Chronic allograft nephropathy in the rat is improved by angiotensin II receptor blockade but not by calcium channel antagonism.
Functional and structural changes of chronic renal allograft failure share similarities with other chronic nephropathies with low nephron number. In models of reduced nephron number, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prevented proteinuria and retarded renal lesions. This study investigates whether blockade of angiotensin II activity prevented chronic allograft injury in the Fisher 344 --> Lewis rat kidney transplant model, and compares its effect with that of calcium channel blockers, the main antihypertensive agents used in transplant patients to control BP. Transplanted rats received either no treatment (control), the type 1 angiotensin II receptor antagonist losartan, or the calcium channel blocker lacidipine. Rats received cyclosporine for the first 10 d posttransplant to prevent acute rejection. Doses of antihypertensive drugs were adjusted to achieve a comparable level of BP control throughout the study. Awake systolic BP was comparable in animals given losartan or lacidipine during the 6-mo observation period. Daily treatment with losartan but not lacidipine resulted in a significant decrease in the amount of proteinuria, preserved glomerular and tubulointerstitial structure, and improved graft survival compared with corresponding parameters in control untreated rats. GFR, measured as inulin and p-aminohippurate clearances, respectively, in rats surviving the 6-mo follow-up, was numerically but not significantly higher in losartan-treated animals than in all other groups. Thus, at comparable levels of BP control, losartan but not lacidipine effectively protects animals from chronic allograft injury and allows long-term survival.
Department of Transplant Immunology and Innovative Antirejection Therapies, Ospedali Riuniti Bergamo, Italy.
S C
SC
Amuchastegui
N
N
Azzollini
M
M
Mister
A
A
Pezzotta
N
N
Perico
G
G
Remuzzi
D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002908:Chronic Disease; D004095:Dihydropyridines / Q000494:pharmacology*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009404:Nephrotic Syndrome / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012016:Reference Values; D015996:Survival Rate; D014184:Transplantation, Homologous
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C060285:lacidipine; D019808:Losartan