Progression of diabetic nephropathy

Background. Diabetic nephropathy is a major cause of renal failure. The decline in glomerular filtration rate (GFR) is highly variable, ranging from 2 to 20, with a median of 12 mL/min/ year. The risk factors of losing filtration power (progression promoters) have not been clearly identified. Furthermore, information on optimal arterial blood pressure, glycemic control, and cholesterol levels are lacking. Methods. We measured GFR with Cr-51-EDTA plasma clearance technique, blood pressure, albuminuria, glycosylated hemoglobin A(1c), and serum cholesterol every year for seven years (range 3 to 14 years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy recruited consecutively during 1983 through 1997. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria >200 mug/min, presence of diabetic retinopathy. and no evidence of other kidney or renal tract disease. In total. 271 patients received antihypertensive treatment at the end of the observation period. Results. Mean arterial blood pressure was 102 +/- 0.4 (SE) mm Hg. The average decline in GFR was 4.0 +/- 0.2 mL/min/year and even lower(1.9 +/- 0.5 mL/min/year) in the 30 persistently normotensive patients, none of whom had ever received antihypertensive treatment (P < 0.01). A multiple linear regression analysis revealed a significant positive correlation between the decline in GFR and mean arterial blood pressure, albuminuria, glycosylated hemoglobin A(1c), and serum cholesterol during follow-up (R-adj(2) = 0.29, P less than or equal to 0.001). No threshold level for blood pressure, glycosylated hemoglobin A(1c), or serum cholesterol was demonstrated. A two-hit model with mean arterial blood pressure and glycosylated hemoglobin A(1c) below and above the median values (102 mm Hg and 9.2%, respectively) revealed a rate of decline in GFR of only 1.5 mL/min/year in the lowest stratum compared with 6.1 mL/min/year in the highest stratum (P < 0.001). Conclusions. The prognosis of diabetic nephropathy has improved during the past decades, predominantly because of effective antihypertensive treatment. Genuine normotensive patients have a slow progression of nephropathy. Several modifiable variables have been identified as progression promoters.