Harris Shelley, Coupes Beatrice M, Roberts Stephen A, Roberts Ian S D, Short Colin D, Brenchley Paul E C
The Renal Research Laboratories, Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Manchester, UK.
J Nephrol. 2007 Mar-Apr;20(2):177-85.
Evidence from experimental models and clinical studies supports a major role for transforming growth factor-beta1 (TGF-beta1) in renal fibrosis. The aim of this study was to use repeated measurement of plasma TGF-beta1 as an indicator of persistent expression in a cohort of patients during the first 2 years post-renal transplantation and to correlate the findings with the development of chronic allograft nephropathy (CAN).
Active plasma TGF-beta1 was quantified in 100 consecutive renal allograft recipients (samples/patient = 35.6 +/- 12.9) under standard clinical management for a mean of 23 months (range 3.4-45 months). All patients were followed up for a minimum of 5 years.
By 5 years, 23 patients had developed biopsy-proven CAN (CAN+), all of whom had been positive for plasma TGF-beta1. Demographic data were compared between patients who were CAN+ and CAN-negative (CAN-) and were not significantly different. TGF-beta1 exposure expressed as area under the curve / day (AUC/day) was correlated with the incidence of CAN. A Cox regression model was used to investigate the interrelationship of CAN, acute cellular rejection (ACR) and TGF-beta1 levels. ACR episodes were predictive of the development of CAN (log-rank test, p=0.003). After allowing for the effect of ACR (hazard ratio [HR]=3.6; 95% confidence ratio [95% CI], 1.5-8.7) between patients with and without ACR episodes, p=0.003), the independent effect of TGF-beta1 was confirmed (HR=1.7; 95% CI, 1.1-2.6; per quartile; p=0.008).
The results demonstrate that episodes of ACR are highly predictive of chronic damage in the graft. Cumulative exposure to TGF-beta1 is identified as an independent predictor of CAN in the first 2 years posttransplantation.
实验模型和临床研究的证据支持转化生长因子-β1（TGF-β1）在肾纤维化中起主要作用。本研究的目的是在肾移植术后的头2年里，将血浆TGF-β1的重复测量作为一组患者中持续表达的指标，并将研究结果与慢性移植肾肾病（CAN）的发生相关联。
在标准临床管理下，对100例连续的肾移植受者（样本/患者 = 35.6 ± 12.9）的活性血浆TGF-β1进行定量，平均随访23个月（范围3.4 - 45个月）。所有患者至少随访5年。
到5年时，23例患者经活检证实发生了CAN（CAN+），所有这些患者的血浆TGF-β1均为阳性。对CAN+和CAN阴性（CAN-）患者的人口统计学数据进行了比较，差异无统计学意义。以曲线下面积/天（AUC/天）表示的TGF-β1暴露量与CAN的发生率相关。使用Cox回归模型研究CAN、急性细胞排斥反应（ACR）和TGF-β1水平之间的相互关系。ACR发作可预测CAN的发生（对数秩检验，p = 0.003）。在考虑ACR的影响后（有和无ACR发作患者之间的风险比[HR] = 3.6；95%置信区间[95%CI]，1.5 - 8.7；p = 0.003），TGF-β1的独立作用得到证实（HR = 1.7；95%CI，1.1 - 2.6；每四分位数；p = 0.008）。
结果表明，ACR发作高度预测移植肾的慢性损伤。TGF-β1的累积暴露被确定为移植后前2年CAN的独立预测因子。
