Zhou Yijun, Qi Chaojun, Li Shu, Shao Xinghua, Mou Shan, Ni Zhaohui
Cell Physiol Biochem. 2018;51(3):1119-1133. doi: 10.1159/000495491. Epub 2018 Nov 26.
BACKGROUND/AIMS: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease. However, no effective treatments for this disease are available. Calcium dobesilate (CaD) is widely used to treat diabetic retinopathy. DKD and retinopathy often co-exist and have similar mechanisms of pathogenesis. The aim of the present study was to elucidate the safety and efficacy of CaD in the treatment of DKD.
In the prospective randomised controlled study, 100 DKD from Type 2 diabetes mellitus (DM) patients with a urinary albumin/ creatinine ratio (ACR) ≥30 mg/g and urinary protein level between 150 mg/24 h and 2 g/24 h with GFR> 90ml/min were enrolled. The patients were randomly divided into the treatment group (500 mg of CaD, administered orally, 3 times per day) and the control group. DKD patients were treated for 3 months. In the case control study, DM patients without proteinuria and healthy individuals were also enrolled. Clinical data and related biochemical parameters were collected. Endothelial function markers (VEGF, ET-1, eNOS, NO) and inflammatory markers (MCP-1, ICAM, PTX3) were detected by ELISA.
In the prospective randomised controlled study, the 24 h urinary albumin and 24 h urinary protein levels significantly decreased after three months of treatment with CaD in the patients with DKD, but the cystatin C-based glomerular filtration rate (GFR) remained unchanged. In addition, the levels of inflammatory markers (PTX3, MCP-1, hsCRP, ICAM) and endothelial dysfunction markers (VEGF, ET-1) were significantly reduced compared to pre-treatment levels, NO was signifcantly increased post treatment. In the case control study, we found that PTX3, MCP-1, ICAM, VEGF and ET-1 levels were positively correlated with urinary albumin in DKD patients, while the NO level was negatively correlated. Logistic regression analysis showed that PTX3, NO and HbAlc were influential factors in DKD. After patients with DKD were treated with CaD for three months, the 24 h urinary albumin and 24 h urinary protein levels significantly decreased, but the cystatin C-based glomerular filtration rate (GFR) remained unchanged. In addition, the levels of inflammatory markers (PTX3, MCP-1, hsCRP, ICAM) and endothelial dysfunction markers (VEGF, NO, ET-1) were significantly reduced compared to pre-treatment levels.
CaD can be safely and effectively used to treatdiabetic nephropathy.
背景/目的：糖尿病肾病（DKD）是终末期肾病的主要病因。然而，目前尚无针对该疾病的有效治疗方法。羟苯磺酸钙（CaD）广泛用于治疗糖尿病视网膜病变。DKD和视网膜病变常同时存在且发病机制相似。本研究旨在阐明CaD治疗DKD的安全性和有效性。
在这项前瞻性随机对照研究中，纳入了100例2型糖尿病（DM）患者，其尿白蛋白/肌酐比值（ACR）≥30mg/g，尿蛋白水平在150mg/24h至2g/24h之间，肾小球滤过率（GFR）>90ml/min。患者被随机分为治疗组（口服500mg CaD，每日3次）和对照组。DKD患者接受3个月的治疗。在病例对照研究中，还纳入了无蛋白尿的DM患者和健康个体。收集临床数据和相关生化参数。通过酶联免疫吸附测定（ELISA）检测内皮功能标志物（血管内皮生长因子（VEGF）、内皮素-1（ET-1）、内皮型一氧化氮合酶（eNOS）、一氧化氮（NO））和炎症标志物（单核细胞趋化蛋白-1（MCP-1）、细胞间黏附分子（ICAM）、五聚素3（PTX3））。
在前瞻性随机对照研究中，DKD患者经CaD治疗3个月后，24小时尿白蛋白和24小时尿蛋白水平显著降低，但基于胱抑素C的肾小球滤过率（GFR）保持不变。此外，与治疗前水平相比，炎症标志物（PTX3、MCP-1、超敏C反应蛋白（hsCRP）、ICAM）和内皮功能障碍标志物（VEGF、ET-1）水平显著降低，治疗后NO显著升高。在病例对照研究中，我们发现DKD患者中PTX3、MCP-1、ICAM、VEGF和ET-1水平与尿白蛋白呈正相关，而NO水平呈负相关。逻辑回归分析表明，PTX3、NO和糖化血红蛋白（HbAlc）是DKD的影响因素。DKD患者经CaD治疗3个月后，24小时尿白蛋白和24小时尿蛋白水平显著降低，但基于胱抑素C的肾小球滤过率（GFR）保持不变。此外，与治疗前水平相比，炎症标志物（PTX3、MCP-1、hsCRP、ICAM）和内皮功能障碍标志物（VEGF、NO、ET-1）水平显著降低。
CaD可安全有效地用于治疗糖尿病肾病。
