Kidney Week

Abstract: FR-PO0871

Beyond Hyperkalemia: Hyponatremia Induced by Trimethoprim-Sulfamethoxazole

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Case Reports - 1
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Ahmed, Zahoor, Jefferson Einstein Philadelphia Hospital, Philadelphia, Pennsylvania, United States

Zahoor Ahmed, MD

• Laroia, Aprajita, Jefferson Einstein Philadelphia Hospital, Philadelphia, Pennsylvania, United States

Aprajita Laroia, MD, MBBS

• Shin, Ji Young, Jefferson Einstein Philadelphia Hospital, Philadelphia, Pennsylvania, United States

Ji Young Shin, MD

• Chewaproug, Daranee, Jefferson Einstein Philadelphia Hospital, Philadelphia, Pennsylvania, United States

Daranee Chewaproug, DO, FASN

Introduction

Trimethoprim-sulfamethoxazole (TMP-SMX) is first-line therapy for Pneumocystis jirovecii pneumonia (PJP). Despite its effectiveness, TMP-SMX is associated with clinically significant electrolyte disturbances, most commonly hyperkalemia, but also hyponatremia. Although hyponatremia is a recognized adverse effect of TMP-SMX, it remains an uncommon and underreported complication in literature.

Case Description

A 44-year-old man with history of HIV, medication nonadherence, CD4 count of 40 cells/µL, and high viral load admitted for evaluation of dyspnea, tachycardia, and hypoxemic respiratory failure. Imaging showed multifocal pulmonary infiltrates, and he was started on TMP-SMX (Bactrim DS x 2 q8 hourly) due to concern for PJP. Serum sodium on presentation was 134 mEq/L with normal baseline kidney function. Sodium decreased to 125 mEq/L on the 4^th day after starting TMP-SMZ. Serum sodium fluctuated between 125–129 mEq/L despite IV fluids, ruling out hypovolemic hyponatremia. Urine studies showed urine sodium of 101 mEq/L and urine osmolality: 321 mOsm/kg. He was placed on fluid restriction for his euvolemic hyponatremia and suspected SIADH. However, his serum sodium did not improve. After ruling out diuretic use, adrenal insufficiency, and hypothyroidism, hyponatremia induced by TMP-SMX was confirmed as patient also had concomitant hyperkalemia (5.1-5.4 mEq/L), non-anion gap metabolic acidosis, and mild creatinine rise, supporting TMP-SMX–related tubular effects. TMP-SMX was discontinued and switched to atovaquone resulting in sodium level rise to 132 mEq/L in three days, and electrolytes were monitored closely.

Discussion

TMP-SMX acts by blocking epithelial sodium channels in distal nephron, causing natriuresis, hyperkalemia, non-anion gap metabolic acidosis, and hyponatremia. Hyponatremia is less common with standard dose TMP-SMX and can occur in about 17.5% of patients. TMP-SMX induced hyponatremia is especially prominent in elderly patients, especially with CKD and with use of thiazide diuretics. TMP-SMX related hyponatremia likely is underdiagnosed and often mistaken for SIADH. It should be considered for patients on TMP-SMX treatment and should be differentiated from SIADH. TMP-associated hyponatremia can be treated with sodium supplementation to offset ongoing urinary losses, if TMP-SMX therapy cannot be discontinued.