A healthy volunteer receives intravenous glucose in gradually increasing doses. Glycosuria first appears when plasma glucose crosses approximately 200 mg/dL, although the calculated filtration load at which individual nephrons saturate corresponds to a plasma level near 260 mg/dL when averaged across all nephrons. What explains the appearance of glucose in urine well before the average maximal transport rate is reached?

• A Increased glomerular capillary hydrostatic pressure raising single-nephron GFR unevenly
• B Nephron-to-nephron variation in SGLT2 capacity, causing some nephrons to saturate early, known as splay ✓
• C Saturation of basolateral GLUT2 transporters in the proximal tubule
• D Inhibition of SGLT2 by rising plasma insulin concentrations

Explanation

The titration curve of glucose excretion does not rise sharply at the theoretical Tm; instead it curves gradually, a phenomenon called splay. Its main basis is anatomic heterogeneity: individual nephrons differ in glomerular size and proximal tubular transport capacity, so low-capacity nephrons spill glucose while others still reabsorb normally. GLUT2 sits on the basolateral membrane but is not rate limiting at these loads. Insulin does not regulate SGLT2 activity, and the splay occurs below, not above, the mean saturation point.

Reference: Vander's Renal Physiology, 8th ed.

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