Cyclophosphamide hyponatremia with

A toxicity that is unique to cyclophosphamide and ifosfamide is cystitis. Dysuria and decreased urinary frequency are the most common symptoms. Rarely, fibrosis and a permanently decreased bladder capacity may ensue. The risk of development of carcinoma of the bladder also is increased. Large intravenous doses have resulted in impairment of renal water excretion, hyponatremia, and increased urine osmolarity and have been associated with hemorrhagic subendocardial necrosis, arrhythmias, and congestive heart failure. Interstitial pulmonary fibrosis may also result from chronic treatment. Other effects of chronic drug treatment include infertility, amenorrhea, and possible mutagenesis and carcinogenesis. 

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. 

Synergy between indometacin and cyclophosphamide has been advanced as the cause of a life-threatening acute water intoxication and severe hyponatremia observed in a patient with multiple myeloma and normal renal function (SEDA-15, 99). 

The most common cause of hyponatremia in hospital patients is SIADH. However, other disorders can cause dilutional hyponatremia and must be differentiated from SIADH. These conditions include (1) congestive heart failure, (2) renal insufficiency, (3) nephrotic syndrome, (4) liver cirrhosis, and (5) hypothyroidism. Excessive administration of hypotonic fluids and treatment with drugs that stimulate AVP (e.g., chlorpropamide, vincristine, clofibrate, carbamazepine, nicotine, phenothiazines, and cyclophosphamide) can cause dilutional hyponatremia as well. Hyponatremia may also occur from renal or extrarenal sodium losses (depietional hyponatremia) as a result of vomiting, diarrhea, excessive sweating, diuretic abuse, saltlosing nephropathy, or mineralocorticoid deficiency. 

Electrolyte balance In a retrospective analysis of data obtained from 84 patients with lupus nephritis or non-Hodgkin s lymphoma, 112 treatment episodes with low-dose intravenous pulse cyclophosphamide (500-750 mg/m ) were evaluated [28. All received 0.45% saline as hydration to prevent hemorrhagic cystitis. There was cyclophosphamide-induced hyponatremia during 15 treatment episodes in 12 patients. Patients with hyponatremia were significantly older than those without, although no factors independently predicted hyponatremia in a multivariate analysis, including cyclophosphamide dose. Cyclophosphamide potentiates the renal action of vasopressin, thereby reducing the ability of the kidney to excrete water, which should warrant the use of hypotonic solutions for prophylactic hydration to prevent hyponatremia. 

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