Effect of GFR on Plasma N-Terminal Connective Tissue Growth Factor (CTGF) Concentrations
Effect of GFR on Plasma N-Terminal Connective Tissue Growth Factor (CTGF) Concentrations
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DOI：
10.1053/j.ajkd.2011.12.019
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发表时间：
2012-05-01
影响因子：
13.2
通讯作者：
Kok, Robbert J.
中科院分区：
文献类型：
--
作者：
Gerritsen, Karin G.;Abrahams, Alferso C.;Kok, Robbert J.
背景：结缔组织生长因子（CTGF）在肾脏和心脏纤维化的发病机制中起关键作用。其氨基末端片段（N-CTGF）是血浆中检测到的CTGF的主要形式，分子量在中等分子范围内（18 kDa）。然而，目前尚不清楚N-CTGF是否是一种尿毒症滞留溶质，在慢性肾脏疾病（CKD）中由于肾清除率降低而蓄积，以及是否可以通过血液透析滤过去除。研究设计：4项患者观察性研究和2项啮齿动物药代动力学研究。设置和参与者：4项单中心研究。第一项研究（横断面）：88例未接受肾脏替代治疗的CKD患者。第二项研究（横断面）：23例接受低通量血液透析的终末期肾病患者。第三项研究：9名肾移植受者在移植前和移植后6个月。第四项研究：11例低通量血液透析患者和12例血液透析滤过患者在一次透析治疗前后的预测指标：第一、第二和第三项研究：（残余）肾小球滤过率（GFR）。第四项研究：结果：在CKD患者中，我们观察到血浆CTGF水平和估计的GFR之间的独立关联（β = -0.72; P < 0.001）。在终末期肾病患者中，血浆CTGF水平与残余肾功能独立相关（β = -0.55; P = 0.046）。成功的肾移植导致血浆CTGF水平降低（P = 0.008），与估计的GFR增加成比例。低通量血液透析不能清除血浆CTGF，而单次血液透析滤过可使其降低68%（P < 0.001）。非尿毒症啮齿动物的药代动力学研究证实，肾脏清除是N-CTGF.Limitations的主要消除途径：观察性研究，患者数量有限。第四项研究：nonrandomized，一个会话的效果评价;随机纵向study is warranted.Conclusion：血浆（N-）CTGF主要由肾脏消除，在CKD中积累，并且通过单个血液透析滤过会话大幅降低。美国肾脏病杂志59（5）：619-627。(C)2012年，美国国家肾脏基金会（National Kidney Foundation，Inc.）
Background: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-CTGF is a uremic retention solute that accumulates in chronic kidney disease (CKD) due to decreased renal clearance and whether it can be removed by hemodiafiltration.Study Design: 4 observational studies in patients and 2 pharmacokinetic studies in rodents.Setting & Participants: 4 single-center studies. First study (cross-sectional): 88 patients with CKD not receiving kidney replacement therapy. Second study (cross-sectional): 23 patients with end-stage kidney disease undergoing low-flux hemodialysis. Third study: 9 kidney transplant recipients before and 6 months after transplant. Fourth study: 11 low-flux hemodialysis patients and 12 hemodiafiltration patients before and after one dialysis session.Predictor: First, second, and third study: (residual) glomerular filtration rate (GFR). Fourth study: dialysis modality.Outcomes & Measurements: Plasma (N-)CTGF concentrations, measured by enzyme-linked immunosorbent assay.Results: In patients with CKD, we observed an independent association between plasma CTGF level and estimated GFR (beta = -0.72; P < 0.001). In patients with end-stage kidney disease, plasma CTGF level correlated independently with residual kidney function (beta = -0.55; P = 0.046). Successful kidney transplant resulted in a decrease in plasma CTGF level (P = 0.008) proportional to the increase in estimated GFR. Plasma CTGF was not removed by low-flux hemodialysis, whereas it was decreased by 68% by a single hemodiafiltration session (P < 0.001). Pharmacokinetic studies in nonuremic rodents confirmed that renal clearance is the major elimination route of N-CTGF.Limitations: Observational studies with limited number of patients. Fourth study: nonrandomized, evaluation of the effect of one session; randomized longitudinal study is warranted.Conclusion: Plasma (N-)CTGF is eliminated predominantly by the kidney, accumulates in CKD, and is decreased substantially by a single hemodiafiltration session. Am J Kidney Dis. 59(5): 619-627. (C) 2012 by the National Kidney Foundation, Inc.