Molecular Mechanisms and Treatment Strategies in Diabetic Nephropathy: New Avenues for Calcium Dobesilate—Free Radical Scavenger and Growth Factor Inhibition

Abstract

Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40–50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues. CaD is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. On the molecular level, CaD reduces oxidative stress and inhibits growth factors such as fibroblast growth factor and vascular endothelial growth factors. Recent findings have demonstrated a strong rationale for its use in reducing urine albumin excretion rate and markers of inflammation as well as improving endothelial function. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of the disease. These findings, although promising, need further confirmation in prospective clinical trials with CaD.

Nephrotoxicity and highly active antiretroviral therapy: Mitigating action of Momordica charantia

“…Our result also shows urea retention in the rats that were treated with triplavar. Low concentration of urea in the kidney suggests a reduced turnover of protein and thus reflects in glomerular filtration rate and worsens renal function [19], more so, increased level of urea in the blood suggests enhanced amino acids fueled gluconeogenesis which leads to increased nitrogen load to the liver where urea is formed [20]. Administration of M. charantia fruit extract was able to restore the urinary metabolites to normal when compared to control rats.…”

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

“…CaD is used in particular in Asia and South America to treat diabetic retinopathy [23], chronic venous insufficiency, and various conditions associated with excessive angiogenesis [43,44]. Recent studies suggested that CaD exerts protective effects against diabetic nephropathy [45,46]. Despite its broad use, the pharmacology of CaD has received little attention.…”

Multicentre Evaluation of a Newly Developed Anti-Calcium Dobesilate-Enzymatic Creatinine Assay Based on Real-World Data in China

“…Recent studies showed its protective effects on diabetic nephropathy and its ability to reduce albuminuria [14,15]. Treatment strategies that include CaD may prevent or delay the progression of DR and nephropathy [16]. However, when CaD is used clinically to prevent and treat DR and/or DN, negative interference with enzymatic creatinine may lead to incorrect evaluation of renal function in patients with diabetes, which can mask the patient's condition and delay treatment, leading to poor clinical outcomes.…”