Zweers M M, de Waart D R, Smit W, Struijk D G, Krediet R T
Department of Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
J Lab Clin Med. 1999 Aug;134(2):124-32. doi: 10.1016/s0022-2143(99)90116-6.
The morphologic alterations in the kidney and the retina that can be present in patients with diabetic microangiopathy are mediated by growth factors. Vascular endothelial growth factor (VEGF) is a mediator of neoangiogenesis in diabetic retinopathy. Transforming growth factor-beta (TGF-beta) is involved in the extracellular matrix proliferation in diabetic nephropathy. The aim of the present study was to investigate the presence of VEGF and TGF-beta1 in peritoneal effluents of patients undergoing continuous ambulatory peritoneal dialysis who are being treated with glucose-containing dialysis solutions in relation to parameters of peritoneal transport. Standard peritoneal permeability analyses with 3.86% glucose dialysate were performed in 16 stable patients undergoing peritoneal dialysis (PD) (median duration of PD 39 months, range 1 to 104 months). The power relationship that is present between dialysate/serum (D/S) ratios of serum proteins that are transported only across the peritoneal membrane and their molecular weights was used to predict the D/S ratios when diffusion would be the only explanation for the measured dialysate concentration. It was assumed that all TGF-beta1 in the circulation was bound to alpha2-macroglobulin. The D/S ratios of VEGF (P < .0005) and TGF-beta1 (P < .015) were significantly higher than expected when VEGF and TGF-beta1 would have been transported from the circulation only by diffusion. No relationship was present between the effluent concentration attributed to the local production of VEGF (LVEGF) and that of TGF-beta1 (LTGF-beta1). LVEGF correlated with the mass transfer area coefficient (MTAC) creatinine value (r = 0.69, P < .007), MTAC urate value (r = 0.60, P < .02), and glucose absorption value (r = 0.75, P < .004), all reflections of the peritoneal vascular surface area. A negative correlation was observed between the transcapillary ultrafiltration (926 mL/4 h, 394 to 1262 mL/4 h) and LVEGF (r = -0.52, P < .045). This negative tendency was also observed between the net ultrafiltration (622 mL/4 h, -43 to 938 mL/4 h) and LVEGF (r = -0.48) but did not reach significance. LVEGF and the duration of treatment did not correlate, possibly because of the relatively small number of patients. LTGF-beta1 showed no relationship with transport parameters or duration of treatment. In conclusion, we found evidence for the local production of both VEGF and TGF-beta1 in the peritoneal membrane of patients undergoing long-term peritoneal dialysis with glucose-based dialysate solutions. The analogy with VEGF in diabetic retinopathy suggests a pathogenetic role of high dialysate glucose concentrations in the development of these alterations in the peritoneal membrane.
糖尿病微血管病变患者肾脏和视网膜中出现的形态学改变是由生长因子介导的。血管内皮生长因子(VEGF)是糖尿病视网膜病变中新血管生成的介质。转化生长因子-β(TGF-β)参与糖尿病肾病中细胞外基质的增殖。本研究的目的是调查接受持续性非卧床腹膜透析且使用含糖透析液治疗的患者腹膜透析液中VEGF和TGF-β1的存在情况,并分析其与腹膜转运参数的关系。对16例稳定的腹膜透析(PD)患者(PD中位病程39个月,范围1至104个月)使用3.86%葡萄糖透析液进行标准腹膜通透性分析。仅通过腹膜转运的血清蛋白的透析液/血清(D/S)比值与其分子量之间的幂关系,用于预测当扩散是测量透析液浓度的唯一解释时的D/S比值。假设循环中的所有TGF-β1均与α2-巨球蛋白结合。当VEGF和TGF-β1仅通过扩散从循环中转运时,VEGF(P <.0005)和TGF-β1(P <.015)的D/S比值显著高于预期。归因于VEGF局部产生(LVEGF)的流出液浓度与TGF-β1(LTGF-β1)的流出液浓度之间无相关性。LVEGF与肌酐的传质面积系数(MTAC)值(r = 0.69,P <.007)、尿酸盐的MTAC值(r = 0.60,P <.02)以及葡萄糖吸收值(r = 0.75,P <.004)相关,这些均反映了腹膜血管表面积。观察到跨毛细血管超滤(926 mL/4 h,394至1262 mL/4 h)与LVEGF之间呈负相关(r = -0.52,P <.045)。在净超滤(622 mL/4 h,-43至938 mL/4 h)与LVEGF之间也观察到这种负趋势(r = -0.48),但未达到显著水平。LVEGF与治疗持续时间无相关性,可能是因为患者数量相对较少。LTGF-β1与转运参数或治疗持续时间无相关性。总之,我们发现证据表明长期使用基于葡萄糖的透析液进行腹膜透析的患者腹膜中存在VEGF和TGF-β1的局部产生。与糖尿病视网膜病变中VEGF的相似性表明,高透析液葡萄糖浓度在腹膜这些改变发展过程中具有致病作用。