Key words: ifosfamide; nephrogenic diabetes insipidus; total dose of ifosfamide was reduced to 11.9 g, and the dose per day to 2.38 g. During the fourth cycle, ...
Nephrol Dial Transplant (1998) 13: 1547–1549
Nephrology Dialysis Transplantation
Case Report
Ifosfamide-induced renal Fanconi syndrome with associated nephrogenic diabetes insipidus in an adult patient Aurelio Negro, Giuseppe Regolisti, Franco Perazzoli, Simona Davoli, Carlo Sani and Ermanno Rossi II Divisione di Medicina Interna, Arcispedale S. Maria Nuova, Reggio Emilia, Italy
Key words: ifosfamide; nephrogenic diabetes insipidus; renal Fanconi syndrome; tubular dysfunction
Introduction Ifosfamide is an alkylating agent with remarkable activity against a wide range of tumours; it may be given as a single agent or combined with other cytotoxic drugs.The adverse effect most frequently reported is haemorrhagic cystitis. However, the increasing use of ifosfamide has revealed that nephrotoxicity is a potentially serious complication which may include tubular dysfunction and occasionally glomerular impairment [1,2]. Fanconi syndrome is a complex of multiple tubular dysfunctions occurring alone or in association with a variety of acquired or congenital disorders. It is characterized by glycosuria, aminoaciduria and excessive urinary excretion of phosphorus, calcium, uric acid, bicarbonate, potassium, sodium, magnesium and LMW proteins [3]. Ifosfamide has been reported to cause this syndrome in the paediatric population and, less frequently, in adults [4]. We report on a case of ifosfamide-induced Fanconi syndrome in an adult patient with cancer.
total dose of ifosfamide was reduced to 11.9 g, and the dose per day to 2.38 g. During the fourth cycle, of 4 days only, the total dose was 10 g, and the dose per day was 2.5 g. Before and during each cycle of chemotherapy, the patient was hydrated with intravenous fluids. A previous course of chemotherapy had been carried out with a different drug schedule (cyclophosphamide, methotrexate, and 5-fluorouracil ); no cisplatin had been used. Before admission, routine blood chemistry and urinalysis yielded normal results, except for alkaline phosphatase (904 U/l ) and lactic dehydrogenase (1606 U/l ) values. Serum phosphorus was 1.13 mmol/l. No plasma bicarbonate values were available. Previous radiographs revealed multiple lytic bone lesions. At presentation the patient was febrile and dehydrated. The electrocardiogram showed U-wave and depression of the ST segment. Thoracic radiographs did not reveal pneumonia. Skeletal radiographs showed diffuse reduction of bone mineral density and cortical thinning. No photon densitometry was performed. Laboratory findings are shown in Table 1. Intravenous fluids and oral supplements of potassium phosphate, magnesium sulphate, low-dose bicarbonate, calcium carbonate and calcitriol were started. Serum concentrations and renal function returned to normal values within 20 days of continuous supplementation. No further data were available, because the patient died 2 weeks later.
Case report A 48-year-old woman with metastatic breast cancer was admitted to our clinic for fever, pancytopenia, polyuria, polydypsia, and profound muscle weakness. She had received five cycles of chemotherapy, the last of which was 1 week prior to admission. The drug regimen included ifosfamide (41 g/m2 total dose 65.2 g) and the uroprotective agent mesna (total dose 34.4 g). During the first two cycles of 5 days each, the total dose was 15.7 g, and the dose per day was 3.14 g. During the third and fifth cycle of 5 days each, the Correspondence and offprint requests to: Dr Aurelio Negro MD, II Divisione di Medicina Interna, Pad. ‘L. Spallanzani’, Viale Umberto I, 50, I-42100 Reggio Emilia, Italy.
Discussion Ifosfamide is a cytotoxic drug used in the treatment of various tumours in adults and children. Nephrotoxicity in humans was first described in 1972 [5], and subsequent reports have defined the range of renal damage seen after treatment with ifosfamide. Toxicity involves both proximal and distal segments of the renal tubule. The impairment of GFR is usually only moderate and secondary to tubular dysfunction. The severity of toxicity spans from subclinical or biochemical evidence of renal damage to a clinically relevant syndrome [1]. Fanconi syndrome is a rare sequela of chemotherapy with ifosfamide, described mainly in the paediatric
© 1998 European Renal Association–European Dialysis and Transplant Association
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Table 1. Laboratory findings at presentation Parameter Serum BUN (mmol/l ) Creatinine clearance, (ml/min/1.73 m2) Albumin (g/l ) Total calcium (mmol/l ) Phosphorus (mmol/l ) Sodium (mmol/l ) Magnesium (mmol/l ) pH Osmolality (mOsm/kg) Urine Urinary volume ( l/24 h) Glucose (dipstick) Osmolality (mOsm/kg) Bicarbonate (mmol/24 h) Sodium (mmol/24 h) Total protein (g/24 h) b -microglobulin (mg/24 h) 2 Fractional TRP (%)
Case findings
5.3 64 23 1.6 0.3 154 0.4 7.38 318 7.5 2+ 80 46 221 2.4 134.4 65
Normal values
Parameter
3.6–8.2 90–125
Creatinine (mmol/l ) Total protein (g/l )
33–52 2.1–2.6 0.9–1.4 136–146 0.8–1.1 7.36–7.44 285–295
Uric acid (mmol/l ) Ionized calcium (mmol/l ) Potassium (mmol/l ) Chloride (mmol/l ) iPTH (pg/ml ) Bicarbonate (mmol/l )
— 0–5.0 — — 85
Protein (dipstick) pH Amino acid Potassium (mmol/24 h) Uric acid (mg/24 h) Albumin (mg/24 h) Renal phosphorus threshold
Case findings
Normal values
97.2 62
53–124 55–80
65.4 0.8 2.1 122 120 17
142–416 1.0–1.3 3.5–5.3 95–110 10–70 22–28
1+ 7.0 FF 122 2120 115 0.5 (mmol/l )
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