Transcript 2016_분당_내과연수강좌_단백뇨혈뇨진단치료 (다운 113회)

단백뇨와 혈뇨
분당서울대병원 내과 진호준
목 차
서론
단백뇨의 진단
단백뇨의 임상적 의미
단백뇨 치료
혈뇨의 진단
단백뇨
단백뇨 의미
• 만성 신질환의 주요 소견
• 신 손상의 증거이자 위험인자
• 심혈관 질환의 위험인자
• 전체 사망의 위험인자
증 례
40/M
-우연히 발견된 단백뇨: 1.5 g/g cr
-BMI 22.5
-BP 130/80
-Cr 0.9 mg/dL
-Dipstick 2+ albuminuria
-Not orthostatic proteinuria
 단백뇨의 의미는?
 단백뇨 감소를 위한 치료는?
단백뇨의 진단
정상 단백뇨 < 150 mg/day proteinuria
60% serum protein, ex) albumin
40% tubular protein, ex) Tamm-Horsefall
반정량: 비중-1.015~1.025
Dipstick test
trace
10 mg/dL
1+
30 mg/dL
2+
100 mg/dL
3+
300 mg/dL
4+
1000 mg/dL
단백뇨의 진단
정량
1) 24시간 뇨 단백
* urine creatinine: 요 수집의 척도
* 믿을 수 있는 소변
:측정된 요 cr/계산된 요 cr 0.9~1.1
2) Spot urine protein/cr ratio, albumin/cr ratio
: 24시간 소변과 상관성 우수
: 24시간 뇨단백 1g/day ~ Urine P/Cr 1.5
단백뇨 분류
1) 사구체성 단백뇨: 주로 albuminuria
2) 세뇨관성 단백뇨: 주로 분자량이 albumin보다
적은 lysozyme, beta2 microglobulin 등
3) Overproduction proteinuria
multiple myeloma, amyloidosis, light chain ds
: light chain
hemolysis or rhabdomyolysis
--> 감별을 위해서
urine protein electrophoresis,
urine immunoelectrophoresis
단백뇨 분류
4) 기능성 단백뇨
= 심한 운동, 발열, 심부전증 등
= Orthostatic proteinuria: 서있는 경우만 단백뇨
-젊은이 <30세
-단백뇨 < 1g/day
-좋은 예후
7AM
소변 버림
10PM
소변모음
단백뇨
7AM
소변 모음
단백뇨
일반인에서 단백뇨 위험인자
SBP <110 vs SBP 110-119 mmHg
Inc.risk
SBP 120-129 vs SBP 110-119 mmHg
SBP 130-139 vs SBP 110-119 mmHg
SBP 140-149 vs SBP 110-119 mmHg
SBP >=150 vs SBP 110-119 mmHg
GFR 60-89 vs GFR >=90 ml/min/1.73 m2
GFR < 60 vs GFR >=90 ml/min/1.73 m2
DM vs Non-DM
BMI <18.5 vs BMI 18.5-24.9 kg/m2
BMI 25-29.9 vs BMI 18.5-24.9 kg/m2
BMI >= 30 vs BMI 18.5-24.9 kg/m2
1/3
1
3
10
RR
Adjusted with groups of age, sex, hypertension, diabetes mellitus, BMI, SBP, DBP,
high salt intake, glucose, which were the urivariate factors to albuminuria
by multiple logistic regression analysis
단백뇨 진단
Proteinuria
Repeat U/A >= trace
Proteinuria(+)
Persistent proteinuria
Proteinuria(-)
Transient proteinuria
By fever, exercise, stress
W/U for
Orthostatic
proteinuria
Pathologic
Proteinuria
Orthostatic
Proteinuria
단백뇨 진단
1. Initial screening studies
R/O false (+) result; highly concentrated urine,
exercise, fever
urinary sediment; glomerular origin
associated systemic disease; DM, HBGN, LN 등
repeat qualitative test if false (+) test or transient
2. Preliminary
Quantification-UACR, UPCR
UPEP/UIEP
Orthostatic proteinuria in young
3. Definitive
Serologic test: IgG/A/M, complements, FANA, ANCA,
HBsAg, HCV ab. , cryoglobulin, VDRL, ACL
Kidney biopsy in glomerular proteinuria
단백뇨 의미
• 만성 신질환의 주요 소견
• 신기능 감소의 예측인자
• 심혈관 질환의 위험인자
• 전체 사망의 위험인자
단백뇨의 의미
• 단백뇨가 증가할 수록 GFR 감소가 있을 확률이 높다
The Prevention of Renal and Vascular End-stage Disease
(PREVEND) study : 6894 general population in Netherland
KI 2004;66;S18
단백뇨의 의미
• 단백뇨가 증가할 수록 4년후 GFR 감소가 있을 확률이
비례하여 증가한다.
Microalbuminuria
KI 2004;66;S18
단백뇨의 의미-신기능 감소
• 비 당뇨성 질환에서 단백뇨가 많을 수록 신 생존율이
감소한다
단백뇨의 의미-ESRD (REIN Trial)
•당뇨성 질환에서 단백뇨가 많을 수록 신 생존율과
전체 생존율이 감소한다
단백뇨의 의미
• 단백뇨가 증가할 수록 4년 후 심혈관 질환이 증가
Eur Heart J. 2000 Dec;21(23):1922-7.
단백뇨의 의미
• 단백뇨가 증가할 수록
추적 시
STROKE,
CHD,
CVD,
Non-CVD,
All Cause mortality가 증가
-일본, 36,739 general population
-10.1 years follow-up
Kidney International (2006) 69, 1264–1271.
단백뇨 치료 효과
Low BP group
(MBP 92 mmHg)
GFR decline rate from baseline (ml/min/yr)
Usual BP group
(MBP 107 mmHg)
MDRD Study
DM
AT 4 Mo FU period
Urine protein vs GFR
Urine protein g/day
단백뇨 치료 효과
REIN STUDY:
Non-DM CKD
-change of Proteinuria vs GFR
The Lancet; Jun 28, 1997; 349:1857
단백뇨 치료 효과-GFR감소
• The MDRD study
– Each 1g/day reduction at 4 mo
(BP and dietary interventions):
: Subsequent GFR decline slowed by 1 ml/min/yr
• The REIN study
– Each 1g/day reduction at 3 mo of ACEI therapy
: Subsequent GFR decline slowed by 2 ml/min/yr
단백뇨 치료 효과
Herbert et al. Kidney Int 2001
단백뇨 치료 방법-BP 조절
Low BP group
(MBP 92 mmHg)
GFR decline rate from baseline (ml/min/yr)
Usual BP group
(MBP 107 mmHg)
Proteinuria > 1g/day
: < 125/75
Urine protein g/day
단백뇨 치료-ARB/ACEI
ARB: ESRD 28% 감소
NEJM 2001;345;861
단백뇨 치료-ARB/ACEI 병합치료
Lancet 2008;372:547
ONTARGET study
- 대상: high risk group
55세 이상이면서
동맥경화 질환 혹은
합병증이 있는 당뇨병
-치료: Ramipril, Telmisartan, both
-outcome:
eGFR 감소,
Cr 2배 증가,
ESRD,
Death
단백뇨 치료-ARB/ACEI 병합치료
ONTARGET study
Outcome
Both vs Ramipril
p-value
ESRD,Cr doubling, death
1.09 (1.01-1.18)
0.037
ESRD, Cr doubling
1.24 (1.01-1.51)
0.038
Acute dialysis
2.19 (1.13-4.22)
0.020
-2.49 vs -1.17
<0.0001
eGFR change baseline to 2 years
Protein Restriction - Summary
• The benefit of marked dietary protein restriction (0.6~0.7
g/kg/day) and its magnitude: controversial
• Only a mildly reduced rate of decline in GFR (0.53mL/min/yr)?
• Only highly compliant patients are likely to comply.
• Diabetic nephropathy could be more responsive.
– Still effective in patients treated with an ACEI or an ARB?
• Optimal dietary treatment in patients with nondiabetic CKD?
Protein Restriction
Group 1, 30 patients with a
decrease of eUUN > 25%
Group 2, 135 patients with a change
of eUUN between a decrease of
<25% and an increase of <25%
Group 3, 56 patients with an
increase of eUUN > 25%
단백뇨 치료-Aldactone
Effect of spironolactone on urinary protein excretion
in spontaneously hypertensive rats.
단백뇨 치료-Aldactone
Effect of spironolactone on urinary protein excretion
in diabetic rat
-TYPE II DM rat에서 단백뇨와 혈압, 소변 MCP-1을 감소시킴
Aldosterone
• Aldosterone, whether local or systemic origin, may
contribute to progressive renal injury as a result of excess
mineralocorticoid receptor stimulation.
– Vascular remodeling and renal fibrosis
• ACEI or ARB fail to provide optimal renal protection.
• Aldosterone blockade in combination with other RAAS
inhibitors may could be renoprotective and and should be
considered as a component of the treatment regimens.
단백뇨 치료-Statin
Lipid / CKD
• Study design: a controlled, prospective, open-label study
• Patients: Mild to moderate CKD, Hypercholesterolemia,
Proteinuria
• The first year :
– Run in period : ACEI /ARB & BP < 140/90 mmHg
• The second year :
– atorvastatin (group A) / No atorvastatin (group B)
Percent Decline in Proteinuria
Group A: Atorvastatin
Group B: Not treated
Fig. 1. The bars indicate the percent decrease in urine protein excretion (UPE) in patients
treated with atorvastatin (group A) and those not treated (group B). The percent decline in
proteinuria was significantly greater in patients treated with atorvastatin than those not
treated (P < 0.01).
Statins and CKD
• May slow the rate of decline of renal function.
– Overall protective effect: 1.9 mL/min/yr
• Cardiovascular benefits and improve cardiovascular
outcomes in patients without renal failure. ( No
completed randomized clinical trial in patients with
ESRD).
단백뇨-결 론
1. 미세알부민뇨 이상의 단백뇨는 신장예후, 심혈관계 질환,
사망률을 높인다.
2. 단백뇨를 감소시킴으로써 신장기능 감소를 억제시킬 수 있다.
3. 단백뇨의 치료에서
혈압조절
Renin-angiotensin system 억제
단백질 섭취 제한/적어도 0.8 mg/kg/day 이상의 단백질 섭취 제한
염분 섬취 제한
혈압약제 선택 (DHCCB는 적어도 유리하지는 않다)
aldactone, statin 치료
가 중요하다.
혈뇨
혈뇨의 정의
• 정상 : RBC output < 1,000/min
• 혈뇨: 1-13% prevalence in
adults
- microscopic > 3/HPF
> 3,000/min
> 8,000/ml
- gross > 10,000/min
혈뇨 검사법
• 소변의 채취
morning first voided urine
midstream catch
Avoid catheterization
• 2시간 이내 검사 시행
• 냉장 보관은 피한다.
Dipstick test
 False positive
• Hemoglobinuria
• Myoglobinuria
• High concentration of pseudoperoxidase activity
(Enterobacteriaceae, staphylococci, streptococci)
 False-negative
• Ascorbic acid : missed low-grade microscopic
hematuria
 High specificity and low sensitivity
혈뇨의 원인
UTI
Urinary tract stone
Tumor
GN-IgA nephropathy, Thin membrane disease, GN, TIN…
Trauma
Renal vascular diseases-AVM, aneurysm, Nutcracker syndrome,
Acute renal failure with severe loin pain and patchy renal
ischemia after anaerobic exercise (ALPE)
Malformation-ADPKD
Coagulopathy-warfarin, congenital
병력 및 이학적 소견
• History
-Trauma, exercise, menstruation, urinary catheterization,
-Recent sore throat, skin infection, weight change,
-Dysuria, frequency, urgency
-Abdominal pain, CVA pain, suprapubic pain,
-Medication, passage of calculus
병력 및 이학적 소견
• Family History
hematuria, deafness,
renal failure, hypertension,
hemophilia, hemoglobinopathy
• Physical Examination
fever, arthritis, rash, nephromegaly,
hypertension, CVAT
사구체성 혈뇨
사구체성 혈뇨
비사구체성 혈뇨
적혈구 원주(RBC
cast)
적혈구 형태
+
-
dysmorphic
normomorphic
현저한 단백뇨 동반
+
-
색깔
검붉은 색
선홍색
Blood clot
-
+
원인 질환
사구체신염
신종양, 요로 결석,
(IgA nephropathy,
외상성 출혈,
Alport syndrome,
방광암, 방광염
thin basement
membrane disease)
Dysmorphic RBC in urine
• Erythrocytes
– Isomorphic : from urinary excretory system
– Dysmorphic : glomerular origin
– > 80% of total erythrocytes
Dysmorphic RBC
RBC cast
혈뇨의 진단적 접근
True hematuria
Urine culture
Culture (-)
Culture (+)
Check PT/aPTT
CBC, platelets
normal
abnormal
Bacterial cystitis,
urethritis
Tbc, pyelonephritis,
Coagulation disorder
proteinuria
RBC cast, dysm RBC
nephronal
non-nephronal
proteinuria
RBC cast, dysm RBC
non-nephronal
nephronal
Kidney Bx
Glomerulonephritis
Vasculitis
Tubulointerstitial nephritis
Alport syndrome
Benign familial hematuria
proteinuria
RBC cast, dysm RBC
nephronal
Kidney Bx
non-nephronal
IVP /sono/CT
(+)
(-)
Upper tract
cystoscopy
disease (+)
(-)
Lower tract
Renal
disease
angiography
(+)
(-)
Unexplained
Vascular
disease
F/U q6m for 3 y