Creatinine-Guided Furosemide Therapy: A Pathophysiological Framework for Precision Diuretic Use in Critically Ill Patients

Objective: To propose a physiology-based, creatinine-guided dosing strategy for furosemide administration in critically ill patients with acute decompensated heart failure (ADHF), acute kidney injury (AKI), or chronic kidney disease (CKD), integrating renal function into diuretic decision-making to optimize safety and efficacy.

Data Sources: Relevant literature was identified through searches of PubMed, Embase, and Scopus using the terms furosemide, loop diuretics, diuretic resistance, organic anion transporters, creatinine, and renal dysfunction. Key randomized and mechanistic studies, including the DOSE, Furosemide Stress Test, ADVOR, PUSH-AHF, and ENACT-HF trials, were reviewed.

Data Synthesis: Furosemide efficacy depends on its active tubular secretion via organic anion transporters (OAT1/3). In renal dysfunction, secretion is reduced, uremic toxins compete for transport, and diuretic resistance ensues. Empiric high-dose bolus therapy, common in practice, often leads to suboptimal response or toxicity. A physiologically derived dosing framework is proposed in which the minimum daily dose of furosemide (mg) equals serum creatinine (mg/dL × 88), applicable up to 5 mg/dL. This rule reflects the relationship between creatinine, tubular drug delivery, and the pharmacodynamic threshold for antidiuresis.

Conclusions: Serum creatinine serves as a practical surrogate for furosemide delivery to its site of action. The proposed creatinine-guided dosing rule provides a rational, individualized approach to diuretic therapy that may improve decongestion efficacy while reducing risk of renal and electrolyte complications in critically ill patients.

Keywords: Furosemide, Loop diuretics, Acute decompensated heart failure, Acute kidney injury, Chronic kidney disease, Diuretic resistance, Creatinine-guided dosing, Critical care