Early Detection and Prevention of Renal Failure
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Early Detection and Prevention of Renal Failure
Linda Fried, MD, MPH
Scope of the Problem The incidence of End-stage renal disease is growing As of 12/31/98, there were more than 200,000 people in
the US on dialysis* End-stage renal disease care accounted for >16 billion
dollars in 1998* The major causes of ESRD are diabetes (45%) and
hypertension (24%) and are therefore potentially preventable
ESRD disproportionately affects minorities and the elderly
*USRDS
Incident rates of ESRD Due to Diabetes & Hypertension, by RaceRate per million population, adjusted for age & gender
USRDS
Incident Rates, by Age & First Modalityadjusted for gender & race
USRDS
Incident Rates, by Primary Diagnosis & First Modalityadjusted for age, gender, & race
USRDS
Identifying People with Early Renal Disease Proteinuria
– Microalbuminuria– Overt Proteinuria/Albuminuria- associated with
lower Creatinine clearance in population* Serum Creatinine- miss early declines in GFR Creatinine Clearance- difficult to do as screen Estimated glomerular filtration rate (GFR) - formulas
from laboratory/clinical variables
*Pinto-Sietsma et al, Groningen, Netherlands, JASN 2000
Proposed NKF Clinical Practice Guideline for Stages of Kidney Disease
Stage Description GFR
(ml/min/1.73m2)
1 Kidney Damage withnormal or GFR >90
2 Mild GFR 60-89
3 Moderate GFR 30-59
4 Severe GFR 15-29
5 Kidney Failure <15 or dialysis
Proposed NKF Clinical Practice Guideline for Stages of Kidney Disease
Marker* No Marker
GFR HTN No HTN HTN No HTN
>90 1 1 HTN Normal
60-89 2 2 2 GFR
30-59 3 3 3 3
15-29 4 4 4 4
<15 or dialysis 5 5 5 5
*Proteinuria, Urinary sediment abnormalities, Structural abnormalities, Alterations in composition of the urine
Proteinuria
The level of proteinuria is a prognostic factor in renal disease
This is true for a wide variety of diseases, including hypertensive renal diseases
Easily performed– Urine dipstick– Albumin sticks– Protein or albumin/creatinine ratio on spot urine
Should we be screening for proteinuria or an elevated creatinine? All diabetics should be screened for microalbuminuria -
ADA and NKF recommendation In the US, the prevalence of proteinuria is low in subjects
without hypertension or diabetes US Preventive Health Services Task Force does not
recommend urinalysis or creatinine as screen in otherwise healthy adults
Are there higher risk groups, such as African Americans or older individuals where screening should be done in asymptomatic individuals without diabetes or hypertension?
Prevalence of Albuminuria in Individuals Without Diabetes: NHANES III
Prevalence by Age Group (years)
Alb/Cr ratio 20-39 40-59 60-69 70+
Normal 93.3% 91.4% 85.4% 72.8%
Microalbuminuria 6.3% 7.9% 13.2% 24.2%
Albuminuria 0.3% 0.7% 1.4% 3.0%
Prevalence of an Increased Creatinine* in Normal, High Normal, and Stage 1 Hypertension : NHANES III
On Medication Not on Medication
NormalHigh-
Normal Stage 1 NormalHigh-
Normal Stage 1Non-HispanicWhite 4.3% 14.2% 12.2% 1.3% 2.3% 3.4%Non-HispanicBlack 19.0 16.2 20.7 2.9 4.6 4.0
Mexican-American 2.0 5.0 3.0 0.3 1.2 1.0
Age 60 2.8 2.5 1.8 5.1 5.8 6.1
*Cr 1.6 men, 1.4 women, Coresh et al, Arch Intern Med 2001
Screening for Renal Disease
Many of those with early renal disease have not been informed of the diagnosis
– In a small pilot study, only 36% (9 of 25) of patients with a creatinine between 1.5 and 3.0 knew of their renal disease
Screening for Renal Disease Microalbuminuria
– Risk factor for cardiovascular events and in nondiabetics this may be a reason to screen, especially in the elderly
– It is a risk factor for progression of diabetic nephropathy, unknown if it is a risk factor in nondiabetics
Overt proteinuria also identifies those at risk for subsequent events*
An elevated creatinine identifies not only those at risk for progression of renal disease, but also those at higher risk for mortality and cardiovascular events
*NHANES 1, Wagener et al Environ Res 1994
Cardiovascular Health Study Population-based, longitudinal study of 5,888 individuals,
age >65 years Random sample from Medicare eligibility lists in:
– Pittsburgh, PA– Forsyth County, NC– Washington County, MD– Sacramento County, CA
Primary objective of CHS is to identify risk factors related to coronary heart disease and stroke
Elderly with Renal Insufficiency
YES
36%NO
64%
YES
28%NO
36%
YES
2%NO
34%
YES
6%NO
28%
N=208 N=370
N=161 N=209
N=14 N=195
N=32 N=163
Clinical CV Disease
Subclinical CV Disease
Diabetes Mellitus
Framingham Risk > 20% / 10 years
N=578
Baseline Cardiovascular Risk in Subjects withan Elevated Creatinine ( 1.5 men or 1.3 women)
Years of follow-up0 2 4 6 8
0.00
0.25
0.50
0.75
1.00
<1.10
1.10-1.29
1.30-1.49
1.50-1.69
1.70+
Survival of Elderly Subjects in CHSby Baseline Creatinine Level
Creatinine
1.1 1.3 1.5 1.7
Rel
ativ
e R
isk
0
1
2
3
4
5
UnadjustedAdjusted
Relative Risk for Cardiovascular Disease: Unadjusted and Fully Adjusted Models
Preventing Decline in Renal Function
Hypertension Control Angiotensin Converting Enzyme Inhibitors/
Angiotensin Receptor Blockers Control of Diabetes Lipid Reduction Smoking cessation- smoking is associated with
a faster decline, no intervention studies Low Protein Diet- falling out of favor
Multifactorial Intervention Slows Progression to Nephropathy in Diabetes: Steno Study
160 Type 2 Diabetes, stratified by level of proteinuria (30-100mg/day, 101-300 mg/day)
Randomized to standard or intensive management Intensive Therapy: behavioral modification (diet,
exercise, smoking cessation) and pharmacologic therapy in step-wise fashion
Primary endpoint was nephropathy (albumin excretion rate >300mg/24 hours)
Lancet 1999
Steno Study Treatment GoalsStandard Intensive
Systolic BP <160 <140
Diastolic BP <95 <85
HbA1c <7.5 <6.5
Triglycerides <2.2 (195 mg/dl) <1.7 (150 mg/dl)
Total chol <6.5 (250 mg/dl) <5.0 (193 mg/dl)
HDL >0.9 (35 mg/dl) >1.1 (42 mg/dl)
ACEI irrespectiveof BP No YesASA in PVD No Yes
ASA in ischemia Yes Yes
Antioxidant vitamins No Yes
Steno Results
8 patients (11%) in intensive vs 19 (25%) in standard therapy grouped developed overt nephropathy after 4 years (p=0.01)
No patient developed end-stage renal disease Lower risk of progression, but not development of
retinopathy Lower risk of progression of autonomic neuropathy No difference in CVD events, though numbers were small Trend towards fewer patients developing a drop in AAI
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