mesna and Acute-Kidney-Injury

There is a critical need to find new antineoplastic drugs that are active in platinum-refractory ovarian cancer. We conducted a phase II trial of single-agent ifosfamide with mesna uroprotection in patients with ovarian cancer previously treated with an organoplatinum compound to assess its activity in this clinical setting.. Ifosfamide (1.0 or 1.2 g/m2/d for 5 days, delivered on a monthly schedule) was administered to the 57 patients entered onto this trial. Dose reductions were permitted for unacceptable toxicities.. Toxicity included severe bone marrow suppression (WBC count less than 1,000/microL and/or platelet count less than 50,000/microL), renal dysfunction (serum creatinine level greater than 2.0 mg/dL), and reversible CNS dysfunction (disorientation, hallucinations, somnolence, and agitation), which occurred in 20%, 14%, and 12% of patients, respectively. Of 41 patients with strictly defined platinum-refractory ovarian cancer, five (12%) demonstrated a partial (four) or complete (one) response to this treatment program.. Single-agent ifosfamide has modest but unequivocal activity in platinum-resistant ovarian cancer. Further studies of this drug used as a front-line agent along with an organoplatinum compound or as part of a dose-intensification program with bone marrow, peripheral stem cell, or colony-stimulating factor support are indicated. In addition, single-agent ifosfamide is a reasonable standard second-line treatment strategy in appropriately selected patients with platinum-refractory ovarian cancer.

Topics: Acute Kidney Injury; Adult; Aged; Carcinoma; Drug Evaluation; Drug Resistance; Female; Humans; Ifosfamide; Mesna; Middle Aged; Ovarian Neoplasms; Platinum

Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS.. A-44-years old woman with a chief complaint of pain in the epigastric area, itching, coughing, nausea, and vomiting was referred to the emergency department. Her medical history was LMS. She had taken Ifosfamide and mesna in her last chemotherapy. Seventy percent of her liver and her left kidney were removed 4 years ago to prevent the progress of the disease. Because of the increase in the level of creatinine and urea in the initial laboratory report, a Shaldon catheter was inserted for the patient, and she was under emergency dialysis for 3 h. In addition, during the six-day hospitalization period, dialysis was done two times. Finally, the patient was discharged with improved clinical tests accompanied by a twice-weekly dialysis order.. Ifosfamide is metabolized into chloroacetaldehyde, which can cause acute kidney injury. Recovery from acute kidney injury may not always be perfect and can lead to some degree of chronic kidney disease. Opposite to hemorrhagic cystitis, mesna is not effective in preventing ifosfamide's nephrotoxicity and N-acetylcysteine may be effective in the prevention of this nephrotoxicity.

Topics: Acetylcysteine; Acute Kidney Injury; Creatinine; Female; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Urea

Reactive oxygen species (ROS) play a key role in renal ischaemia-reperfusion injury. After establishing the in vitro anti-oxidative potential of mesna, a sulfhydryl-containing compound, its effect on kidney function and morphology in a rat model of ischaemic acute renal failure (ARF) was examined.. Mesna (180 mg/kg) was administered at different time points relative to ischaemia and/or reperfusion onset. Kidney function was assessed by glomerular filtration rate (GFR) and fractional sodium excretion (FE(Na)) before a 45-min period of unilateral renal artery clamping and following 90 min of reperfusion. Mesna was administered by bolus, 30 min before the induction of ischaemia, 5 min before ischaemia, 5 min before reperfusion, and 5 min after the onset of reperfusion.. Mesna improved function of the ischaemic kidney at each administration. When mesna was administered 5 min before the onset of reperfusion, GFR reached 90-100% of its pre ischaemic value and FE(Na) was improved by 75%. The beneficial effect of mesna was also demonstrated by light and electron microscopy. Kidneys treated with mesna 5 min before reperfusion resembled ischaemic non-reperfused kidneys and showed subtle morphological and ultrastructural changes compared with ischaemic-reperfused kidneys. Mesna had no haemodynamic effect on renal blood flow and did not induce any osmotic diuresis.. We suggest that mesna acts as an antioxidant. Its antioxidant potential together with optimal protection achieved when administered 5 min before reperfusion, supports the conclusion that mesna scavenges ROS generated at the onset of reperfusion, thus diminishing reperfusion injury and organ damage.

Topics: Acute Kidney Injury; Animals; Antioxidants; Female; Free Radical Scavengers; Glomerular Filtration Rate; Ischemia; Kidney; Mesna; Microscopy, Electron; Natriuresis; Oxidation-Reduction; Protective Agents; Rats; Rats, Sprague-Dawley; Renal Circulation; Sulfhydryl Compounds

A 62-year-old woman developed subacute renal failure after the repeated administration of ifosfamide (IFX), despite its combination with continuous sodium 2-mercaptoethane sulfonate (mesna) infusion. Biopsy findings, the possible underlying mechanism, and the existing literature are discussed.

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma; Dose-Response Relationship, Drug; Female; Humans; Ifosfamide; Kidney; Mercaptoethanol; Mesna; Middle Aged; Ovarian Neoplasms

Topics: Acute Kidney Injury; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Humans; Ifosfamide; Male; Mesna; Vomiting