Diabetic Nephropathy Can Be Treated with Calcium Dobesilate by Alleviating the Chronic Inflammatory State and Improving Endothelial Cell Function

Abstract

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. Methods: 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. Results: 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. Conclusion: CaD can be safely and effectively used to treatdiabetic nephropathy.

Changes of serum pentraxin-3 and hypersensitive CRP levels during pregnancy and their relationship with gestational diabetes mellitus

“…In recent years, many studies have shown that metabolic syndrome is associated with inflammatory mediators, the most representative of which is hs-CRP: elevated serum hs-CRP level has been found in patients with diabetes, hypertension, obesity, hyperlipidemia, and even cardiovascular diseases [15]. PTX3 is similar to CRP in structure and function and has a good correlation with hs-CRP.…”

Calcium dobesilate reduces VEGF signaling by interfering with heparan sulfate binding site and protects from vascular complications in diabetic mice

“…In addition, our experiments show that CaD prevents the increase and upregulation/activation of several pro-inflammatory cytokines (IL-6, CXCL1, IL-1ß, TNF-α, and MCP-1) that play a significant role in renal-disease progression. Although the anti-inflammatory properties of CaD have been previously reported [25,59,60], to the best of our knowledge, our report is the first involving a diabeticnephropathy animal model. These findings are therefore important due to the pivotal role of inflammation in the pathogenesis of diabetic nephropathy.…”

Deneysel piyelonefrit modelinde Ca-Dobesilate'in renal skar oluşumuna etkisi

“…Wang et al, recently published that CaD supressed renal interstitial fibrosis by promoting anti-apoptotic effects through Sirt1/p53 signaling pathway 26 . CaD was also reported to attenuate diabetes-induced endothelial dysfunction and chronic inflammation in diabetic nephropathy via reducing inflammatory and endothelial dysfunction markers 27 . However; none of the markers mentioned above was investigated in this study.…”

“…It inhibits inflammatory factors and improves circulation by lowering blood viscosity, supressing platelet activity and capillary permeability. In diabetic nephropathy patients, improved CaD endothelial cell function and chronic inflammation 8 . CaD was reported to inhibit TGFb and bFGF in a diabetic nephropathy model and basal cell carcinoma respectively 9,10 .…”