Urinary monocyte chemoattractant protein-1 (MCP-1) in renal transplant recipients: implications in proteinuric patients

A. Amara, L. Shalamanova, Asheesh Sharma, A. Shenkin, A. Bakran, Ajay K. Sharma, A. Hammad, R. Rustom
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Abstract

Background: After the first year of transplantation chronic allograft nephropathy is the most important cause of renal graft loss and hypertension and proteinuria occur commonly. In native nephropathies, proteinuria and progression to renal failure are linked and renal tubulo-interstitial fibrosis determines prognosis. Monocyte chemoattractant protein-1 (MCP-1) is a powerful chemokine promoting tubulo-interstitial fibrosis but data are limited in a transplant context. Hence this observational cross-sectional study. Methods: The MAP, 24h urinary creatinine clearance, proteinuria and MCP-1 were measured in 81 renal transplant pa- tients (43 with chronic allograft nephropathy). Most patients were on calcineurin-inhibitor based immunosuppression. Re- gression analysis was applied and comparisons made with 64 patients with native nephropathies and comparable function. Results: One fifth (18/81) of all renal transplant patients had less than optimally controlled hypertension. Proteinuria was heaviest in non-transplanted patients (average 3.0 g/24h, 0.1-12.2) and the ciclosporin-treated transplant patients (1.2 g/24h, 0.02-6.4). Proteinuria and MCP-1 were positively correlated in all patients (r 0.54, p<0.0001) and r 0.84, p<0.0001 in 19 transplant patients receiving angiotensin-converting enzyme inhibitors. MCP-1 levels were highest in non-transplant and ciclosporin-treated patients; geometric mean (SE), 412.4(1.16) and 314.5(1.21) pg/24h respectively. MCP-1 levels were unrelated to age, MAP, creatinine clearance, or blood ciclosporin or tacrolimus levels. Conclusions: Urinary MCP-1 may be a useful non-invasive marker of chronic graft dysfunction in transplant patients fa- cilitating monitoring of progression and response to treatment even in proteinuric patients.
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肾移植受者尿单核细胞趋化蛋白-1 (MCP-1):对蛋白尿患者的影响
背景:同种异体移植术后一年后慢性肾病是导致移植肾丧失的最主要原因,高血压和蛋白尿是常见的。在原发性肾病中,蛋白尿和肾功能衰竭的进展是相关的,肾小管间质纤维化决定了预后。单核细胞趋化蛋白-1 (MCP-1)是一种促进小管间质纤维化的强大趋化因子,但在移植背景下数据有限。因此进行了这项观察性横断面研究。方法:测定81例肾移植患者(43例为慢性肾移植肾病)的MAP、24h尿肌酐清除率、蛋白尿和MCP-1。大多数患者采用钙调磷酸酶抑制剂为基础的免疫抑制。采用回归分析方法对64例原发性肾病患者进行比较。结果:五分之一(18/81)的肾移植患者的高血压未达到最佳控制。蛋白尿在未移植患者(平均3.0 g/24h, 0.1-12.2)和环孢素治疗的移植患者(1.2 g/24h, 0.02-6.4)中最重。所有患者的蛋白尿与MCP-1呈正相关(r 0.54, p<0.0001), 19例接受血管紧张素转换酶抑制剂的移植患者的r 0.84, p<0.0001。MCP-1水平在未移植和环孢素治疗的患者中最高;几何平均(SE)分别为412.4(1.16)和314.5(1.21)pg/24h。MCP-1水平与年龄、MAP、肌酐清除率或血液环孢素或他克莫司水平无关。结论:尿MCP-1可能是移植患者慢性移植物功能障碍的有用的无创标志物,有助于监测进展和对治疗的反应,甚至在蛋白尿患者中也是如此。
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