Successful Rescue in a Patient with High Dose Methotrexate-Induced Nephrotoxicity and Acute Renal Failure
ABSTRACT We describe the case of a 35-year old male who developed acute renal failure following high dose methotrexate therapy for Burkitt's non Hodgkin lymphoma. Serum methotrexate levels reached 37 micromol/l, and remained higher than 1 micromol/l for more than a week. Folinic acid rescue was intensified to 200-400 mg intravenously every 4 hours. As methotrexate binds markedly to proteins, plasma exchange was initially chosen, 4 sessions being performed from day 2 to day 4. The methotrexate pharmacokinetic profile was not significantly modified during plasma exchange, and serum drug level was 3 micromol/l. Continuous veno-venous hemodiafiltration was therefore performed from day 5 to day 10. This procedure also seemed ineffective, with evidence of low ultrafiltrate clearance. No extrarenal toxicity was observed in our patient. Thus, conventional extrarenal procedures appear to have a limited role in the setting of overexposure to methotrexate. The use of very high doses of folinic acid in our case probably played a major role in the eventual favorable outcome.
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ABSTRACT: A 54-year-old patient with primary cerebral lymphoma was treated with two 4-weekly cycles of high-dose intravenous cytarabine (12 g/m2) and methotrexate (3 g/m2). The administration of the first course proceeded without notable complications. Before the administration of methotrexate in the second cycle blood cell counts and chemistry showed no abnormalities except for slightly increased alkaline phosphatase and gamma-glutamyl-transpeptidase levels which was attributed to diphantoin comedication. The patient developed symptoms of acute renal failure 7 h after methotrexate infusion which resulted in a very high serum methotrexate level (39.84 micromol/l) at 20 h after infusion. Rescue therapy was intensified: the leucovorin dosage was increased (1,200 mg continuous i.v. infusion every 24 h) and combined with thymidine rescue therapy (8 g/m2 per day continuous i.v. infusion every 24 h). Urine alkalinization was increased and diphantoin therapy was stopped. Leucovorin eye drops and mouth washes were started 5 days after methotrexate administration to prevent conjunctivitis and mucositis as a result of high methotrexate levels (>2.4 micromol/l). In spite of the fact that serum methotrexate levels remained persistently higher than 0.1 micromol/l for 12 days, the patient experienced no further short-term systemic toxicity except for anaemia (grade 3 according to NCI Common Toxicity Criteria). After day 12 intensified rescue therapy and the frequency of alkalinization were decreased to standard procedures and stopped on day 19. It is concluded that i.v. administration with high-dose methotrexate can result in unpredictable acute toxicity. In our patient, acute methotrexate toxicity was treated successfully by intensification of classical leucovorin rescue therapy in combination with thymidine infusion. In addition, leucovorin mouth washes and eye drops may have prevented mucositis and conjunctivitis, respectively.Cancer Chemotherapy and Pharmacology 07/2001; 47(6):537-40. DOI:10.1007/s002800000269 · 2.57 Impact Factor
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ABSTRACT: High-dose methotrexate (HDMTX)-induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX-induced nephrotoxicity has been managed with high-dose leucovorin, dialysis-based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase-G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX-induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis-based methods of MTX removal with treatment using CPDG2. The literature was reviewed for osteosarcoma trials, use of dialysis-based methods for MTX removal, and reports of MTX-induced nephrotoxicity, including information regarding recovery of renal function. Clinical trial databases of select osteosarcoma studies were reviewed. The efficacy of CPDG2 and renal recovery after CPDG2 rescue was obtained from the database of a compassionate-release trial. Approximately 1.8% of patients with osteosarcoma (68 of 3887 patients) who received HDMTX developed nephrotoxicity Grade >/= 2. The mortality rate among those patients was 4.4% (3 of 68 patients). Dialysis-based methods of MTX removal were used frequently but had limited effectiveness in removing MTX compared with the rapid reductions > 98% in plasma MTX concentrations achieved with CPDG2. CPDG2 did not appear to increase the time to recovery of renal function compared with supportive treatment that included dialysis-based methods. HDMTX-induced renal dysfunction continues to occur in approximately 1.8% of patients with osteosarcoma who are treated on clinical protocols with optimal supportive care. For patients with delayed MTX excretion and high plasma MTX concentrations, CPDG2 should be considered over hemodialysis to lower plasma MTX concentrations rapidly and efficiently.Cancer 05/2004; 100(10):2222-32. DOI:10.1002/cncr.20255 · 4.90 Impact Factor
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ABSTRACT: Psoriasis is a common skin disease or condition that causes the skin to present with erythema and irritation and affects people of all ages, but especially those aged fifteen to thirty five. The erythema is caused by hyperemia of the capillaries in the lower layers of the skin. Most people with psoriasis have thick, red skin with flaky, silver-white patches called scales. Although psoriasis is not contagious it plays a critical role in self-esteem of the individual suffering from the condition. The etiology of psoriasis is unknown at the present time but many doctors and scientists believe the condition to be the result of an autoimmune attack of healthy skin cells. Traditional approaches to treat psoriatic lesions have included the following: topical therapy, phototherapy, and systemic therapy, some of which lie outside the scope of the practicing chiropractor. This paper will review and reflect the efficacy of traditional treatments of psoriasis, with its attendant shortcomings and then end with a discussion on techniques and strategies that encompass the scope of Chiropractic and enlist the skill set of the trained Chiropractic physician such as nutritional counseling, stress management, and chiropractic adjustments.10/2012, Degree: Doctor of Chiropractic, Supervisor: Rodger Tepe