Early Detection and Prevention of Renal Failure Linda Fried, MD, MPH

Scope of the Problem u The incidence of End-stage renal disease is growing u As of 12/31/98, there were more than 200,000 people in the US on dialysis* u End-stage renal disease care accounted for >16 billion dollars in 1998* u The major causes of ESRD are diabetes (45%) and hypertension (24%) and are therefore potentially preventable u ESRD disproportionately affects minorities and the elderly *USRDS

Incident rates of ESRD Due to Diabetes & Hypertension, by Race Rate per million population, adjusted for age & gender USRDS

Incident Rates, by Age & First Modality adjusted for gender & race USRDS

Incident Rates, by Primary Diagnosis & First Modality adjusted for age, gender, & race USRDS

Identifying People with Early Renal Disease u Proteinuria –Microalbuminuria –Overt Proteinuria/Albuminuria- associated with lower Creatinine clearance in population* u Serum Creatinine- miss early declines in GFR u Creatinine Clearance- difficult to do as screen u 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

* Proteinuria, Urinary sediment abnormalities, Structural abnormalities, Alterations in composition of the urine

Proteinuria u The level of proteinuria is a prognostic factor in renal disease u This is true for a wide variety of diseases, including hypertensive renal diseases u Easily performed –Urine dipstick –Albumin sticks –Protein or albumin/creatinine ratio on spot urine

Should we be screening for proteinuria or an elevated creatinine? u All diabetics should be screened for microalbuminuria - ADA and NKF recommendation u In the US, the prevalence of proteinuria is low in subjects without hypertension or diabetes u US Preventive Health Services Task Force does not recommend urinalysis or creatinine as screen in otherwise healthy adults u 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 of an Increased Creatinine* in Normal, High Normal, and Stage 1 Hypertension : NHANES III *Cr  1.6 men, 1.4 women, Coresh et al, Arch Intern Med 2001

Screening for Renal Disease u 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 u 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 u Overt proteinuria also identifies those at risk for subsequent events* u 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 u Population-based, longitudinal study of 5,888 individuals, age >65 years u Random sample from Medicare eligibility lists in: –Pittsburgh, PA –Forsyth County, NC –Washington County, MD –Sacramento County, CA u 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=208N=370 N=161 N=209 N=14N=195 N=32N=163 Clinical CV Disease Subclinical CV Disease Diabetes Mellitus Framingham Risk > 20% / 10 years N=578 Baseline Cardiovascular Risk in Subjects with an Elevated Creatinine (  1.5 men or 1.3 women)

Survival of Elderly Subjects in CHS by Baseline Creatinine Level

Relative Risk for Cardiovascular Disease: Unadjusted and Fully Adjusted Models

Preventing Decline in Renal Function u Hypertension Control u Angiotensin Converting Enzyme Inhibitors/ Angiotensin Receptor Blockers u Control of Diabetes u Lipid Reduction u Smoking cessation- smoking is associated with a faster decline, no intervention studies u Low Protein Diet- falling out of favor

Multifactorial Intervention Slows Progression to Nephropathy in Diabetes: Steno Study u 160 Type 2 Diabetes, stratified by level of proteinuria (30-100mg/day, mg/day) u Randomized to standard or intensive management u Intensive Therapy: behavioral modification (diet, exercise, smoking cessation) and pharmacologic therapy in step-wise fashion u Primary endpoint was nephropathy (albumin excretion rate >300mg/24 hours) Lancet 1999

Steno Study Treatment Goals

Steno Results u 8 patients (11%) in intensive vs 19 (25%) in standard therapy grouped developed overt nephropathy after 4 years (p=0.01) u No patient developed end-stage renal disease u Lower risk of progression, but not development of retinopathy u Lower risk of progression of autonomic neuropathy u No difference in CVD events, though numbers were small u Trend towards fewer patients developing a drop in AAI