The Activity of Proximal Tubule Enzymes in the Urine of Cephalexin-Treated Patients

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The Activity of Proximal Tubule Enzymes in the Urine of Cephalexin-Treated Patients

The activities of alanine aminopeptidase (AAP), γ-glutamyltransferase (GGT) and N-acetyl-β-D-glucosaminidase (NAG), enzymes dominantly localised in the epithelial proximal tubule cells, were measured with an aim of determining the nephrotoxicity of a cephalosporin antibiotic cephalexin. Enzymatic activities were measured in the 12-h urine samples of patients receiving cephalexin orally for 15 days in daily doses of 50 mg/kg body mass against Gram-positive infections of the respiratory or urinary tract. The same enzymes were determined in the 12-h urine samples of the corresponding control. Both the control and the experimental group consisted of 30 examinees of both sexes, age range 3-10 years. Statistically significant differences in AAP and GGT activities expressed as U/mmol creatinine were recorded after 12 days of cephalexin therapy in comparison with the control (p < 0.01). At the same time, no significant differences in NAG activity of the patients in relation to the control were observed during the entire course of the therapy. Based on the obtained results it can be concluded that treatment of 3-10 years old patients with the applied cephalexin doses for 15 days results in mild nephrotoxic changes close to the end of therapy accompanied by increased activities of AAP and GGT, the enzymes known as very sensitive indicators of nephrotoxicity. The results showing that during the entire period of cephalexin application no changes in NAG, as a lysosomal enzyme, were observed, could be taken as a proof that this antibiotic did not lead to severe injuries of epithelial proximal tubule cells at the level of cell organelles.

Diaz OAJ, Sumano LH, Ocampo CL, Mateos TG. Evaluation of the nephrotoxicity of the administration of sodium cephalexin with gentamicin sulphate in dogs. Vet Mex 1995; 26: 247-9.

Plumb's Veterinary Drug Handbook, 5th ed., Blackwell Publishing. 2005; 206-9: 864-7.

Longstreth KL, Robbins SD, Chaing MD, Doe NS, Facp MD. Cephalexin-induced acute tubular necrosis. Pharmacotherapy 2004; 24: 808-11.

Rossert J. Drug-induced acute interstitial nephritis. Kidney Int 2001; 60: 804-17.

Alper AB. Nephritis, interstitial. Kidney Int 2006; 69: 213-17.

Shugarts S, Benet LZ. The role of transporters in the pharmacokinetics of orally administered drugs. Pharm Res 2009; 26: 2039-54.

Srimaroeng C, Perry JL, Pritchard JB. Physiology, structure and regulation of the cloned organic anion transporters. Xenobiotica 2008; 38: 889-935.

Grover A, Benet LZ. Effects of drug transporters on volume of distribution. AAPS 2009; 11: 250-61.

Tune BM. Nephrotoxicity of beta-lactam antibiotics: mechanisms and strategies for prevention. Pediatr Nephrol 1997; 11: 768-72.

Westhuyzen J, Endre ZH, Recce G, Reith DM, Saltissi D, Morgan TJ. Measurement of tubular enzymuria facilitates early detection of acute renal impairment in the intensive care unit. Nephrol Dial Transplant 2003; 18: 543-51.

Lisowska-Myjak B. Serum and urinary biomarkers of acute kidney injury. Blood Purif 2010; 29: 357-65.

Che M, Xue B, Dai H, Qian J, Ni Z, Axelsson J, et al. Clinical usefulness of novel biomarkers for the detection of acute kidney injury following elective cardiac surgery. Nephron Clin Prac 2010; 115: 66-72.

Werner M, Muruhn D, Atoba M. Use of gel filtration in the assay of urinary enzymes. J Chromatog 1969; 40: 254-63.

Jung K, Scholz D. An optimized assay of alanine aminopeptidase activity in urine. Clin Chem 1980; 26: 1251-4.

Persijn JP, Van der Slik W. A new method for determination of gamma-glutamyltransferase in serum. J Chem Clin Biochem 1976; 14: 421-7.

Szasz G. A kinetic colorimetric method for determination of gamma-glutamyltranspeptidase in serum. Z Klin Chem Klin Biochem 1974; 12: 228-32.

Maksime J, Saito E, Obuchi M, Kanayma M, Yosida U. Improved kinetic rate assay of urinary N-acetyl-ß-D-glucosaminidase with 2-chloro-4-nitrophenyl-N-acetyl-β-D-glucosaminidase as substrate. Clin Chem 1990; 36: 319-22.

Bartels H, Böhmer M. Eine Mikromethode zur Kreatininbestimmung. Clin Chim Acta 1971; 32: 81-5.

Trof RJ, Di Maggio F, Leemreis J, Goeneved AB. Biomarkers of acute renal injury and renal failure. Shock 2006; 26: 245-53.

Davidović-Plavšić B, Vujić T, Uletilović S, Predojević-Samardžić J, Malčić D, Saničanin Ž. Urinary activities of proximal tubule enzymes in neonates treated with gentamicin. Journal of Medical Biochemistry 2010; 29: 44-7.

Davidović B, Predojević-Samardžić J, Uletilović S, Malčić D, Saničanin Ž. Activities of proximal tubule enzymes in urine of patients treated with gentamicin. J Med Biochem 2007; 26: 46-50.

Ćorić V, Plješa-Ercegovac M, Matić M, et al. The role of GSTM1 and GSTT1 polymorphism in patients with ranal cell carcinoma. Journal of Medical Biochemistry 2010; 29: 204-10.

Daghero O, Andreoni G, Arione R, Bendiscioli L, Bramato C, Cimino T, et al. Cephalosporins and enzymuria. Minerva Med 1986; 77: 231-7.

Cunha BA. Third generation of cephalosporins: a review. Clin Therap 1992; 14: 616-52.

Journal of Medical Biochemistry

The Journal of Society of Medical Biochemists of Serbia

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