Familial aggregation of renal disease in a population-based case-control study

Family history of renal disease has been associated with an increased risk of end-stage renal disease (ESRD). It is uncertain whether this risk is mediated by familial aggregation of risk factors for ESRD, such as diabetes and hypertension. The association of ESRD with familial aggregation of renal disease was examined in a large, population-based case-control study conducted in Maryland, Virginia, West Virginia, and Washington, DC. The number of first-degree relatives who were affected with any type of renal disease was compared between 689 newly treated ESRD patients registered in the Medicare ESRD program (92% of all eligible incident cases presenting between January and July of 1991) and 361 control subjects without ESRD who were selected by random-digit dialing (90% response rate). Patients and control subjects were frequency matched by age; patients with ESRD caused by polycystic kidney disease and other known hereditary kidney diseases were excluded. Analysis was conducted using multiple logistic regression. After controlling for the proband's age, gender, race, family size, socioeconomic status, and personal and family histories of diabetes and hypertension, having one first-degree relative with renal disease increased the odds of ESRD by 1.3 (95% confidence interval, 0.7 to 2.6) and having two or more affected first-degree relatives increased the odds of ESRD by 10.4 (95% confidence interval, 2.7 to 40.2). These data support familial aggregation of renal disease in excess of that predicted by clustering of diabetes and hypertension within families, suggesting that either genetic susceptibility or environmental exposures shared within families increase the risk of developing ESRD. This risk is also much higher when two or more first-degree relatives have renal disease. Unraveling the molecular basis of this increase in risk may provide new avenues for treatment and prevention of ESRD.