The Forgotten Antiproteinuric Properties of Diuretics

Am J Nephrol. 2021;52(6):435-449. doi: 10.1159/000517020. Epub 2021 Jul 7.

Abstract

Background: Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration.

Summary: Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.

Keywords: Aldosterone antagonists; Diuretics; Proteinuria; Sodium-glucose cotransporter-2 inhibitors; Thiazides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Chlorthalidone / therapeutic use
  • Combined Modality Therapy
  • Diet, Sodium-Restricted*
  • Diuresis / drug effects
  • Diuretics / pharmacology
  • Diuretics / therapeutic use*
  • Humans
  • Hypertension / drug therapy
  • Indapamide / therapeutic use
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Natriuresis / drug effects
  • Proteinuria / diet therapy*
  • Proteinuria / drug therapy*
  • Proteinuria / prevention & control
  • Sodium Chloride Symporters / drug effects
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Thiazides / pharmacology
  • Thiazides / therapeutic use*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Diuretics
  • Mineralocorticoid Receptor Antagonists
  • Sodium Chloride Symporters
  • Sodium Potassium Chloride Symporter Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiazides
  • Indapamide
  • Chlorthalidone