Impaired autoregulation of the glomerular filtration rate in patients with nondiabetic nephropathies

Background. The ability of the kidney to maintain constancy of the glomerular filtration rate (GFR) over a wide range of renal perfusion pressures is termed autoregulation. Defective autoregulation of GFR has been demonstrated in diabetic nephropathy. Whether this is also the case in patients with nondiabetic nephropathies is not known. Methods. We investigated the effect of acute lowering of blood pressure (BP) on GFR in 16 (8 males and 8 females) albuminuric subjects suffering from different nondiabetic nephropathies and in 14 (7 males and 7 females) controls matched with respect to sex, age, BP, and baseline GFR. The subjects received in random order an intravenous injection of either clonidine (150 to 225 mu g) or saline (0.154 mmol/liter) within two weeks. We measured GFR ([Cr-51]-EDTA), albuminuria (enzyme-linked immunosorbent assay; ELISA), and BP (Takeda TM-2420). Results. Clonidine induced similar reductions in mean arterial BP 17 (2) versus 19 (2) mm Hg [mean (SE)] in patients with nephropathy and in controls, respectively. GFR diminished in average from 89 (6) to 82 (5) ml/min/1.73 m(2) (P < 0.05), and albuminuria declined from a geometric mean of 1218 (antilog SE 1.3) mu g/min to 925 (1.3) in the patients with nondiabetic nephropathies (P < 0.05), whereas these variables remained unchanged in the control group. The mean difference between changes in GFR (95% confidence interval) between the nondiabetic macroalbuminuric and control subjects was 6.1 (-0.03 to 12.21) ml/min/1.73 m(2) (P = 0.051). Conclusion. Our study suggests that albuminuric patients with nondiabetic nephropathies frequently suffer from impaired autoregulation of GFR.