A patient with nephrotic syndrome is on furosemide but shows poor diuretic response. The mechanism of this 'loop diuretic resistance' unique to the nephrotic state is:

• A Hypoalbuminemia reduces furosemide plasma protein binding, increasing its volume of distribution and renal clearance
• B Nephrotic glomerulopathy reduces furosemide filtration at the glomerulus, decreasing tubular drug delivery
• C Heavy albuminuria means furosemide is bound to urinary albumin in the tubular lumen, reducing free drug available to inhibit NKCC2 ✓
• D Elevated urinary aldosterone in nephrotic syndrome directly competes with furosemide for the NKCC2 binding site

Explanation

Furosemide acts from the luminal (tubular) side of the thick ascending limb by inhibiting NKCC2 transporters. It is a highly protein-bound drug (>98%) and reaches the tubular lumen primarily by active secretion via OAT1/3 in the proximal tubule (not by filtration). In nephrotic syndrome, massive albuminuria means the tubular fluid contains high albumin concentrations; furosemide binds avidly to this intraluminal albumin. The bound furosemide-albumin complex cannot interact with NKCC2, greatly reducing the free drug available for its pharmacological effect. Adding albumin infusion before furosemide can partially restore responsiveness in clinical practice.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.