Increased concentrations of soluble CD40 ligand may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria

Abstract

Recent studies on the pathogenesis of diabetic complications have demonstrated the important role of a number of aberrantly expressed molecules acting together in the development of early diabetic microvascular complications. Soluble CD40 ligand (sCD40L) is supposed to be one of the most likely candidates for both retinopathy and nephropathy. In January 1989, sCD40L was measured in 340 normoalbuminuric diabetic adolescents and young adults. Participants were examined at baseline and biannually thereafter. sCD40L was measured every 2 years during a 16-year follow-up period. sCD40L was also measured in parents. Over 16 years, 32 out of 340 patients developed persistent microalbuminuria; no patient developed overt diabetic nephropathy. The risk of developing microalbuminuria was higher in children with increased sCD40L at the beginning of the study (using 6 ng/mL as the arbitrary cut-off value) (group A) compared with those with normal sCD40L (group B). Sex did not influence predictive value, sensitivity, or specificity. sCD40L was not significantly correlated with duration of diabetes. The percentage of offspring with both parents having sCD40L above the mean values was significantly higher in group A than in group B. The odds ratio (OR) for the occurrence of microalbuminuria after adjustment for confounding variables in patients with elevated baseline sCD40L was 4.2 (95% CI, 2.1-10.7). Persistently increased sCD40L levels from the onset of diabetes might help to identify those normotensive and normoalbuminuric young patients at increased risk of developing incipient nephropathy later in life.