Journal Article

Impact of chronic allograft nephropathy and subsequent modifications of immunosuppressive therapy on late graft outcomes in renal transplantation

Giuseppe Montagnino, Giovanni Banfi, Maria Rosaria Campise, Patrizia Passerini, Adriana Aroldi, Bruno Mario Cesana and Claudio Ponticelli

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 10, pages 2622-2629
Published in print October 2004 | ISSN: 0931-0509
Published online August 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh453
Impact of chronic allograft nephropathy and subsequent modifications of immunosuppressive therapy on late graft outcomes in renal transplantation

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Background. Chronic allograft nephropathy (CAN) is the leading cause of organ failure in renal transplant recipients. We retrospectively evaluated the impact of varying immunosuppression in CAN patients on long-term graft survival.

Methods. We retrospectively analysed 158 cyclosporin (CsA)-treated renal transplant recipients with biopsy-proven CAN with follow-up of >1 year. Immunosuppression remained unchanged in 75 (NOVAR) and was modified in 83 patients (VAR). In 36.1% of VAR patients, it was increased; in 63.8%, the addition of other immunosuppressants was associated with a 20% reduction in or withdrawal of CsA. A regression model, for creatinine clearance (CrCl) slope analysis after therapy variation, and Cox's analysis were applied.

Results. In VAR patients, two-phase regression did not show a correlation between the inflection point in the CrCl slope and treatment variation. Changing immunosuppression gave a borderline advantage in long-term graft survival compared with NOVAR (P = 0.088). In univariate analysis, severe histological lesions, proteinuria >0.5 g/day and CrCl <25 ml/min at biopsy correlated with poor graft outcome (P = 0.0009). In multivariate analysis, only proteinuria and low CrCl remained significative. Stratifying histological lesions in relation to therapy variation showed that severe lesions significantly decreased survival in both VAR and NOVAR groups; however, the highly negative impact of severe lesions in NOVAR patients on graft survival [relative risk (RR) 3.602] was reduced in VAR patients (RR 1.951), with a 10 year graft survival since biopsy of 0.16 vs 0.34 (P = 0.0001).

Conclusions. In transplant patients with CAN, variation of immunosuppression can reduce the negative impact of severe chronic lesions.

Keywords: anti-rejection therapy variation; chronic allograft nephropathy; histology of chronic allograft nephropathy; outcome assessment

Journal Article.  5095 words.  Illustrated.

Subjects: Nephrology

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