An unusual cause of severe kidney tubular dysfunction: Answers

Due to her previous history of chemotherapy and clinical symptoms associated with laboratory alterations of hypokalemia, hypophosphatemia, hypomagnesemia, hypocalcemia, hyperchloremia, increased creatinine, metabolic acidosis, proteinuria, and glucosuria, the diagnoses of Fanconi syndrome and urinary concentration deficit secondary to ifosfamide chemotherapy, and acute kidney injury due to hydration deficit were made.

Treatment should be aimed at correcting the acid–base disorder and electrolyte balance. Thus, 45 ml/day sodium citrate and potassium citrate solution (1.06 mEq potassium, 1.14 mEq sodium, and 2.2 mEq citrate/ml of solution), 50 ml/day phosphorus syrup (40 mg elemental phosphorus/ml), 1.5 g/day calcium carbonate, 20 ml/day magnesium pidolate (130 mg magnesium/10 ml), and 6 slow K pills/day (315 mg of potassium/600 mg potassium chloride pill) were administered. The patient stayed in hospital for 45 days and drug doses were adjusted according to laboratory test results. Her serum potassium levels returned to normal, but she remained polyuric. Thus, Moduretic® 1pill/day (50 mg hydrochlorothiazide and 5 mg amiloride) was prescribed. Diuresis decreased from 4000 to 2200 ml. The patient was then discharged from hospital, and was followed up on an outpatient basis every 3–4 weeks, when laboratory tests were performed for drug dosage adjustment. After 11 months of follow-up, the patient has regained weight and remains on replacement therapy (191.6 mEq/day potassium, 4 g/day phosphorus, 264 mEq/day alkaline solution, 68.4 mEq/day sodium, 208 mg/day magnesium, and 1.5 g/day calcium). Her blood test results were: sodium 140 mmol/L, potassium 4.1 mmol/L, magnesium 2.0 mg/dL, calcium 10.7 mg/dL, phosphorus 4.4 mg/dL, bicarbonate 21.5 mmol/L, chloride 102 mg/dL, creatinine 0.8 mg/dL, and urea 21 mg/dL; and urinary tests were pH 7.0, density 1.015, negative protein, + 3 glucose, rare leukocytes, and rare RBCs. A 24-h urine collection revealed a 74% phosphate reabsorption rate. She also continues to take 1 pill/day of Moduretic (50 mg hydrochlorothiazide and 5 mg of amiloride) and is under polyuria control.

Among the chemotherapeutic agents used, ifosfamide is the one associated with the clinical and laboratory features seen in our patient. Ifosfamide-induced kidney damage is clinically manifested primarily by the following signs of tubular dysfunction: hypophosphatemia, proximal tubular cell dysfunction, kidney potassium wasting, kidney tubular acidosis, and/or polyuria [1, 2]. Hypophosphatemia induced by decreased proximal phosphate reabsorption can lead to rickets in children or osteomalacia in adults [3]. In patients with tubulopathy, a reduction of 24% in phosphate reabsorption rate has been reported [3]. Proximal tubular cell dysfunction (Fanconi syndrome) is manifested by glucosuria, bicarbonaturia, aminoaciduria, and tubular proteinuria [4]. Drug-induced Fanconi syndrome is described more frequently in children than in adults, with an incidence of 1–7% whereas the subclinical form occurs in 9–15% of patients [5, 6]. Kidney potassium loss can cause severe hypokalemia that may lead to polyuria and muscle weakness [1, 3, 4]. Kidney tubular acidosis with normal anion gap (hyperchloremia) characterizes severe metabolic acidosis [1, 4]. Polyuria due to nephrogenic diabetes insipidus is relatively rare [1, 4].

The persistently severe hypomagnesemia shown by our patient may also have resulted from the administration of cisplatin. Hypomagnesemia is reported in 10–30% of chldren treated with cisplatin [1].