Nephrotic Syndrome, Cardiovascular Disease Risk and the Effect of Statin Therapy

Arbor Research Collaborative For Health, Ann Arbor MI

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Abstract

DESCRIPTION (provided by applicant): Nephrotic syndrome is a common presentation of multiple disease entities, including rare primary glomerular disease such as minimal change disease, focal segmental glomeruloscerosis and membranous nephropathy. The syndrome is characterized by significant proteinuria, low serum albumin, edema and hyperlipidemia. Cardiovascular disease is the major morbidity for patients with chronic kidney disease. Patients with nephrotic syndrome are presumed to have an increased risk of cardiovascular disease due to the proteinuria and hyperlipidemia associated with the syndrome, but the magnitude of risk, the impact of specific risk factors, and effect of therapy has not been established in this subset of kidney disease patients. We propose a retrospective cohort study of patients with nephrotic syndrome due to primary glomerular diseases to determine the risk of cardiovascular disease, to identify risk factors and to determine the effect of statin (HMG-CoA reducatse inhibitors) therapy. AIM 1: To determine the risk of cardiovascular events in nephrotic syndrome patients compared to patients without nephrotic syndrome. AIM 2: To identify risk factors for cardiovascular events within nephrotic syndrome patients. AIM 3: To determine if the use of HMG-CoA reductase inhibitor (statin) therapy is associated with decreased risk of cardiovascular events in nephrotic syndrome, and to determine if this association differs compared to patients without nephrotic syndrome. We will use the health improvement network (THIN), a U.K. primary care database composed of anonymous data collected from the general practitioners of more than 9 million patients. It contains diagnostic codes, prescription information and laboratory data and is uniquely suited for population-based studies of rare diseases. We will perform a survival analysis, using a Cox proportional hazards model, to determine the hazard ratio for cardiovascular events, and then to identify risk factors and to determine effect of statin therapy on that hazard. The proposed project will use the skills that th applicant gained working towards a Masters of Science in Clinical Epidemiology, specifically fundamentals of epidemiology, biostatistical analysis and study design. This applicant's long-term objectives for this project are to manage and analyze the data, prepare manuscripts for publication, inform future studies and build upon the data for a future application to a K grant application.