4.5 Review

The Forgotten Antiproteinuric Properties of Diuretics

Journal

AMERICAN JOURNAL OF NEPHROLOGY
Volume -, Issue -, Pages -

Publisher

KARGER
DOI: 10.1159/000517020

Keywords

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

Funding

  1. Red de Investigacion Renal (RedInRen) [RD12/0021/0029]
  2. ISCIII [PI 16/01685/FEDER]

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Diuretics, including thiazides, mineralocorticoid receptor antagonists, and other types, have potential antiproteinuric properties. SGLT2 inhibitors have shown revolutionary effects in kidney and heart protection, with their early antiproteinuric effect being predictive of long-term kidney function preservation.
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.

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