Renin-Angiotensin System Blockage and Avoiding High Doses of Calcineurin Inhibitors Prevent Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant Recipients.

Abstract

Chronic allograft dysfunction is a complex and multifactorial process characterized by progressive interstitial fibrosis and tubular atrophy. The finding of interstitial fibrosis and tubular atrophy is prevalent among kidney transplant patients receiving a calcineurin inhibitor-based immunosuppressive regimen and may be considered as a surrogate of allograft survival. Both immune (acute rejection episodes, sensitization, and HLA incompatibility) and nonimmune (donor age, delayed graft function, calcineurin inhibitor toxicity, infections, and hypertension) mechanisms play a role in chronic allograft dysfunction, and different causes all lead to similar histologic and clinical final pathways, with the end result of graft loss. In our study, we aimed to compare the outcomes of kidney transplant recipients with or without interstitial fibrosis and tubular atrophy in protocol biopsies to determine the conditions that may affect allograft survival. We divided 192 kidney transplant recipients into 2 groups (96 patients with interstitial fibrosis and tubular atrophy; 96 patients without interstitial fibrosis and tubular atrophy) according to protocol biopsy at 6 months. Patient groups were compared according to their risk factors for chronic allograft dysfunction (cold ischemia time, delayed graft function, donor age, infections, mean blood calcineurin levels, and hypertension). Cold ischemia time, delayed graft function, high 24-hour proteinuria levels, and higher mean blood calcineurin levels were found to be major risk factors for poor graft function in kidney transplant recipients with interstitial fibrosis and tubular atrophy. Renin-angiotensin system blockage with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was found to be preventive for interstitial fibrosis and tubular atrophy after kidney transplant. Preventing prolongation of cold ischemia time, lowering blood cholesterol levels, angiotensin-converting enzyme inhibitors and angiotensin receptor blocker treatment even without existing proteinuria and avoiding higher doses of calcineurin inhibitors should be major approaches in kidney transplant recipients.