Observational Study

. 2015 Aug;46(8):2075-80.

doi: 10.1161/STROKEAHA.115.009861. Epub 2015 Jun 30.

Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study

Danielle K Sandsmark¹, Steven R Messé², Xiaoming Zhang², Jason Roy², Lisa Nessel², Lotuce Lee Hamm², Jiang He², Edward J Horwitz², Bernard G Jaar², Radhakrishna R Kallem², John W Kusek², Emile R Mohler 3rd², Anna Porter², Stephen L Seliger², Stephen M Sozio², Raymond R Townsend², Harold I Feldman², Scott E Kasner²; CRIC Study Investigators

Affiliations

¹ From 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.
² From 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.).

PMID: 26130097
PMCID: PMC4519405
DOI: 10.1161/STROKEAHA.115.009861

Observational Study

Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study

Danielle K Sandsmark et al. Stroke. 2015 Aug.

. 2015 Aug;46(8):2075-80.

doi: 10.1161/STROKEAHA.115.009861. Epub 2015 Jun 30.

Authors

Affiliations

¹ From 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.
² From 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.).

PMID: 26130097
PMCID: PMC4519405
DOI: 10.1161/STROKEAHA.115.009861

Abstract

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.

Keywords: albuminuria; kidney diseases; proteinuria; risk factors; stroke.

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Conflict of interest statement

DISCLOSURES

None of the authors report any financial conflict with the content of this manuscript. Dr. Jaar has received an honorarium from UpToDate for an unrelated medical chapter.

Figures

**Figure 1**
(A) Kaplan-Meier curves of stroke-free survival according to degree of albuminuria. (B) Risk of stroke in subjects with albuminuria and treatment with inhibitors of the renin-angiotensin system (ACEI/ARB). Error bars indicate 95% confidence intervals.

See this image and copyright information in PMC

Comment in

Response to Letter Regarding Article, "Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study".
Sandsmark DK, Kasner SE. Sandsmark DK, et al. Stroke. 2015 Nov;46(11):e240. doi: 10.1161/STROKEAHA.115.011033. Epub 2015 Oct 13. Stroke. 2015. PMID: 26463697 Free PMC article. No abstract available.
Letter by Tsuda Regarding Article, "Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study".
Tsuda K. Tsuda K. Stroke. 2015 Nov;46(11):e239. doi: 10.1161/STROKEAHA.115.011018. Epub 2015 Oct 13. Stroke. 2015. PMID: 26463699 No abstract available.

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1. Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012;379:165–180. - PubMed
1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C-Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305. - PubMed
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Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study

Affiliations

Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous