End-stage renal disease (ESRD) clusters in families, including ESRD without known hereditary causes, a Norwegian study found.

The study, by Rannveig Skrunes, MD, of Haukeland University Hospital in Bergen, and colleagues, included 5,119,134 individuals recorded in the Norwegian Population Registry. These were people born in Norway and who were alive in 1980, when the Norwegian Renal Registry started registering all individuals developing ESRD requiring chronic renal replacement therapy.

ESRD developed in 8,203 subjects during follow-up; 27,046 had a first-degree relative with ESRD. The researchers defined first-degree relatives as parents, siblings, or children.

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Subjects who had a first-degree relative with ESRD had a 7.2 times higher risk of ESRD compared with individuals who did not. In separate analyses that excluded known hereditary nephropathies, individuals with a first-degree relative with ESRD had a 3.7 times increased risk of ESRD.

Dr. Skrunes’ team looked at the relative risk of ESRD according to its cause. As expected, the investigators noted, those who had a first-degree relative with ESRD due to hereditary renal disease had a significant 36 times higher risk of ESRD and a 5.2, 4.7, 2.6, and 2.6 times higher risk of ESRD if a first degree relative was diagnosed with glomerular disease, interstitial nephritis, diabetic nephropathy, or hypertensive nephropathy respectively, compared with subjects who did not have a first-degree relative with ESRD.

“In our opinion, the findings of higher risks of hypertensive and diabetic nephropathy argue for the importance of multifactorial genetic risk factors that also could include potentially modifiable risk factors for more rapid progression of renal fibrosis,” the authors concluded in a paper published online ahead of print in the Clinical Journal of the American Society of Nephrology.

The researchers pointed out that individuals who share genetic risk factors often also share environmental risk factors. The higher risk of ESRD among individuals with first-degree relatives with ESRD may be monogenic or multifactorial, they noted. “It has not been possible to quantify environmental factors or the interplay between genes and environment,” they wrote. “The take-home messages are, nevertheless, that ESRD clusters in families and that screening of first-degree relatives of patients with ESRD with regard to renal dysfunction might be considered.”