Montagnino Giuseppe, Banfi Giovanni, Campise Maria Rosaria, Passerini Patrizia, Aroldi Adriana, Cesana Bruno Mario, Ponticelli Claudio
Divisione di Nefrologia e Dialisi, Ospedale Maggiore di Milano, IRCCS, Via Commenda 15, 20122 Milan, Italy.
Nephrol Dial Transplant. 2004 Oct;19(10):2622-9. doi: 10.1093/ndt/gfh453. Epub 2004 Aug 17.
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.
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.
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).
In transplant patients with CAN, variation of immunosuppression can reduce the negative impact of severe chronic lesions.
慢性移植肾肾病（CAN）是肾移植受者器官衰竭的主要原因。我们回顾性评估了CAN患者不同免疫抑制方案对长期移植肾存活的影响。
我们回顾性分析了158例经活检证实为CAN且接受环孢素（CsA）治疗、随访时间超过1年的肾移植受者。75例患者（NOVAR组）免疫抑制方案保持不变，83例患者（VAR组）免疫抑制方案进行了调整。在VAR组36.1%的患者中，免疫抑制强度增加；在63.8%的患者中，加用其他免疫抑制剂并同时将CsA剂量减少20%或停用CsA。应用回归模型分析治疗方案改变后肌酐清除率（CrCl）斜率，并进行Cox分析。
在VAR组患者中，两阶段回归分析未显示CrCl斜率的拐点与治疗方案改变之间存在相关性。与NOVAR组相比，改变免疫抑制方案在长期移植肾存活方面有微弱优势（P = 0.088）。单因素分析中，活检时严重组织学病变、蛋白尿>0.5 g/天以及CrCl<25 ml/min与移植肾预后不良相关（P = 0.0009）。多因素分析中，只有蛋白尿和低CrCl仍具有统计学意义。根据治疗方案改变对组织学病变进行分层分析显示，严重病变在VAR组和NOVAR组均显著降低了生存率；然而，严重病变对NOVAR组患者移植肾存活的高度负面影响[相对危险度（RR）3.602]在VAR组患者中有所降低（RR 1.951），自活检后10年的移植肾存活率分别为0.16和0.34（P = 0.0001）。
在患有CAN的移植患者中，免疫抑制方案的调整可降低严重慢性病变的负面影响。
