The Diabetes Control and Complications Trial (DCCT) has demonstrated that intensive diabetes treatment delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy in patients with IDDM. A detailed description of the effects of this treatment on diabetic nephropathy is presented here. In the primary prevention cohort, intensive treatment reduced the mean adjusted risk of the cumulative incidence of microalbuminuria (> or = 28 micrograms/min) by 34% (95% CI 2, 56%; P = 0.04). Furthermore, intensive treatment decreased the albumin excretion rate (AER) by 15% after the first year of therapy (6.5 vs. 7.7 micrograms/min, P < 0.001). Thereafter the rates of change for AER within each treatment group were no different from zero, retaining a constant difference in AER between groups in the trial. In the secondary intervention cohort with baseline AER < 28 micrograms/min, intensive therapy reduced the mean adjusted risk of microalbuminuria (> or = 28 micrograms/min) by 43% (95% CI 21, 58%; P < 0.0001); the risk of a more advanced level of microalbuminuria (> or = 70 micrograms/min) by 56% (95% CI 26, 74%; P = 0.002); and the risk of clinical albuminuria (> or = 208 micrograms/min) by 56% (95% CI 18, 76%; P < 0.01). In the secondary intervention cohort, values for AER at year 1 were identical at 9 micrograms/min, but the 6.5% change per year in the conventional group greatly exceeded the rate of change of -0.3% in the intensive group (P < 0.001). Among the 73 secondary cohort subjects with AER levels > or = 28 micrograms/min but < or = 139 micrograms/min at baseline, the reduction of progression to clinical albuminuria with intensive therapy was not statistically significant. The longitudinal treatment effect of conventional versus intensive therapy (11.0% vs. 2.5% per year, respectively, P = 0.087) was similar in magnitude to that among patients with AER < 28 micrograms/min at baseline. For the primary, secondary and combined cohorts, there were no significant differences in the rates of change in creatinine clearance (CCr) between treatment groups during the study. Only seven subjects in the entire study (2 intensive, 5 conventional) developed urinary AER > or = 208 micrograms/min coupled with a CCr < 70 ml/min/1.73 m2. Neither the rate of change of blood pressure nor the appearance of hypertension (BP > 140/90 mm Hg) differed significantly between treatment groups in the primary, secondary or combined cohorts.(ABSTRACT TRUNCATED AT 400 WORDS)