Renin-Angiotensin-Aldosterone system inhibitors and statins prolong graft survival in post-transplant glomerulonephritis.
J. PazikJoanna OstrowskaZbigniew LewandowskiAndrzej MrózAgnieszka Perkowska‐PtasińskaTeresa BączkowskaMagdalena Durlik
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BACKGROUND Novel immunosuppressives neither prevent nor attenuate post-transplant glomerulonephritis, third common cause of late allograft loss. Data addressing influence of ACEI/ARA and statins on kidney transplants survival is contradictory. The aim of this study was to evaluate efficacy of therapeutic interventions undertaken in post-transplant glomerulonephritis. MATERIAL/METHODS In 75 individuals with biopsy-confirmed post-transplant glomerulonephritis, engrafted in Warsaw Transplantation Institute, graft survival from index biopsy to permanent dialysis need, in regard to numerous therapeutic interventions was analysed. Evaluation of graft survival was performed using Kaplan-Meier estimator, log-rank and Wilcoxon tests. Relations between introduced treatment and time to graft loss was expressed with hazard ratio (HR), results regarded significant at p<0.05. RESULTS Glomerulonephritis diagnosis was established 50.2+/-39.5 months after engraftment. Maintenance immunosuppression modifications included: methylprednisolone infusions (n=28), cyclofosfamide/ chlorambucil introduction (n=10), mycophenolate mofetil addition to maintenance treatment (n=23). Immunosuppression modifications did not result in graft survival prolongation. Statins (n=20) and renin-angiotensin-system blockers (n=49) substantially diminished the risk of graft loss (respectively: HR=0.37 (95% CI 0.15-0.88), p<0.02. and HR=0.39 (95% CI 0.16-0.98; p<0.05). The effect persisted after adjustment for presentation with nephrotic syndrome, graft dysfunction, mean arterial pressure, immunosuppression enhancement with mycophenoalte mofetil. Best result was obtained with combined RAASB and statin treatment (HR=0.24; 95% CI 0.69-0.09, p=0.008). CONCLUSIONS According to our data statins and renal renin-angiotensin system blockers prolong graft survival in patients with posttransplant glomerulonephritis. We feel that these relatively safe agents, bringing also other pro fi ts, should be routinely applied in patients with post transplant glomerulonephritis.Keywords:
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Abstract Optimization of maintenance immunosuppression (mIS) regimens in the transplant recipient requires a balance between sufficient potency to prevent rejection and avoidance of excessive immunosuppression to prevent toxicities and complications. The optimal regimen after simultaneous liver‐kidney (SLK) transplantation remains unclear, but small single‐center reports have shown success with steroid‐sparing regimens. We studied 4184 adult SLK recipients using the Scientific Registry of Transplant Recipients, from March 1, 2002, to February 28, 2017, on tacrolimus‐based regimens at 1 year post‐transplant. We determined the association between mIS regimen and mortality and graft failure using Cox proportional hazard models. The use of steroid‐sparing regimens increased post‐transplant, from 16.1% at discharge to 88.0% at 5 years. Using multi‐level logistic regression modeling, we found center‐level variation to be the major contributor to choice of mIS regimen (ICC 44.5%; 95% CI: 36.2%‐53.0%). In multivariate analysis, use of a steroid‐sparing regimen at 1 year was associated with a 21% decreased risk of mortality compared to steroid‐containing regimens (aHR 0.79, P = .01) and 20% decreased risk of liver graft failure (aHR 0.80, P = .01), without differences in kidney graft loss risk (aHR 0.92, P = .6). Among SLK recipients, the use of a steroid‐sparing regimen appears to be safe and effective without adverse effects on patient or graft survival.
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Evidence suggests that steroid sparing in renal transplantation is associated with good outcomes, although there are limited data regarding steroid sparing in Tacrolimus and Mycophenolate Mofetil (MMF)-based regimes. In this study we describe the use of these agents in 101 consecutive patients undergoing renal transplantation using only a 7-day course of prednisolone. Median follow-up was 33 months (range 18-44). Patient and graft survival at 1 year were 100% and 98%, respectively. The acute rejection rate at both 6 and 12 months was 19%, with two episodes beyond 12 months. Anti-CD25 monoclonal antibody (anti-CD25 mAb) was administered to 25 patients at high immunological risk: a trend toward a lower rejection rate was seen in these patients compared with those at lower risk but not receiving induction therapy (8% vs. 22%; p = 0.11). Two patients experienced recurrent rejection. Of the twenty-three rejection episodes in total, 26% showed vascular involvement. Allograft function was preserved at 12 months with a mean creatinine of 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. At 12 months, the incidence of post-transplant diabetes mellitus was 3.5%. This steroid-sparing regime is associated with excellent patient and graft outcomes, and a low incidence of side effects.
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Corticosteroids have been a component of maintenance immunosuppression for renal transplant since the 1960s and have helped to reduce the rate of acute rejection. Corticosteroids, however, have many adverse effects, and with the development of new immunosuppressive medications, many transplant centers have adopted protocols that eliminate or completely avoid the use of corticosteroids. Despite promising short-term results, the impact of corticosteroid elimination on long-term kidney function still is unclear. This single-center, retrospective, sequential study analyzed 212 renal transplant patients with a median follow-up of 5 yr. All patients received induction with IL-2 receptor antagonist and maintenance immunosuppression with mycophenolate mofetil and tacrolimus. Ninety-six patients were maintained on chronic prednisone, and 116 were maintained without chronic prednisone (rapid steroid elimination). Kaplan-Meier patient and graft survival at 7 yr after transplantation were not statistically different between the two groups. Rate and severity of acute cellular rejection were similar. Furthermore, the slope of GFR decline per month at 5 yr after transplantation was not statistically different between the two groups. Prednisone-treated patients had a significantly higher incidence of hyperlipidemia and posttransplantation diabetes when compared with patients with rapid steroid elimination. It was concluded that with the current immunosuppressive medications, the use of chronic prednisone to maintain long-term kidney function and prevent acute cellular rejection is not justified.
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Early renal dysfunction following liver transplantation is associated with increased morbidity and mortality. To evaluate the impact of delayed initiation of calcineurin inhibitor on renal function, we conducted a retrospective study comparing 118 liver transplant recipients who received rabbit anti-thymocyte globulin and delayed initiation of calcineurin inhibitor with 80 liver transplant recipients who received no antibody and early initiation of calcineurin inhibitor (control group). All patients received mycophenolate mofetil and steroids. Delayed calcineurin inhibitor initiation with anti-thymocyte globulin was associated with significant improvement in renal function throughout the first year post-transplant. At 12 months post-transplant, patients treated with this regimen experienced lower serum creatinine (1.4 ± 0.5 versus 1.7 ± 0.5 mg/dL, P < 0.001), a higher estimated glomerular filtration rate (57.4 ± 20.5 versus 43.7 ± 14.4 mL/min/1.73 m2, P < 0.001), and less dependence on dialysis (0.8% versus 13%, P < 0.001) in comparison with no antibody and early calcineurin inhibitor initiation. Patient survival and graft survival were similar between groups; however, there was a trend of a lower incidence of early biopsy-proven acute rejection with anti-thymocyte globulin. Overall infection and cytomegalovirus infection were significantly lower in anti-thymocyte globulin–treated patients, and there was no increased incidence of hepatitis C recurrence in comparison with controls. In conclusion, delayed initiation of calcineurin inhibitor with anti-thymocyte globulin in liver transplant recipients is safe and is associated with improvements in renal function and a lower incidence of early acute rejection in comparison with no antibody and early initiation of calcineurin inhibitor. Liver Transpl 14:66–72, 2008. © 2007 AASLD.
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