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NDT Advance Access published online on August 17, 2004
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfh453
© 2004 by European Renal Association - European Dialysis and Transplant Association
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Received March 4, 2004
Accepted June 23, 2004

Original Papers

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

Giuseppe Montagnino 1*, Giovanni Banfi 1, Maria Rosaria Campise 1, Patrizia Passerini 1, Adriana Aroldi 1, Bruno Mario Cesana 2, Claudio Ponticelli 1

1 Divisione di Nefrologia e Dialisi, Ospedale Maggiore di Milano, IRCCS, Via Commenda 15, Italy
2 Laboratorio Epidemiologico, Ospedale Maggiore di Milano, IRCCS, Via F. Sforza 28, 20122 Milan, Italy

* To whom correspondence should be addressed. E-mail: monta{at}policlinico.mi.it.



  Abstract

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.
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