Synergistic effect of mycophenolate mofetil and angiotensin-converting enzyme inhibitor in patients with chronic allograft nephropathy

Abstract

Experimental data and few clinical non-randomized studies have shown that inhibition of the renin-angiotensin system by angiotensin-converting enzyme (ACE) associated or not with the use of mycophenolate mofetil (MMF) could delay or even halt the progression of chronic allograft nephropathy (CAN). In this retrospective historical study, we investigated whether ACE inhibition (ACEI) associated or not with the use of MMF has the same effect in humans as in experimental studies and what factors are associated with a clinical response. A total of 160 transplant patients with biopsy-proven CAN were enrolled. Eightyone of them were on ACE therapy (G1) and 80 on ACEI-free therapy (G2). Patients were further stratified for the use of MMF. G1 patients showed a marked decrease in proteinuria and stabilized serum creatinine with time. Five-year graft survival after CAN diagnosis was more frequent in G1 (86.9 vs 67.7%; P < 0.05). In patients on ACEI-free therapy, the use of MMF was associated with better graft survival. The use of ACEI therapy protected 79% of the patients against graft loss (OR = 0.079, 95%CI = 0.015-0.426; P = 0.003). ACEI and MMF or the use of MMF alone after CAN diagnosis conferred protection against graft loss. This finding is well correlated with experimental studies in which ACEI and MMF interrupt the progression of chronic allograft dysfunction and injury. The use of ACEI alone or in combination with MMF significantly reduced proteinuria and stabilized serum creatinine, consequently improving renal allograft survival.

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

“…[10][11][12]22 Our results indicate up-regulation of Angio II convertingenzyme and Angio II with high expression in various structures of the allograft in the CAN group. However, there were no significant association between Angio II tissue expression with CAN grades and the severity of interstitial fibrosis; ACE expression was lower in the atrophic areas.…”

“…Experimental studies and clinical observations have been shown a role of RAS in CAN. 7,22 Renal gene and protein expression of SRA components, mainly in tubulo-interstitial compartment show correlation with increased activity of growth factors and the severity of lesions.…”

Effect of renin‐angiotensin system inhibitors on survival in kidney transplant recipients: A systematic review and meta‐analysis

“…Of these, we excluded 12 for the following reasons: 6 provided insufficient data; 4 study pairs investigated the same population, so we excluded the 4 with the shortest follow‐up, smallest population, or least complete outcome; 1 study was only reporting a protocol and 1 study used ACEI/ARBs in both the experimental and control arms. Therefore, 24 studies involving a total of 54,096 patients were included [26–49], of which 9 were RCTs (n = 1569) and 15 were cohort studies (n = 52,527).…”

“…Another study reported adult recipients receiving kidney transplant from paediatric donors, with the donor age of the experimental and control groups being 4.4 ± 2.9 y and 5.3 ± 2.8 y, respectively [44]. Four of the studies only included patients with biopsy‐proved chronic allograft nephropathy (CAN) [27,28,34,36], and two studies included patients with biopsy‐proved post‐transplant glomerulonephritis [39,42].…”

Renin-Angiotensin System and Renal Allograft Long-Term Outcome: A Review

“…Moscoso-Solorzano et al [44] showed a synergistic effect between ACE inhibition and mycophenolate mofetil (MMF), maintaining serum creatinine stable and decreasing and limiting the progression of proteinuria, as well as histological lesions. The death-censored graft survival analysis was much better for the group treated with ACE inhibition alone, following the group treated with ACE inhibition in combination with MMF.…”