ALKALINE PHOSPHATASE ENZYME AND LACTATE DEHYDROGENASE ACTIVITY IN URINE OF PATIENTS TREATED WITH METHOTREXATE
DOI:
https://doi.org/10.7251/COMEN1401146VAbstract
In order study methotrexate nephrotoxicity, the activities of proximal tubule epithelial cell membrane enzymes: alkaline phosphatase (AP) and lactate dehydrogenase (LDH) were determined in 12-h-urine samples of 30 patients with lymphoblastomous leukemia. The patients were i.v. receiving 4 individual methotrexate doses of 2000 mg/m2 every 15 days followed by leucovorin as a protector. Control and methotrexate-treated group, each consisting of 30 examinees, included 4-10 years old children of both sexes.
Statistically significant increase of AP and LDH activities, expressed as unuts/mmol creatinine was observed after the second therapy (p < 0.05) in relation to the control. Based on these results it can concluded that nephrotoxic methotrexate action is ireversible during the time period after the second applications at the level of proximal tubule epithelal cellReferences
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[2] A. Comandone, R. Passera, A. Boglione et al., High-dose methotrexate in adult patients with osteosarcoma: clinical and pharmacokinetic results, Acta Oncol, Vol. 44 (2005) 406−409.
[3] H. Marika, M. D. Grönroos, Long-term follow-up of renal function after high-dose methotrexate treatment in children, Pediatr Blood Cancer, Vol. 51 (2008) 535−539.
[4] K. A. Janeway, H. E. Grier, Sequelae of osteosarcoma medical therapy: a review of rare acute toxicities and late effects, Lnacet Oncol., Vol. 11 (2010) 670−678.
[5] U. Erdbr Ȕngger, K. de Groot, Is methotrexate nephrotoxic? Dose-dependency, comorbidities and comedication, Z Rheumatol, Vol. 70 (2011) 549−552.
[6] K. Suzuki, K. Doki, M. Homma et al., Co-administration of proton pum inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy, Br Clin Pharmacol., Vol. 67 (2009) 44−49.
[7] R. Santucci, D. Leveque, K. Lascoute, et al., Delayed elimination of methotrxate assiciated with co-administration of proton pump inhibitors, Anticancer Res, Vol. 30 (2010) 3807−3812.
[8] B. C. Widemman, F. M. Balis, A. Kim, et al., Glucarpidase, leucovorin and thymidine for high-dose methotrexate − induced − renal dysfunction: clinical and pharmacologic factors affecting outcome, J Clin Oncol., Vol. 28 (2010) 3979−3984.
[9] L. Hempel, J. Misselwitz, C. Fleck, D. Appenroth, et al., Influence of high-dose methotrexate therapy (HD-MTX) on glomerular and tubular kidney function, Med Pediatr Oncol, Vol. 40 (2003) 348−354.
[10] H. Matsando, M. Fahim, D. S. Gill, et al., High dose methotrexate and extended hours high-flux hemodialysis for the treatment of primary central nervous system lymphoma in a patient with and stage renal disease, Am J Blood Res, Vol. 2 (2012) 66−70.
[11] I. Badaganani, R. A. Castro, T. R. Taylor, et al., Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and genetic variants, J Pharmacol Exp Their., Vol. 318 (2006) 521−529.
[12] C. Bazzi, Composition of proteinuria in primary glomerulonephritides: association with tubolo-interstitial damage, outcome and response to therapy, G Ital Nefrol, Vol. 20 (2003) 346−355.
[13] E. Batlle-Gualda, A. C. Martinez, A. Guerra et al., Urinary albumin excretion in patients with systemic lupus erythematosus without renal disease, Ann Rheum Dis, Vol. 56 (1997) 386−389.
[14] W. S. Hsu, J. T. Kao, J. S. Chen, Clinical significance of urinary N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase, Taiwan Yi Xue Hui Za Zhi, Vol. 88 (1989) 407−409.
[15] S. Skalova, The diagnostic role of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the detection of renal tubular impairment, Acta Medica, Vol. 48 (2005) 75−80.
[16] M. Werner, D. Muruhn, M. Atoba, Use of gel filtration in the assay of urinary enzymes, J Chromatog, Vol. 40 (1969) 254−263.
[17] N. W. Tietz, D. Rinker, L. Shaw, IFCC method for measurement of catalytic concentration of enzymes. Parts 5 IFCC methods for alkaline phosphatase, J Clin Chem Clin Biochem, Vol. 21 (1983) 731−748.
[18] I. Witt, C. Trendelenburg, Determination of urine lactate dehydrogenase, Clin Chem Clin Biochem, Vol. 20 (1982) 235−242.
[19] H. Bartels, M. Böhmer, Micro-determination of creatinine, Clin Chim Acta, Vol. 32 (1971) 81−85.
[20] Y. M. El Miedany, I. H. Abubaker, M. El Baddini, Effect of low dose methotrexate on markers of bone metabolism in patients with rheumatoid arthritis, J Rheumatol, Vol. 25 (1998) 2083−2087.
[21] N. J. Minuar, C. Jefferiss, A. K. Bhalla, et al., Methotrexate in the treatment of rheumatoid arthritis, Rheumatology, Vol. 41 (2002) 735−740.
[22] J. Westhuyzen, H. Z. Endre, G. Recce, et al., Measurement of tubular enzymuria facilitates early detection of acute renal impairment in the intensive care unit, Nephrol Dial Transplant, Vol. 18 (2003) 543−551.
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2014-09-26
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