High-dose Methotrexate Of Renal Damage Affect On Other Related Adverse

Background:High-dose methotrexate(HD-MTX) is the treatment of leukemia, especially acute lymphoblastic leukemia (ALL), Also is an important means of lymphoma and CNS leukemia, The incidence of adverse reactions and severity depend on the MTX blood drug concentration and duration. High dose methotrexate (HD-MTX) of the main side effects were bone marrow suppression, skin and mucous membrane reaction, liver and kidney damage, stomatitis, oral ulcers, sore throat, nausea, vomiting, abdominal pain, diarrhea, gastrointestinal bleeding, especially in renal function damage is more important.Foreign literature shows high dose methotrexate induced renal damage ratio of2.41%, the domestic has not been reported. Because HD-MTX renal function damage induced by relatively rare, did not pay attention, the domestic literature mostly case reports, once the incidence of renal adverse effects related to the injury is more serious, the mortality rate is very high. Now the application of methotrexate after adverse reactions in patients with kidney impairment to statistics, to the clinical application in practice can be used as reference.Materials and methods:Between January2001and December2012in Henan Cancer hospital, a total of 540patients with acute leukemia and lymphoma, aged3～65years, with a median age of32years. HD-MTX before treatment the WBC>3.0×109/L, the ANC>1.5x109/L, liver and renal function were normal, urine protein (-), creatinine clearance rate were within the normal range. Bone marrow hyperplasia, were in remission. The amount of MTX was2-3g/m2, while giving the hydration and alkalization and calcium folinate rescue. And in the application of intravenous infusion of MTX, application on the same day, and after application regularly collected venous blood monitoring blood routine and renal function were observed after treatment, changes in body temperature and oral mucosa, changes were observed in the peripheral blood and other related adverse reaction. The relationship between these adverse reaction and renal function given by statistical analysis software SPSS17.0.Results:1The incidence of renal damage in540patients, a total of13cases, the percentage of renal damage is2.41%.213patients with renal injury appeared in the change of skin and mucous membrane in7cases, chest CT clear tips of lung inflammation in9cases,5cases of herpes zoster,4cases of pleural effusion, pericardial effusion in3cases, urinary tract infection in3cases, subcutaneous bleeding in6cases, skin mucosai ecchymosis in3cases, G, GM. test positive in2cases,7cases of diarrhea, electrolyte disorder in3cases, intestinal infection in2cases, blood culture or pharyngeal expression confirmed positive in4cases.313cases of renal injury patients, found that the average time of renal damage from chemotherapy was3.69days, the median time of4days (3～4days). Injury of renal function recovery after chemotherapy in the average time was14days, the median time of17days (9-24days). The BUN range is10.4～44.7mmol/L, CR ranges from138to390umol/L.4Agranulocytosis ratio is100%, the average time to agranulocytosis neutropenia from chemotherapy was9.77days, the median time of9days (5～12days). Agranulocytosis lasted for an average of20days, the median time of20days (14～29days). Renal damage more serious and the longer the duration of the agranulocytosis5The proportion of Platelets less than20x109/L is100%, the decrease of platelet to average distance of time chemotherapy for20x109/L for11.5days, the median time of11days (8～23days). Platelet lower than20×109/L lasted for an average of21days, the median time of20days (8-31days). The duration of renal injury more longer of serious platelet<20×109/L.613patients have lost red blood cell and platelet record. Mean platelet transfusion5.55treatment, the average number of red blood cell transfusion of8units. There are3cases with infusion of fresh frozen plasma.7Heating ratio is100%, the degree of heat in9cases, fever in4cases. And the fever continued for a long time. Start heating time (from chemotherapy) in an average of10.3days, the median time of11days (3～15days). The fever lasted for an average of18days, the median time of16days (14～31days).8Oral mucosal erosion ratio of100%. The average time of oral mucosal erosion from chemotherapy was9.25days, the median time of7.5days (6～14days). Oral mucosal erosion duration was21.5days, the median time of21.5days (13～36days).Among the patients with renal injury913cases,2patients died,2patients gave up treatment of complications in patients with follow-up confirmed after discharge and died of HD-MTX chemother apy. Mortality rate as high as30.8%, improved after treatment in9patients. Of which1cases died of renal failure,2cases died of septic shock,1cases died of hemorrhage of digestive tract.Conclusions:1Renal function caused by high-dose methotrexate damage is reversible.2The death of renal function injury caused by high-dose methotrexate is the main reason:abnormal renal function decreased excretion to methotrexate, MTX accumulation in the body, caused by severe bone marrow suppression, agranulocytosis and bleeding, and bleeding.