Transient proximal tubular dysfunction (Fanconi-like Syndrome) associated with semaglutide therapy in the setting of rapid weight loss and severe dietary restriction: a diagnostic challenge

Semaglutide is generally regarded as renoprotective, although acute kidney injury from volume depletion or interstitial nephritis has been reported. Fanconi-like proximal tubular dysfunction has not been well characterized with this agent. A 34-year-old woman with obesity lost 15.2 kg (15.8% of her body weight) over 12 weeks of semaglutide therapy while eating roughly one meal per day, without vomiting or diarrhea. She presented with fatigue, weakness, and orthostatic dizziness and was found to be volume depleted, with acute kidney injury (creatinine 0.78 to 1.82 mg/dL), hypokalemia, hypophosphatemia, mild normal anion gap metabolic acidosis, normoglycemic glucosuria, phosphaturia, uricosuria with hypouricemia, and proteinuria associated with proximal tubular dysfunction (urinary β2-microglobulin markedly elevated), consistent with an acquired Fanconi-like tubulopathy. Alternative causes, including paraproteinemia, autoimmune disease, and infection, were excluded, and there was no history of exposure to heavy metals or other nephrotoxins. No kidney biopsy was performed, so interstitial nephritis could not be excluded histologically. Semaglutide was stopped, and she received hydration, electrolyte repletion, and nutritional rehabilitation. Renal function normalized and tubular markers improved markedly within four weeks, with sustained recovery at three months. The Naranjo score was 4 (possible adverse drug reaction). Rapid weight loss with severe caloric and protein restriction during semaglutide therapy may be associated with a reversible Fanconi-like proximal tubulopathy, probably of multifactorial origin (drug-related appetite suppression, self-directed dietary restriction, and volume depletion). Clinicians should monitor renal function, electrolytes, and nutritional adequacy during rapid weight loss on GLP-1 receptor agonist therapy. Not applicable.