Sirolimus Conversion in Liver Transplant Recipients With Renal Dysfunction: A Prospective, Randomized, Single-Center Trial

Shenoy, Surendra; Hardinger, Karen L.; Crippin, Jeffrey S.; Desai, Niraj M.; Korenblat, Kevin; Lisker‐Melman, Mauricio; Lowell, Jeffrey A.; Chapman, William C.

doi:10.1097/01.tp.0000261630.63550.41

Cited by 65 publications

(59 citation statements)

References 23 publications

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“…In addition, patients switched early after transplantation may have an increased ACR risk, whereas those switching later may have already experienced additional detrimental effects on kidney function. We also acknowledge the large loading dose of sirolimus mandated by the study protocol due to the abrupt withdrawal of calcineurin inhibitor immunosuppression (10-15 mg; mean loading dose 10.3 ± 2.1 mg [range, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]), which may have impacted certain aspects of the results (e.g. TEAEs, discontinuations, etc).…”

Section: Discussionmentioning

confidence: 99%

“…One randomized, single-center trial observed improvements in creatinine clearance at 3 months following CNI withdrawal and conversion to SRL, but between-group differences were not significant at 12 months (17). A second single-center trial evaluating 27 patients ≥6 months post-LT showed that patients switched to SRL had improvement in GFR after 3 (p = 0.001) and 12 months (p = 0.02) compared with those continuing CNI-based immunosuppression (18).…”

Section: Introductionmentioning

confidence: 99%

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Sirolimus Conversion Regimen Versus Continued Calcineurin Inhibitors in Liver Allograft Recipients: A Randomized Trial

Abdelmalek

Humar

Stickel

et al. 2012

American Journal of Transplantation

113

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A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)-to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI-to SRL-based immunosuppression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sirolimus Conversion Regimen Versus Continued Calcineurin Inhibitors in Liver Allograft Recipients: A Randomized Trial

Abdelmalek

Humar

Stickel

et al. 2012

American Journal of Transplantation

113

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“…55,56 As regards conversion to Sirolimus in patients with CNI induced nephrotoxicity, several studies did show better GFR at 3 months following conversion to Sirolimus, but there was no difference between Sirolimus versus low dose CNI arm at 1 year. [57][58][59] Use of Sirolimus is not advised in presence of proteinuria of more than 0.8 g/ day because of risk of further worsening of renal function. 56 Also, in presence of significant kidney disease (GFR < 40 ml/min), Sirolimus may not be reno-protective and use of low dose CNI and MMF combination is probably the best strategy.…”

Section: Kidney Injury and Immunosuppressionmentioning

confidence: 99%

Current Status of Immunosuppression in Liver Transplantation

Choudhary

Saigal

Shukla

et al. 2013

Journal of Clinical and Experimental Hepatology

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With advancements in immunosuppressive strategies and availability of better immunosuppressive agents, survival rate following liver transplantation has improved significantly in the recent times. Besides improvements in surgical techniques, the most important factor that has contributed to this better outcome is the progress made in the field of immunosuppression. Over the last several years, the trend has changed to tailored immunosuppression with the aim of achieving optimal graft function while avoiding its undesirable side effects. Induction agents are no longer used routinely and the aim is to provide minimal immunosuppression in the maintenance phase. The present review discusses the various types of immunosuppressive agents, their mechanism of action, clinical utility, advantages and disadvantages, and their side effects in short and long-term. It also discusses about tailoring immunosuppression in presence of various situations such as renal dysfunction, metabolic syndrome, hepatitis C recurrence, cytomegalovirus infections and so on. The issue of chronic kidney disease and the available renal sparing immunosuppressive strategies has been particularly stressed upon. Finally, it discusses about the practical aspects of various immunosuppression regimens including drug monitoring. ( J CLIN EXP HEPATOL 2013;3:150-158)

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“…(2,15,16) A potential concern with CNI withdrawal is the risk of under-immunosuppression and ensuing rejection, which has been described in several reports (6,17). (18)(19)(20)(21)(22)(23)(24)(25)(26) (23)(24)(25)(26), concurrent non-CNI-related renal disease (25) and interval from transplantation (25,26 in which there was little improvement in the renal function of LT recipients after nonnephrotoxic drug implementation maintenance (27). …”

Section: Skin Disorders Developed In 2 Patients During the Entire Fomentioning

confidence: 99%

Early Withdrawal of Calcineurin Inhibitors and Everolimus Monotherapy in de novo Liver Transplant Recipients Preserves Renal Function

Masetti¹,

Montalti²,

Rompianesi³

et al. 2010

American Journal of Transplantation

134

181

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We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novo liver transplantation (LT) patients would result in superior renal function compared to a CsA-based immunosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy-eight patients were randomized (Evr n = 52; CsA n = 26). The 1-year freedom from efficacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p < 0.001). The incidence of CKD stage ≥3 (estimated glomerular filtration rate <60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function, with a similar incidence of rejection and major complications.

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Sirolimus Conversion in Liver Transplant Recipients With Renal Dysfunction: A Prospective, Randomized, Single-Center Trial

Cited by 65 publications

References 23 publications

Sirolimus Conversion Regimen Versus Continued Calcineurin Inhibitors in Liver Allograft Recipients: A Randomized Trial

Sirolimus Conversion Regimen Versus Continued Calcineurin Inhibitors in Liver Allograft Recipients: A Randomized Trial

Current Status of Immunosuppression in Liver Transplantation

Early Withdrawal of Calcineurin Inhibitors and Everolimus Monotherapy in de novo Liver Transplant Recipients Preserves Renal Function

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