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 angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on albuminuria in glomerular disease. Because progression of glomerular disease is not consistently halted by these agents, there is a need to explore potential renoprotective effects of other drugs. Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner. A randomized, crossover design was used to assess the human relevance of the experimental data in 15 normotensive, nonsmoking type 1 diabetic mellitus patients with good glycemic control (age, 37.3 +/- 6.6 yr; 9 men/6 women; duration of diabetes, 23.6 +/- 5.1 yr) with baseline urinary albumin excretion rates (AER) >20 microg/min in the run-in phase. AER was assessed in overnight timed urine collections. The patients were assigned to a 3-wk placebo and a 3-wk moxonidine (0.2 mg twice a day) period, respectively, in random order. This dose causes modest BP lowering in hypertensive individuals but 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 mm Hg on moxonidine). There was a significant (P< 0.006) difference of the treatment effects between placebo and moxonidine, respectively, on AER; median AER at the end of the placebo period was 39.8 microg/min (range, 15.9 to 117 microg/min) versus 29.0 (range, 9.03 to 85.8 microg/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 the finding.
Strojek
Krzysztof
K
Department of Internal Diseases and Diabetology, Silesian Medical Academy, Zabrze, Poland.
Grzeszczak
Wladyslaw
W
Department of Internal Diseases and Diabetology, Silesian Medical Academy, Zabrze, Poland.
Górska
Juta
J
Department of Internal Diseases and Diabetology, Silesian Medical Academy, Zabrze, Poland.
Leschinger
Monika I
MI
Lilly Deutschland GmbH, Bad Homburg, Germany.
Ritz
Eberhard
E
Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany.
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D013565:Sympatholytics / Q000627:therapeutic use*
D007093:Imidazoles; D013565:Sympatholytics; C043482:moxonidine