The role of renin–angiotensin system in the chronic allograft nephropathy: an immunohistochemical study

Abstract

Background: Evidences suggest a role of renin-angiotensin system (RAS) in the development of chronic allograft injury. Methods: We correlated intrarenal angiotensin-converting enzyme, angiotensin II (Angio II) and transforming growth factor b 1 (TGFb 1 ) expression in 58 biopsiesproven chronic allograft nephropathy (CAN) with tissue injury and allograft survival. Results: The biopsies with CAN were graded according to Banff classification as I (22 cases), II (17) and III (19); 27 biopsies also showed a mononuclear inflammatory infiltrate in scarred areas. There were increased expression of angiotensin converting-enzyme (ACE), Angio II and TGFb 1 mainly in tubulointerstitial compartment in the group with CAN; there was no association of Angio II and TGFb 1 expression with interstitial fibrosis. There were no significant differences of ACE, Angio II and TGFb 1 expression between the patients treated and untreated with RAS blockade, and with the graft outcome. Interstitial inflammatory infiltrate had positive correlation with interstitial fibrosis and significant impact on graft survival at 8 years. Conclusions: Our study showed in a group of cases with CAN a high percentage of inflammatory infiltrate that correlated with interstitial fibrosis and graft outcome. The chronic inflammatory changes in these cases did not show significant association with local RAS expression.

Randomized Controlled Trial of Mineralocorticoid Receptor Blockade in Children with Chronic Kidney Allograft Nephropathy

“…In renal biopsy samples, it is characterized by tubulo-interstitial fibrosis and tubular atrophy (IF/TA), and it can be due to immunologic or nonimmunologic factors, including previous history of acute cellular rejection, chronic humoral rejection, ischemia/reperfusion injury, infectious tubulo-interstitial nephritis, hypertension, dyslipidemia, and nephrotoxicity due to calcineurin inhibitors (CIs) (2). IF/TA is present in 53%-90% of protocol biopsy samples at 12 months post-transplant, and its severity correlates with renal dysfunction and proteinuria (3,4). Even though the use of CIs has improved graft survival in kidney transplant patients, their clinical use is often restricted due to their nephrotoxic side effects, which can manifest as acute or chronic nephrotoxicity (5).…”