title: Proteinuria, but Not eGFR, Predicts Stroke Risk in Chronic Kidney Disease: Chronic Renal Insufficiency Cohort Study.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Sandsmark
authors.affiliation: 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.).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Messé
authors.affiliation: 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.).
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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.).
authors.forename: Jason
authors.initials: J
authors.lastname: Roy
authors.affiliation: 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.).
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.affiliation: 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.).
authors.forename: Lotuce
authors.initials: L
authors.lastname: Lee Hamm
authors.affiliation: 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.).
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: 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.).
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Horwitz
authors.affiliation: 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.).
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Jaar
authors.affiliation: 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.).
authors.forename: Radhakrishna R
authors.initials: RR
authors.lastname: Kallem
authors.affiliation: 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.).
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.affiliation: 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.).
authors.forename: Emile R
authors.initials: ER
authors.lastname: Mohler
authors.affiliation: 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.).
authors.forename: Anna
authors.initials: A
authors.lastname: Porter
authors.affiliation: 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.).
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Seliger
authors.affiliation: 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.).
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Sozio
authors.affiliation: 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.).
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: 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.).
authors.forename: Harold I
authors.initials: HI
authors.lastname: Feldman
authors.affiliation: 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.).
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
mesh_terms: D000368:Aged; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011507:Proteinuria / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis* / Q000453:epidemiology / Q000378:metabolism
keywords: albuminuria; kidney diseases; proteinuria; risk factors; stroke