Cyclophosphamide nephrotoxicity

Even low-dose intravenous cyclophosphamide can cause a syndrome that resembles inappropriate secretion of antidiuretic hormone, with severe hyponatremia and symptoms of water intoxication (SEDA-19, 347 SEDA-21, 386). A direct effect on the renal tubules is likely, but no other nephrotoxic effects have been documented. 

Adverse Effects. Cyclophosphamide is used very cautiously as an immunosuppressant because of the possibility of severe side effects, including carcinogenic effects during long-term use. Other side effects include hematologic disorders (leukopenia, thrombocytopenia), cardiotoxicity, nephrotoxicity, and pulmonary toxicity. 

Cyclophosphamide can also cause tubular necrosis in experimental animals [82]. No clinical nephrotoxicity has been described, even when carefully assessed in patients receiving high doses of cyclophosphamide [83, 84]. Although there are no detectable alterations of renal function tests, some subtle changes in tubular kidney physiology do occur. Bode and associates [85] studied the mechanism of water retention that occurs from cyclophosphamide. They determined that cyclophosphamide directly affected the tubules, causing increased water resorbtion and sodium loss. This water retention is self-limited and lasts only a day or two. It is not a major clinical problem. 

Cyclophosphamide, a nitrogen mustard alkylating agent, is a widely used cancer chemotherapeutic drug to treat lymphomas, leukemias, multiple myeloma and a numerous solid tumors. Cyclophosphamide can induce nephrotoxicity characterized as decreased water excretion and an inappropriate concentration of urine. These effects are due to a direct effect of one or more alkylating cyclophosphamide metabolites at distal tubules and collecting ducts. Special caution is warranted to avoid water-induced diuresis or diuretic therapy in these patients as hyponatremia can become a problem. 

Carboplatin and cyclophosphamide are indicated in the treatment of advanced ovarian carcinoma. Cisplatin and carboplatin produce predominantly interstrand DNA crosslinks rather than DNA-protein cross-links, and the effect is cell-cycle nonspecific. Carboplatin is not bound to plasma proteins, whereas platinum from carboplatin becomes bound to plasma protein and is eliminated slowly with a half-life of 5 days. The major route of elimination of carboplatin is the kidneys, and its doses should be reduced in renal impairment. Furthermore, the coadministration of aminoglycosides increases the chance of nephrotoxicity. Carboplatin causes anemia, neutropenia, leukopenia, and thrombocytopenia requiring transfusions. Cisplatin and, to a lesser extent, carboplatin cause emesis, which requires treatment with antiemetic agents. Alopecia, pain, and asthenia do occur (see also Figure 15). 

It bears repeating that there is a significantly higher risk of bladder toxicity and nephrotoxicity with ifosfamide than with cyclophosphamide. This is because ... 

In patients given nephrotoxic chemotherapy, such as cisplatin cyclophosphamide, ifosfamide, methotrexate, bleomycin, streptozotocin, pentostatin, or other nephrotoxic drugs, and in patients in whom extensive tumor lysis with hyperuricemia, hypercal-... 

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