Some identified mechanisms and their possible solutions for limited response to loop diuretics in patients with renal insufficiency
| Limitation of Response | Potential Mechanism | Potential Solution |
|---|---|---|
| OAT, organic anion transporter; TSC, thiazide-sensitive cotransporter. | ||
| Decreased renal diuretic delivery | Decreased renal blood flow | Optimize BP and body fluids to restore renal blood flow |
| Decreased basal fractional NaCl reabsorption | Limits effects of less-active diuretics | Select a loop, not a thiazide, as initial diuretic |
| Decreased proximal tubule diuretic secretion | Competition with urate and organic anions for basolateral uptake by OAT | Correct uremic milieu and hyperuricemia |
| Acidosis impairs secretion | Correct acidosis | |
| Competition with drugs for tubular secretion by OAT | Avoid 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 preserved | Consider bumetanide or torsemide to prevent accumulation and ototoxicity at high plasma levels |
| Enhanced NaCl reabsorption in downstream segments | Enhanced distal tubule fluid and NaCl delivery | Use thiazide or metolazine with loop diuretic in resistant patients |
| Enhanced TSC expression | ||