Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

Int J Mol Sci. 2020 Jul 13;21(14):4939. doi: 10.3390/ijms21144939.

Abstract

Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called "diabetic hepatopathy or diabetic liver disease". NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.

Keywords: chronic kidney disease; diabetic hepatopathy; diabetic nephropathy; glucagon-like peptide 1; peroxisome proliferator-activated receptor; sodium–glucose cotransporter 2.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / physiopathology
  • Dysbiosis / complications
  • Dysbiosis / therapy
  • Gastrointestinal Microbiome
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • MAP Kinase Kinase Kinase 5 / antagonists & inhibitors
  • Models, Biological
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Prebiotics
  • Probiotics / therapeutic use
  • Renal Insufficiency, Chronic / drug therapy

Substances

  • Anti-Inflammatory Agents
  • Antihypertensive Agents
  • Antioxidants
  • Hypoglycemic Agents
  • Peroxisome Proliferator-Activated Receptors
  • Prebiotics
  • MAP Kinase Kinase Kinase 5
  • MAP3K5 protein, human