Water intoxication induced by low-dose cyclophosphamide in two patients with systemic lupus erythematosus

Abstract

Cyclophosphamide (CY) is an alkylating agent used to treat a variety of autoimmune disorders. Water intoxication is a well-known complication of high-dose intravenous (i.v.) CY, but is rare in patients treated with low dose i.v. CY. We describe two patients with lupus nephritis and water intoxication following low dose i.v. CY. The first patient was treated with oral prednisolone and azathioprine for eight weeks with inadequate response and persistent renal inflammatory activity. Eight hours after the first i.v. CY pulse she had a grand mal seizure. The second patient had WHO class III lupus nephritis, and after a single i.v. CY pulse developed vomiting, diarrhoea and grand mal seizures. They were both fluid-restricted and their serum sodium levels returned to normal. In conclusion, even at low doses i.v. CY may induce hyponatremia related to inappropriate antidiuretic hormone secretion. This potentially life-threatening complication of i.v. CY could be minimized by avoidance of overhydration following pulse i.v. CY.

Forensic aspects of water intoxication: Four case reports and review of relevant literature

“…A low dose of oral cyclophosphamide used in the treatment of some rheumatic diseases or autoimmune glomerulonephritis can cause WI. One or more cyclophosphamide metabolites may directly alter water permeability in the kidney leading to DI [24][25][26][27][28].…”

Severe Hyponatremia in a Patient with Mantle Cell Lymphoma Treated with Bortezomib: A Case Report and Review of the Literature

“…Even low-dose cyclophosphamide may induce hyponatremia in patients with systemic lupus erythematosus [28,29]. Probably less known is that hyponatremia has also been attributed to several new substances (tyrosine kinase inhibitors and antibodies) used in today's targeted oncologic treatment (table 1).…”

Water intoxication associated with moderate dose of cyclophosphamide pulse therapy in an elderly patient: a case report and literature review

“…6 However, as listed in Table 1, patients with water intoxication associated with lower doses of CY have been reported since the 1980s, probably due to the increasing numbers of patients receiving low to moderate doses of CY which targets nonmalignant disorders such as rheumatic diseases. [10][11][12][13][14] Bressler and Huston first reported that water intoxication developed after a moderate dose of CY in a patient with systemic lupus erythematosus. 10 Webberley and Murray reported a patient with multiple myeloma, in whom water intoxication developed following treatment with oral indomethacin and lowdose IVCY.…”

“…[5][6][7][8][9] Recently, lifethreatening water intoxication was also reported to occur even by low (10 mg/kg) to moderate (15-20 mg/kg) doses of CY applied to treat rheumatic disorders. [10][11][12][13][14] Here, we describe a patient with polyarteritis nodosa demonstrating water intoxication after administration of IVCY at a moderate dose.…”