Lowering of Proteinuria in Response to Antihypertensive Therapy Predicts Improved Renal Function in Late but Not in Early Diabetic Nephropathy: A Pooled Analysis

In late diabetic nephropathy (DN) the initial lowering of albumin excretion rate (AER) with antihypertensive therapy is proportional to the degree of subsequent preservation of glomerular filtration rate (GFR). Whether a similar relationship exists between AER and GFR in early diabetes is not known. The present analysis has compared AER and GFR responses to antihypertensive therapy in 33 published studies (77 treatment groups) of early and late DN in type 1 (T1) and type 2 (T2) diabetes, analyzed on an intention-to-treat basis. Prospective trials were included if the initial change in AER during the first year of therapy and the change in GFR during at least 2 years of follow-up could be estimated from group mean data. The initial % decreases in AER were 5.9 +/- 4.3 (T1), 10.5 +/- 5.4 (T2, normotensive) and 18.4 +/- 6.2 (T2, hypertensive) in early DN and 7.6 +/- 11.1 (T1) and 20.8 +/- 5.5 (T2) in late DN. The corresponding annual % rates of decline of GFR were 2.0 +/- 0.5 (T1), 1.6 +/- 0.5 (T2, normotensive) and 2.1 +/- 0.3 (T2, hypertensive) in early DN and 9.8 +/- 1.5 (T1) and 9.2 +/- 1.1 (T2) in late DN. AER and GFR responses in each treatment group were closely correlated in late nephropathy (T1, r = -0.67, p = 0.03; T2, r = 0.57, p = 0.02) but not in early nephropathy. In contrast to late DN, the initial decrease in AER with antihypertensive therapy was not shown to predict the subsequent rate of decline of GFR in early DN. It follows that assessment of renoprotection during antihypertensive therapy in early nephropathy should be based not only on albuminuria but also on the GFR response.