Overview
Renal Mechanism and the Early eGFR Dip
SGLT2 inhibitors include empagliflozin, dapagliflozin, and canagliflozin.
SGLT2 inhibitors include empagliflozin, dapagliflozin, and canagliflozin. They act in the proximal convoluted tubule, where the sodium-glucose cotransporter 2 normally reabsorbs most filtered glucose back into the bloodstream. Blocking this transporter leaves glucose and sodium in the tubular fluid. Glucose is then excreted in urine, producing an insulin-independent reduction in plasma glucose. Sodium loss produces mild natriuresis and an osmotic diuresis. Because the medication does not stimulate insulin release, it does not usually cause hypoglycaemia when used alone. More sodium reaches the macula densa in the distal nephron. The kidney interprets this as improved filtration and restores tubuloglomerular feedback, increasing afferent arteriolar tone. In the first weeks after starting therapy, eGFR commonly falls and serum creatinine rises modestly. This is an expected haemodynamic effect, not acute kidney injury by itself. The longer-term pattern matters more than the first creatinine value. SGLT2 inhibitors slow the rate of kidney function decline over time. Do not assume that an early eGFR dip means the drug is harming the kidneys. Instead, assess the whole picture: volume status, blood pressure, symptoms, urine output, concurrent illness,...
