Familial Clustering of Diabetic Kidney Disease

Diabetic nephropathy develops in less than half of all patients with diabetes. To study heredity as a possible risk factor for diabetic kidney disease, we examined the concordance rates for diabetic nephropathy in two sets of families in which both probands and siblings had diabetes mellitus. In one set, the probands (n = 11) had no evidence of diabetic nephropathy, with normal creatinine clearance and a urinary albumin excretion rate below 45 mg per day. In the other set, the probands (n = 26) had undergone kidney transplantation because of diabetic nephropathy. Evidence of nephropathy was found in 2 of the 12 diabetic siblings of the probands without nephropathy (17 percent). Of the 29 diabetic siblings of probands with diabetic nephropathy, 24 (83 percent) had evidence of nephropathy (P<0.001), including 12 with end-stage renal disease. No significant differences were noted between the sibling groups with respect to the duration of diabetes, blood pressure, glycemic control, or glycosylated hemoglobin levels. Logistic regression analysis found nephropathy in the proband to be the only factor significantly predictive of the renal status of the diabetic sibling. We conclude that diabetic nephropathy occurs in familial clusters. This is consistent with the hypothesis that heredity helps to determine susceptibility to diabetic nephropathy. However, this study cannot rule out the possible influences of environmental factors shared by siblings. DIABETIC nephropathy is a devastating complication of diabetes^1,2 and is among the leading indications for dialysis and kidney transplantation in this country.³ Natural-history studies suggest that diabetic nephropathy, heralded by proteinuria, eventually develops in 30 to 50 percent of diabetic persons.^4,5 A patient usually has diabetes for several years before the clinical manifestations of nephropathy are apparent, but the absence of such clinical signs after 35 years of disease suggests that the patient may be spared. Why some diabetic persons are susceptible to diabetic nephropathy and others are not has intrigued investigators. Many believe that hypertension⁶ and poor glycemic control…