
-
공여자 or 이식자의 CMV Ab titer 반드시 측정
-
★Table 490-8
-
reactivation state
/
*apparent 1-3mo
/
90% : asymptomatic & self-limited
/ 5∼10%
: death
/
Treatment
:
low-dose immunosuppressive agents with antiviral agent
:
*gancyclovir & anti-CMV
immunoglobulin IV
/
kidney biopsy
: rejection의 mo