Comparing the Effects of Different Diuretic Agents on Renal Function, Electrolyte Balance, and Survival in Rats: A Systematic Review
Abstract
Diuretics alleviate fluid retention and electrolyte abnormalities; however, comparative preclinical animal studies remain limited. This systematic review evaluated the effects of loop diuretics (furosemide), thiazide diuretics (hydrochlorothiazide), and potassium-sparing agents (amiloride, triamterene) on renal function, electrolyte balance, and survival in rats. PRISMA 2020 guidelines were followed to search PubMed, Web of Science, and Google Scholar for comparative studies published between 2015 and 2025 investigating diuretic effects on glomerular filtration rate, creatinine clearance, urinary sodium/potassium/chloride excretion, plasma electrolytes, kidney injury biomarkers, and survival in rats. Dual screening and data extraction were performed independently by two reviewers, and risk of bias was assessed using the ARRIVE 2.0 checklist. Twelve studies (440 rats) were included. Thiazides (1.3–2.0-fold) and potassium-sparing agents (1.1–1.4-fold) increased urine volume less than loop diuretics (2.8–3.5-fold). Loop diuretics increased urinary potassium excretion and reduced plasma potassium to clinically dangerous levels (2.3–2.5 mmol/L), increasing the risk of hypokalemia by 2.3–3.2-fold. Thiazides showed moderate efficacy but also posed a significant risk of hypokalemia (1.5–1.9-fold K⁺ loss). Combination therapy with loop and potassium-sparing agents increased diuretic efficacy by 30–94% and reduced electrolyte disturbances by 30–50%. Diuretic resistance (approximately…
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Evidence Hub reads this as a systematic review, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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