Progression of diabetic nephropathy in normotensive type 1 diabetic patients

Background. The first aim of our long-term study was to describe the natural history of diabetic nephropathy in 59 normotensive type 1 diabetic patients. Secondly, we evaluated genetic and nongenetic progression promoters. Methods. The following progression promoters were determined: the insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene, blood pressure, albuminuria, hemoglobin A_1c, cholesterol, smoking, height, and gender. We studied the natural history by measuring ⁵¹Cr-EDTA plasma clearance at yearly intervals at least three times during [median (range)] 5.5 (2.2 to 18.3) years. Results. At baseline the three groups (II, N = 11; ID, N = 25, and DD, N = 23) had comparable GFR (103 ± 16; 99 ± 19; 113 ± 22 ml/min/1.73 m², respectively; mean ± SD), arterial blood pressure, albuminuria, and hemoglobin A_1c. During the follow-up there was a median rate of decline in GFR in all 59 patients of 1.2 (range 12.9 to -4.4) ml/min/year. During the study period no significant differences were observed in: the rate of decline in glomerular filtration rate [median (range) 0.9 (10.6 to -1.9); 2.5 (12.9 to -4.4); 1.4 (10.8 to -1.9 ml/min/year)], arterial blood pressure, albuminuria, hemoglobin A_1c or cholesterol between the three groups (II, ID and DD), respectively. At baseline, multiple linear regression analysis including the above-mentioned putative risk factors revealed that albuminuria, short stature, and male gender independently predict an enhanced decline in GFR [R² (adjusted) = 0.33; P < 0.002]. During the follow-up period, only albuminuria acted as an independent progression promoter [R² (adjusted) = 0.37; P > 0.0001]. Conclusions. Our study revealed a rather slow progression of kidney disease in normotensive type 1 diabetic patients with diabetic nephropathy. Albuminuria, short stature, and male gender act as progression promoters in such patients.