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Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study
Danielle K Sandsmark1, Steven R Messé2, Xiaoming Zhang2
1From the Department of Neurology (D.K.S., S.R.M., S.E.K.), Renal, Electrolyte, and Hypertension Division (R.R.K., R.R.T.) and Division of Vascular Medicine (E.R.M.), Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia (X.Z., J.R., L.N., H.I.F.); Department of Medicine, Tulane University, New Orleans, LA (L.L.H.); Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (J.H.); Department of Medicine, Metrohealth, Cleveland, OH (E.J.H.); Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (B.G.J.); Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (J.W.K.); Department of Nephrology, University of Illinois, Chicago (A.P.); Department of Medicine, University of Maryland, Baltimore (S.L.S.); and Department of Medicine, Johns Hopkins University, Baltimore, MD (S.M.S.). danielle.sandsmark@uphs.upenn.edu.
Background And Purpose:
Chronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors.
Methods:
The study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates.
Results:
In 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria.
Conclusions:
Proteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation.
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