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

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. Eighty-one 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 percent; 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 percent of the patients against graft loss (OR = 0.079, 95 percentCI = 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.

Are the current chronic allograft nephropathy grading systems sufficient to predict renal allograft survival?

A major problem in renal transplantation is identifying a grading system that can predict long-term graft survival. The present study determined the extent to which the two existing grading systems (Banff 97 and chronic allograft damage index, CADI) correlate with each other and with graft loss. A total of 161 transplant patient biopsies with chronic allograft nephropathy (CAN) were studied. The samples were coded and evaluated blindly by two pathologists using the two grading systems. Logistic regression analyses were used to evaluate the best predictor index for renal allograft loss. Patients with higher Banff 97 and CADI scores had higher rates of graft loss. Moreover, these measures also correlated with worse renal function and higher proteinuria levels at the time of CAN diagnosis. Logistic regression analyses showed that the use of angiotensin-converting enzyme inhibitor (ACEI), hepatitis C virus (HCV), tubular atrophy, and the use of mycophenolate mofetil (MMF) were associated with graft loss in the CADI, while the use of ACEI, HCV, moderate interstitial fibrosis and tubular atrophy and the use of MMF were associated in the Banff 97 index. Although Banff 97 and CADI analyze different parameters in different renal compartments, only some isolated parameters correlated with graft loss. This suggests that we need to review the CAN grading systems in order to devise a system that includes all parameters able to predict long-term graft survival, including chronic glomerulopathy, glomerular sclerosis, vascular changes, and severity of chronic interstitial fibrosis and tubular atrophy.

Outcomes of Kidney Transplantation from Spousal Donors: Comparison with Kidney Transplantation from Living-related Donors / 대한신장학회잡지

BACKGROUND: Although transplantation is the best treatment for many people with end-stage renal disease, the gap between the number of organs and the number of potential recipients continues to widen. In addition to living-related individuals, the primary source of donor kidney, the severe organ shortage has led to consideration of genetically unrelated but emotionally related persons as donor candidates. The aim of this study was to compare the results of spousal kidney transplantation with those of living-related kidney transplantation and to analyze the characteristics of spousal kidney transplantation. METHODS: Clinical data were retrospectively analyzed from 21 patients with spousal kidney transplantation and 205 patients with living-related kidney transplantation. Cumulative renal allograft survival was compared between the two groups using Kaplan-Meier curve and log-rank test. Subgroup analysis was done within the patients with spousal kidney transplantation. RESULTS: The patients were significantly older in spousal group (43.7+/-7.8 years) than in living-related group (36.2+/-10.8 years). Donor age was also significantly higher in spousal group (43.0+/-8.4 years) than in living-related group (39.8+/-13.9 years). The number of HLA mismatch was significantly larger in spousal group (3.79+/-1.03) than in living-related group (2.60+/-1.21). The episodes of acute rejection occurring within a year after the transplantation were more frequent in spousal group (5/21) than in living-related group (13/205). Kaplan-Meier curves for cumulative survival of renal allograft revealed no difference between spousal group and living-related group. Renal allograft survival rates in spousal group were 85.2% at 1 year, 75.2% at 5 years, and 67.7% at 10 years after the transplantation. In living-related group, renal allograft survival rates were 96.6% at 1 year, 85.9% at 5 years, and 69.9% at 10 years after the transplantation. Within the patients with spousal kidney transplantation, cumulative renal allograft survival was superior in cases with absent acute rejection, husband-to-wife transplantation, and the number of HLA mismatch less than 5. CONCLUSION: Spousal kidney transplantation shares comparable results with living-related kidney transplantation despite older age, poorer HLA matching and a higher rate of acute rejection. Spousal donor transplants could be a real alternative especially when the donors are husband and the number of HLA mismatch is less than 5.