A 55-year-old woman with type 2 diabetes and eGFR 45 mL/min/1.73m² is started on a SGLT-2 inhibitor. Which haemodynamic mechanism most directly reduces her cardiorenal risk beyond glycaemic control?

• A Inhibition of the renin-angiotensin-aldosterone system at the juxtaglomerular apparatus
• B Reduction in tubuloglomerular feedback by lowering proximal sodium reabsorption ✓
• C Direct suppression of NF-κB inflammatory signalling in mesangial cells
• D Increased renal prostaglandin synthesis restoring afferent arteriolar tone

Explanation

SGLT-2 inhibitors reduce proximal tubular sodium reabsorption, increasing distal NaCl delivery to the macula densa, which restores tubuloglomerular feedback-mediated afferent arteriolar vasoconstriction, thereby lowering intraglomerular hypertension — the primary cardiorenal haemodynamic mechanism. This is independent of glycaemic effects and has been demonstrated in trials such as CREDENCE and DAPA-CKD. RAAS inhibition and anti-inflammatory effects occur indirectly or secondarily.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.