Impact of chronic allograft nephropathy and subsequent modifications of immunosuppressive therapy on late graft outcomes in renal transplantation.
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.
Divisione di Nefrologia e Dialisi, Ospedale Maggiore di Milano, IRCCS, Via Commenda 15, 20122 Milan, Italy. monta@policlinico.mi.it
Giuseppe
G
Montagnino
Giovanni
G
Banfi
Maria Rosaria
MR
Campise
Patrizia
P
Passerini
Adriana
A
Aroldi
Bruno Mario
BM
Cesana
Claudio
C
Ponticelli
D000328:Adult; D002908:Chronic Disease; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine