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  • Title: Impact of chronic allograft nephropathy and subsequent modifications of immunosuppressive therapy on late graft outcomes in renal transplantation.
    Author: Montagnino G, Banfi G, Campise MR, Passerini P, Aroldi A, Cesana BM, Ponticelli C.
    Journal: Nephrol Dial Transplant; 2004 Oct; 19(10):2622-9. PubMed ID: 15316096.
    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.
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