Unraveling Amphotericin-Induced Kidney Complications: Type 3 Renal Tubular Acidosis (RTA), Fanconi Syndrome, and Pseudohypophosphatemia

Introduction: Understanding the renal consequences of amphotericin is crucial in clinical practice, as it can cause type 3 RTA, as well as pseudohypophosphatemia Case Description: 35-year-old male was found down and subsequently diagnosed with Staphylococcus and Enterococcus bacteremia, followed by candidemia. He had a liver transplant and a prolonged hospital course complicated by a cecal perforation, Candida retinitis, pancreatitis and a cerebellar abscess. He underwent a craniotomy, and cultures revealed Aspergillus fumigatus. Amphotericin was initiated systemically and intrathecally. Nephrology consulted for polyuria, hypomagnesemia and hypophosphatemia. He experienced polyuria (5L/day) with a negative water deprivation test. The polyuria was due to osmotic diuresis, with a total daily osmolar output of 1750 mosm. Fanconi syndrome was confirmed by: a fractional excretion of magnesium (Mg) of 22% (serum Mg: 1 mg/dL, 24-hour urine Mg: 362 mg) and a fractional excretion of phosphorus (P) of 31% (serum P: 1.3 mg/dL, 24-hour urine P: 1184 mg), alongside glycosuria with normoglycemia and hyperuricosuria with hypouricemia The presence of a non-anion gap metabolic acidosis (bicarbonate: 19 mmol/L), a positive urine anion gap, a urine pH of 7, and a urine osmolal gap of 18.4 were noted. He was maintained on oral Mg and P supplements. Upon re-initiation of amphotericin a few weeks later, he developed hypophosphatemia. We relayed our concerns to the clinical pathologist, who, after reviewing the spectrophotometric curves, suggested pseudohypophosphatemia. His phosphorus levels normalized after amphotericin was discontinued Discussion: Differentiation between proximal and distal RTA can be achieved by assessing the fractional excretion of bicarbonate after a bicarbonate challenge (typically elevated in proximal RTA) or by evaluating the urine osmolar gap (low in distal RTA). The typical renal response to chronic metabolic acidosis involves increased ammonium excretion, potentially exceeding 200 meq/day. This patient's urine osmolar gap was consistent with distal RTA, but he also had proximal RTA and Fanconi's syndrome. Notably, amphotericin can cause type 3 RTA, a rare mixed type 1 and type 2 disorder. Pseudohypophosphatemia, another potential consequence of amphotericin, warrants inclusion in the differential diagnosis