Nephrotoxicity

Nephrotoxicity was noted initially in early-phase studies of cisplatin-based chemotherapy; a decreased glomerular filtration rate and elevated serum creatinine occurred in up to 36% of patients.16 Modern cisplatin administration schedules incorporating forced saline diuresis1317 have decreased the rate of significant renal impairment to fewer than 5% of patients.141718 Less commonly, damage to the proximal convoluted tubules can result in a magnesium-wasting nephropathy, which can cause hypo-magnesemia severe enough to precipitate cerebral seizures.19,20 This can be prevented using intravenous and oral magnesium replacement.

When renal biopsy specimens from patients with cisplatin-induced renal damage have been examined, several histologic patterns have been observed. These include acute focal necrosis of the distal convoluted tubules and collecting ducts, dilatation of the convoluted tubules, and the formation of casts1621(Table 27-1).

Although cisplatin is responsible for the majority of the nephrotoxicity observed during the treatment of germ cell tumors, a number of other drugs may contribute to the problem. In particular, methotrexate is also excreted by the kidneys and can cause an interstitial nephritis when used as a single agent. In combination with cisplatin, such as in the cisplatin/vincristine/methotrexate/bleomycin and actinomycin D/cyclophosphamide/etoposide (POMB/ACE) regimen used for poor-prognosis tumors,22 these nephrotoxic effects may become synergistic (see Chapter 14). Additional nephrotox-ins may also be introduced in the form of aminogly-coside antibiotics used in the management of febrile neutropenia and may exacerbate renal impairment due to cytotoxic agents.

Downstream from the kidneys, ifosfamide is well known to cause hemorrhagic cystitis.23 Once established, hemorrhagic cystitis is difficult to treat; thus, prevention is important. Aggressive hydration, continuous infusion schedules, and the use of mesna (a sulfhydryl compound that binds the degradation products of ifosfamide within the bladder) have reduced the incidence of this complication from 18 to 40% of patients to 5 to 10% of patients.923

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