Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease

Abstract

Background and Purpose Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular events. However, the impact of CKD 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 two 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 (eGFR) and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not eGFR, 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 eGFR. The impact of therapies targeting proteinuria/albuminuria in individuals with CKD on stroke prevention warrants further investigation.

Proteinuria Is an Independent Risk Factor for First Incident Stroke in Adults Under Treatment for Hypertension in China

“…These findings are similar to previous studies. Recently, reports from the Kailuan study and the Chronic Renal Insufficiency Cohort (CRIC) study both showed that proteinuria but not reduced eGFR increased the risk of stroke in a general and CKD population, respectively . The JATOS study demonstrated that baseline reduced eGFR per se (<60 versus ≥60 mL/min per 1.73 m 2 ) was not significantly associated with cardiovascular events ( P =0.1723); however, the presence of proteinuria was significantly correlated with cardiovascular event rates ( P =0.0001), an association that was more apparent in patients with an eGFR <60 mL/min per 1.73 m 2 ( P <0.0001) .…”

Association of Chronic Kidney Disease with Coronary Heart Disease and Stroke Risks in Patients with Type 2 Diabetes Mellitus

“…[2829] Furthermore, the Chronic Renal Insufficiency Cohort study recently reported that compared to eGFR, albuminuria is a better predictor of stroke risk in patients with CKD. [30]…”

Response by Peralta et al to Letter Regarding Article, “Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial”

“…First, the levels of proteinuria are likely to be randomly distributed in both arms, and thus of similar magnitude at baseline. Second, we do not expect the SPS3 population to have a high prevalence of severe proteinuria because participants had a relatively low prevalence of diabetes and, unlike CRIC 2 , SPS3 was not enriched for kidney disease. In addition, the use of inhibitors of the renin angiotensin system (ACE/ARB) was very high in both groups throughout the study.…”