Top

Published in:

01-11-2009 | Original Article

Conversion to sirolimus of patients with chronic allograft nephropathy—a retrospective analysis of outcome and influencing factors

Authors: Oliver Witzke, Ondrej Viklicky, Tobias R. Türk, Jens Lutz, Benjamin Wilde, Isabel Willenberg, Stefan Vitko, Uwe Heemann

Published in: Langenbeck's Archives of Surgery | Issue 6/2009

Abstract

Purpose

The purpose of this study was to analyse the outcome and its influencing factors in patients whose therapy was converted from calcineurin inhibitors (CNI) to sirolimus (SRL) due to chronic allograft nephropathy (CAN).

Materials and methods

Therapies of 78 patients (44 men) with CAN from three European transplant centres were converted from CNI therapy to SRL and followed 24 months. Slopes for creatinine clearance before and after conversion were calculated. Influencing factors were analysed by a multivariance analysis.

Results

The slope of the creatinine clearance improved significantly (−0.90 vs. −0.34 ml min⁻¹ month⁻¹; p < 0.01). In patients whose therapy was converted from cyclosporine A (CyA) to SRL, the slope improved significantly, whereas conversion from Tacrolimus (Tac) to SRL did not affect the slope. The benefit was more pronounced in (1) patients with low or moderate baseline creatinine clearance, (2) patients receiving SRL after conversion without additional mycophenolate mofetil and (3) patients with low or moderate proteinuria.

Conclusion

Conversion from CyA to SRL but not from Tac to CRL is associated with a reduced loss of renal allograft function in patients with CAN.

de Mattos A, Olyaei A, Bennet W (2000) Nephrotoxicity of immunosuppressive drugs: long-term consequences and challenges for the future. Am J Kidney Dis 35:333. doi:10.1016/S0272-6386(00)70348-9 CrossRefPubMed

Joosten S, van Kooten C, Paul L (2003) Pathogenesis of chronic allograft rejection. Transpl Int 16:137. doi:10.1111/j.1432-2277.2003.tb00277.x CrossRefPubMed

Artz MA, Boots JMM, Ligenberg G et al (2004) Conversion from cyclosporine to tacrlimus improves quality-of-life indices, renal graft function and cardiovascular risk profile. Am J Transplant 4:937–945. doi:10.1111/j.1600-6143.2004.00427.x CrossRefPubMed

Hohage H, Welling U, Zeh M, Gerhardt U, Suwelack B (2005) Switching immunosuppression from cyclosporine to tacrolimus improves long-term kidney function: a 6-year study. Transplant Proc 37(4):1898–1899. doi:10.1016/j.transproceed.2005.02.113 CrossRefPubMed

Meier M, Nitschke M, Weidtmann B, Jabs WJ, Wong W, SueTace S et al (2006) Slowing down the progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus: a randomized controlled trial. Transplantation 81(7):1035–1040. doi:10.1097/01.tp.0000220480.84449.71 CrossRefPubMed

Suwelack B, Gerhardt U, Hohage H (2004) Withdrawal of cyclosporine or tacrolimus after addition of mycophenolate mofetile in patients with chronic allograft nephropathy. Am J Transplant 4:655–662. doi:10.1111/j.1600-6143.2004.00404.x CrossRefPubMed

Stoves J, Newstead CG, Baczkowski AJ, Owens G, Paraoan M, Hammad AQ (2004) A randomized controlled trial of immunosuppression conversion for the treatment of chronic allograft nephropathy. Nephrol Dial Transplant 19:2113–2120. doi:10.1093/ndt/gfh188 CrossRefPubMed

Francois H, Durrbach A, Amor M, Djeffal R, Kriaa F, Paradis V, Bedossa P, Charpentier B (2003) The long-term effect of switching from cyclosporin A to mycophenolate mofetil in chronic renal graft dysfunction compared with conventional management. Nephrol Dial Transplant 18(9):1909–1916. doi:10.1093/ndt/gfg250 CrossRefPubMed

Schmid C, Heemann U, Azuma H, Tilney NL (1995) Rapamycin inhibits transplant vasculopathy in long-surviving rat heart allografts. Transplantation 60(7):729–733. doi:10.1097/00007890-199510000-00020 CrossRefPubMed

10.

Lutz J, Zou H, Liu S, Antus B, Heemann U (2003) Apoptosis and treatment of chronic allograft nephropathy with everolimus. Transplantation 76(3):508–515. doi:10.1097/01.TP.0000074722.79186.A9 CrossRefPubMed

11.

Flechner SM, Kobashigawa J, Klinthalm G (2008) Calcineurin inhibitor-sparing regimes in solid organ transplantation: focus on improving renal function and nephrotoxicity. Clin Transplant 22:1–15PubMed

12.

Johnson RWG, Kreis H, Oberbauer R, Brattstrom C, Claesson K, Eris J (2001) Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 72:777–786. doi:10.1097/00007890-200109150-00007 CrossRefPubMed

13.

Sennesael JJ, Bosmans JL, Bogers JP, Verbeelen D, Verpooten GA (2005) Conversion from cyclosporine to sirolimus in stable renal transplant recipients. Transplantation 80(11):1578–1585. doi:10.1097/01.tp.0000184623.35773.6a CrossRefPubMed

14.

Mulay AV, Cockfield S, Stryker R, Fergusson D, Knoll GA (2006) Conversion from calcineurin inhibitors to sirolimus for chronic renal allograft dysfunction: a systematic review of the evidence. Transplantation 82(9):1153–1162. doi:10.1097/01.tp.0000237101.58974.43 CrossRefPubMed

15.

Diekmann F, Budde K, Oppenheimer F et al (2004) Predictors of success in conversion from calcineurin inhibitor to sirolimus in chronic allograft dysfunction. Am J Transplant 4:1869–1875. doi:10.1111/j.1600-6143.2004.00590.x CrossRefPubMed

16.

Diekmann F, Budde K, Oppenheimer F et al (2008) Conversion to sirolimus for chronic allograft dysfunction: long-term results confirm predictive value of proteinuria. Transpl Int 21(2):152–155PubMed

17.

Boratynska M, Banasik M, Watorek E, Falkiewicz K, Patrzalek D, Szyber P, Klinger M (2006) Conversion to sirolimus from cyclosporine may induce nephrotic proteinuria and progressive deterioration of renal function in chronic allograft nephropathy patients. Transplant Proc 38(1):101–104. doi:10.1016/j.transproceed.2005.12.023 CrossRefPubMed

18.

Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16(1):31–41. doi:10.1159/000130554 CrossRefPubMed

19.

Bumbea V, Kamar N, Ribes D, Esposito L, Modesto A, Guitard J, Nasou G, Durand D, Rostaing L (2005) Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus. Nephrol Dial Transplant 20(11):2517–2523. doi:10.1093/ndt/gfh957 CrossRefPubMed

20.

Ruiz JC, Diekmann F, Campistol JM, Sanchez-Fructuoso A, Rivera C, Oliver J, Fernandez-Fresnedo G, Arias M (2005) Evolution of proteinuria after conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) in renal transplant patients: a multicenter study. Transplant Proc 37(9):3833–3835. doi:10.1016/j.transproceed.2005.09.127 CrossRefPubMed

21.

Stallone G, Infante B, Schena A, Battaglia M, Ditonno P, Loverre A, Gesualdo L, Schena FP, Grandaliano G (2005) Rapamycin for treatment of chronic allograft nephropathy in renal transplant patients. J Am Soc Nephrol 16(12):3755–3762. doi:10.1681/ASN.2005060635 CrossRefPubMed

22.

Kreis H, Oberbauer R, Campistol JM, Mathew T, Daloze P, Schena FP, Burke JT, Brault Y, Gioud-Paquet M, Scarola JA, Neylan JF, Rapamune Maintenance Regimen Trial (2004) Long-term benefits with sirolimus-based therapy after early cyclosporine withdrawal. J Am Soc Nephrol 15(3):809–817. doi:10.1097/01.ASN.0000113248.59077.76 CrossRefPubMed

23.

Diekmann F, Campistol JM (2006) Conversion from calcineurin inhibitors to sirolimus in chronic allograft nephropathy: benefits and risks. Nephrol Dial Transplant 21:562–568. doi:10.1093/ndt/gfi336 CrossRefPubMed

24.

Bestetti R, Theodoropoulos TA, Burdmann EA, Filho MA, Cordeiro JA, Villafanha D (2006) Switch from calcineurin inhibitors to sirolimus-induced renal recovery in heart transplant recipients in the midterm follow-up. Transplantation 81(5):692–696. doi:10.1097/01.tp.0000177644.45192.a3 CrossRefPubMed

Title: Conversion to sirolimus of patients with chronic allograft nephropathy—a retrospective analysis of outcome and influencing factors
Authors: Oliver Witzke
Ondrej Viklicky
Tobias R. Türk
Jens Lutz
Benjamin Wilde
Isabel Willenberg
Stefan Vitko
Uwe Heemann
Publication date: 01-11-2009
Publisher: Springer-Verlag
Published in: Langenbeck's Archives of Surgery / Issue 6/2009
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-008-0435-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Conversion to sirolimus of patients with chronic allograft nephropathy—a retrospective analysis of outcome and influencing factors

Abstract

Purpose

Materials and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Materials and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2009

Cholangitis prevention in endoscopic Klatskin tumor palliation: air cholangiography technique

Caudate lobe resection: an Egyptian center experience

Reply to Dr. Peparini’s Letter to the Editor regarding the publication titled “Immunohistochemical detection of receptor tyrosine kinases c-kit, EGF-R and PDGF-R in colorectal adenocarcinomas”

Protective effect of Verapamil on hepatic ischemia–reperfusion injury during hepatectomy in the cirrhotic patients with hepatocellular carcinoma

28th Annual Meeting of the German Association of Endocrine Surgeons (CAEK)

Is routine MR cholangiopancreatography (MRCP) justified prior to cholecystectomy?