Case Presentation: A 60-year-old female with history of hypertension and diabetes on valsartan and amlodipine presented with acute onset dizziness, recurrent falls, and oliguria two months after empagliflozin initiation. The physical exam was significant for tachycardia, hypotension, and gait unsteadiness. Imaging studies excluded acute cerebrovascular events. Labs revealed acute kidney injury with creatinine 7 mg/dL (baseline 1.3 mg/dL seven months prior) and BUN 99 mg/dL. Urinalysis showed bacteriuria, hyaline casts, and calcium oxalate crystals. Clinical and lab findings suggested acute tubular necrosis, with empagliflozin likely contributory per family history of starting the drug two months prior. Workup excluded thrombotic microangiopathy, post-infectious glomerulonephritis, and vasculitis; serologies were negative, and CT abdomen showed no obstruction. The patient received hemodialysis on hospital day 2, after which urine output and mental status were normalized. Renal function and creatinine kinase trended to normal; patient was discharged on hospital day 5.
Discussion: Empagliflozin combined with concomitant antihypertensive agents created a high-risk scenario for volume depletion and hemodynamic compromise. SGLT2 inhibitors induce osmotic diuresis and natriuresis through inhibition of proximal tubular glucose and sodium reabsorption. ACE inhibitors/ARBs amplify the risk of AKI through synergistic hemodynamic effects: SGLT2i increases NaCl delivery to the macula densa causing afferent arteriolar vasoconstriction, while ACE-I/ARBs cause efferent arteriolar vasodilation, together decreasing glomerular filtration pressure and GFR, particularly during SGLT2 inhibitor-induced volume contraction. Concurrent urinary tract infection further exacerbated renal hypoperfusion. This case represents a rare but recognized complication associated with SGLT2 inhibitors. Rapid renal function recovery following dialysis and volume optimization, with valsartan and amlodipine held, indicates reversible hemodynamic and tubular dysfunction rather than permanent parenchymal injury. The combination of volume depletion, triple antihypertensive therapy, hypotension, and concurrent infection precipitated renal hypoperfusion and tubular injury. Although SGLT2 inhibitors provide net kidney protection in vast majority of cases, this case demonstrates the importance of careful patient selection, avoiding excessive hemodynamic-active agent combinations, baseline and periodic renal monitoring, and heightened vigilance for volume depletion and acute illness in patients receiving SGLT2 inhibitors.
Conclusions: This case illustrates an important paradox: a renal-protective medication causing acute kidney injury. Although SGLT2 inhibitors reduce AKI risk in most populations, empagliflozin combined with concomitant antihypertensive agents disrupted renal hemodynamics, precipitating acute tubular necrosis. Rapid recovery following a single session of dialysis and volume optimization suggested this was a preventable iatrogenic complication rather than inherent drug toxicity. Clinicians must recognize that SGLT2 inhibitor benefits do not apply universally and require careful consideration of concurrent medications and baseline renal function to prevent unintended hemodynamic compromise.