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Insulin resistance and hyperinsulinaemia in kidney disease: mechanisms and metabolic effects - PubMed

5 hours ago
  • #Chronic Kidney Disease
  • #Metabolic Syndrome
  • #Insulin Resistance
  • Insulin resistance and hyperinsulinaemia significantly impact kidney function, contributing to chronic kidney disease (CKD) development and progression, even beyond diabetes.
  • Insulin plays a crucial role in kidney metabolism, regulating podocyte integrity, tubular sodium handling, and gluconeogenesis; these functions are disrupted in insulin resistance.
  • Disruptions from insulin resistance lead to glomerular hyperfiltration, proteinuria, sodium retention, progressive kidney injury, and worsened hyperglycaemia.
  • Chronic hyperinsulinaemia activates pro-growth and pro-fibrotic pathways, causing vascular dysfunction, inflammation, and fibrosis in the kidneys.
  • The cardiovascular-kidney-metabolic syndrome framework redefines kidney disease as a result of systemic metabolic dysfunction, with insulin resistance at its core.
  • The article highlights therapeutic implications for renoprotective agents like SGLT2 inhibitors, GLP-1 receptor agonists, and thiazolidinediones.
  • Recognizing the pathogenic role of insulin resistance and hyperinsulinaemia is key to developing new therapies to prevent and slow CKD progression.