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.

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%; 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.

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.

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.

Single dose of Rituximab plus plasmapheresis in an HIV patient with acute humoral kidney transplant rejection: a case report.

Before the highly active antiretroviral therapy (HAART) era, kidney transplantation was not considered an option for patients infected with human immunodeficiency virus (HIV) because of its poor outcome. However, recent studies have demonstrated results comparable to those of recipients without HIV infections. They have shown that HIV-positive patients maintained on HAART mount an immune response. Immunosuppressive agents are chosen to minimize aggravation of HIV infection, bearing in mind the potential side effects of the combination of HAART and immunosuppressive drugs. Herein we have reported the case of a 43-year-old HIV- and hepatitis C virus-infected woman with preserved immune function who received a cadaveric kidney transplant and developed an acute humoral rejection, which was successfully treated with Rituximab.

Impact of therapeutic changes on renal graft survival with posttransplant glomerulonephritis.

INTRODUCTION: Posttransplant glomerulonephritis (GN) is the third cause of graft loss after 1 year of transplant follow-up; few approaches have been efficient in reversing this outcome. The aim of this study was to evaluate whether the modification of the immunosuppressive therapy for treating posttransplant GN had an impact on allograft survival. PATIENTS AND METHODS: Forty-nine patients who underwent renal transplantation and developed posttransplant GN were divided into two groups: group 1, 22 patients with modified immunosuppressive treatment (72.3%, pulse of methylprednisolone; 13.6%, high-dose oral corticosteroid), and group 2, where it was maintained. Additionally, the impact of the concomitant use of drugs that promote the renin-angiotensin-aldosterone system blockade (RAASB) was analyzed in terms of graft survival. RESULTS: We established the diagnosis of GN at 17.9 months (range, 0.57 to 153.4) after transplantation, when serum creatinine (Cr) was 2.2 mg/dL (range, 0.8 to 12.5) and proteinuria 3.2 g/L (range, 0.2 to 24.2). Graft survivals at 1 and 3 years after diagnosis were 69.2% and 52.9%, respectively. The patients of group 1 showed a lower prevalence of graft loss (27.2% versus 48.1%, P = .40) and better survival at the end of 1 year (73.2% versus 60.4%) and 3 years (62.5% versus 38.0%, P = .26), but the differences were not significant. RAASB showed a positive impact on survival at the end of 3 years in both groups: for group 1, 83.8% with RAASB, 41.4% without RAASB; and for group 2, 75% with RAASB and 14.8% without RAASB (P < .001). CONCLUSION: Although treatment of posttransplant GN with modification of immunosuppression seemed to improve graft survival in the first 3 years after diagnosis, RAASB improved this effect.