SUN-185 Severe Hyponatremia and Type 4 Renal Tubular Acidosis (Functional Hypoaldosteronism) Secondary to Trimethoprim

Introduction: Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly used antibiotic. We present a case of severe hyponatremia and Type 4 renal tubular acidosis (functional hypoaldosteronism) in a patient treated with TMP-SMX. Clinical Case: A 62 year old gentleman with hypertension, dyslipidemia and a surgically repaired abdominal aortic aneurysm developed an aortic graft infection. He was admitted to hospital for acute right lower limb ischemia with embolic phenomena, and underwent surgical graft explantation. He required multiple courses of antibiotics post operatively. He was initially referred to Endocrinology for severe hyponatremia, deemed likely to be from a salt losing nephropathy secondary to polymyxin. Thyroid function and morning cortisol levels were normal. He was managed with intravenous hypertonic saline and oral salt tablets. The hyponatraemia resolved a week after polymyxin was stopped. Intravenous TMP-SMX was commenced the next day at 240 mg BD. A week later, the hyponatremia recurred, with concomitant hyperkalemia and a normal anion gap metabolic acidosis. The serum sodium was 126 mmol/L (reference interval (RI) 135-145) and the serum osmolality 275 mmol/kg (RI 275- 305). Urine studies showed a high urinary sodium (154 mmol/L) and osmolality (481 mmol/kg), consistent with renal salt wasting. The serum potassium rose to a peak of 6.1 mmol/L (RI 3.5 - 5.0), with a normal anion gap metabolic acidosis (bicarbonate 17 mmol/L (RI 21 – 31)). A paired urine pH of 8 pointed to an inability to acidify the urine. Given the clinical course and laboratory investigations, the diagnosis of TMP-associated hyponatremia and Type 4 RTA was made. Oral resonium was started to correct hyperkalemia, with a combination of oral sodium chloride and sodium bicarbonate used to treat the hyponatremia and metabolic acidosis. Fludrocortisone was not used given the concerns of causing hypertension in a patient with a diseased aortic graft. The dose of TMP-SMX was gradually reduced with improvement of the acid-base and electrolyte abnormalities, lending weight to our diagnosis. After the dose of the TMP-SMX was reduced to 80 mg BD, the hyperkalemia and metabolic acidosis resolved. The oral sodium chloride and sodium bicarbonate were gradually tailed off and stopped after cessation of the TMP-SMX. Clinical Lesson: Trimethoprim blocks the epithelial sodium channel (ENaC) of the principal cells in the terminal portion of the nephron, similar to potassium sparing diuretics like amiloride and triampterene. The resulting hyponatremia, hyperkalemia and metabolic acidosis can be life threatening. Therefore, monitoring of electrolytes and acid base status is important, particularly in susceptible patients or in those where a high dose of trimethoprim is required.