Conversion to Rapamycin Immunosuppression in Renal Transplant Recipients: Report of an Initial Experience1

118

177

Xavier Iriart, iriart.x@chu-toulouse.fr y Both authors contributed equally. Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case-control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uniand multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprimsulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gammaglobulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3-10.4), CMV infection (OR: 5.2, 95% CI: 1.8-14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4-10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

Section: Discussioncontrasting

confidence: 62%

Risk Factors of Pneumocystis Pneumonia in Solid Organ Recipients in the Era of the Common Use of Posttransplantation Prophylaxis

Iriart

Belval²,

Fillaux³

et al. 2015

118

177

“…In addition, several studies on conversion from CNI-based to SRL-based regimens in chronic kidney transplant patients were published. Promising results of a pilot study on conversion from CNI-based to SRLbased immunosuppression were published by Dominguez and co-workers (12). Twenty patients were converted from a CNI-based regime to a SRL-based protocol for various reasons, including 12 patients with CNI toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies showed beneficial effects, feasibility and safety of CNI withdrawl and introduction of SRL for various reasons in heterogenous groups of chronic renal transplant patients (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Predictors of Success in Conversion from Calcineurin Inhibitor to Sirolimus in Chronic Allograft Dysfunction

Diekmann

Budde

Oppenheimer

et al. 2004

224

Chronic allograft dysfunction (CAD) is a major cause of graft loss in long-term kidney transplant recipients. To identify predictors of successful conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) we investigated 59 renal transplant patients with CAD without histological signs of acute rejection. They received 12-15 mg SRL once, then 4-5 mg/day, target trough level 8-12 ng/mL. CNI dose was reduced by 50% simultaneously, and withdrawn at 1-2 months. Concomitant immunosuppression remained unchanged. After 1 year patient survival was 100% and graft survival 92%. In responders (54%) creatinine improved (2.75 ± 0.75 to 2.22 ± 0.64 mg/dL; p < 0.01). In nonresponders (46%) creatinine deteriorated (3.15 ± 1.02 to 4.44 ± 1.60 mg/dL; p < 0.01). Baseline renal function did not differ, however, baseline proteinuria (519 ± 516 vs. 1532 ± 867 mg/day, p < 0.01), histological grade of chronic allograft nephropathy (CAN) (1.2 ± 0.5 vs. 1.9 ± 0.6; p < 0.01), grade of vascular fibrous intimal thickening (1.2 ± 0.7 vs. 1.7 ± 0.7; p = 0.048) and number of acute rejections before conversion (0.73 ± 0.69 vs. 1.27 ± 0.96; p < 0.05) differed significantly between responders and nonresponders. In a multivariate analysis low proteinuria was the only independent variable. Proteinuria below 800 mg/day has a positive predictive value of 90%. Proteinuria at conversion below 800 mg/day is the only independent predictor for positive outcome in conversion from CNI to SRL in CAD.

“…Sirolimus has been shown to be effective as de novo therapy after renal transplantation (15,16), and as long-term maintenance therapy with steroids (17)(18)(19)(20). It may also have a role as an effective substitute for CNI therapy late after transplantation to avoid further CNI nephrotoxicity (21)(22)(23), although its use in this setting has not been previously subjected to evaluation by a randomized controlled study.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Controlled Trial of Late Conversion from CNI‐Based to Sirolimus‐Based Immunosuppression Following Renal Transplantation

Watson

Firth

Williams

et al. 2005

123

Maintenance immunosuppression with calcineurin inhibitors (CNIs) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. We aimed to assess whether conversion to sirolimusbased immunosuppression would affect the progression of renal impairment.In this single center, randomized controlled trial, 40 renal transplant recipients between 6 months and 8 years post-transplant were randomly assigned to remain on their CNI (cyclosporin or tacrolimus) or to switch to sirolimus. The primary outcome measure was change in glomerular filtration rate (GFR) measurement at 12 months. Analysis was by intention-totreat.Of the 40 patients randomized, 2 patients never took the study drugs and were excluded, leaving 19 patients per group. There was a significant change in GFR at 12 months following conversion to sirolimus (12.9 mL/min, 95% CI 6.1-19.7; p < 0.001). Following conversion, the principal adverse events were the development of rashes (68%), particularly acne, and mouth ulcers (32%). No patient in either group experienced an acute rejection episode.In renal transplant recipients, a change in maintenance therapy from CNIs to sirolimus is associated with significant improvement in GFR at 12 months.