Lowering of microalbuminuria in diabetic patients by a sympathicoplegic agent: Novel approach to prevent progression of diabetic nephropathy?

There is convincing evidence for a specific BP-independent effect of angiot ensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular diseas e is not consistently halted by these agents, there is a need to explore po tential renoprotective effects of other drugs. Recent animal work documente d that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent mann er. A randomized, crossover design was used to assess the human relevance o f the experimental data in 15 normotensive, nonsmoking type 1 diabetic mell itus patients with good glycemic control (age, 37.3 +/- 6.6 yr; 9 men/6 wom en; duration of diabetes, 23.6 +/- 5.1 yr) with baseline urinary albumin ex cretion rates (AER) >20 mug/min in the run-in phase. AER was assessed in ov ernight timed urine collections. The patients were assigned to a 3-wk place bo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in rand om order. This dose causes modest BP lowering in hypertensive individuals b ut does not affect BP in normotensive individuals. There was no significant effect on ambulatory BP (mean arterial pressure, 91.8 +/- 7.1 mmHg in the third week of placebo and 91.1 +/- 8.7 mmHg on moxonidine). There was a sig nificant (P < 0.006) difference of the treatment effects between placebo an d moxonidine, respectively, on AER; median AER at the end of the placebo pe riod was 39.8 <mu>g/min (range, 15.9 to 117 mug/min) versus 29.0 (range, 9. 03 to 85.8 mug/min) at the end of the moxonidine period. The data document an antialbuminuric effect of nonhypotensive doses of moxonidine. Diminished sympathetic traffic to the kidney is the most plausible explanation for th e finding.