Does kidney dysfunction confound 1,5-anhydroglucitol interpretation?

Elevated cystatin C with a reduced cystatin C–based eGFR is consistent with impaired glomerular filtration. In a 70-year-old man, this makes renal physiology directly relevant when interpreting 1,5-anhydroglucitol (1,5-AG), a marker often used to reflect recent hyperglycemic excursions.

Clinical interpretation

• Kidney dysfunction can confound 1,5-AG. The marker is filtered at the glomerulus and normally almost completely reabsorbed in the proximal tubule. Its circulating concentration falls when glucose in the tubular fluid competitively impairs 1,5-AG reabsorption, leading to urinary loss.
• Consequently, 1,5-AG reflects recent glucosuric glucose excursions rather than average glycemia alone. Reduced filtration, nephron loss, altered proximal-tubular transport, and a changed renal glucose threshold can all weaken the usual relationship between low 1,5-AG and high glucose.
• This concern is greatest in advanced renal impairment. Associations between 1,5-AG and glycemic markers persisted at measured GFR values of at least 30 mL/min/1.73 m² but weakened below this level. Another study found eGFR independently associated with 1,5-AG specifically in CKD stages 4–5.

Mechanistic and medication considerations

• The key mechanism is renal handling: glomerular filtration followed by proximal-tubular reabsorption that is disrupted by glucosuria and potentially by CKD-related tubular and filtration changes.
• SGLT2 inhibitors can lower 1,5-AG by deliberately inducing glucosuria, even without worsening glycemia. A low result during SGLT2 treatment therefore should not be interpreted as straightforward evidence of poorer glucose control.

Bottom line

• Kidney dysfunction may meaningfully confound 1,5-AG interpretation. With high cystatin C and low cystatin C–based eGFR, 1,5-AG should be interpreted alongside the degree and persistence of kidney impairment, medication exposure—especially SGLT2 inhibitors—and corroborating glucose measures rather than as an isolated glycemic indicator.