Abstract
Diabetic nephropathy is becoming a more predominant cause of end-stage renal disease, as the prevalence of diabetes mellitus worldwide is on the rise. In this systematic review, we aimed to define the role of endothelin receptor antagonists, in the prevention and treatment of diabetic nephropathy, in addition to determining their safety. For this review, PubMed, Google Scholar, and Cochrane Library databases, in addition to ClinicalTrials.gov, were searched for publications in the last 20 years. We included 14 studies, seven randomized control trials, and seven post hoc analyses in this paper. Atrasentan decreased albuminuria, reduced blood pressure, and improved lipid profiles with more manageable fluid overload-related adverse events than avosentan and bosentan. Overall, endothelin receptor antagonists, in combination with renin-angiotensin-aldosterone system inhibitors, effectively reduce albuminuria and prevent the progression of diabetic kidney disease. However, more extensive clinical trials still need to be conducted to confirm these relationships and to learn more about the specific factors affecting their efficacy in individual patients.
Highlights
BackgroundAccording to the World Health Organization (WHO), approximately 422 million people suffer from diabetes mellitus worldwide, regardless of their economic status [1]
Medical Subject Heading (MeSH) terms and the following keywords were searched in various combinations: "Diabetes mellitus," "Endothelin receptor antagonists," Bosentan, Avosentan, Atrasentan, "Diabetic nephropathy," and proteinuria
The remaining publications were individually screened by two reviewers, using the following inclusion criteria: (1) Studies published between 2001-2021 (2) Studies published in the English language (3) Human studies (4) Randomized control trials comparing endothelin receptor antagonists with placebo (5) Studies performed in diagnosed diabetic patients, with evidence of proteinuria and decline in glomerular filtration rate Studies in languages other than English, animal research studies, studies involving non-diabetic patients, and studies that were not randomized control trials were excluded
Summary
BackgroundAccording to the World Health Organization (WHO), approximately 422 million people suffer from diabetes mellitus worldwide, regardless of their economic status [1]. Diabetic nephropathy is characterized by thickening of the glomerular basement membrane, mesangial expansion, and hyaline accumulation in the afferent and efferent arterioles [4]. This leads to glomerular hyperfiltration, proteinuria, fall in glomerular filtration rate (GFR) and ESRD [4,5]. The urinary albumin excretion rate (UAER) is used to clinically categorize diabetic kidney disease into the following stages: normoalbuminuria (UAER < 30 mg/g creatinine), microalbuminuria (UAER 30-300 mg/g) or macroalbuminuria (UAER > 300 mg/g) [7]. The urine albumin creatinine ratio (UACR) is used in addition to the estimated glomerular filtration rate (eGFR), to classify diabetic kidney disease into three categories: A1 (30 mg/mmol) [9]
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