Randomized placebo-controlled study on the effects of losartan and carvedilol on albuminuria in renal transplant recipients.
BACKGROUND
The renoprotective effects of agents inhibiting the renin-angiotensin system in renal transplant recipients have been supposed but not finally proven. To shed more light on this issue, we performed a double-blind, placebo-controlled, crossover study to evaluate the influence of the AT-1 angiotensin II receptor blocker, losartan, on the surrogate marker of kidney injury, albuminuria, in patients after renal transplantation. The safety of this therapy was also evaluated.


METHODS
Fourteen of 16 patients (nine male, five female), age 45.36 +/- 3.04 years, 65.5 +/- 10.0 months after kidney transplantation, with hypertension and stable serum creatinine 123 +/- 4 micromol/L without proteinuria, completed the protocol. Each patient underwent two 8-week treatment periods (one with losartan 50-100 mg and one with carvedilol 12.5-25 mg) in random order, allowing an 8-week placebo washout between treatments. The target office trough blood pressure was below 130/85 mmHg.


RESULTS
The ambulatory blood pressure did not differ in the treatment periods. Losartan significantly reduced albuminuria relative to placebo and carvedilol (27.62+/-17.58 vs. 49.55 +/- 25.33 v. 44.77 +/- 21.9 mg/g creatinine; P < 0.01). A significant but not clinically relevant decrease in hemoglobin level after losartan was observed (losartan: 129 +/- 3.1 g/l, placebo: 134.2 +/- 3.2, carvedilol: 137.1 +/- 3.7; P < 0.001). Serum potassium, creatinine, creatinine clearance, and trough blood cyclosporine levels were unaffected.


CONCLUSIONS
Losartan decreases microalbuminuria in renal transplant recipients with clinically minimal side effects.
Tylicki
Leszek
L
Department of Nephrology, Transplantology, and Internal Medicine, Medical University of Gdansk, Poland. leszek.tylicki@amg.gda.pl
Biedunkiewicz
Bogdan
B
Chamienia
Andrzej
A
Wojnarowski
Klaudiusz
K
Zdrojewski
Zbigniew
Z
Rutkowski
Boleslaw
B
D000419:Albuminuria / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D016572:Cyclosporine / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*
D002227:Carbazoles; D010919:Placebos; D011412:Propanolamines; D000077261:Carvedilol; D016572:Cyclosporine; D019808:Losartan