Campistol, JM

Castro, A

Gutiérrez, A

Mota, A

Pinto, JR

Prats, D

Ruiz, JC

Name not available

Early cyclosporine a withdrawal in kidney transplant recipients under a sirolimus-based immunosuppressive regimen: pathological study of graft biopsies at 1-year posttransplant

CHUC Institutional Repository

Repositório Institucional dos Hospitais da Universidade de Coimbra

Early Cyclosporine A Withdrawal in Kidney Transplant RecipientsUnder a Sirolimus-Based Immunosuppressive Regimen: PathologicalStudy of Graft Biopsies at 1-Year PosttransplantJ.C. Ruiz, J.M. Campistol, A. Mota, D. Prats, A. Gutie´rrez, A. Castro, J.R. Pinto, J. Garcı´a, J.M. Morales,J.M. Grinyo, and M. AriasTHE ROLE of anticalcineurin agents, cyclosporine A(CyA) and tacrolimus (TRC), in the development ofchronic allograft nephropathy (CAN) and subsequentlyin long-term graft survival seems to be of major impor-tance owing to their nephrotoxic effect.1 Unfortunately,no successful alternatives are available to date. Sirolimushas shown a similar efficacy to CyA when used alone withrespect to graft rejection rates and short-term graftsurvival, either in combination with steroids and azathio-prine or with steroids and mofetil mycophenolate(MMF).2,3 With the objective of a low rejection rate andthe minimization of CyA nephrotoxicity a multicenter,randomized, phase III trial at 3 years is currently ongoingin 57 centers in Europe, Canada, and Australia with atotal of 525 patients enrolled. This trial compares twoarms, a control arm (A) using CyA, fixed doses ofsirolimus, and steroids, and a study arm (B) with CyA,concentration-controlled sirolimus, and steroids with sus-pension of CyA at 3 months’ postransplant. Partialresults of this study at 1 year have shown a low rejectionrate in both arms with a significantly better graft functionat 1 year in group B.4 Nevertheless, the pathologicaleffects of CyA withdrawal have not yet been analyzed. Inthis report we present the results of graft biopsy evalua-tions at 1 year in a subgroup of patients.MATERIALS AND METHODSGraft biopsies at the moment of transplantation and at 1-yearposttransplant were analyzed in the subgroup of patients includedin Spain and Portugal. All patients with a functioning graft at 1 yearand the two biopsies performed were considered (70 patients and140 biopsies, corresponding to 35 patients in every group). Biopsieswere evaluated locally according to the Banff’95 classification andchronicity changes (ah, eg, ci, ct, and cv) were computed.5 Achronicity score (CS) was calculated as the sum of the last fouritems. These findings as well as renal function at 1 year werecompared between the two groups. We considered the existence ofprogression of chronicity lesions when Banff encoding for everylesion was higher in the 1-year biopsy than in the transplant (basal)biopsy. When it was equal or lower it was considered as noprogression. The CS was analyzed in the same way. It wasconsidered the percentage of patients with progression of chronic-ity findings in every group (individual lesions and CS) and com-pared using the chi square test.RESULTSAmong the 140 biopsies evaluated, 83 (59%) were consid-ered as adequate (more than 6 glomeruli and at least 1artery), 31 (22%) were considered as marginal, and theremaining 24 (19%) were not satisfactory. One-year plasmacreatinine level was 1.88 mg/dL in group A and 1.48 mg/dLin group B (P  .05). Progression of lesions was as follows(percentage of patients in group A and B, respectively): cg18.5% vs 19.2% (n  53; P  NS); ci 61.3% vs 56.7% (n 61; P  NS); ct 51.6% vs 50% (n  61; P  NS); cv 32% vs31.6% (n  44; P  NS); ah 36.7% vs 32.3% (n  61; P NS). When the CS was considered it was observed progress-ing in 64% of cases in group A and in only 47.4% of casesin group B (n  44), although this difference was notstatistically significant.CONCLUSIONSEarly CyA withdrawal in a regimen including sirolimus isfollowed by an improvement in graft function as well as inthe pathological parameters that define chronic allograftnephropathy. This reduced severity of chronic lesions whenCyA is eliminated might be attributed to a decreasedchronic nephrotoxicity without an increase in the immuno-logical response against the allograft. Nevertheless, theabsence of a central pathological evaluation should serve toconsider these results with caution.From H. Valdecilla, Santander, Spain; H. Clinic i Provincial,Barcelona, Spain; H. Da Universidade De Coimbra, Coimbra,Portugal; H. Clinico, Madrid, Spain; H. Miguel Servet, Zaragoza,Spain; H. Geral de Santo Antonio, Porto, Portugal; H. CurryCabral, Lisboa, Portugal; H. La Fe, Valencia, Spain; H. 12 deOctubre, Madrid, Spain; H. Bellvitge, Barcelona, Spain.Address reprint requests to J.C. Ruiz, Hospital UniversitarioValdecilla, Servicio de Nefrologia, 39008, Santander, Spain.0041-1345/02/$–see front matter © 2002 by Elsevier Science Inc.PII S0041-1345(01)02827-5 655 Avenue of the Americas, New York, NY 1001092 Transplantation Proceedings, 34, 92–93 (2002)AKNOWLEDGMENTSWe thank Dr Ana Sa´nchez (H. San Carlos, Madrid, Spain) for herinestimable collaboration in statistical analysis.REFERENCES1. Paul LC: Kidney Int 56:783, 19992. Groth CG, Ba¨ckman L, Morales J-M, et al: Transplantation67:1036, 19993. Kreis H, Cisterne JM, Land W, et al: Transplantation 69:1252,20004. Johnson R, Oberbauer R, Kreis H, et al: XVIII InternationalCongress of the Transplantation Society. Rome, 20005. Solez K, Benediktsson H, Cavallo T, et al: Transplant Proc28:441, 1996EARLY CYCLOSPORINE WITHDRAWAL 93

Early cyclosporine a withdrawal in kidney transplant recipients under a sirolimus-based immunosuppressive regimen: pathological study of graft biopsies at 1-year posttransplant

Abstract

Similar works

Full text

Available Versions

Name not available

CHUC Institutional Repository

Repositório Institucional dos Hospitais da Universidade de Coimbra