INCREASED GLOMERULAR-FILTRATION RATE AFTER WITHDRAWAL OF LONG-TERM ANTIHYPERTENSIVE TREATMENT IN DIABETIC NEPHROPATHY

Initiation of antihypertensive treatment (AHT) in hypertensive insulin -dependent diabetic (IDDM) patients with diabetic nephropathy (DN) ind uces a faster initial (0 to 6 months) and a slower subsequent (6 month s to end of observation) decline in GFR [Delta>GFR (ml/min/month) appr oximately 1.5 vs. 0.35]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged AHT is not known. To elucidate these mechanisms we investigated 42 hypert ensive IDDM patients (16F/26M, age 40 +/- 7 years, mean +/- SD) with D N receiving AHT (angiotensin converting enzyme inhibition, N = 30) for 6 (2 to 15) years [median (range)]. GFR (ml/min/1.73 m(2)), arterial blood pressure (BP, mm Hg) and albuminuria (mg/24 hr) were measured th e last day on AHT and one month after withdrawal of AHT. The measured variables were all significantly elevated after withdrawal of AHT: GFR [mean(SEM)] from 76(4) to 81(4) (P < 0.0001), BP [mean(SEM)] from 140 /82 (2/1) to 151/89 (2/1) (P < 0.0005) and albuminuria [geometric mean (antilog SEM)] from 704 (1.2) to 1122 (1.2) (P < 0.0001). A correlatio n between relative rise in systolic blood pressure (Delta Sys%) and re lative change in GFR (Delta GFR%) was found (r = 0.44, P < 0.005). Our results render some support of the hypothesis that the faster initial decline in GFR is due to a functional (hemodynamic) effect of AHT, wh ich does not attenuate over time, while the subsequent slower decline reflects the beneficial effect on progression of diabetic nephropathy.