Severe cyclophosphamide-related hyponatremia in a patient with acute glomerulonephritis

Abstract

Cyclophosphamide is frequently used to treat cancer, autoimmune and renal diseases, such as rapidly progressive glomerulonephritis. Its side effects are well-known, including bone marrow depression, infections, alopecia, sterility, bladder malignancy and hemorrhagic cystitis. Moreover, in some cases cyclophosphamide use has been related to the onset of hyponatremia, by development of a syndrome of inappropriate antidiuresis. Indeed, severe hyponatremia has been previously reported in patients treated with high-dose or moderate-dose of intravenous cyclophosphamide, while only few cases have been reported in patients treated with low dose. Here, we discuss a case of a syndrome of inappropriate antidiuresis followed to a single low-dose of intravenous cyclophosphamide in a patient with a histological diagnosis of acute glomerulonephritis, presenting as acute kidney injury. After cyclophosphamide administration (500 mg IV), while renal function gradually improved, the patient developed confusion and headache. Laboratory examinations showed serum sodium concentration dropped to 122 mmol per liter associated with an elevated urinary osmolality of 199 mOsm/kg, while common causes of acute hyponatremia were excluded. He was successfully treated with water restriction and hypertonic saline solution infusion with the resolution of the electrolyte disorder. This case, together with the previous ones already reported, highlights that electrolyte profile should be strictly monitored in patients undergoing cyclophosphamide therapy in order to early recognize the potentially life-threatening complications of acute water retention.

Systematic evaluation of different doses of cyclophosphamide induction therapy for lupus nephritis

“…Longer medication regimens and larger doses lead to earlier and severer adverse reactions. [ 28 ] Recently, many researchers have proposed an improved low-dose CTX regimen, [ 29 – 32 ] which is safer with an equivalent efficacy to that of the high-dose CTX treatment. However, these results are based on small sample size studies, which lack confirmation by large-scale clinical RCTs.…”

Symptomatic hyponatremia induced by low-dose cyclophosphamide in patient with systemic lupus erythematosus

“…Seven cases are associated with autoimmune diseases (AIDs), including SLE, [ 1 – 3 ] Sjögren syndrome, [ 12 ] pemphigus, [ 13 ] systemic sclerosis, [ 14 ] and rapidly histological glomerulonephritis. [ 15 ] The other 7 cases are about malignancy associated with multiple myeloma, [ 7 , 16 ] breast cancer. [ 17 – 21 ] Most of them are female except 2 men, and the average age was 56 years (range 26–69 years).…”

“…[ 1 ] Besides, simultaneous administration of corticosteroid, non-steroid anti-inflammatory drugs, antidepressants, and other cytotoxic drugs may accelerate the acute water intoxication. [ 15 ]…”

Chronic Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis (SIAD) in an Adult Woman with Corpus Callosum Agenesis (CCA)

“…This patient also had a three-year history of systemic lupus erythematosus (SLE), which was treated with cyclophosphamide, which is an alkylating agent used in the treatment of malignant and autoimmune disease. Hyponatremia due to the SIAD has previously been reported as an adverse effect of cyclophosphamide treatment [ 16 ]. However, before the patient received cyclophosphamide treatment, she already had hyponatremia.…”