Table 3.

Some identified mechanisms and their possible solutions for limited response to loop diuretics in patients with the nephrotic syndrome

Limitation of ResponseMechanismPotential Solution
ACEI, angiotension-converting enzyme inhibitor; ARB, angiotension receptor blocker; ANP, atrial natriuretic peptide.
Decreased diuretic delivery to the kidneyDecreased serum albumin concentration increases VD and reduces renal diuretic deliveryPremix intravenous diuretic with albumin in syringe
Decreased tubular secretion of active diureticDecreased serum albumin concentration limits proximal secretionDecrease albuminuria with an ACEI or ARB and protein restriction
Increased renal metabolism of furosemideDecreased serum albumin concentration increases tubular uptake and inactivation by glucuronidizationConsider bumetanide or torsemide, which are hepatically metabolized
Decreased blockade of tubular NaCl reabsorptionBinding of free drug to filtered albuminDecrease albuminuria with an ACEI or ARB and protein restriction
Adaptive enhancement of reabsorption in downstream nephron segmentsFunctional adaptation of the distal tubule collecting ductConsider thiazide use with loop diuretic
Enhanced reabsorption in the collecting ductsANP resistanceIncrease dose of diuretic