Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clofarabine is used as second-line therapy for acute myeloid leukemia. Acute renal impairment is reported with clofarabine; however, it is more likely to occur in patients with confounding factors that may underlie the adverse event. We describe a 65-year-old man treated with clofarabine for relapsed acute myeloid leukemia who experienced severe acute kidney injury and proteinuria temporally related to clofarabine administration. The morning after completion of clofarabine administration, his serum creatinine concentration increased to approximately 1.4-fold above his baseline value, and peaked at 2.8-3.6-fold over baseline within 72 hours. A 24-hour urine collection contained 4100 mg of protein. His serum creatinine concentration gradually returned to within 1.5 times his baseline value. Examination of the patient's clinical course, vital signs, and laboratory results did not yield any compelling evidence of alternative causes for acute kidney injury. The patient's comorbidities included a left ventricular ejection fraction of 35-40% and diabetes mellitus. His drug therapy with potential renal effects-lisinopril, furosemide, tobramycin, allopurinol, and valacyclovir-that preceded clofarabine administration was evaluated, and none was determined to be a major factor in the development of this adverse event. Bone marrow evaluations were negative for residual leukemia after clofarabine therapy. After approximately 11 weeks of hospitalization, the patient and his family made an informed decision to continue supportive care at home. Acute kidney injury in this patient was attributed to clofarabine administration due to the time course of events with respect to potential contributing factors. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of renal effects and clofarabine therapy. To our knowledge, this is the first report of medically significant proteinuria associated with administration of clofarabine. Clinicians should be aware of the potential for acute kidney injury if their patients are administered clofarabine.
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PMID:Clofarabine-associated acute kidney injury and proteinuria. 2192 94

Clofarabine is a purine nucleoside analog indicated for treatment of relapsed or refractory acute lymphoblastic leukaemia in children. The drug is also increasingly used, outside of its FDA approved indication, for treatment of relapsed or refractory acute myeloid leukemia in adults. It acts by inhibiting DNA synthesis, the enzyme ribonucleotide reductase and repair and activation of mitochondrial repair processes. We describe a case of a 48-year-old male with refractory acute myeloid leukemia with acute kidney injury associated with clofarabine treatment. We conducted a review of the literature and utilized the Food and Drug Administration Adverse Event Reporting System to identify spontaneous reporting of renal adverse events with this drug in 29 other cases. Since clofarabine inhibits ribonucleotide reductase, we postulate by extrapolation from the animal studies that collapsing glomerulopathy or severe tubular injury or a combination of both may be the mechanism of acute kidney injury observed with this agent. This would be consistent with the observed severe acute kidney injury and proteinuria in humans.
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PMID:Clofarabine-induced kidney toxicity. 2408 Dec 20