Moderate dietary protein restriction improves prognosis in type 1 diabetic patients with progressive diabetic nephropathy in addition to the beneficial effect of antihypertensive treatment.

No abstract

Initiation of antihypertensive treatment (AHT) in hypertensive insulin-dependent diabetic (IDDM) patients with diabetic nephropathy (DN) induces a faster initial (0 to 6 months) and a slower subsequent (6 months to end of observation) decline in GFR [delta GFR (ml/min/month) approximately 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 hypertensive IDDM patients (16F/26M, age 40 +/- 7 years, mean +/- SD) with DN receiving AHT (angiotensin converting enzyme inhibition, N = 30) for 6 (2 to 15) years [median (range)]. GFR (ml/min/1.73 m2), arterial blood pressure (BP, mm Hg) and albuminuria (mg/24 hr) were measured the 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 correlation between relative rise in systolic blood pressure (delta Sys%) and relative 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, which does not attenuate over time, while the subsequent slower decline reflects the beneficial effect on progression of diabetic nephropathy.

We investigated the effect of acute lowering of blood pressure (BP) upon glomerular filtration rate (GFR) in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients, 14 with diabetic nephropathy and 12 with normoalbuminuria. The study was performed twice with the subjects receiving an intravenous injection of either clonidine (150 to 225 micrograms) or saline (0.154 mmol/liter). We assessed GFR, albuminuria, and BP. The two groups were well matched with respect to demographic data, baseline GFR and BP. Clonidine induced similar reductions in mean arterial blood pressure 19 (SE +/- 4) and 21 (SE +/- 3) mm Hg in patients with and without nephropathy, respectively. In the nephropathy group GFR diminished in average from 90 (SE +/- 6) to 81 (SE +/- 7) ml/min/1.73 m2 (P = 0.006), fractional clearance of albumin (x 10(-6)) declined from a geometric mean of 219 (antilog SE /divided by 1.3) to 186 (antilog SE /divided by 1.3) (P = 0.04), and four patients had a complete pressure-passive vasculature, defined as delta GFR% = delta MABP%. A significant correlation between relative reductions in MABP and GFR (r = 0.78, P < 0.001) was demonstrated in albuminuric patients. None of the normoalbuminuric patients had a complete pressure-passive vasculature and there were no significant differences in GFR between the two examinations, but five had abnormal autoregulation of GFR. Mean difference between changes in GFR (95% confidence interval) between the nephropathic and normoalbuminuric group was 5.5 (divided by 2.7 to 13.7) ml/min/1.73 m2 (P = 0.18). Our study suggests that hypertensive NIDDM patients, particularly patients with nephropathy, frequently suffer from impaired or abolished autoregulation of GFR.

The beneficial effect of captopril in arresting the rise in systemic blood pressure and albuminuria is long lasting. A loss in GFR is minimal in most patients with diabetic nephropathy if normotension is sustained by prospective treatment with ACE inhibitors or restored by implementation of other antihypertensive medications with the development of hypertension.