Table 2.

Some identified mechanisms and their possible solutions for limited response to loop diuretics in patients with renal insufficiency

Limitation of ResponsePotential MechanismPotential Solution
OAT, organic anion transporter; TSC, thiazide-sensitive cotransporter.
Decreased renal diuretic deliveryDecreased renal blood flowOptimize BP and body fluids to restore renal blood flow
Decreased basal fractional NaCl reabsorptionLimits effects of less-active diureticsSelect a loop, not a thiazide, as initial diuretic
Decreased proximal tubule diuretic secretionCompetition with urate and organic anions for basolateral uptake by OATCorrect uremic milieu and hyperuricemia
Acidosis impairs secretionCorrect acidosis
Competition with drugs for tubular secretion by OATAvoid codosing with probencid, NSAIAs, β-lactam and sulphonamide antibiotics, valproic acid, methorexate, cimetidine, and antiviral agents
Maintained metabolic but decreased renal clearance (furosemide only)Hepatic metabolism of bumetanide and torsemide preservedConsider bumetanide or torsemide to prevent accumulation and ototoxicity at high plasma levels
Enhanced NaCl reabsorption in downstream segmentsEnhanced distal tubule fluid and NaCl deliveryUse thiazide or metolazine with loop diuretic in resistant patients
Enhanced TSC expression