Some identified mechanisms and their possible solutions for limited response to loop diuretics in patients with the nephrotic syndrome
| Limitation of Response | Mechanism | Potential Solution |
|---|---|---|
| ACEI, angiotension-converting enzyme inhibitor; ARB, angiotension receptor blocker; ANP, atrial natriuretic peptide. | ||
| Decreased diuretic delivery to the kidney | Decreased serum albumin concentration increases VD and reduces renal diuretic delivery | Premix intravenous diuretic with albumin in syringe |
| Decreased tubular secretion of active diuretic | Decreased serum albumin concentration limits proximal secretion | Decrease albuminuria with an ACEI or ARB and protein restriction |
| Increased renal metabolism of furosemide | Decreased serum albumin concentration increases tubular uptake and inactivation by glucuronidization | Consider bumetanide or torsemide, which are hepatically metabolized |
| Decreased blockade of tubular NaCl reabsorption | Binding of free drug to filtered albumin | Decrease albuminuria with an ACEI or ARB and protein restriction |
| Adaptive enhancement of reabsorption in downstream nephron segments | Functional adaptation of the distal tubule collecting duct | Consider thiazide use with loop diuretic |
| Enhanced reabsorption in the collecting ducts | ANP resistance | Increase dose of diuretic |