When Trimethoprim-Sulfamethoxazole Turns Pernicious: Type 4 Renal Tubular Acidosis in a Diabetic Patient With Sjögren’s Syndrome

Type 4 renal tubular acidosis (RTA) is an underrecognized but potentially life-threatening complication characterized by hyperkalemic, non-anion gap metabolic acidosis. Trimethoprim-sulfamethoxazole (TMP-SMX), commonly used for treating <i>Pneumocystis jirovecii</i> pneumonia (PCP), has been implicated as a reversible trigger of this condition, especially in metabolically vulnerable patients. We report the case of a 63-year-old woman with type 2 diabetes mellitus and Sjögren's syndrome who developed type 4 RTA during intravenous TMP-SMX therapy for PCP. Although initial arterial blood gas (ABG) analysis showed a near-normal pH, further evaluation revealed decreased serum bicarbonate (HCO₃⁻) and a partial pressure of carbon dioxide (PaCO₂) lower than expected by Winter's formula, consistent with a mixed acid-base disorder. Hyperkalemia and a positive urine anion gap confirmed the diagnosis of type 4 RTA. Distal (type 1) RTA, commonly associated with Sjögren's syndrome, was ruled out based on urine pH and potassium status. TMP-SMX was continued with close monitoring, and the acid-base abnormalities resolved following treatment completion. This case underscores the importance of considering medication-induced type 4 RTA in immunocompromised patients presenting with unexplained hyperkalemia and normal anion gap metabolic acidosis. TMP-SMX, although widely used and effective, necessitates vigilant electrolyte monitoring in susceptible individuals.