Is diabetic nephropathy inherited? Studies of glomerular structure in type1 diabetic sibling pairs

Only a minority of patients with type 1 diabetes develop diabetic nephropat hy (DN), Poor glycemic control cannot fully explain DN risk, and family stu dies suggest genetic susceptibility factors. To understand familial DN conc ordance, we evaluated glomerular structure in families with type 1 diabetic sibling pairs. Kidney function and biopsy studies were performed in 21 pro bands (P) (first to develop diabetes) and 21 siblings (S) (second to develo p diabetes),most with normal urinary albumin excretion rates (UAER), Glomer ular structure was measured by morphometry, Intrafamilial correlation was e stimated by one-way random-effects ANOVA and by mixed-effects ANOVA, adjust ing for age and duration of diabetes. Diabetes duration was, by definition, longer in P than in S, while age and sex were similar, HbA(1c) over 5 year s and blood pressure were not different in P and S and were without familia l effect. UAER was greater in P than in S (P < 0.05), with strong familial effect (P = 0.03), A strong concordance among siblings for mesangial fracti onal volume (P less than or equal to 0.01) remained significant after adjus tment for diabetes duration and age (P = 0.04), Results were similar for me sangial cell (P = 0.01; adjusted P = 0.04) and mesangial matrix fractional volumes (P < 0.01; adjusted P = 0.06), There was also clustering of the pat terns of glomerular lesions. For example, if P had relatively marked glomer ular basement membrane thickening compared with mesangial matrix expansion, S had a similar pattern (chi(2), P < 0.025), Strong concordance in severit y and patterns of glomerular lesions in type 1 diabetic siblings, despite l ack of concordance in glycemia, supports an important role for genetic fact ors in DN risk.