Glucose and Blood Pressure-Dependent Pathways-The Progression of Diabetic Kidney Disease

Int J Mol Sci. 2020 Mar 23;21(6):2218. doi: 10.3390/ijms21062218.

Abstract

The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such as methylglyoxal which activate intracellular pathways to promote fibrosis and inflammation in the kidney. Recent studies have identified a novel molecular interaction between hemodynamic and metabolic pathways which could lead to new treatments for DKD. This should lead to a further improvement in the outlook of DKD building on positive results from RAAS blockade and more recently newer classes of glucose-lowering agents such as SGLT2 inhibitors and GLP1 receptor agonists.

Keywords: diabetic complications; diabetic kidney disease; diabetic nephropathy; vasoactive pathways.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Blood Glucose
  • Blood Pressure*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology*
  • Disease Progression
  • Glucose / metabolism*
  • Hemodynamics
  • Humans
  • Metabolic Networks and Pathways*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology
  • Renin-Angiotensin System / drug effects
  • Signal Transduction

Substances

  • Biomarkers
  • Blood Glucose
  • Protective Agents
  • Glucose