Acute Kidney Injury After Accelerated Dosing of Tirzepatide in a Patient with Multiple Comorbidities: A Case Report.

BACKGROUND Tirzepatide is effective for glycemic control and weight management in type 2 diabetes and obesity. Clinical trials have demonstrated tirzepatide's lower risk of acute kidney injury (AKI) compared with existing glucagon-like peptide-1 receptor agonists, along with benefits including reduced albuminuria and stable estimated glomerular filtration rate. Rare cases of AKI have been reported, potentially associated with dehydration from gastrointestinal side effects, polypharmacy, or comorbidities. We describe AKI in a non-diabetic, multimorbid patient after rapid tirzepatide dose escalation, underscoring the importance of identifying susceptible patient phenotypes. CASE REPORT A 66-year-old man with morbid obesity (body mass index 61.4 kg/m²), hypertension, prediabetes, hypothyroidism, and polypharmacy presented for weight management before bariatric surgery. Tirzepatide was initiated at 2.5 mg weekly and escalated to 12.5 mg over 4 months, resulting in weight loss of 35 kg. Preoperative evaluation revealed AKI, with a serum creatinine level of 2.4 mg/dL, potassium of 6.8 mmol/L, and metabolic acidosis (pH 7.31). Potential contributors included pharmacodynamic interactions with antihypertensive agents or dehydration secondary to gastrointestinal side effects. Management involved intensive care unit admission, antihyperkalemic therapy, intravenous fluids, and tirzepatide discontinuation. Renal function improved (creatinine 1.18 mg/dL) by discharge. CONCLUSIONS The AKI in this case may have resulted from the combination of rapid tirzepatide dose escalation, polypharmacy, and multimorbidity, potentially compounded by subclinical volume depletion or hemodynamic alterations. Clinicians should utilize standard titration schedules, closely monitor blood pressure and renal function, and exercise caution in patients with complex medication regimens to maximize tirzepatide's therapeutic benefits while minimizing renal risk.