Furosemide's diuretic effect is diminished in nephrotic syndrome despite normal renal function. The primary reason is:

• A Reduced GFR due to heavy proteinuria prevents tubular delivery of furosemide
• B Hypoalbuminaemia increases the volume of distribution, reducing plasma drug concentration
• C Urinary albumin binds furosemide in the tubular lumen, reducing the free drug available to inhibit the NKCC2 transporter in the loop of Henle ✓
• D Nephrotic patients have downregulated NKCC2 transporters due to chronic oedema

Explanation

Furosemide acts from the luminal (tubular) side of the thick ascending limb of the loop of Henle. It enters the tubular lumen primarily via organic anion transporters (OAT1/3) in the proximal tubule. In nephrotic syndrome, massive proteinuria delivers large amounts of albumin to the tubular lumen; since furosemide is highly protein-bound, urinary albumin sequesters free furosemide in the tubule, dramatically reducing the concentration available to inhibit NKCC2. This 'urinary protein binding' explains diuretic resistance.

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

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Written and medically reviewed by the StethoPrep medical team.