Mitigating risk of aldosterone in diabetic kidney disease

Curr Opin Nephrol Hypertens. 2020 Jan;29(1):145-151. doi: 10.1097/MNH.0000000000000557.

Abstract

Purpose of review: Diabetic kidney disease is a growing problem leading to end-stage kidney disease but also atherosclerotic cardiovascular disease and heart failure. Aldosterone is a key risk factor promoting inflammation and fibrosis causing cardio-renal failure. Current options and challenges with mitigating the risk of aldosterone are reviewed.

Recent findings: More aggressive renin-angiotensin-aldosterone system (RAAS) blockade can be maintained in individuals with hyperkalemia if new potassium binders are added. Aldosterone synthase inhibitors may lower aldosterone without causing hyperkalemia. Novel nonsteroidal mineralocorticoid receptor antagonists (MRA) are able to lower proteinuria and markers of heart failure, with limited potassium problems and without renal impairment. Ongoing clinical trials are evaluating the safety and potential benefits of nonsteroidal MRAs on progression of renal disease and development of cardiovascular outcomes in type 2 diabetes and kidney disease.

Summary: Aldosterone is an important driver of inflammation and fibrosis leading to renal and cardiovascular complications. MRA lower albuminuria but data showing prevention of end-stage kidney disease are lacking. Side effects including hyperkalemia have previously prevented long-term studies in diabetic kidney disease but new treatment strategies with potassium binders, aldosterone synthase inhibitors and nonsteroidal MRA have been developed for clinical testing.

Publication types

  • Review

MeSH terms

  • Aldosterone / physiology*
  • Cytochrome P-450 CYP11B2 / antagonists & inhibitors*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / prevention & control*
  • Humans
  • Hyperkalemia / drug therapy
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Renin-Angiotensin System / drug effects
  • Risk Factors

Substances

  • Mineralocorticoid Receptor Antagonists
  • Aldosterone
  • Cytochrome P-450 CYP11B2