Cancer treatments predisposing to late renal injury and hypertension include specific chemotherapeutic drugs (cisplatin, carboplatin, and ifosfamide), renal radiation therapy, and nephrectomy. Cisplatin can cause glomerular and tubular damage resulting in a diminished glomerular filtration rate (GFR) and electrolyte wasting (particularly magnesium, calcium, and potassium). Approximately 50% of patients may experience long-lasting hypomagnesemia. The use of ifosfamide concurrently with cisplatin increases the risk of renal injury.
Carboplatin is a cisplatin analog and is less nephrotoxic than cisplatin. In a prospective, longitudinal, single-center, cohort study of children followed up for more than 10 years after cisplatin or carboplatin therapy, older age at treatment was found to be the major risk factor for nephrotoxicity, especially for patients receiving carboplatin, while cisplatin dose schedule and cumulative carboplatin dose were also important predictors of toxicity. Platinum nephrotoxicity did not change significantly over 10 years. The combination of carboplatin/ifosfamide may be associated with more renal damage than the combination of cisplatin/ifosfamide.[3,4,5] As with ototoxicity, however, additional follow-up in larger numbers of survivors treated with carboplatin must be evaluated before potential renal toxicity can be better defined.
Ifosfamide can also cause glomerular and tubular toxicity, with renal tubular acidosis, and Fanconi syndrome, a proximal tubular defect characterized by impairment of resorption of glucose, amino acids, phosphate, and bicarbonate. Ifosfamide doses greater than 60 g/m2 to 100 g/m2, age younger than 5 years at time of treatment, and combination with cisplatin and carboplatin increase the risk of ifosfamide-associated renal tubular toxicity.[6,7,8] Abnormalities in glomerular filtration are less common, and when found, are usually not clinically significant. More common are abnormalities with proximal tubular function greater than distal tubular function, although the prevalence of these findings is uncertain, and further study of larger cohorts with longer follow-up is required.[2,9,10,11,12]
A French study that evaluated the incidence of late renal toxicity after ifosfamide reported normal tubular function in 90% of pediatric cancer survivors (median follow-up of 10 years); 79% of the cancer survivors had normal GFR, and all had normal serum bicarbonate and calcium. Hypomagnesemia and hypophosphatemia were seen in 1% of cancer survivors. Glycosuria was detected in 37% of cancer survivors but was mild in 95% of cases. Proteinuria was observed in 12% of cancer survivors. In multivariate analysis, ifosfamide dose and interval from therapy were predictors of tubulopathy, and older age at diagnosis and interval from therapy were predictors of abnormal GFR.