title: Angiotensin II blockade in kidney transplant recipients.
abstract: Interstitial fibrosis/tubular atrophy (IF/TA) contributes to the loss of kidney allografts, and treatment or preventive options are lacking. We conducted a double-blind, randomized, placebo-controlled trial to determine whether angiotensin II blockade prevents the expansion of the cortical interstitial compartment, the precursor of fibrosis. We randomly assigned 153 transplant recipients to receive losartan, 100 mg (n=77), or matching placebo (n=76) within 3 months of transplantation, continuing treatment for 5 years. The primary outcome was a composite of doubling of the fraction of renal cortical volume occupied by interstitium from baseline to 5 years or ESRD from IF/TA. In the intention-to-treat analysis, using only patients with adequate structural data, the primary endpoint occurred in 6 of 47 patients who received losartan and 12 of 44 who received placebo (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.13-1.15; P=0.08). We found no significant effect of losartan on time to a composite of ESRD, death, or doubling of creatinine level. In a secondary analysis, losartan seemed to reduce the risk of a composite of doubling of interstitial volume or all-cause ESRD (OR, 0.36; 95% CI, 0.13-0.99; P=0.05), but this finding requires validation. In conclusion, treatment with losartan did not lead to a statistically significant reduction in a composite of interstitial expansion or ESRD from IF/TA in kidney transplant recipients.
authors: Division of Renal Diseases and Hypertension, Department of Medicine, University of Minnesota, Minneapolis, MN 55414, USA. Ibrah007@umn.edu
authors: Hassan N
authors: HN
authors: Ibrahim
authors: Scott
authors: S
authors: Jackson
authors: Jeffery
authors: J
authors: Connaire
authors: Arthur
authors: A
authors: Matas
authors: Arthur
authors: A
authors: Ney
authors: Behzad
authors: B
authors: Najafian
authors: Ann
authors: A
authors: West
authors: Nicole
authors: N
authors: Lentsch
authors: Jensina
authors: J
authors: Ericksen
authors: Jenny
authors: J
authors: Bodner
authors: Bertram
authors: B
authors: Kasiske
authors: Michael
authors: M
authors: Mauer
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D016030:Kidney Transplantation; D019808:Losartan / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000804:Angiotensin II; D019808:Losartan