American Journal of Kidney Diseases

The Risk of Cardiovascular Events in Individuals With Primary Glomerular Diseases

      Rationale & Objective

      Little is known about the risk of cardiovascular disease (CVD) in patients with various primary glomerular diseases. In a population-level cohort of adults with primary glomerular disease, we sought to describe the risk of CVD compared with the general population and the impact of traditional and kidney-related risk factors on CVD risk.

      Study Design

      Observational cohort study.

      Setting & Participants

      Adults with membranous nephropathy (n = 387), minimal change disease (n = 226), IgA nephropathy (n = 759), and focal segmental glomerulosclerosis (n = 540) from a centralized pathology registry in British Columbia, Canada (2000-2012).


      Traditional CVD risk factors (diabetes, age, sex, dyslipidemia, hypertension, smoking, prior CVD) and kidney-related risk factors (type of glomerular disease, estimated glomerular filtration rate [eGFR], proteinuria).


      A composite CVD outcome of coronary artery, cerebrovascular, and peripheral vascular events, and death due to myocardial infarction or stroke.

      Analytical Approach

      Subdistribution hazards models to evaluate the outcome risk with non-CVD death treated as a competing event. Standardized incidence rates (SIR) calculated based on the age- and sex-matched general population.


      During a median 6.8 years of follow-up, 212 patients (11.1%) experienced the CVD outcome (10-year risk, 14.7% [95% CI, 12.8%-16.8%]). The incidence rate was high for the overall cohort (24.7 per 1,000 person-years) and for each disease type (range, 12.2-46.1 per 1,000 person-years), and was higher than that observed in the general population both overall (SIR, 2.46 [95% CI, 2.12-2.82]) and for each disease type (SIR range, 1.38-3.98). Disease type, baseline eGFR, and proteinuria were associated with a higher risk of CVD and, when added to a model with traditional risk factors, led to improvements in model fit (R2 of 14.3% vs 12.7%), risk discrimination (C-statistic of 0.81 vs 0.78; difference, 0.02 [95% CI, 0.01-0.04]), and continuous net reclassification improvement (0.4 [95% CI, 0.2-0.6]).


      Ascertainment of outcomes and comorbidities using administrative data.


      Patients with primary glomerular disease have a high absolute risk of CVD that is approximately 2.5 times that of the general population. Consideration of eGFR, proteinuria, and type of glomerular disease may improve risk stratification of CVD risk in these individuals.

      Plain-Language Summary

      Patients with chronic kidney disease are known to be at high risk of cardiovascular disease. Cardiovascular risk in patients with primary glomerular diseases is poorly understood because these conditions are rare and require a kidney biopsy for diagnosis. In this study of 1,912 Canadian patients with biopsy-proven IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy, the rate of cardiovascular events was 2.5 times higher than in the general population and was high for each disease type. Consideration of disease type, kidney function, and proteinuria improved the prediction of cardiovascular events. In summary, our population-level study showed that patients with primary glomerular diseases have a high cardiovascular risk, and that inclusion of kidney-specific risk factors may improve risk stratification.

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        • Matsushita K.
        • van der Velde M.
        • et al.
        • Chronic Kidney Disease Prognosis Consortium
        Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.
        Lancet. 2010; 375: 2073-2081
        • Van der Velde M.
        • Matsushita K.
        • Coresh J.
        • et al.
        Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality: a collaborative meta-analysis of high-risk population cohorts.
        Kidney Int. 2011; 79: 1341-1352
        • Klausen K.
        • Borch-Johnsen K.
        • Feldt-Rasmussen B.
        • et al.
        Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes.
        Circulation. 2004; 110: 32-35
        • Wheeler D.C.
        • Bernard D.B.
        Lipid abnormalities in the nephrotic syndrome: causes, consequences, and treatment.
        Am J Kidney Dis. 1994; 23: 331-346
        • Radhakrishnan J.
        • Appel A.S.
        • Valeri A.
        • Appel G.B.
        The nephrotic syndrome, lipids, and risk factors for cardiovascular disease.
        Am J Kidney Dis. 1993; 22: 135-142
        • Westerweel P.E.
        • Luyten R.K.
        • Koomans H.A.
        • Derksen R.H.
        • Verhaar M.C.
        Premature atherosclerotic cardiovascular disease in systemic lupus erythematosus.
        Arthritis Rheum. 2007; 56: 1384-1396
        • Cohen Tervaert J.W.
        Cardiovascular disease due to accelerated atherosclerosis in systemic vasculitides.
        Best Pract Res Clin Rheumatol. 2013; 27: 33-44
        • Bai Y.H.
        • Li Z.Y.
        • Chang D.Y.
        • Chen M.
        • Kallenberg C.G.
        • Zhao M.H.
        The BVAS is an independent predictor of cardiovascular events and cardiovascular disease-related mortality in patients with ANCA-associated vasculitis: a study of 504 cases in a single Chinese center.
        Semin Arthritis Rheum. 2018; 47: 524-529
        • Mackinnon B.
        • Deighan C.J.
        • Ferrell W.R.
        • Sattar N.
        • Fox J.G.
        Endothelial function in patients with proteinuric primary glomerulonephritis.
        Nephron Clin Pract. 2008; 109: c40-c47
        • Karp I.
        • Abrahamowicz M.
        • Fortin P.R.
        • et al.
        Recent corticosteroid use and recent disease activity: independent determinants of coronary heart disease risk factors in systemic lupus erythematosus?.
        Arthritis Rheum. 2008; 59: 169-175
        • Zeier M.
        • Van Der Giet M.
        Calcineurin inhibitor sparing regimens using m-target of rapamycin inhibitors: an opportunity to improve cardiovascular risk following kidney transplantation?.
        Transplant Int. 2011; 24: 30-42
        • Myllymaki J.
        • Syrjanen J.
        • Helin H.
        • Pasternack A.
        • Kattainen A.
        • Mustonen J.
        Vascular diseases and their risk factors in IgA nephropathy.
        Nephrol Dial Transplant. 2006; 21: 1876-1882
        • Mahmoodi B.K.
        • ten Kate M.K.
        • Waanders F.
        • et al.
        High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study.
        Circulation. 2008; 117: 224-230
        • Lee T.
        • Derebail V.K.
        • Kshirsagar A.V.
        • et al.
        Patients with primary membranous nephropathy are at high risk of cardiovascular events.
        Kidney Int. 2016; 89: 1111-1118
        • Ordoñez J.D.
        • Hiatt R.A.
        • Killebrew E.J.
        • Fireman B.H.
        The increased risk of coronary heart disease associated with nephrotic syndrome.
        Kidney Int. 1993; 44: 638-642
        • Heaf J.
        • Løkkegaard H.
        • Larsen S.
        The epidemiology and prognosis of glomerulonephritis in Denmark 1985-1997.
        Nephrol Dial Transplant. 1999; 14: 1889-1897
        • Hutton H.L.
        • Levin A.
        • Gill J.
        • Djurdjev O.
        • Tang M.
        • Barbour S.J.
        • Cardiovascular risk is similar in patients with glomerulonephritis compared to other types of chronic kidney disease: a matched cohort study
        BMC Nephrol. 2017; 18: 95
        • O’Shaughnessy M.M.
        • Liu S.
        • Montez-Rath M.E.
        • Lafayette R.A.
        • Winkelmayer W.C.
        Cause of kidney disease and cardiovascular events in a national cohort of US patients with end-stage renal disease on dialysis: a retrospective analysis.
        Eur Heart J. 2019; 40: 887-898
      1. KDIGO 2013 clinical practice guideline for lipid management in chronic kidney disease.
        Kidney Int Suppl. 2013; 3: 259-305
        • Discharge Abstract Database (Hospital Separations)
        V2. Canadian Institute for Health Information, University of British Colombia, Population Data BC, 2016.
        • British Columbia Ministry of Health
        Medical Services Plan (MSP) Payment Information File. University of British Colombia, Population Data BC, 2016.
        • Government of British Colombia
        Ministry of Health. PharmaNet. V2. Data Extract. Data Stewardship Committee, 2011.
        • Government of British Colombia
        Vital Statistics Agency. Vital Statistics Births. University of British Colombia, Population Data BC, BC Vital Statistics Agency, 2016.
        • Canney M.
        • Induruwage D.
        • Sahota A.
        • et al.
        Socioeconomic position and incidence of glomerular diseases.
        Clin J Am Soc Nephrol. 2020; 15: 367-374
        • Hogan M.C.
        • Reich H.N.
        • Nelson P.J.
        • et al.
        The relatively poor correlation between random and 24-hour urine protein excretion in patients with biopsy-proven glomerular diseases.
        Kidney Int. 2016; 90: 1080-1089
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Komenda P.
        • Beaulieu M.
        • Seccombe D.
        • Levin A.
        Regional implementation of creatinine measurement standardization.
        J Am Soc Nephrol. 2008; 19: 164-169
        • Canadian Institute for Health Information
        Treatment of End-Stage Organ Failure in Canada, Canadian Organ Replacement Register, 2009 to 2018: End-Stage Kidney Disease and Kidney Transplants Data Tables. CIHI.
        • Baigent C.
        • Landray M.J.
        • Reith C.
        • et al.
        The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.
        Lancet. 2011; 377: 2181-2192
        • Marso S.P.
        • Daniels G.H.
        • Brown-Frandsen K.
        • et al.
        Liraglutide and cardiovascular outcomes in type 2 diabetes.
        N Engl J Med. 2016; 375: 311-322
        • Marso S.P.
        • Bain S.C.
        • Consoli A.
        • et al.
        Semaglutide and cardiovascular outcomes in patients with type 2 diabetes.
        N Engl J Med. 2016; 375: 1834-1844
        • Neal B.
        • Perkovic V.
        • Mahaffey K.W.
        • et al.
        Canagliflozin and cardiovascular and renal events in type 2 diabetes.
        N Engl J Med. 2017; 377: 644-657
        • Zinman B.
        • Wanner C.
        • Lachin J.M.
        • et al.
        Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes.
        N Engl J Med. 2015; 373: 2117-2128
        • Fine J.
        • Gray R.
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Stat Assoc. 1999; 94: 496-509
        • Uno H.
        • Cai T.
        • Pencina M.J.
        • D’Agostino R.B.
        • Wei L.J.
        On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data.
        Stat Med. 2011; 30: 1105-1117
        • Chambless L.E.
        • Cummiskey C.P.
        • Cui G.
        Several methods to assess improvement in risk prediction models: extension to survival analysis.
        Stat Med. 2011; 30: 22-38
        • O’Quigley J.
        • Xu R.
        • Stare J.
        Explained randomness in proportional hazards models.
        Stat Med. Feb 15 2005; 24: 479-489
        • Government of British Colombia
        Population estimates. BC Stats.
        • Breslow N.E.
        • Day N.E.
        Statistical methods in cancer research: Vol. 2, the design and analysis of cohort studies.
        IARC Sci Publ. 1987; 82: 1-406
        • Kim H.
        • Yoo T.H.
        • Choi K.H.
        • et al.
        Baseline cardiovascular characteristics of adult patients with chronic kidney disease from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).
        J Korean Med Sci. 2017; 32: 231-239
        • Xie Z.
        • Li Z.
        • Dong W.
        • et al.
        Metabolic syndrome and concomitant diabetes mellitus are associated with higher risk of cardiovascular comorbidity in patients with primary glomerular diseases: a retrospective observational study.
        Clin Cardiol. 2020; 43: 949-956