Long-term nephrotoxicity of cisplatin, ifosfamide, and methotrexate in osteosarcoma

Abstract

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4+/-2.2 (+/-SD) years after chemotherapy (total cumulative dose: methotrexate 41+/-31 g/m2, ifosfamide 39+/-14 g/m2, cisplatin 674+/-188 mg/m2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.

Renal function during and after treatment for acute lymphoblastic leukemia in children

“…Many antineoplastic drugs such as ifosfamide, methotrexate, cisplatin, and carboplatin cause acute or chronic renal failure [1,2,8]. In ALL renal impairment may result from leukemic infiltration or tumor lysis syndrome or be secondary to chemotherapy and supportive treatment [1,2].…”

Evaluation of Novel Biomarkers of Nephrotoxicity in Two Strains of Rat Treated with Cisplatin

“…Therefore, in the absence of glomerular injury, which can cause an increased filtered load that can saturate proximal tubular reabsorption mechanisms resulting in frank proteinuria, the presence of small amounts of albumin in urine is considered indicative of reduced functional (reabsorptive) capacity in the proximal tubules (Russo et al 2007). Microalbuminuria, defined as a urinary albumin loss of 30-300 mg/24 hours, has also been reported in humans treated with cisplatin (Kern et al 2000;Koch Nogueira et al 1998), ifosfamide (Koch Nogueira et al 1998, methotrexate (Koch Nogueira et al 1998), and gentamicin (Tugay et al 2006). However, microalbuminuria may also occur in the setting of vigorous exercise, urinary tract infection, and dehydration .…”

Biomarkers of nephrotoxic acute kidney injury

“…Therefore, microalbuminuria may prove to be a useful marker of AKI and concomitant proximal tubular cell damage. Microalbuminuria has previously been reported with shortterm and long-term administration of nephrotoxic chemotherapeutics (Koch Nogueira et al, 1998;Kern et al, 2000) and antibiotics (Tugay et al, 2006). Microalbuminuria, however, may also occur in the setting of vigorous exercise, hematuria, urinary tract infection, dehydration, fever, and poor glycemic control.…”