Reduction of proteinuria; combined effects of receptor blockade and low dose angiotensin-converting enzyme inhibition.
OBJECTIVE
Angiotensin-converting enzyme inhibitors (ACEI) show an antiproteinuric and thus nephroprotective effect in patients suffering from glomerulonephritis. Angiotensin II-receptor-antagonists (AT1RA) are also efficacious in reducing proteinuria. The study was performed to investigate the antiproteinuric effect of AT1RA candesartan in patients diagnosed with chronic glomerulonephritis by biopsy, and who were already being treated with an ACEI.


METHODS
A total of 12 patients with a persistent proteinuria of at least 1 g/day who were already being treated with an ACEI for more than 3 months were included. The study was performed using a double-blind, placebo-controlled and randomized method with two treatment periods of 8 weeks (placebo or candesartan 8 mg/day) and a wash-out period of 4 weeks in between. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin- and PAH-clearances at the beginning and the end of each treatment period.


RESULTS
Proteinuria significantly decreased from 2 +/- 0.4 g/day to 1.3 +/- 0.3 g/day (P < 0.05) with the addition of candesartan treatment, whereas it remained unchanged (from 1.8 +/- 0.3 g/day to 1.9 +/- 0.3 g/day) under placebo. GFR (candesartan: from 66 +/- 13 to 58 +/- 11 ml/min per 1.73 m2, placebo: from 64 +/- 11 to 62 +/- 13 ml/min per 1.73 m2) and ERPF (candesartan: from 329 +/- 44 to 304 +/- 37 ml/min per 1.73 m2, placebo: from 362 +/- 48 to 315 +/- 46 ml/min per 1.73 m2) did not alter significantly after 8 weeks of treatment. The addition of candesartan treatment significantly reduced systolic blood pressure (from 129 +/- 3 to 123 +/- 2 mmHg, P < 0.05) and diastolic blood pressure (from 79 +/- 2 to 76 +/- 2 mmHg, P < 0.05) compared with placebo (systolic: 128 +/- 3 to 127 +/- 3 mmHg, diastolic: 79 +/- 2 to 79 +/- 2 mmHg).


CONCLUSIONS
Candesartan promotes a complementary antiproteinuric and a small antihypertensive effect after a treatment period of 8 weeks in patients with chronic glomerulonephritis when given in conjunction with an ACEI. Renal hemodynamics did not vary significantly.
Berger
Elke D
ED
University of Tuebingen, Department of Internal Medicine, Section for Nephrology and Hypertension, Germany.
Bader
Birgit D
BD
Ebert
Carola
C
Risler
Teut
T
Erley
Christiane M
CM
D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000503:physiopathology; D044140:Receptor, Angiotensin, Type 1; D017596:Renal Plasma Flow, Effective / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C081643:candesartan