Angiotensin II blockade in kidney transplant recipients

Area of Science:

• Nephrology
• Transplantation Immunology
• Pharmacology

Background:

• Interstitial fibrosis/tubular atrophy (IF/TA) is a major cause of kidney allograft loss.
• Current preventive or therapeutic options for IF/TA are limited.

Purpose of the Study:

• To investigate if angiotensin II blockade with losartan can prevent the expansion of the cortical interstitial compartment, a precursor to fibrosis.
• To evaluate the efficacy of losartan in preventing IF/TA and end-stage renal disease (ESRD) in kidney transplant recipients.

Main Methods:

• A double-blind, randomized, placebo-controlled trial involving 153 kidney transplant recipients.
• Patients received either losartan (100 mg) or a placebo for 5 years, starting within 3 months post-transplantation.
• The primary outcome was a composite of interstitial volume expansion or ESRD attributed to IF/TA.

Main Results:

• The primary endpoint occurred in 6 of 47 patients on losartan versus 12 of 44 on placebo (OR, 0.39; P=0.08), not reaching statistical significance.
• No significant effect of losartan was observed on time to ESRD, death, or creatinine doubling.
• A secondary analysis indicated losartan might reduce the risk of interstitial volume doubling or all-cause ESRD (OR, 0.36; P=0.05), requiring validation.

Conclusions:

• Losartan treatment did not achieve a statistically significant reduction in interstitial expansion or ESRD from IF/TA in kidney transplant recipients.
• The potential benefit suggested in secondary analyses warrants further investigation and validation in larger studies.