Laufer G, Laczkovics A, Wollenek G, Buxbaum P, Seitelberger R, Holzinger C, Horvat R, Havel M, Wolner E
Second Department of Surgery, University of Vienna, Austria.
Transplantation. 1991 Jan;51(1):184-9. doi: 10.1097/00007890-199101000-00029.
The natural course of mild acute cardiac allograft rejection (MAR) under cyclosporine-based therapy is generally considered benign, and usually antirejection therapy is not instituted. The present study was undertaken to determine the frequency of and the risk factors for progression of MAR into a clinically significant (moderate or severe) rejection on subsequent endomyocardial biopsy (EMB). Among 167 cardiac recipients, transplanted from 3/1984 to 4/1990, MAR under cyclosporine-based therapy was diagnosed on 220 EMBs. Depending upon the outcome on the subsequent EMB, MAR was categorized as progressive or nonprogressive. This served as the dependent variable for a stepwise logistic regression analysis evaluating 11 covariates as potential risk factors: perioperative antibody prophylaxis (ATG vs. OKT3), maintenance therapy, underlying disease, HLA-mismatches for A- and B + DR-loci, serum creatinine (mg/dl) and cyclosporine HPLC blood level (ng/ml) at diagnosis of MAR and at subsequent biopsy, recipient age, donor age. 40 (18.2%) of 220 MARs became progressive as opposed to 37 (7.3%) of a control cohort of 507 negative EMBs (P less than 0.0001). Stepwise logistic regression yielded the type of maintenance therapy (P = 0.0019) and serum creatinine level at diagnosis of MAR (P = 0.0615) as independent predictors of progression of MAR. After adjustment for influence of maintenance therapy and serum creatinine none of the cyclosporine variables provided any additional information. MARs without maintenance steroids and low serum creatinine levels had the highest risk (37.2% observed incidence) to develop moderate or severe rejection on subsequent EMB. This analysis supports evidence that diagnosis of MAR on EMB is associated with a considerable high progression rate into clinically significant rejection when compared to negative EMBs. Progression particularly occurs in MAR under steroid-free maintenance therapy and suggests early augmentation of immunosuppression. In terms of progression of MAR serum creatinine values, obviously indicating cyclosporine nephrotoxicity, appear to reflect the extent of cyclosporine-mediated immunosuppressive activity more properly than parameters of its bioavailability by measuring cyclosporine HPLC blood levels.
在基于环孢素的治疗下，轻度急性心脏移植排斥反应（MAR）的自然病程通常被认为是良性的，通常不进行抗排斥治疗。本研究旨在确定在随后的心内膜心肌活检（EMB）中，MAR进展为具有临床意义（中度或重度）排斥反应的频率及危险因素。在1984年3月至1990年4月间接受心脏移植的167例受者中，基于环孢素的治疗下，在220次EMB中诊断出MAR。根据随后EMB的结果，MAR被分类为进展性或非进展性。这作为一个因变量，用于逐步逻辑回归分析，评估11个协变量作为潜在危险因素：围手术期抗体预防（抗胸腺细胞球蛋白与OKT3）、维持治疗、基础疾病、A和B + DR位点的HLA错配、MAR诊断时及随后活检时的血清肌酐（mg/dl）和环孢素HPLC血药浓度（ng/ml）、受者年龄、供者年龄。220例MAR中有40例（18.2%）进展，而507例阴性EMB的对照队列中有37例（7.3%）进展（P小于0.0001）。逐步逻辑回归得出维持治疗类型（P = 0.0019）和MAR诊断时的血清肌酐水平（P = 0.0615）是MAR进展的独立预测因素。在调整维持治疗和血清肌酐的影响后，环孢素的变量均未提供任何额外信息。未接受维持性类固醇且血清肌酐水平低的MAR在随后的EMB中发生中度或重度排斥反应的风险最高（观察到的发生率为37.2%）。该分析支持以下证据：与阴性EMB相比，EMB诊断出的MAR进展为具有临床意义的排斥反应的发生率相当高。进展尤其发生在无类固醇维持治疗的MAR中，提示早期增加免疫抑制。就MAR的进展而言，明显表明环孢素肾毒性的血清肌酐值似乎比通过测量环孢素HPLC血药浓度来反映其生物利用度的参数更能恰当地反映环孢素介导的免疫抑制活性的程度。
