TY - JOUR
T1 - Angiotensin II blockade in kidney transplant recipients
AU - Ibrahim, Hassan N
AU - Jackson, Scott
AU - Connaire, Jeffery
AU - Matas, Arthur
AU - Ney, Arthur L
AU - Najafian, Behzad
AU - West, Ann
AU - Lentsch, Nicole
AU - Ericksen, Jensina
AU - Bodner, Jenny
AU - Kasiske, Bert L
AU - Mauer, Michael
PY - 2013/1/31
Y1 - 2013/1/31
N2 - 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.
AB - 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.
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U2 - 10.1681/ASN.2012080777
DO - 10.1681/ASN.2012080777
M3 - Article
C2 - 23308016
AN - SCOPUS:84873362249
SN - 1046-6673
VL - 24
SP - 320
EP - 327
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 2
ER -