We read with interest the article by Wanic et al. (1) in which they present the first prospective data on polymorphisms in carnosinase genes and progression of diabetic nephropathy in diabetic patients. Prior studies, in which a polymorphism in carnosinase gene CNDP1 was identified and confirmed as a risk factor, were cross-sectional and mostly in patients with type 2 diabetes (2–4). At variance with these cross-sectional studies, Wanic et al. did not find a significantly increased risk for development of nephropathy in the cross-sectional part of their study (1).
Wanic et al. mention that power of the prospective part of their study was high and sufficient to detect a relative risk of 1.5. The prospective part of the study by Wanic et al. is indeed relatively large, with many cases of the end point end-stage renal disease (ESRD). As the authors mention—and adequately perform—it is important to adjust for diabetes duration in studies on diabetes complications (5). In studies on ESRD, however, it is equally important to adjust for baseline renal function and proteinuria (6,7). In our opinion, to actually exclude polymorphisms in carnosinase genes as risk factors for progression in diabetic nephropathy, Wanic et al. should have included data on these parameters in their Cox proportional hazards regression analyses. Optimally, they should also have included data on mortality in their cohort because patients with diabetic nephropathy are at high risk for nonrenal mortality. A survival advantage or disadvantage for the CNDP1 polymorphism could not only underlie associations with diabetic nephropathy in prior cross-sectional studies (2–4) but also obscure a relationship with development of ESRD in a prospective study. Thus, we disagree with the conclusion that CNDP1 polymorphisms can be excluded as a risk factor for nephropathy in type 1 diabetes.
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