5-Azacytidine and renal tubular dysfunction.
During initial trials of 5-azacytidine in adults with advanced acute leukemia, we unexpectedly observed acid-base, fluid, and electrolyte abnormalities that contributed directly to the deaths of two early patients. To evaluate this toxicity further, we studied 22 patients who received a total of 33 courses of combination chemotherapy that included 5-azacytidine. During 29 courses (88%) of treatment, polyuria, glucosuria, and/or transient changes in the serum concentrations of bicarbonate or phosphorus were detected. Spontaneous polyuria with demonstrable salt wasting and orthostatic hypotension occurred during seven courses (21%) of treatment. Inappropriate glucosuria was observed in nine courses (27%). In 24 courses (73%) the serum bicarbonate fell below the normal range. The urine became alkaline during 12 of these instances; the anion gap was not increased during the acidosis. Hypophosphatemia with serum phosphorus concentrations as low as 0.3 mg/dl occurred in 21 of 32 evaluable courses (66%). In the three patients studied the tubular reabsorption of phosphorus was 10%-18%. The renal abnormalities that were observed suggest both proximal and distal tubular damage from 5-azacytidine. Patients receiving 5-azacytidine should be monitored closely for manifestations of renal toxicity.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000009:adverse effects* / Q000627:therapeutic use; D001639:Bicarbonates / Q000097:blood; D006029:Glycosuria / Q000503:physiopathology; D006801:Humans; D007684:Kidney Tubules / Q000503:physiopathology*; D007938:Leukemia / Q000188:drug therapy*; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood / Q000652:urine; D011141:Polyuria / Q000139:chemically induced; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood
D001639:Bicarbonates; D010758:Phosphorus; D012964:Sodium; D001374:Azacitidine; D011188:Potassium