vedomostiregmedРегуляторные исследования и экспертиза лекарственных средствRegulatory Research and Medicine Evaluation3034-30623034-3453Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)10.30895/1991-2919-2024-631vedomostiregmed-631Research ArticleДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯPRECLINICAL STUDIESКомплексная оценка функционального состояния мочевыделительной системы в доклинических исследованиях. Часть 2. Маркеры нефротоксичности (обзор)Complex Assessment of the Functional State of the Urinary System in Preclinical Studies. Part 2. Markers of Nephrotoxicity (Review)https://orcid.org/0000-0002-9828-3242МирошниковМ. В.MiroshnikovM. V.

Мирошников Михаил Владимирович, канд. мед. наук 

Заводская ул., д. 3, к. 245, г.п. Кузьмоловский, Всеволожский район, Ленинградская обл., 188663

Mikhail V. Miroshnikov, Cand. Sci. (Med.) 

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad region 188663

miroshnikov.mv@doclinika.ruhttps://orcid.org/0000-0002-9846-8335СултановаК. Т.SultanovaK. T.

Султанова Кира Тимуровна, канд. мед. наук 

Заводская ул., д. 3, к. 245, г.п. Кузьмоловский, Всеволожский район, Ленинградская обл., 188663

Kira T. Sultanova, Cand. Sci. (Med.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad region 188663

sultanova.kt@doclinika.ruhttps://orcid.org/0000-0003-3176-6386МакароваМ. Н.MakarovaM. N.

Макарова Марина Николаевна, д-р мед. наук 

Заводская ул., д. 3, к. 245, г.п. Кузьмоловский, Всеволожский район, Ленинградская обл., 188663

Marina N. Makarova, Dr. Sci. (Med.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad region 188663

makarova.mn@doclinika.ruhttps://orcid.org/0000-0002-6866-5741ФаустоваН. М.FaustovaN. M.

Фаустова Наталья Михайловна, канд. хим. наук 

Заводская ул., д. 3, к. 245, г.п. Кузьмоловский, Всеволожский район, Ленинградская обл., 188663

Natalia M. Faustova, Cand. Sci. (Chem.)

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad region 188663

faustova.nm@doclinika.ruhttps://orcid.org/0000-0001-6792-2091ХанС. О.KhanS. O.

Хан Станислав Олегович

Заводская ул., д. 3, к. 245, г.п. Кузьмоловский, Всеволожский район, Ленинградская обл., 188663

Stanislav O. Khan

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad region 188663

han.so@doclinika.ruhttps://orcid.org/0000-0002-4668-217XЛосеваЕ. А.LosevaE. A.

Лосева Екатерина Александровна 

Заводская ул., д. 3, к. 245, г.п. Кузьмоловский, Всеволожский район, Ленинградская обл., 188663

Ekaterina A. Loseva

3/245 Zavodskaya St., Kuzmolovsky urban-type settlement, Vsevolozhsky district, Leningrad region 188663

loseva.ea@doclinika.ruАкционерное общество «Научно-производственное объединение «ДОМ ФАРМАЦИИ»РоссияResearch-and-manufacturing company “HOME OF PHARMACY”Russian Federation202420082024144448462Copyright © Мирошников М.В., Султанова К.Т., Макарова М.Н., Фаустова Н.М., Хан С.О., Лосева Е.А., 20242024Мирошников М.В., Султанова К.Т., Макарова М.Н., Фаустова Н.М., Хан С.О., Лосева Е.А.Miroshnikov M.V., Sultanova K.T., Makarova M.N., Faustova N.M., Khan S.O., Loseva E.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.vedomostincesmp.ru/jour/article/view/631ВВЕДЕНИЕ

ВВЕДЕНИЕ. Определение маркеров нефротоксичности является целесообразным и необходимым этапом детекции почечного поражения в экспериментах на животных, позволяющим точно определить локализацию повреждения органа. В связи с разнообразием существующих повреждающих агентов и установленных механизмов нефротоксичности, а также с учетом видового разнообразия лабораторных животных на сегодня не существует общепризнанного маркера почечного повреждения, который соответствовал бы всем предъявляемым требованиям.

ЦЕЛЬ

ЦЕЛЬ. Систематизация данных литературы о маркерах нефротоксичности, анализ их прогностической значимости, формирование общих рекомендаций для оценки функционального состояния мочевыделительной системы в доклинических исследованиях.

ОБСУЖДЕНИЕ

ОБСУЖДЕНИЕ. Проведен сравнительный анализ маркеров нефротоксичности, рекомендованных регуляторными органами для мониторинга лекарственно-индуцированного повреждения почек. Отмечено, что наиболее часто используемыми и прогностически значимыми маркерами острого повреждения почек в доклинических исследованиях являются цистатин С, альбумин, общий белок, молекула повреждения почек-1 (KIM-1), липокалин-2 (NGAL) и кластерин. Маркерами хронического повреждения почек являются как вышеперечисленные маркеры, так и скорость клубочковой фильтрации, креатинин, мочевина и остеопонтин. Определение содержания электролитов может быть использовано для дифференциальной диагностики преренальной азотемии и острого повреждения почек. Возможными ограничениями при использовании маркеров в рутинной практике исследований являются высокая стоимость их количественного анализа и недостаток информации о применимости данных на разных видах лабораторных животных.

ВЫВОДЫ

ВЫВОДЫ. На основании сравнительной оценки прогностической значимости используемых биомаркеров предложены общие рекомендации для комплексной оценки функционального состояния мочевыделительной системы в доклинических исследованиях, включающей проведение лабораторных, инструментальных, а также гистопатологических исследований. Дизайн исследования следует выбирать в зависимости от целей работы, вида или видов лабораторных животных, их количества, специфики тестируемого объекта.

INTRODUCTION

INTRODUCTION. The determination of nephrotoxicity markers is a useful and necessary step in the detection of renal injury in animal experiments; these markers help accurately localise organ damage. With multiple damaging agents, known nephrotoxicity mechanisms, and laboratory animal species, there is currently no widely accepted renal injury marker that meets all the prerequisites.

AIM

AIM. This study aimed to collate literature data on nephrotoxicity markers, evaluate their prognostic significance, and formulate general recommendations for assessing urinary system function in preclinical studies.

DISCUSSION

DISCUSSION. This article describes a comparative analysis of the nephrotoxicity markers recommended by regulatory authorities for monitoring drug-induced kidney injury. According to the results, the most commonly used and prognostically significant markers of acute kidney injury in preclinical studies are cystatin C, albumin, total protein, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin-2 (NGAL), and clusterin. Chronic kidney injury markers include the above, plus the glomerular filtration rate, creatinine, urea, and osteopontin. An electrolyte panel can be used for the differential diagnosis of pre-renal azotaemia and acute kidney injury. Potential limitations for the routine use of kidney injury markers in preclinical research include the high cost of their quantitative determination and the lack of information on the applicability of data obtained from different species of laboratory animals.

CONCLUSIONS

CONCLUSIONS. Having compared the prognostic significance of common biomarkers, the authors provided general recommendations for a comprehensive preclinical assessment of urinary system function, including laboratory investigations, instrument-based tests, and necropsy. A preclinical study design should be based on the study aims, the species and number of animals used, and special considerations for the test article.

доклинические исследованиянефротоксичностьбиомаркерыальбуминобщий белокKIM-1NGALβ2-микроглобулинNAGL-FABPpreclinical studiesnephrotoxicitybiomarkersalbumintotal proteinKIM-1NGALβ2-microglobulinNAGL-FABPReferencesСмирнов АВ, Наточин ЮВ. Нефрология: фундаментальная и клиническая. Нефрология. 2019;23(4):9–26. https://doi.org/10.24884/1561-6274-2019-23-4-9-26Smirnov AV, Natochin YuV. Nephrology: fundamental and clinical. Nephrology (Saint-Petersburg). 2019;23(4):9–26. https://doi.org/10.24884/1561-6274-2019-23-4-9-26Брюханов ВМ, Зверев ЯФ, Лампатов ВВ, Жариков АЮ. Методические подходы к изучению функции почек в эксперименте на животных. Нефрология. 2009;13(3):52–62. EDN: LKFRPVBryukhanov VM, Zverev YaF, Lampatov VV, Zharikov AYu. Methodical approaches to the study of renal function in animal experiments. Nephrology (Saint-Petersburg). 2009;13(3):52–62 (In Russ.). EDN: LKFRPVAl-Naimi MS, Rasheed HA, Hussien NR, Al-Kuraishy HM, Al-Gareeb AI. Nephrotoxicity: role and significance of renal biomarkers in the early detection of acute renal injury. J Adv Pharm Technol Res. 2019;10(3):95–9. https://doi.org/10.4103/japtr.JAPTR_336_18Al-Naimi MS, Rasheed HA, Hussien NR, Al-Kuraishy HM, Al-Gareeb AI. Nephrotoxicity: role and significance of renal biomarkers in the early detection of acute renal injury. J Adv Pharm Technol Res. 2019;10(3):95–9. https://doi.org/10.4103/japtr.JAPTR_336_18Zhang WR, Parikh CR. Biomarkers of acute and chronic kidney disease. Annu Rev Physiol. 2019;81:309–33. https://doi.org/10.1146/annurev-physiol-020518-114605Zhang WR, Parikh CR. Biomarkers of acute and chronic kidney disease. Annu Rev Physiol. 2019;81:309–33. https://doi.org/10.1146/annurev-physiol-020518-114605Vaidya VS, Ferguson MA, Bonventre JV, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008;48:463–93. https://doi.org/10.1146/annurev.pharmtox.48.113006.094615Vaidya VS, Ferguson MA, Bonventre JV, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol. 2008;48:463–93. https://doi.org/10.1146/annurev.pharmtox.48.113006.094615Gu X, Yang B. Methods for assessment of the glomerular filtration rate in laboratory animals. Kidney Dis (Basel). 2022;8(5):381–91. https://doi.org/10.1159/000525049Gu X, Yang B. Methods for assessment of the glomerular filtration rate in laboratory animals. Kidney Dis (Basel). 2022;8(5):381–91. https://doi.org/10.1159/000525049Waldrop JE. Urinary electrolytes, solutes, and osmolality. Vet Clin North Am Small Anim Pract. 2008;38(3):503–12. https://doi.org/10.1016/j.cvsm.2008.01.011Waldrop JE. Urinary electrolytes, solutes, and osmolality. Vet Clin North Am Small Anim Pract. 2008;38(3):503–12. https://doi.org/10.1016/j.cvsm.2008.01.011Hard GC. Species comparison of the content and composition of urinary proteins. Food Chem Toxicol. 1995;33(9):731–46. https://doi.org/10.1016/0278-6915(95)00041-yHard GC. Species comparison of the content and composition of urinary proteins. Food Chem Toxicol. 1995;33(9):731–46. https://doi.org/10.1016/0278-6915(95)00041-yMaddens B, Heiene R, Smets P, Svensson M, Aresu L, Van der Lugt J, et al. Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers. J Vet Intern Med. 2011;25(5):1075–83. https://doi.org/10.1111/j.1939-1676.2011.0772.xMaddens B, Heiene R, Smets P, Svensson M, Aresu L, Van der Lugt J, et al. Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers. J Vet Intern Med. 2011;25(5):1075–83. https://doi.org/10.1111/j.1939-1676.2011.0772.xGriffin BR, Faubel S, Edelstein CL. Biomarkers of drug-induced kidney toxicity. Ther Drug Monit. 2019;41(2):213–26. https://doi.org/10.1097/FTD.0000000000000589Griffin BR, Faubel S, Edelstein CL. Biomarkers of drug-induced kidney toxicity. Ther Drug Monit. 2019;41(2):213–26. https://doi.org/10.1097/FTD.0000000000000589Sato T, Ishikawa A, Homma Y. Effect of reduced form of coenzyme Q10 on cyclosporine nephrotoxicity. Exp Clin Transplant. 2013;11(1):17–20. https://doi.org/10.6002/ect.2012.0126Sato T, Ishikawa A, Homma Y. Effect of reduced form of coenzyme Q10 on cyclosporine nephrotoxicity. Exp Clin Transplant. 2013;11(1):17–20. https://doi.org/10.6002/ect.2012.0126Abdel-Latif RG, Morsy MA, El-Moselhy MA, Khalifa MA. Sildenafil protects against nitric oxide deficiency-related nephrotoxicity in cyclosporine A treated rats. Eur J Pharmacol. 2013;705(1–3):126–34. https://doi.org/10.1016/j.ejphar.2013.02.039Abdel-Latif RG, Morsy MA, El-Moselhy MA, Khalifa MA. Sildenafil protects against nitric oxide deficiency-related nephrotoxicity in cyclosporine A treated rats. Eur J Pharmacol. 2013;705(1–3):126–34. https://doi.org/10.1016/j.ejphar.2013.02.039Fuchs TC, Hewitt P. Preclinical perspective of urinary biomarkers for the detection of nephrotoxicity: what we know and what we need to know. Biomark Med. 2011;5(6):763–79. https://doi.org/10.2217/bmm.11.86Fuchs TC, Hewitt P. Preclinical perspective of urinary biomarkers for the detection of nephrotoxicity: what we know and what we need to know. Biomark Med. 2011;5(6):763–79. https://doi.org/10.2217/bmm.11.86Ennulat D, Adler S. Recent successes in the identification, development, and qualification of translational biomarkers: the next generation of kidney injury biomarkers. Toxicol Pathol. 2015;43(1):62–9. https://doi.org/10.1177/0192623314554840Ennulat D, Adler S. Recent successes in the identification, development, and qualification of translational biomarkers: the next generation of kidney injury biomarkers. Toxicol Pathol. 2015;43(1):62–9. https://doi.org/10.1177/0192623314554840Kim YD, Yim DH, Eom SY, Moon SI, Park CH, Kim GB, et al. Temporal changes in urinary levels of cadmium, N-acetyl-β-d-glucosaminidase and β2-microglobulin in individuals in a cadmium-contaminated area. Environ Toxicol Pharmacol. 2015;39(1):35–41. https://doi.org/10.1016/j.etap.2014.10.016Kim YD, Yim DH, Eom SY, Moon SI, Park CH, Kim GB, et al. Temporal changes in urinary levels of cadmium, N-acetyl-β-d-glucosaminidase and β2-microglobulin in individuals in a cadmium-contaminated area. Environ Toxicol Pharmacol. 2015;39(1):35–41. https://doi.org/10.1016/j.etap.2014.10.016Viau C, Bernard A, Ouled A, Lauwerys R. Determination of rat β2-microglobulin in urine and in serum. II. Application of its urinary measurement to selected nephrotoxicity models. J Appl Toxicol. 1986;6(3):191–5. https://doi.org/10.1002/jat.2550060310Viau C, Bernard A, Ouled A, Lauwerys R. Determination of rat β2-microglobulin in urine and in serum. II. Application of its urinary measurement to selected nephrotoxicity models. J Appl Toxicol. 1986;6(3):191–5. https://doi.org/10.1002/jat.2550060310Vlasakova K, Erdos Z, Troth SP, McNulty K, Chapeau-Campredon V, Mokrzycki N, et al. Evaluation of the relative performance of 12 urinary biomarkers for renal safety across 22 rat sensitivity and specificity studies. Toxicol Sci. 2014;138(1):3–20. https://doi.org/10.1093/toxsci/kft330Vlasakova K, Erdos Z, Troth SP, McNulty K, Chapeau-Campredon V, Mokrzycki N, et al. Evaluation of the relative performance of 12 urinary biomarkers for renal safety across 22 rat sensitivity and specificity studies. Toxicol Sci. 2014;138(1):3–20. https://doi.org/10.1093/toxsci/kft330Kuwata K, Nakamura I, Ide M, Sato H, Nishikawa S, Tanaka M. Comparison of changes in urinary and blood levels of biomarkers associated with proximal tubular injury in rat models. J Toxicol Pathol. 2015;28(3):151–64. https://doi.org/10.1293/tox.2014-0039Kuwata K, Nakamura I, Ide M, Sato H, Nishikawa S, Tanaka M. Comparison of changes in urinary and blood levels of biomarkers associated with proximal tubular injury in rat models. J Toxicol Pathol. 2015;28(3):151–64. https://doi.org/10.1293/tox.2014-0039Dieterle F, Perentes E, Cordier A, Roth DR, Verdes P, Grenet O, et al. Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat Biotechnol. 2010;28(5):463–9. https://doi.org/10.1038/nbt.1622Dieterle F, Perentes E, Cordier A, Roth DR, Verdes P, Grenet O, et al. Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat Biotechnol. 2010;28(5):463–9. https://doi.org/10.1038/nbt.1622Nabity MB, Lees GE, Cianciolo R, Boggess MM, Steiner JM, Suchodolski JS. Urinary biomarkers of renal disease in dogs with X-linked hereditary nephropathy. J Vet Intern Med. 2012;26(2):282–93. https://doi.org/10.1111/j.1939-1676.2012.00891.xNabity MB, Lees GE, Cianciolo R, Boggess MM, Steiner JM, Suchodolski JS. Urinary biomarkers of renal disease in dogs with X-linked hereditary nephropathy. J Vet Intern Med. 2012;26(2):282–93. https://doi.org/10.1111/j.1939-1676.2012.00891.xVinge L, Lees GE, Nielsen R, Kashtan CE, Bahr A, Christensen EI. The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol Dial Transplant. 2010;25(8):2458–67. https://doi.org/10.1093/ndt/gfq044Vinge L, Lees GE, Nielsen R, Kashtan CE, Bahr A, Christensen EI. The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol Dial Transplant. 2010;25(8):2458–67. https://doi.org/10.1093/ndt/gfq044Ozer JS, Dieterle F, Troth S, Perentes E, Cordier A, Verdes P, et al. A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat Biotechnol. 2010;28(5):486–94. https://doi.org/10.1038/nbt.1627Ozer JS, Dieterle F, Troth S, Perentes E, Cordier A, Verdes P, et al. A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat Biotechnol. 2010;28(5):486–94. https://doi.org/10.1038/nbt.1627Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol. 2006;290(2):F517–29. https://doi.org/10.1152/ajprenal.00291.2005Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol. 2006;290(2):F517–29. https://doi.org/10.1152/ajprenal.00291.2005Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol. 2004;286(3):F552–63. https://doi.org/10.1152/ajprenal.00285.2002Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol. 2004;286(3):F552–63. https://doi.org/10.1152/ajprenal.00285.2002Zhou Y, Vaidya VS, Brown RP, Zhang J, Rosenzweig BA, Thompson KL, et al. Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium. Toxicol Sci. 2008;101(1):159–70. https://doi.org/10.1093/toxsci/kfm260Zhou Y, Vaidya VS, Brown RP, Zhang J, Rosenzweig BA, Thompson KL, et al. Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium. Toxicol Sci. 2008;101(1):159–70. https://doi.org/10.1093/toxsci/kfm260Zhao X, Zhang Y, Li L, Mann D, Imig JD, Emmett N, et al. Glomerular expression of kidney injury molecule-1 and podocytopenia in diabetic glomerulopathy. Am J Nephrol. 2011;34(3):268–80. https://doi.org/10.1159/000330187Zhao X, Zhang Y, Li L, Mann D, Imig JD, Emmett N, et al. Glomerular expression of kidney injury molecule-1 and podocytopenia in diabetic glomerulopathy. Am J Nephrol. 2011;34(3):268–80. https://doi.org/10.1159/000330187Dong Y, Zhang Q, Wen J, Chen T, He L, Wang Y, et al. Ischemic duration and frequency determines AKI-to-CKD progression monitored by dynamic changes of tubular biomarkers in IRI mice. Front Physiol. 2019;10:153. https://doi.org/10.3389/fphys.2019.00153Dong Y, Zhang Q, Wen J, Chen T, He L, Wang Y, et al. Ischemic duration and frequency determines AKI-to-CKD progression monitored by dynamic changes of tubular biomarkers in IRI mice. Front Physiol. 2019;10:153. https://doi.org/10.3389/fphys.2019.00153Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H, et al. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (KIM-1) over time. Am J Physiol Renal Physiol. 2009;296(5):F1136-45. https://doi.org/10.1152/ajprenal.00541.2007Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H, et al. Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (KIM-1) over time. Am J Physiol Renal Physiol. 2009;296(5):F1136-45. https://doi.org/10.1152/ajprenal.00541.2007Rouse RL, Zhang J, Stewart SR, Rosenzweig BA, Espandiari P, Sadrieh NK. Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats. Kidney Int. 2011;79(11):1186–97. https://doi.org/10.1038/ki.2010.463Rouse RL, Zhang J, Stewart SR, Rosenzweig BA, Espandiari P, Sadrieh NK. Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats. Kidney Int. 2011;79(11):1186–97. https://doi.org/10.1038/ki.2010.463Jeong M, Kim YW, Min JR, Kwon M, Han BS, Kim JG, et al. Kidney toxicity induced by 13 weeks exposure to the fruiting body of Paecilomyces sinclairii in rats. Toxicol Res. 2012;28(3):179–85. https://doi.org/10.5487/TR.2012.28.3.179Jeong M, Kim YW, Min JR, Kwon M, Han BS, Kim JG, et al. Kidney toxicity induced by 13 weeks exposure to the fruiting body of Paecilomyces sinclairii in rats. Toxicol Res. 2012;28(3):179–85. https://doi.org/10.5487/TR.2012.28.3.179Hussein AM, Malek HA, Saad MA. Renoprotective effects of aliskiren on adenine-induced tubulointerstitial nephropathy: possible underlying mechanisms. Can J Physiol Pharmacol. 2016;94(8):829–37. https://doi.org/10.1139/cjpp-2015-0364Hussein AM, Malek HA, Saad MA. Renoprotective effects of aliskiren on adenine-induced tubulointerstitial nephropathy: possible underlying mechanisms. Can J Physiol Pharmacol. 2016;94(8):829–37. https://doi.org/10.1139/cjpp-2015-0364Lippi I, Perondi F, Meucci V, Bruno B, Gazzano V, Guidi G. Clinical utility of urine kidney injury molecule-1 (KIM-1) and gamma-glutamyl transferase (GGT) in the diagnosis of canine acute kidney injury. Vet Res Commun. 2018;42(2):95–100. https://doi.org/10.1007/s11259-018-9711-7Lippi I, Perondi F, Meucci V, Bruno B, Gazzano V, Guidi G. Clinical utility of urine kidney injury molecule-1 (KIM-1) and gamma-glutamyl transferase (GGT) in the diagnosis of canine acute kidney injury. Vet Res Commun. 2018;42(2):95–100. https://doi.org/10.1007/s11259-018-9711-7Ennulat D, Ringenberg M, Frazier KS. Toxicologic Pathology Forum Opinion Paper*: recommendations for a tiered approach to nonclinical mechanistic nephrotoxicity evaluation. Toxicol Pathol. 2018;46(6):636–46. https://doi.org/10.1177/0192623318788302Ennulat D, Ringenberg M, Frazier KS. Toxicologic Pathology Forum Opinion Paper*: recommendations for a tiered approach to nonclinical mechanistic nephrotoxicity evaluation. Toxicol Pathol. 2018;46(6):636–46. https://doi.org/10.1177/0192623318788302Kharasch ED, Schroeder JL, Bammler T, Beyer R, Srinouanprachanh S. Gene expression profiling of nephrotoxicity from the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (“compound A”) in rats. Toxicol Sci. 2006;90(2):419–31. https://doi.org/10.1093/toxsci/kfj088Kharasch ED, Schroeder JL, Bammler T, Beyer R, Srinouanprachanh S. Gene expression profiling of nephrotoxicity from the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (“compound A”) in rats. Toxicol Sci. 2006;90(2):419–31. https://doi.org/10.1093/toxsci/kfj088Rached E, Hoffmann D, Blumbach K, Weber K, Dekant W, Mally A. Evaluation of putative biomarkers of nephrotoxicity after exposure to ochratoxin A in vivo and in vitro. Toxicol Sci. 2008;103(2):371–81. https://doi.org/10.1093/toxsci/kfn040Rached E, Hoffmann D, Blumbach K, Weber K, Dekant W, Mally A. Evaluation of putative biomarkers of nephrotoxicity after exposure to ochratoxin A in vivo and in vitro. Toxicol Sci. 2008;103(2):371–81. https://doi.org/10.1093/toxsci/kfn040Tsuchiya Y, Tominaga Y, Matsubayashi K, Jindo T, Furuhama K, Suzuki KT. Investigation on urinary proteins and renal mRNA expression in canine renal papillary necrosis induced by nefiracetam. Arch Toxicol. 2005;79(9):500–7. https://doi.org/10.1007/s00204-005-0666-4Tsuchiya Y, Tominaga Y, Matsubayashi K, Jindo T, Furuhama K, Suzuki KT. Investigation on urinary proteins and renal mRNA expression in canine renal papillary necrosis induced by nefiracetam. Arch Toxicol. 2005;79(9):500–7. https://doi.org/10.1007/s00204-005-0666-4Yoshida T, Kurella M, Beato F, Min H, Ingelfinger JR, Stears RL, et al. Monitoring changes in gene expression in renal ischemia-reperfusion in the rat. Kidney Int. 2002;61(5):1646–54. https://doi.org/10.1046/j.1523-1755.2002.00341.xYoshida T, Kurella M, Beato F, Min H, Ingelfinger JR, Stears RL, et al. Monitoring changes in gene expression in renal ischemia-reperfusion in the rat. Kidney Int. 2002;61(5):1646–54. https://doi.org/10.1046/j.1523-1755.2002.00341.xCorrea-Rotter R, Hostetter TH, Manivel JC, Eddy AA, Rosenberg ME. Intrarenal distribution of clusterin following reduction of renal mass. Kidney Int. 1992;41(4):938–50. https://doi.org/10.1038/ki.1992.144Correa-Rotter R, Hostetter TH, Manivel JC, Eddy AA, Rosenberg ME. Intrarenal distribution of clusterin following reduction of renal mass. Kidney Int. 1992;41(4):938–50. https://doi.org/10.1038/ki.1992.144Ishii A, Sakai Y, Nakamura A. Molecular pathological evaluation of clusterin in a rat model of unilateral ureteral obstruction as a possible biomarker of nephrotoxicity. Toxicol Pathol. 2007;35(3):376–82. https://doi.org/10.1080/01926230701230320Ishii A, Sakai Y, Nakamura A. Molecular pathological evaluation of clusterin in a rat model of unilateral ureteral obstruction as a possible biomarker of nephrotoxicity. Toxicol Pathol. 2007;35(3):376–82. https://doi.org/10.1080/01926230701230320Hidaka S, Kränzlin B, Gretz N, Witzgall R. Urinary clusterin levels in the rat correlate with the severity of tubular damage and may help to differentiate between glomerular and tubular injuries. Cell Tissue Res. 2002;310(3):289–96. https://doi.org/10.1007/s00441-002-0629-5Hidaka S, Kränzlin B, Gretz N, Witzgall R. Urinary clusterin levels in the rat correlate with the severity of tubular damage and may help to differentiate between glomerular and tubular injuries. Cell Tissue Res. 2002;310(3):289–96. https://doi.org/10.1007/s00441-002-0629-5Harpur E, Ennulat D, Hoffman D, Betton G, Gautier JC, Riefke B, et al. Biological qualification of biomarkers of chemical-induced renal toxicity in two strains of male rat. Toxicol Sci. 2011;122(2):235–52. https://doi.org/10.1093/toxsci/kfr112Harpur E, Ennulat D, Hoffman D, Betton G, Gautier JC, Riefke B, et al. Biological qualification of biomarkers of chemical-induced renal toxicity in two strains of male rat. Toxicol Sci. 2011;122(2):235–52. https://doi.org/10.1093/toxsci/kfr112Eti S, Cheng CY, Marshall A, Reidenberg MM. Urinary clusterin in chronic nephrotoxicity in the rat. Proc Soc Exp Biol Med. 1993;202(4):487–90. https://doi.org/10.3181/00379727-202-43564Eti S, Cheng CY, Marshall A, Reidenberg MM. Urinary clusterin in chronic nephrotoxicity in the rat. Proc Soc Exp Biol Med. 1993;202(4):487–90. https://doi.org/10.3181/00379727-202-43564Zhou X, Ma B, Lin Z, Qu Z, Huo Y, Wang J, et al. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs. Toxicol Appl Pharmacol. 2014;280(1):30–5. https://doi.org/10.1016/j.taap.2014.07.002Zhou X, Ma B, Lin Z, Qu Z, Huo Y, Wang J, et al. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs. Toxicol Appl Pharmacol. 2014;280(1):30–5. https://doi.org/10.1016/j.taap.2014.07.002McMahon BA, Koyner JL, Murray PT. Urinary glutathione S-transferases in the pathogenesis and diagnostic evaluation of acute kidney injury following cardiac surgery: a critical review. Curr Opin Crit Care. 2010;16(6):550–5. https://doi.org/10.1097/MCC.0b013e32833fdd9aMcMahon BA, Koyner JL, Murray PT. Urinary glutathione S-transferases in the pathogenesis and diagnostic evaluation of acute kidney injury following cardiac surgery: a critical review. Curr Opin Crit Care. 2010;16(6):550–5. https://doi.org/10.1097/MCC.0b013e32833fdd9aSwain A, Turton J, Scudamore CL, Pereira I, Viswanathan N, Smyth R, et al. Urinary biomarkers in hexachloro-1: 3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression. J Appl Toxicol. 2011;31(4):366–77. https://doi.org/10.1002/jat.1624Swain A, Turton J, Scudamore CL, Pereira I, Viswanathan N, Smyth R, et al. Urinary biomarkers in hexachloro-1: 3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression. J Appl Toxicol. 2011;31(4):366–77. https://doi.org/10.1002/jat.1624Wadey RM, Pinches MG, Jones HB, Riccardi D, Price SA. Tissue expression and correlation of a panel of urinary biomarkers following cisplatin-induced kidney injury. Toxicol Pathol. 2014;42(3):591–602. https://doi.org/10.1177/0192623313492044Wadey RM, Pinches MG, Jones HB, Riccardi D, Price SA. Tissue expression and correlation of a panel of urinary biomarkers following cisplatin-induced kidney injury. Toxicol Pathol. 2014;42(3):591–602. https://doi.org/10.1177/0192623313492044Chen Y, Brott D, Luo W, Gangl E, Kamendi H, Barthlow H, et al. Assessment of cisplatin-induced kidney injury using an integrated rodent platform. Toxicol Appl Pharmacol. 2013;268(3):352–61. https://doi.org/10.1016/j.taap.2013.01.032Chen Y, Brott D, Luo W, Gangl E, Kamendi H, Barthlow H, et al. Assessment of cisplatin-induced kidney injury using an integrated rodent platform. Toxicol Appl Pharmacol. 2013;268(3):352–61. https://doi.org/10.1016/j.taap.2013.01.032Miyagawa Y, Takemura N, Hirose H. Evaluation of the measurement of serum cystatin C by an enzyme-linked immunosorbent assay for humans as a marker of the glomerular filtration rate in dogs. J Vet Med Sci. 2009;71(9):1169–76. https://doi.org/10.1292/jvms.71.1169Miyagawa Y, Takemura N, Hirose H. Evaluation of the measurement of serum cystatin C by an enzyme-linked immunosorbent assay for humans as a marker of the glomerular filtration rate in dogs. J Vet Med Sci. 2009;71(9):1169–76. https://doi.org/10.1292/jvms.71.1169Wehner A, Hartmann K, Hirschberger J. Utility of serum cystatin C as a clinical measure of renal function in dogs. J Am Anim Hosp Assoc. 2008;44(3):131–8. https://doi.org/10.5326/0440131Wehner A, Hartmann K, Hirschberger J. Utility of serum cystatin C as a clinical measure of renal function in dogs. J Am Anim Hosp Assoc. 2008;44(3):131–8. https://doi.org/10.5326/0440131Braun JP, Perxachs A, Chereau D, De La Farge F. Plasma cystatin C in the dog: reference values and variations with renal failure. Comp Clin Path. 2002;11:44–9. https://doi.org/10.1007/s580-002-8081-2Braun JP, Perxachs A, Chereau D, De La Farge F. Plasma cystatin C in the dog: reference values and variations with renal failure. Comp Clin Path. 2002;11:44–9. https://doi.org/10.1007/s580-002-8081-2Togashi Y, Sakaguchi Y, Miyamoto M, Miyamoto Y. Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats. Exp Toxicol Pathol. 2012;64(7–8):797–805. https://doi.org/10.1016/j.etp.2011.01.018Togashi Y, Sakaguchi Y, Miyamoto M, Miyamoto Y. Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats. Exp Toxicol Pathol. 2012;64(7–8):797–805. https://doi.org/10.1016/j.etp.2011.01.018Song S, Meyer M, Türk TR, Wilde B, Feldkamp T, Assert R, et al. Serum cystatin C in mouse models: a reliable and precise marker for renal function and superior to serum creatinine. Nephrol Dial Transplant. 2009;24(4):1157–61. https://doi.org/10.1093/ndt/gfn626Song S, Meyer M, Türk TR, Wilde B, Feldkamp T, Assert R, et al. Serum cystatin C in mouse models: a reliable and precise marker for renal function and superior to serum creatinine. Nephrol Dial Transplant. 2009;24(4):1157–61. https://doi.org/10.1093/ndt/gfn626Song L, Wang, K, Yin J, Yang Y, Li B, Zhang D, et al. Traditional Chinese Medicine Fufang-Zhenzhu-Tiaozhi capsule prevents renal injury in diabetic minipigs with coronary heart disease. Chin Med. 2022;17(1):102. https://doi.org/10.1186/s13020-022-00648-xSong L, Wang, K, Yin J, Yang Y, Li B, Zhang D, et al. Traditional Chinese Medicine Fufang-Zhenzhu-Tiaozhi capsule prevents renal injury in diabetic minipigs with coronary heart disease. Chin Med. 2022;17(1):102. https://doi.org/10.1186/s13020-022-00648-xUchino H, Fujishima J, Fukuoka K, Iwakiri T, Kamikuri A, Maeda H, et al. Usefulness of urinary biomarkers for nephrotoxicity in cynomolgus monkeys treated with gentamicin, cisplatin, and puromycin aminonucleoside. J Toxicol Sci. 2017;42(5):629–40. https://doi.org/10.2131/jts.42.629Uchino H, Fujishima J, Fukuoka K, Iwakiri T, Kamikuri A, Maeda H, et al. Usefulness of urinary biomarkers for nephrotoxicity in cynomolgus monkeys treated with gentamicin, cisplatin, and puromycin aminonucleoside. J Toxicol Sci. 2017;42(5):629–40. https://doi.org/10.2131/jts.42.629Yamaguchi I, Myojo K, Sanada H, Takami A, Suzuki Y, Imaizumi M, et al. Five-sixth nephrectomy in female common marmosets (Callithrix jacchus) as a chronic renal failure model — a longitudinal course of serum biochemical, hema tological and histopathological changes. J Toxicol Pathol. 2014;27(3–4):183–95. https://doi.org/10.1293/tox.2013-0055Yamaguchi I, Myojo K, Sanada H, Takami A, Suzuki Y, Imaizumi M, et al. Five-sixth nephrectomy in female common marmosets (Callithrix jacchus) as a chronic renal failure model — a longitudinal course of serum biochemical, hema tological and histopathological changes. J Toxicol Pathol. 2014;27(3–4):183–95. https://doi.org/10.1293/tox.2013-0055Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008;52(3):595–605. https://doi.org/10.1053/j.ajkd.2008.01.020Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis. 2008;52(3):595–605. https://doi.org/10.1053/j.ajkd.2008.01.020Lee YJ, Hu YY, Lin YS, Chang CT, Lin FY, Wong ML, et al. Urine neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute canine kidney injury. BMC Vet Res. 2012;8:248. https://doi.org/10.1186/1746-6148-8-248Lee YJ, Hu YY, Lin YS, Chang CT, Lin FY, Wong ML, et al. Urine neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute canine kidney injury. BMC Vet Res. 2012;8:248. https://doi.org/10.1186/1746-6148-8-248Silberstein JL, Sprenkle PC, Su D, Power NE, Tarin TV, Ezell P, et al. Neutrophil gelatinase-associated lipocalin (NGAL) levels in response to unilateral renal ischaemia in a novel pilot two-kidney porcine model. BJU Int. 2013;112(4):517–25. https://doi.org/10.1111/bju.12066Silberstein JL, Sprenkle PC, Su D, Power NE, Tarin TV, Ezell P, et al. Neutrophil gelatinase-associated lipocalin (NGAL) levels in response to unilateral renal ischaemia in a novel pilot two-kidney porcine model. BJU Int. 2013;112(4):517–25. https://doi.org/10.1111/bju.12066Palm CA, Segev G, Cowgill LD, LeRoy BE, Kowalkowski KL, Kanakubo K, et al. Urinary neutrophil gelatinase-associated lipocalin as a marker for identification of acute kidney injury and recovery in dogs with gentamicin-induced nephrotoxicity. J Vet Intern Med. 2016;30(1):200–5. https://doi.org/10.1111/jvim.13819Palm CA, Segev G, Cowgill LD, LeRoy BE, Kowalkowski KL, Kanakubo K, et al. Urinary neutrophil gelatinase-associated lipocalin as a marker for identification of acute kidney injury and recovery in dogs with gentamicin-induced nephrotoxicity. J Vet Intern Med. 2016;30(1):200–5. https://doi.org/10.1111/jvim.13819Burt D, Crowell SJ, Ackley DC, Magee TV, Aubrecht J. Application of emerging biomarkers of acute kidney injury in development of kidney-sparing polypeptide-based antibiotics. Drug Chem Toxicol. 2014;37(2):204–12. https://doi.org/10.3109/01480545.2013.834360Burt D, Crowell SJ, Ackley DC, Magee TV, Aubrecht J. Application of emerging biomarkers of acute kidney injury in development of kidney-sparing polypeptide-based antibiotics. Drug Chem Toxicol. 2014;37(2):204–12. https://doi.org/10.3109/01480545.2013.834360Wang Y, Wang B, Qi X, Zhang X, Ren K. Resveratrol protects against post-contrast acute kidney injury in rabbits with diabetic nephropathy. Front Pharmacol. 2019;10:833. https://doi.org/10.3389/fphar.2019.00833Wang Y, Wang B, Qi X, Zhang X, Ren K. Resveratrol protects against post-contrast acute kidney injury in rabbits with diabetic nephropathy. Front Pharmacol. 2019;10:833. https://doi.org/10.3389/fphar.2019.00833Bazzi C, Rizza V, Olivieri G, Casellato D, D’Amico G. Tubular reabsorption of high, middle and low molecular weight proteins according to the tubulo-interstitial damage marker N-acetyl-β-D-glucosaminidase in glomerulonephritis. J Nephrol. 2015;28(5):541–8. https://doi.org/10.1007/s40620-014-0139-zBazzi C, Rizza V, Olivieri G, Casellato D, D’Amico G. Tubular reabsorption of high, middle and low molecular weight proteins according to the tubulo-interstitial damage marker N-acetyl-β-D-glucosaminidase in glomerulonephritis. J Nephrol. 2015;28(5):541–8. https://doi.org/10.1007/s40620-014-0139-zŚliwińska-Mossoń M, Sobiech K, Dolezych B, Madej P, Milnerowicz H. N-acetyl-beta-d-glucosaminidase in tissues of rats chronically exposed to cadmium and treated with ozone. Ann Clin Lab Sci. 2019;49(2):193–203. PMID: 31028064Śliwińska-Mossoń M, Sobiech K, Dolezych B, Madej P, Milnerowicz H. N-acetyl-beta-d-glucosaminidase in tissues of rats chronically exposed to cadmium and treated with ozone. Ann Clin Lab Sci. 2019;49(2):193–203. PMID: 31028064Bosomworth MP, Aparicio SR, Hay AW. Urine N-acetyl-beta-D-glucosaminidase — a marker of tubular damage? Nephrol Dial Transplantat. 1999;14(3):620–6. https://doi.org/10.1093/ndt/14.3.620Bosomworth MP, Aparicio SR, Hay AW. Urine N-acetyl-beta-D-glucosaminidase — a marker of tubular damage? Nephrol Dial Transplantat. 1999;14(3):620–6. https://doi.org/10.1093/ndt/14.3.620Hanbeyoğlu A, Kazez A, Üstündağ B, Akpolat N. Determination of urinary N-acetyl-β-D glucosaminidase (NAG) levels in experimental blunt renal trauma. Ulus Travma Acil Cerrahi Derg. 2011;17(6):475–81. https://doi.org/10.5505/tjtes.2011.57973Hanbeyoğlu A, Kazez A, Üstündağ B, Akpolat N. Determination of urinary N-acetyl-β-D glucosaminidase (NAG) levels in experimental blunt renal trauma. Ulus Travma Acil Cerrahi Derg. 2011;17(6):475–81. https://doi.org/10.5505/tjtes.2011.57973Suzuki CAM, Thomas BH, Mueller R. Evaluation of enzymuria as an indicator of amikacin-induced renal damage in guinea pigs. Toxicol Lett. 1992;62(1):101–14. https://doi.org/10.1016/0378-4274(92)90083-vSuzuki CAM, Thomas BH, Mueller R. Evaluation of enzymuria as an indicator of amikacin-induced renal damage in guinea pigs. Toxicol Lett. 1992;62(1):101–14. https://doi.org/10.1016/0378-4274(92)90083-vTürkmen M, Kavukcu S, Islekel H, Sarioğlu S, Akhunlar H, Gökden N, et al. Urinary N-acetyl-β-D-glucosaminidase activity in rabbits with experimental hypercalciuria. Pediatr Nephrol. 1997;11:481–4. https://doi.org/10.1007/s004670050321Türkmen M, Kavukcu S, Islekel H, Sarioğlu S, Akhunlar H, Gökden N, et al. Urinary N-acetyl-β-D-glucosaminidase activity in rabbits with experimental hypercalciuria. Pediatr Nephrol. 1997;11:481–4. https://doi.org/10.1007/s004670050321Pressler BM. Clinical approach to advanced renal function testing in dogs and cats. Clin Lab Med. 2015;35(3):487–502. https://doi.org/10.1016/j.cll.2015.05.001Pressler BM. Clinical approach to advanced renal function testing in dogs and cats. Clin Lab Med. 2015;35(3):487–502. https://doi.org/10.1016/j.cll.2015.05.001Adedeji AO, Sonee M, Chen Y, Lynch K, Peron K, King N, et al. Evaluation of novel urinary biomarkers in beagle dogs with Amphotericin B-induced kidney injury. Int J Toxicol. 2023;42(2):146–55. https://doi.org/10.1177/10915818221142542Adedeji AO, Sonee M, Chen Y, Lynch K, Peron K, King N, et al. Evaluation of novel urinary biomarkers in beagle dogs with Amphotericin B-induced kidney injury. Int J Toxicol. 2023;42(2):146–55. https://doi.org/10.1177/10915818221142542Ruiz P, Durán Á, Duque FJ, González MA, Cristóbal JI, Nicolás P, et al. Urinary cystatin C and N-acetyl-beta-D-gluco saminidase (NAG) as early biomarkers for renal disease in dogs with leishmaniosis. Vet Parasitol. 2023;318:109930. https://doi.org/10.1016/j.vetpar.2023.109930Ruiz P, Durán Á, Duque FJ, González MA, Cristóbal JI, Nicolás P, et al. Urinary cystatin C and N-acetyl-beta-D-gluco saminidase (NAG) as early biomarkers for renal disease in dogs with leishmaniosis. Vet Parasitol. 2023;318:109930. https://doi.org/10.1016/j.vetpar.2023.109930Gautier JC, Zhou X, Yang Y, Gury T, Qu Z, Palazzi X, et al. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin. Toxicol Appl Pharmacol. 2016;303:1–10. https://doi.org/10.1016/j.taap.2016.04.012Gautier JC, Zhou X, Yang Y, Gury T, Qu Z, Palazzi X, et al. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin. Toxicol Appl Pharmacol. 2016;303:1–10. https://doi.org/10.1016/j.taap.2016.04.012Watanabe A, Ohata K, Oikawa T, Sugaya T, Miyazaki M, Satoh H, et al. Preliminary study of urinary excretion of liver-type fatty acid-binding protein in a cat model of chronic kidney disease. Can J Vet Res. 2021;85(2):156–60.Watanabe A, Ohata K, Oikawa T, Sugaya T, Miyazaki M, Satoh H, et al. Preliminary study of urinary excretion of liver-type fatty acid-binding protein in a cat model of chronic kidney disease. Can J Vet Res. 2021;85(2):156–60.Matsui K, Kamijo-Ikemorif A, Sugaya T, Yasuda T, Kimura K. Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity. Am J Pathol. 2011;178(3):1021–32. https://doi.org/10.1016/j.ajpath.2010.12.002Matsui K, Kamijo-Ikemorif A, Sugaya T, Yasuda T, Kimura K. Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity. Am J Pathol. 2011;178(3):1021–32. https://doi.org/10.1016/j.ajpath.2010.12.002Kamijo-Ikemori A, Ichikawa D, Matsui K, Yokoyama T, Sugaya T, Kimura K. Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan. Rinsho Byori. 2013;61(7):635–40 (In Japanese). PMID: 24205707Kamijo-Ikemori A, Ichikawa D, Matsui K, Yokoyama T, Sugaya T, Kimura K. Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan. Rinsho Byori. 2013;61(7):635–40 (In Japanese). PMID: 24205707Yamamoto T, Noiri E, Ono Y, D o i K, Negishi K, Kamijo A, et al. Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol. 2007;18(11):2894–902. https://doi.org/10.1681/ASN.2007010097Yamamoto T, Noiri E, Ono Y, D o i K, Negishi K, Kamijo A, et al. Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol. 2007;18(11):2894–902. https://doi.org/10.1681/ASN.2007010097Kanaguchi Y, Suzuki Y, Osaki K, Sugaya T, Horikoshi S, Tomino Y. Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis. Nephrol Dial Transplant. 2011;26(11):3465–73. https://doi.org/10.1093/ndt/gfr110Kanaguchi Y, Suzuki Y, Osaki K, Sugaya T, Horikoshi S, Tomino Y. Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis. Nephrol Dial Transplant. 2011;26(11):3465–73. https://doi.org/10.1093/ndt/gfr110Lin Z, Wan X, Zhang T, Huo H, Zhang X, Li K, et al. Trefoil factor 3: new highlights in chronic kidney disease research. Cell Signal. 2022;100:110470. https://doi.org/10.1016/j.cellsig.2022.110470Lin Z, Wan X, Zhang T, Huo H, Zhang X, Li K, et al. Trefoil factor 3: new highlights in chronic kidney disease research. Cell Signal. 2022;100:110470. https://doi.org/10.1016/j.cellsig.2022.110470Yu Y, Jin H, Holder D, Ozer JS, Villarreal S, Shughrue P, et al. Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nat Biotechnol. 2010;28(5):470–7. https://doi.org/10.1038/nbt.1624Yu Y, Jin H, Holder D, Ozer JS, Villarreal S, Shughrue P, et al. Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nat Biotechnol. 2010;28(5):470–7. https://doi.org/10.1038/nbt.1624Reeves BW, Kwon O, Ramesh G. Netrin-1 and kidney injury. II. Netrin-1 is an early biomarker of acute kidney injury. Am J Physiol Renal Physiol. 2008;294(4):F731–8. https://doi.org/10.1152/ajprenal.00507.2007Reeves BW, Kwon O, Ramesh G. Netrin-1 and kidney injury. II. Netrin-1 is an early biomarker of acute kidney injury. Am J Physiol Renal Physiol. 2008;294(4):F731–8. https://doi.org/10.1152/ajprenal.00507.2007Rajasundari A, Pays L, Mehlen P, Ramesh G. Netrin-1 overexpression in kidney proximal tubular epithelium ameliorates cisplatin nephrotoxicity. Lab Invest. 2011;91(12):1717–26. https://doi.org/10.1038/labinvest.2011.126Rajasundari A, Pays L, Mehlen P, Ramesh G. Netrin-1 overexpression in kidney proximal tubular epithelium ameliorates cisplatin nephrotoxicity. Lab Invest. 2011;91(12):1717–26. https://doi.org/10.1038/labinvest.2011.126White JJ, Mohamed R, Jayakumar C, Ramesh G. Tubular injury markers netrin-1 is elevated early in experimental diabetes. J Nephrol. 2013;26(6):1055–64. https://doi.org/10.5301/jn.5000303White JJ, Mohamed R, Jayakumar C, Ramesh G. Tubular injury markers netrin-1 is elevated early in experimental diabetes. J Nephrol. 2013;26(6):1055–64. https://doi.org/10.5301/jn.5000303Bai J, Hao J, Zhang X, Cui H, Han J, Cao N. Netrin-1 attenuates the progression of renal dysfunction by blocking endothelial-to-mesenchymal transition in the 5/6 nephrectomy rat model. BMC Nephrol. 2016;17(1):47. https://doi.org/10.1186/s12882-016-0260-4Bai J, Hao J, Zhang X, Cui H, Han J, Cao N. Netrin-1 attenuates the progression of renal dysfunction by blocking endothelial-to-mesenchymal transition in the 5/6 nephrectomy rat model. BMC Nephrol. 2016;17(1):47. https://doi.org/10.1186/s12882-016-0260-4García-Martínez JD, Tvarijonaviciute A, Cerón JJ, Caldin M, Martínez-Subiela S. Urinary clusterin as a renal marker in dogs. J Vet Diagn Invest. 2012;24(2):301–6. https://doi.org/10.1177/1040638711435112García-Martínez JD, Tvarijonaviciute A, Cerón JJ, Caldin M, Martínez-Subiela S. Urinary clusterin as a renal marker in dogs. J Vet Diagn Invest. 2012;24(2):301–6. https://doi.org/10.1177/1040638711435112Son JY, Kang YJ, Kim KS, Kim TH, Lim SK, Lim HJ, et al. Evaluation of renal toxicity by combination exposure to melamine and cyanuric acid in male Sprague-Dawley rats. Toxicol Res. 2014;30(2):99–107. https://doi.org/10.5487/TR.2014.30.2.099Son JY, Kang YJ, Kim KS, Kim TH, Lim SK, Lim HJ, et al. Evaluation of renal toxicity by combination exposure to melamine and cyanuric acid in male Sprague-Dawley rats. Toxicol Res. 2014;30(2):99–107. https://doi.org/10.5487/TR.2014.30.2.099Adedeji AO, Gu YZ, Pourmohamad T, Kanerva J, Chen Y, Atabakhsh E, et al. The utility of novel urinary biomarkers in mice for drug development studies. Int J Toxicol. 2021;40(1):15–25. https://doi.org/10.1177/1091581820970498Adedeji AO, Gu YZ, Pourmohamad T, Kanerva J, Chen Y, Atabakhsh E, et al. The utility of novel urinary biomarkers in mice for drug development studies. Int J Toxicol. 2021;40(1):15–25. https://doi.org/10.1177/1091581820970498Stubbs JR, Zhang S, Jansson KP, Fields TA, Boulanger J, Liu S, et al. Critical role of osteopontin in maintaining urinary phosphate solubility in CKD. Kidney360. 2022;3(9):1578–89. https://doi.org/10.34067/KID.0007352021Stubbs JR, Zhang S, Jansson KP, Fields TA, Boulanger J, Liu S, et al. Critical role of osteopontin in maintaining urinary phosphate solubility in CKD. Kidney360. 2022;3(9):1578–89. https://doi.org/10.34067/KID.0007352021Phillips JA, Holder DJ, Ennulat D, Gautier JC, Sauer JM, Yang Y, et al. Rat urinary osteopontin and neutrophil gelatinase-associated lipocalin improve certainty of detecting drug-induced kidney injury. Toxicol Sci. 2016;151(2):214–23. https://doi.org/10.1093/toxsci/kfw038Phillips JA, Holder DJ, Ennulat D, Gautier JC, Sauer JM, Yang Y, et al. Rat urinary osteopontin and neutrophil gelatinase-associated lipocalin improve certainty of detecting drug-induced kidney injury. Toxicol Sci. 2016;151(2):214–23. https://doi.org/10.1093/toxsci/kfw038Zhang Q, Davis KJ, Hoffmann D, Vaidya VS, Brown RP, Goering PL. Urinary biomarkers track the progression of nephropathy in hypertensive and obese rats. Biomark Med. 2014;8(1):85–94. https://doi.org/10.2217/bmm.13.106Zhang Q, Davis KJ, Hoffmann D, Vaidya VS, Brown RP, Goering PL. Urinary biomarkers track the progression of nephropathy in hypertensive and obese rats. Biomark Med. 2014;8(1):85–94. https://doi.org/10.2217/bmm.13.106Dobrek Ł, Arent Z, Nalik-Iwaniak K, Fic K, Kopańska M. Osteopontin and fatty acid binding protein in ifosfamide-treated rats. Open Medicine. 2019;14(1):561–71. https://doi.org/10.1515/med-2019-0063Dobrek Ł, Arent Z, Nalik-Iwaniak K, Fic K, Kopańska M. Osteopontin and fatty acid binding protein in ifosfamide-treated rats. Open Medicine. 2019;14(1):561–71. https://doi.org/10.1515/med-2019-0063Carlos CP, Sonehara NM, Oliani SM, Burdmann EA. Predictive usefulness of urinary biomarkers for the identification of cyclosporine A-induced nephrotoxicity in a rat model. PLoS One. 2014;9(7):e103660. https://doi.org/10.1371/journal.pone.0103660Carlos CP, Sonehara NM, Oliani SM, Burdmann EA. Predictive usefulness of urinary biomarkers for the identification of cyclosporine A-induced nephrotoxicity in a rat model. PLoS One. 2014;9(7):e103660. https://doi.org/10.1371/journal.pone.0103660Harjen HJ, Nicolaysen TV, Negard T, Lund H, Sævik BK, Anfinsen KP, et al. Serial serum creatinine, SDMA and urinary acute kidney injury biomarker measurements in dogs envenomated by the European adder (Vipera berus). BMC Vet Res. 2021;17(1):154. https://doi.org/10.1186/s12917-021-02851-8Harjen HJ, Nicolaysen TV, Negard T, Lund H, Sævik BK, Anfinsen KP, et al. Serial serum creatinine, SDMA and urinary acute kidney injury biomarker measurements in dogs envenomated by the European adder (Vipera berus). BMC Vet Res. 2021;17(1):154. https://doi.org/10.1186/s12917-021-02851-8Gu YZ, Vlasakova K, Troth SP, Peiffer RL, Tournade H, Pasello dos Santos FR, et al. Performance assessment of new urinary translational safety biomarkers of drug-induced renal tubular injury in tenofovir-treated cynomolgus monkeys and beagle dogs. Toxicol Pathol. 2018;46(5):553–63. https://doi.org/10.1177/0192623318775023Gu YZ, Vlasakova K, Troth SP, Peiffer RL, Tournade H, Pasello dos Santos FR, et al. Performance assessment of new urinary translational safety biomarkers of drug-induced renal tubular injury in tenofovir-treated cynomolgus monkeys and beagle dogs. Toxicol Pathol. 2018;46(5):553–63. https://doi.org/10.1177/0192623318775023Monti P, Benchekroun G, Berlato D, Archer J. Initial evaluation of canine urinary cystatin C as a marker of renal tubular function. J Small Anim Pract. 2012;53(5):254–9. https://doi.org/10.1111/j.1748-5827.2012.01198.xMonti P, Benchekroun G, Berlato D, Archer J. Initial evaluation of canine urinary cystatin C as a marker of renal tubular function. J Small Anim Pract. 2012;53(5):254–9. https://doi.org/10.1111/j.1748-5827.2012.01198.xGhys LFE, Meyer E, Paepe D, Delanghe J, Daminet S. Analytical validation of a human particle-enhanced nephelometric assay for cystatin C measurement in feline serum and urine. Vet Clin Pathol. 2014;43(2):226–34. https://doi.org/10.1111/vcp.12144Ghys LFE, Meyer E, Paepe D, Delanghe J, Daminet S. Analytical validation of a human particle-enhanced nephelometric assay for cystatin C measurement in feline serum and urine. Vet Clin Pathol. 2014;43(2):226–34. https://doi.org/10.1111/vcp.12144Gil A, Brod V, Awad H, Heyman SN, Abassi Z, Frajewicki V. Neutrophil gelatinase-associated lipocalin in a triphasic rat model of adenine-induced kidney injury. Ren Fail. 2016;38(9):1448–54. https://doi.org/10.1080/0886022X.2016.1194164Gil A, Brod V, Awad H, Heyman SN, Abassi Z, Frajewicki V. Neutrophil gelatinase-associated lipocalin in a triphasic rat model of adenine-induced kidney injury. Ren Fail. 2016;38(9):1448–54. https://doi.org/10.1080/0886022X.2016.1194164Sekulic M, Pichler Sekulic S. A compendium of urinary biomarkers indicative of glomerular podocytopathy. Patholog Res Int. 2013;2013:782395. https://doi.org/10.1155/2013/782395Sekulic M, Pichler Sekulic S. A compendium of urinary biomarkers indicative of glomerular podocytopathy. Patholog Res Int. 2013;2013:782395. https://doi.org/10.1155/2013/782395Pan QR, Ren YL, Zhu JJ, Hu YJ, Zheng JS, Fan H, et al. Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet. Nutrients. 2014;6(7):2619–31. https://doi.org/10.3390/nu6072619Pan QR, Ren YL, Zhu JJ, Hu YJ, Zheng JS, Fan H, et al. Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet. Nutrients. 2014;6(7):2619–31. https://doi.org/10.3390/nu6072619Мирошников МВ, Султанова КТ, Макарова МН, Фаустова НМ, Хан СО, Лосева Е.А. Комплексная оценка функционального состояния мочевыделительной системы в доклинических исследованиях. Часть 1: инструментальные и лабораторные методы оценки (обзор). Регуляторные исследования и экспертиза лекарственных средств. 2024;14(3):283–94. https://doi.org/10.30895/1991-2919-2024-14-3-283-294Miroshnikov MV, Sultanova KT, Makarova MN, Fausto va NM, Khan SO, Loseva EA. Complex assessment of the functional state of the urinary system in preclinical studies. Part 1: Instrumental and laboratory assessment methods (review). Regulatory Research and Medicine Evaluation. 2024;14(3):283–94 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-3-283-294

The authors declare that there are no conflicts of interest present.