arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2018-24-2-223-236arthyper-796Research ArticleСтатьиArticlesМаркеры поражения почек у больных артериальной гипертензией: новые против старыхBiomarkers of kidney injury in hypertension: conventional versus novelМироноваС. А.MironovaS. A.

аспирант очной формы обучения научно-исследовательской лаборатории (НИЛ) патогенеза и терапии артериальной гипертензии научно- исследовательского отдела (НИО) артериальной гипертензии

MD, PhD, Student, Department for Arterial Hypertension

panarinasa@gmail.comЮдинаЮ. С.YudinaYu. S.

аспирант очной формы обучения, младший научный сотрудник НИЛ патогенеза и терапии артериальной гипертензии НИО артериальной гипертензии

MD, PhD, Student, Department for Arterial Hypertension

ИоновМ. В.IonovM. V.

аспирант очной формы обучения, младший научный сотрудник НИЛ патогенеза и терапии артериальной гипертензии НИО артериальной гипертензии ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России, младший научный сотрудник Института трансляционной медицины Университета ИТМО

MD, PhD, Student, Department for Arterial Hypertension, Almazov National Medical Research Centre; Junior Researcher, Translational Medicine Institute of the ITMO University

АвдонинаН. Г.AvdoninaN. G.

старший научный сотрудник НИЛ патогенеза и терапии артериальной гипертензии НИО артериальной гипертензии

MD, Senior Researcher, Department for Arterial Hypertension, Department for Arterial Hypertension

ЕмельяновИ. В.EmelyanovI. V.

кандидат медицинских наук, старший научный сотрудник НИЛ патогенеза и терапии артериальной гипертензии НИО артериальной гипертензии

MD, PhD, Senior Researcher, Department for Arterial Hypertension, Department for Arterial Hypertension

ВасильеваЕ. Ю.Vasil’evaE. Yu.

заведующая центральной клинико-диагностической лабораторией

Head, Central Clinical and Diagnostic Laboratory

ЗвартауН. Э.ZvartauN. E.

кандидат медицинских наук, старший научный сотрудник НИЛ патогенеза и терапии артериальной гипертензии НИО артериальной гипертензии ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России, старший научный сотрудник Института трансляционной медицины Университета ИТМО

MD, PhD, Senior Researcher, Department for Arterial Hypertension, Department for Arterial Hypertension, Almazov National Medical Research Centre, Senior Researcher, Translational Medicine Institute, ITMO University

КонрадиА. О.KonradiA. O.

доктор медицинских наук, профессор, член-корреспондент РАН, руководитель НИО артериальной гипертензии, заместитель генерального директора по научной работе ФГБУ «НМИЦ им. В.А. Алмазова» Минздрава России, директор Института трансляционной медицины Университета ИТМО

MD, PhD, DSc, Professor, Head, Department for Arterial Hypertension, Deputy General Director on Research, Almazov National Medical Research Centre, Director, Translational Medicine Institute, ITMO University

Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской Федерации, Санкт-ПетербургРоссияAlmazov National Medical Research Centre, St PetersburgRussian FederationФедеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр имени В. А. Алмазова» Министерства здравоохранения Российской Федерации, Санкт-Петербург; Университет ИТМО, Санкт-ПетербургРоссияAlmazov National Medical Research Centre, St Petersburg; ITMO University, St PetersburgRussian Federation201815052018242223236Copyright © Миронова С.А., Юдина Ю.С., Ионов М.В., Авдонина Н.Г., Емельянов И.В., Васильева Е.Ю., Звартау Н.Э., Конради А.О., 20182018Миронова С.А., Юдина Ю.С., Ионов М.В., Авдонина Н.Г., Емельянов И.В., Васильева Е.Ю., Звартау Н.Э., Конради А.О.Mironova S.A., Yudina Y.S., Ionov M.V., Avdonina N.G., Emelyanov I.V., Vasil’eva E.Y., Zvartau N.E., Konradi A.O.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/796

Цель исследования — оценить уровень различных более ранних и стандартных биомаркеров почечного повреждения у больных артериальной гипертензией (АГ) различной степени тяжести и длительности и сопоставить с уровнем у практически здоровых лиц. Материалы и методы. Были обследованы 92 пациента (46 мужчин) с АГ, средний возраст которых составил 50,7 ± 12,2 года, впоследствии разделенных на 4 группы в зависимости от степени тяжести АГ: АГ 1‑й степени (n = 24), АГ 2‑й степени (n = 26), АГ 3‑й степени (n = 17) и резистентная АГ (n = 25) и практически здоровые лица в количестве 34 человек (16 мужчин), средний возраст которых составил 49,9 ± 11,4 года. Для оценки поражения почек пациентам основной и контрольной групп выполнялись: измерение цистатина С и креатинина в сыворотке крови, определение маркеров поражения почек в суточной моче — NGAL, KIM‑1 и L‑FABP и уровня альбуминурии. Расчет скорости клубочковой фильтрации (СКФ) проводился по уровню креатинина и цистатина С сыворотки крови при помощи расчетных формул MDRD и CKD-EPI (СКФ_CKD-EPI_CysC, СКФ_CKD-EPI_CysC_Cr). Инструментальное обследование включало в себя измерение «офисных» значений артериального давления (АД), суточное мониторирование АД (СМАД) с использованием прибора SpaceLabs (SpaceLabs Medical, США), оценку центрального аортального давления (ЦАД) методом аппланационной тонометрии — с помощью прибора SphygmoCor (AtCor Medical, Сидней, Австралия). Результаты. Пациенты контрольной группы и пациенты с АГ значимо различались по уровню креатинина крови, СКФ и альбуминурии, однако значения креатинина крови оставались в пределах нормальных значений, несмотря на увеличение степени тяжести АГ, а повышение альбуминурии наблюдалось только у пациентов с тяжелой АГ. У пациентов с АГ отмечался существенно более высокий уровень цистатина С в крови по сравнению с группой контроля, что встречалось уже у пациентов с АГ 1‑й и 2‑й степени, и его повышение отмечалось чаще, чем повышение уровня креатинина крови и альбуминурии. Также было отмечено значимое снижение функции почек у пациентов с АГ по сравнению с контрольной группой по данным СКФ_CKD-EPI_CysC и СКФ_CKD-EPI_CysC_Cr. Данные биомаркеры у пациентов с АГ были ассоциированы с уровнем «офисного» систолического АД (САД), систолического ЦАД (ЦАДс) и диастолического ЦАД (ЦАДд) и со многими показателями СМАД. Сравнительный анализ показателей NGAL и KIM‑1 в суточной моче не выявил значимых различий между группой здоровых лиц и пациентов с АГ, в том числе и с увеличением степени тяжести АГ, однако в группе пациентов с тяжелой АГ уровень KIM‑1 в моче был ассоциирован с показателями «офисного» САД, среднесуточного диастолического АД (ДАД) и показателями ЦАДс и ЦАДд. В то же время значимое увеличение уровня L‑FABP в моче было отмечено в группе с начальной АГ по сравнению с группой контроля, и дальнейшее увеличение его концентрации у пациентов с тяжелой АГ, а также ассоциация уровня L‑FABP с показателями «офисного» САД и ДАД, ЦАДс и ЦАДд и показателями СМАД. Выводы. Сочетанное определение креатинина и цистатина С в сыворотке крови, а также расчет СКФ по формуле CKD-EPI является более точным методом определения стадии хронической болезни почек, в том числе гипертензивной; уровень L‑FABP в моче может рассматриваться как наиболее ранний биомаркер поражения почек при АГ, отражающий прогрессирование тубулоинтерстициального повреждения почечной ткани.

Objective. The aim of the present study was to compare conventional and novel, potentially earlier biomarkers of kidney injury in patients with different severity and duration of arterial hypertension (HTN) and healthy controls. Design and methods. Urine levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule‑1 (KIM‑1), liver fatty-acid binding protein (L‑FABP), albuminuria and serum levels of cystatin C and creatinine were measured in 92 hypertensive patients (46 male, mean age 50,7 ± 12,2 years) and 34 healthy control subjects (16 male, mean age 49,9 ± 11,4 years). Hypertensive patients were divided into four age- and sex-matched groups according to HTN severity: 1st grade (n = 24), 2nd grade (n = 26), 3rd grade (n = 17) and resistant hypertension (n = 25). Glomerular filtration rate (GFR) was estimated by the level of serum creatinine and cystatin C by MDRD and CKD-EPI formulas. Instrumental examination included measuring office blood pressure (BP), 24‑hour ambulatory BP monitoring (ABPM, SpaceLabs 90207), applanation tonometry (SphygmoCor, Artcor Medical) with the calculation of central aortic pressure. Results. As compared to healthy control subjects, hypertensive patients were characterized by higher creatinine and albuminuria levels, and lower GFR, however, creatinine levels remained within the normal range despite the increase in the severity of HTN. Levels of albuminuria increased only in patients with severe HTN. Also as compared to healthy controls, HTN patients had significantly higher levels of cystatin C, which already was found in patients with 1st and 2nd stages of HTN, which occurs more often than an increase of creatinine and albuminuria levels. Patients with HTN had significantly lower sCys-estimated GFR and creatinine-sCys-estimated GFR. In HTN patients these biomarkers were associated with office systolic BP (SBP), central aortic systolic and diastolic (CAP) and mean 24‑hour BP level. There were no differencesin NGAL, KIM‑1 levels between the groups, however, KIM‑1 levels were associated with office SBP, mean daily 24‑hour of diastolic BP (DBP) and systolic and diastolic CAP in patients with severe HTN. At the same time, as compared with healthy controls, patients with initial HTN were characterized by higher levels of urine L‑FABP and its concentration increased in patients with severe HTN. In addition, L‑FABP levels were associated with office SBP and DBP, mean 24‑hour BP and systolic and diastolic CAP. Conclusions. The simultaneous assessment of creatinine and cystatin C levels, and the calculation of GFR using the formula CKD-EPI seems to be more accurate method for CKD stage classification in general and, in particular, in hypertensive patients; in hypertensive patients L‑FABP appears to be earlier biomarker of kidney injury, reflecting the progression of tubulointerstitial injury.

артериальная гипертензиятубулоинтерстициальное повреждение почекбиомаркеры поражения почекхроническая болезнь почекhypertensiontubulointerstitial kidney injurybiomarkers of kidney injurychronic kidney diseaseАнализ данных и подготовка статьи к публикации проведены при поддержке Гранта Президента Российской Федерации по государственной поддержке ведущих научных школ Российской Федерации НШ 5508.2018.7 (соглашение № 14. W02.18.5508 НШ от 17.01.2018). / The data analysis and the publication were supported by the Grant of the President of Russian Federation for the Leading Scientific Schools of Russia НШ 5508.2018.7 (agreement № 14. W02.18.5508 НШ, 17.01.2018).ReferencesHaroun MK, Jaar BG, Hoffman SC, Comstock GW, Klag MJ, Coresh J. Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol. 2003;14(11):2934–2941.Haroun MK, Jaar BG, Hoffman SC, Comstock GW, Klag MJ, Coresh J. Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol. 2003;14(11):2934–2941.Segura J, Campo C, Gil P, Roldán C, Vigil L, Rodicio JL et al. Development of chronic kidney disease and cardiovascular prognosis in essential hypertensive patients. J Am Soc Nephrol. 2004;15(6):1616–1622.Segura J, Campo C, Gil P, Roldán C, Vigil L, Rodicio JL et al. Development of chronic kidney disease and cardiovascular prognosis in essential hypertensive patients. J Am Soc Nephrol. 2004;15(6):1616–1622.Ощепкова Е. В., Долгушева Ю. А., Жернакова Ю. В., Чазова И. Е., Шальнова С. А., Яровая Е. Б. и др. Распространенность нарушения функции почек при артериальной гипертонии (по данным эпидемиологического исследования ЭССЕ-РФ). Системные гипертензии. 2015;12(3):19–24.Oshchepkova EV, Dolgusheva IuA, Zhernakova IuV, Chazova IE, Shal’nova SA, Iarovaia EB et al. The prevalence of renal dysfunction in arterial hypertension (in the framework of the ESSE-RF study). Sistemnye Gipertenzii = Systemic Hypertension. 2015;12(3):9–24. In RussianLisowska-Myjak B. Serum and urinary biomarkers of acute kidney injury. Blood Purification. 2010;29(4):357–365. doi:10.1159/000309421Lisowska-Myjak B. Serum and urinary biomarkers of acute kidney injury. Blood Purification. 2010;29(4):357–365. doi:10.1159/000309421Abassi Z, Sagi O, Armaly Z, Bishara B. Neutrophil gelatinase-associated lipocalin (NGAL): a novel biomarker for acute kidney injury. Harefuah. 2011;150(2):111–116.Abassi Z, Sagi O, Armaly Z, Bishara B. Neutrophil gelatinase-associated lipocalin (NGAL): a novel biomarker for acute kidney injury. Harefuah. 2011;150(2):111–116.Mårtensson J, Martling CR, Bell M. Novel biomarkers of acute kidney injury and failure: clinical applicability. Br J Anaesth. 2012;109(6):843–850. doi:10.1093/bja/aes357Mårtensson J, Martling CR, Bell M. Novel biomarkers of acute kidney injury and failure: clinical applicability. Br J Anaesth. 2012;109(6):843–850. doi:10.1093/bja/aes357Kamijo-Ikemori A, Sugaya T, Kimura K. Urinary fatty acid binding protein in renal disease. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2006;374(1–2):1–7.Kamijo-Ikemori A, Sugaya T, Kimura K. Urinary fatty acid binding protein in renal disease. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2006;374(1–2):1–7.Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(2):337–344. doi:10.2215/CJN.03530708Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(2):337–344. doi:10.2215/CJN.03530708Devarajan P. The use of targeted biomarkers for chronic kidney disease. Adv Chronic Kidney Dis. 2010;17(6):469–479. doi:10.1053/j.ackd.2010.09.002Devarajan P. The use of targeted biomarkers for chronic kidney disease. Adv Chronic Kidney Dis. 2010;17(6):469–479. doi:10.1053/j.ackd.2010.09.002Satoh-Asahara N, Suganami T, Majima T, Kotani K, Kato Y, Araki R et al. Urinary cystatin C as a potential risk marker for cardiovascular disease and chronic kidney disease in patients with obesity and metabolic syndrome. Clin J Am Soc Nephrol. 2011;6 (2):265–273. doi:10.2215/CJN.04830610Satoh-Asahara N, Suganami T, Majima T, Kotani K, Kato Y, Araki R et al. Urinary cystatin C as a potential risk marker for cardiovascular disease and chronic kidney disease in patients with obesity and metabolic syndrome. Clin J Am Soc Nephrol. 2011;6 (2):265–273. doi:10.2215/CJN.04830610Bolignano D, Lacquaniti A, Coppolino G, Campo S, Arena A, Buemi M. Neutrophil gelatinase-associated lipocalin reflects the severity of renal impairment in subjects affected by chronic kidney disease. Kidney Blood Press Res. 2008;31(4):255–258. doi:10.1159/000143726Bolignano D, Lacquaniti A, Coppolino G, Campo S, Arena A, Buemi M. Neutrophil gelatinase-associated lipocalin reflects the severity of renal impairment in subjects affected by chronic kidney disease. Kidney Blood Press Res. 2008;31(4):255–258. doi:10.1159/000143726Ko GJ, Grigoryev DN, Linfert D, Jang HR, Watkins T, Cheadle C et al. Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol. 2010;298(6): F1472–F1483. doi:10.1152/ajprenal.00619.2009Ko GJ, Grigoryev DN, Linfert D, Jang HR, Watkins T, Cheadle C et al. Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol. 2010;298(6): F1472–F1483. doi:10.1152/ajprenal.00619.2009Shankar A, Teppala S. Relationship between serum cystatin C and hypertension among US adults without clinically recognized chronic kidney disease. J Am Soc Hypertens. 2011;5 (5):378–384. doi:10.1016/j.jash.2011.03.003Shankar A, Teppala S. Relationship between serum cystatin C and hypertension among US adults without clinically recognized chronic kidney disease. J Am Soc Hypertens. 2011;5 (5):378–384. doi:10.1016/j.jash.2011.03.003Moura Rdo S, Vasconcelos DF, Freitas E, de Moura FJ, Rosa TT, Veiga JP. Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension. Arq Bras Cardiol. 2014;102(1):54–59. doi:10.5935/abc.20130210Moura Rdo S, Vasconcelos DF, Freitas E, de Moura FJ, Rosa TT, Veiga JP. Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension. Arq Bras Cardiol. 2014;102(1):54–59. doi:10.5935/abc.20130210Padhy M, Kaushik S, Girish MP, Mohapatra S, Shah S, Koner BC. Serum neutrophil gelatinase associated lipocalin (NGAL) and cystatin C as early predictors of contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention. Clin Chim Acta. 2014;435:48–52. doi:10.1016/j. cca.2014.04.016Padhy M, Kaushik S, Girish MP, Mohapatra S, Shah S, Koner BC. Serum neutrophil gelatinase associated lipocalin (NGAL) and cystatin C as early predictors of contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention. Clin Chim Acta. 2014;435:48–52. doi:10.1016/j. cca.2014.04.016Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophil-gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol. 2006;26(3):287–292.Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Dobrzycki S. Neutrophil-gelatinase-associated lipocalin and renal function after percutaneous coronary interventions. Am J Nephrol. 2006;26(3):287–292.Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Pawlak K, Mysliwiec M et al. Could neutrophilgelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values? Kidney Blood Press Res. 2007;30 (6):408–415.Bachorzewska-Gajewska H, Malyszko J, Sitniewska E, Malyszko JS, Pawlak K, Mysliwiec M et al. Could neutrophilgelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values? Kidney Blood Press Res. 2007;30 (6):408–415.Ghonemy TA, Amro GM. Plasma neutrophil gelatinase-associated lipocalin (NGAL) and plasma cystatin C (CysC) as biomarker of acute kidney injury after cardiac surgery. Saudi J Kidney Dis Transpl. 2014;25(3):582–588.Ghonemy TA, Amro GM. Plasma neutrophil gelatinase-associated lipocalin (NGAL) and plasma cystatin C (CysC) as biomarker of acute kidney injury after cardiac surgery. Saudi J Kidney Dis Transpl. 2014;25(3):582–588.Kidher E, Harling L, Ashrafian H, Naase H, Chukwueme- ka A, Anderson J et al. Pulse wave velocity and neutrophil gelatinase-associated lipocalin as predictors of acute kidney injury following aortic valve replacement. J Cardiothorac Surg. 2014;9:89. doi:10. 1186/1749–8090–9.Kidher E, Harling L, Ashrafian H, Naase H, Chukwueme- ka A, Anderson J et al. Pulse wave velocity and neutrophil gelatinase-associated lipocalin as predictors of acute kidney injury following aortic valve replacement. J Cardiothorac Surg. 2014;9:89. doi:10. 1186/1749–8090–9.Пролетов Я. Ю., Саганова Е. С., Смирнов А. В. Биомаркеры в диагностике острого повреждения почек. Нефрология. 2014;18(4):25–35.Proletov IaIu, Saganova ES, Smirnov AV. Biomarkers in the diagnosis of acute kidney injury. Nephrology. 2014;18(4):25–35. In RussianMakris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med. 2009;47(1):79–82. doi:10.1515/CCLM.2009.004Makris K, Markou N, Evodia E, Dimopoulou E, Drakopoulos I, Ntetsika K et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients. Clin Chem Lab Med. 2009;47(1):79–82. doi:10.1515/CCLM.2009.004Chaudhary K, Phadke G, Nistala R, Weidmeyer CE, McFar-lane SI, Whaley-Connell A. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease. Curr Diab Rep. 2010;10(1):37–42. doi:10.1007/s11892–009–0080-zChaudhary K, Phadke G, Nistala R, Weidmeyer CE, McFar-lane SI, Whaley-Connell A. The emerging role of biomarkers in diabetic and hypertensive chronic kidney disease. Curr Diab Rep. 2010;10(1):37–42. doi:10.1007/s11892–009–0080-zBlumczynski A, Sołtysiak J, Lipkowska K, Silska M, Poprawska A, Musielak A et al. Hypertensive nephropathy in children — do we diagnose early enough? Blood Press. 2012;21 (4):233–9. doi:10.3109/08037051.2012.666393Blumczynski A, Sołtysiak J, Lipkowska K, Silska M, Poprawska A, Musielak A et al. Hypertensive nephropathy in children — do we diagnose early enough? Blood Press. 2012;21 (4):233–9. doi:10.3109/08037051.2012.666393Aksan G, İnci S, Nar G, Siğirci S, Gedikli Ö, Soylu K et al. Serum neutrophıl gelatınase-assocıated lıpocalın levels in patients with non-dipper hypertension. Clin Invest Med. 2015;38 (2):E53–E62.Aksan G, İnci S, Nar G, Siğirci S, Gedikli Ö, Soylu K et al. Serum neutrophıl gelatınase-assocıated lıpocalın levels in patients with non-dipper hypertension. Clin Invest Med. 2015;38 (2):E53–E62.Peralta CA, Katz R, Bonventre JV, Sabbisetti V, Siscovick D, Sarnak M et al. Associations of urinary levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) with kidney function decline in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Kidney Dis. 2012;60(6):904–11. doi:10.1053/j.ajkd.2012.05.014Peralta CA, Katz R, Bonventre JV, Sabbisetti V, Siscovick D, Sarnak M et al. Associations of urinary levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) with kidney function decline in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Kidney Dis. 2012;60(6):904–11. doi:10.1053/j.ajkd.2012.05.014Leoncini G, Mussap M, Viazzi F, Fravega M, Degrandi R, Bezante GP et al. Combined use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and albumin as markers of early cardiac damage in primary hypertension. Clin Chim Acta. 2011;412 (21–22):1951–1956. doi:10.1016/j.cca.2011.06.043Leoncini G, Mussap M, Viazzi F, Fravega M, Degrandi R, Bezante GP et al. Combined use of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and albumin as markers of early cardiac damage in primary hypertension. Clin Chim Acta. 2011;412 (21–22):1951–1956. doi:10.1016/j.cca.2011.06.043Parikh CR, Thiessen-Philbrook H, Garg AX, Kadiyala D, Shlipak MG, Koyner JL et al. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol. 2013;8(7):1079–88. doi:10.2215/CJN.10971012Parikh CR, Thiessen-Philbrook H, Garg AX, Kadiyala D, Shlipak MG, Koyner JL et al. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol. 2013;8(7):1079–88. doi:10.2215/CJN.10971012Szeto CC, Kwan BC, Lai KB, Lai FM, Chow KM, Wang G et al. Urinary expression of kidney injury markers in renal transplant recipients. Clin J Am Soc Nephrol. 2010;5(12):2329–2337. doi:10.2215/CJN.01910310Szeto CC, Kwan BC, Lai KB, Lai FM, Chow KM, Wang G et al. Urinary expression of kidney injury markers in renal transplant recipients. Clin J Am Soc Nephrol. 2010;5(12):2329–2337. doi:10.2215/CJN.01910310Hawkins R. New biomarkers of acute kidney injury and the cardio-renal syndrome. Korean J Lab Med. 2011;31(2):72–80. doi:10.3343/kjlm.2011.31.2.72Hawkins R. New biomarkers of acute kidney injury and the cardio-renal syndrome. Korean J Lab Med. 2011;31(2):72–80. doi:10.3343/kjlm.2011.31.2.72Hisamichi M, Kamijo-Ikemori A, Sugaya T, Ichikawa D, Hoshino S, Hirata K et al. Increase in urinary markers during the acute phase reflects the degree of chronic tubulointerstitial injury after ischemia-reperfusion renal injury. Biomarkers. 2017;22(1):5–13. doi:10.3109/1354750X.2016.1153723Hisamichi M, Kamijo-Ikemori A, Sugaya T, Ichikawa D, Hoshino S, Hirata K et al. Increase in urinary markers during the acute phase reflects the degree of chronic tubulointerstitial injury after ischemia-reperfusion renal injury. Biomarkers. 2017;22(1):5–13. doi:10.3109/1354750X.2016.1153723Waanders F, Vaidya VS, van Goor H, Leuvenink H, Damman K, Hamming I et al. Effect of renin-angiotensinaldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial. Am J Kidney Dis. 2009;53(1):16–25. doi:10.1053/j.ajkd.2008.07.021Waanders F, Vaidya VS, van Goor H, Leuvenink H, Damman K, Hamming I et al. Effect of renin-angiotensinaldosterone system inhibition, dietary sodium restriction, and/or diuretics on urinary kidney injury molecule 1 excretion in nondiabetic proteinuric kidney disease: a post hoc analysis of a randomized controlled trial. Am J Kidney Dis. 2009;53(1):16–25. doi:10.1053/j.ajkd.2008.07.021Heijnen BF, Van Essen H, Schalkwijk CG, Janssen BJ, Struijker-Boudier HA. Renal inflammatory markers during the onset of hypertension in spontaneously hypertensive rats. Hypertens Res. 2014;37(2):100–109. doi:10.1038/hr.2013.99Heijnen BF, Van Essen H, Schalkwijk CG, Janssen BJ, Struijker-Boudier HA. Renal inflammatory markers during the onset of hypertension in spontaneously hypertensive rats. Hypertens Res. 2014;37(2):100–109. doi:10.1038/hr.2013.99Hosohata K, Yoshioka D, Tanaka A, Ando H, Fujimura A. Early urinary biomarkers for renal tubular damage in spontaneously hypertensive rats on a high salt intake. Hypertens Res. 2016;39(1):19–26. doi:10.1038/hr.2015.103Hosohata K, Yoshioka D, Tanaka A, Ando H, Fujimura A. Early urinary biomarkers for renal tubular damage in spontaneously hypertensive rats on a high salt intake. Hypertens Res. 2016;39(1):19–26. doi:10.1038/hr.2015.103Kadioglu T, Uzunlulu M, Yigit Kaya S, Oguz A, Ggonenli G, Isbilen B et al. Urinary kidney injury molecule-1 levels as a marker of early kidney injury in hypertensive patients. Minerva Urol Nefrol. 2016;68(5):456–461.Kadioglu T, Uzunlulu M, Yigit Kaya S, Oguz A, Ggonenli G, Isbilen B et al. Urinary kidney injury molecule-1 levels as a marker of early kidney injury in hypertensive patients. Minerva Urol Nefrol. 2016;68(5):456–461.Doi K, Noiri E, Sugaya T. Urinary L-type fatty acid-binding protein as a new renal biomarker in critical care. Curr Opin Crit Care. 2010;16(6):545–9. doi:10.1097/MCC.0b013e32833e2fa4Doi K, Noiri E, Sugaya T. Urinary L-type fatty acid-binding protein as a new renal biomarker in critical care. Curr Opin Crit Care. 2010;16(6):545–9. doi:10.1097/MCC.0b013e32833e2fa4McMahon BA, Murray PT. Urinary liver fatty acid-binding protein: another novel biomarker of acute kidney injury. Kidney Int. 2010;77(8):657–9. doi:10.1038/ki.2010.5McMahon BA, Murray PT. Urinary liver fatty acid-binding protein: another novel biomarker of acute kidney injury. Kidney Int. 2010;77(8):657–9. doi:10.1038/ki.2010.5Mori K, Mukoyama M, Kasahara M, Yokoi H, Nakao K. Disease biomarkers for CKD. Nihon Rinsho. 2012;70 (5):864–868.Mori K, Mukoyama M, Kasahara M, Yokoi H, Nakao K. Disease biomarkers for CKD. Nihon Rinsho. 2012;70 (5):864–868.Xu Y, Xie Y, Shao X, Ni Z, Mou S. L-FABP: A novel biomarker of kidney disease. Clin Chim Acta. 2015;445:85–90. doi:10.1016/j.cca.2015.03.017Xu Y, Xie Y, Shao X, Ni Z, Mou S. L-FABP: A novel biomarker of kidney disease. Clin Chim Acta. 2015;445:85–90. doi:10.1016/j.cca.2015.03.017Matsui K, Kamijo-Ikemori A, Imai N, Sugaya T, Yasuda T, Tatsunami S et al. Clinical significance of urinary liver-type fatty acid-binding protein as a predictor of ESRD and CVD in patients with CKD. Clin Exp Nephrol. 2016;20(2):195–203. doi:10.1007/s10157–015–1144–9Matsui K, Kamijo-Ikemori A, Imai N, Sugaya T, Yasuda T, Tatsunami S et al. Clinical significance of urinary liver-type fatty acid-binding protein as a predictor of ESRD and CVD in patients with CKD. Clin Exp Nephrol. 2016;20(2):195–203. doi:10.1007/s10157–015–1144–9Yokoyama T, Kamijo-Ikemori A, Sugaya T, Hoshino S, Yasuda T, Kimura K. Urinary excretion of liver type fatty acid binding protein accurately reflects the degree of tubulointerstitial damage. Am J Pathol. 2009;174(6):2096–2106. doi:10.2353/ajpath.2009.080780Yokoyama T, Kamijo-Ikemori A, Sugaya T, Hoshino S, Yasuda T, Kimura K. Urinary excretion of liver type fatty acid binding protein accurately reflects the degree of tubulointerstitial damage. Am J Pathol. 2009;174(6):2096–2106. doi:10.2353/ajpath.2009.080780Sasaki H, Kamijo-Ikemori A, Sugaya T, Yamashita K, Yokoyama T, Koike J et al. Urinary fatty acids and liver-type fatty acid binding protein in diabetic nephropathy. Nephron Clin Pract. 2009;112(3):148–156. doi:10.1159/000214210Sasaki H, Kamijo-Ikemori A, Sugaya T, Yamashita K, Yokoyama T, Koike J et al. Urinary fatty acids and liver-type fatty acid binding protein in diabetic nephropathy. Nephron Clin Pract. 2009;112(3):148–156. doi:10.1159/000214210Kamijo-Ikemori A, Sugaya T, Yasuda T, Kawata T, Ota A, Tatsunami S et al. Clinical significance of urinary liver-type fatty acid-binding protein in diabetic nephropathy of type 2 diabetic patients. Diabetes Care. 2011;34(3):691–696. doi:10.2337/dc10–1392.Kamijo-Ikemori A, Sugaya T, Yasuda T, Kawata T, Ota A, Tatsunami S et al. Clinical significance of urinary liver-type fatty acid-binding protein in diabetic nephropathy of type 2 diabetic patients. Diabetes Care. 2011;34(3):691–696. doi:10.2337/dc10–1392.Ishimitsu T, Ohta S, Saito M, Teranishi M, Inada H, Yoshii M et al. Urinary excretion of liver fatty acid-binding protein in health-check participants. Clin Exp Nephrol. 2005;9(1):34–9.Ishimitsu T, Ohta S, Saito M, Teranishi M, Inada H, Yoshii M et al. Urinary excretion of liver fatty acid-binding protein in health-check participants. Clin Exp Nephrol. 2005;9(1):34–9.Malyszko J, Bachorzewska-Gajewska H, Sitniewska E, Malyszko JS, Poniatowski B, Dobrzycki S. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in non-diabetic patients with stage 2–4 chronic kidney disease. Ren Fail. 2008;30(6):625–628. doi:10.1080/08860220802134607Malyszko J, Bachorzewska-Gajewska H, Sitniewska E, Malyszko JS, Poniatowski B, Dobrzycki S. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in non-diabetic patients with stage 2–4 chronic kidney disease. Ren Fail. 2008;30(6):625–628. doi:10.1080/08860220802134607Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130 (6):461–470. doi:10.7326/0003-4819-130-6-199903160-00002Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130 (6):461–470. doi:10.7326/0003-4819-130-6-199903160-00002Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12. doi:10.7326/0003-4819-150-9-200905050-00006Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12. doi:10.7326/0003-4819-150-9-200905050-00006Stevens LA, Claybon MA, Schmid CH, Chen J, Horio M, Imai E et al. Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities. Kidney Int. 2011;79(5):555– 562. doi:10.1038/ki.2010.462Stevens LA, Claybon MA, Schmid CH, Chen J, Horio M, Imai E et al. Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities. Kidney Int. 2011;79(5):555– 562. doi:10.1038/ki.2010.462Моисеев B. C., Мухин Н. А., Кобалава Ж. Д., Бобкова И. Н., Виллевальде С. В., Ефремовцева М. А. и др. Cердечно-сосудистый риск и хроническая болезнь почек: стратегии кардионефропротекции. Российский кардиологический журнал. 2014;8(112):7–37. doi:10.15829/1560-4071-2014-8-7-37Moiseev VC, Mukhin NA, Kobalava JD, Bobkova IN, Ville- valde SV, Efremovtseva MA et al. Cardiovascular risk and chronic kidney disease: cardio-nephroprotection strategies. Russian Journal of Cardiology. 2014;8 (112):7–37. doi:10.15829/1560-4071-2014-8-7-37. In RussianVerbeke F, Lindley E, Van Bortel L, Vanholder R, London G, Cochat P et al. A European Renal Best Practice (ERBP) position statement on the kidney disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure in nondialysis-dependent chronic kidney disease: an endorsement with caveats for real-life application. Nephrol Dial Transplant. 2014;29(3):490–96. doi:10.1093/ndt/gft321Verbeke F, Lindley E, Van Bortel L, Vanholder R, London G, Cochat P et al. A European Renal Best Practice (ERBP) position statement on the kidney disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure in nondialysis-dependent chronic kidney disease: an endorsement with caveats for real-life application. Nephrol Dial Transplant. 2014;29(3):490–96. doi:10.1093/ndt/gft321Вельков В. В. Цистатин С: новые возможности и новые задачи для лабораторной диагностики (часть 1). Клинико-лабораторный консилиум. 2010;5(1):25–31.Velkov VV. Cystatin C: new opportunities and new tasks in laboratory diagnostics (part 1). Kliniko-laboratorniy Konsilium = Clinical and Laboratory Consilium. 2010;5(1):25–31. In RussianKGIGO 2012. Clinical practice guideline for the evaluation and management of Chronic Kidney Disease. Kidney International Supplements. 2013;3(1):1–150. doi:10.1038KGIGO 2012. Clinical practice guideline for the evaluation and management of Chronic Kidney Disease. Kidney International Supplements. 2013;3(1):1–150. doi:10.1038Watanabe S, Okura T, Liu J, Miyoshi K, Fukuoka T, Hiwada K et al. Serum cystatin C level is marker of end-organ damage in patients with essential hypertension. Hypertens Res. 2003;26(11):895–899.Watanabe S, Okura T, Liu J, Miyoshi K, Fukuoka T, Hiwada K et al. Serum cystatin C level is marker of end-organ damage in patients with essential hypertension. Hypertens Res. 2003;26(11):895–899.Peralta CA, Whooley MA, Ix JH, Shlipak MG. Kidney function and systolic blood pressure new insights from cystatin C: data from the Heart and Soul Study. Am J Hypertens. 2006;19 (9):939–946.Peralta CA, Whooley MA, Ix JH, Shlipak MG. Kidney function and systolic blood pressure new insights from cystatin C: data from the Heart and Soul Study. Am J Hypertens. 2006;19 (9):939–946.Mena C, Robles NR, de Prado JM, Gallego FG, Cidoncha A. Cystatin C and blood pressure: results of 24 h ambulatory blood pressure monitoring. Eur J Intern Med. 2010;21 (3):185–90. doi:10.1016/j.ejim.2010.01.016Mena C, Robles NR, de Prado JM, Gallego FG, Cidoncha A. Cystatin C and blood pressure: results of 24 h ambulatory blood pressure monitoring. Eur J Intern Med. 2010;21 (3):185–90. doi:10.1016/j.ejim.2010.01.016Rogacev KS, Pickering JW, Seiler S, Zawada AM, Emrich I, Fliser D et al. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation incorporating both cystatin C and creatinine best predicts individual risk: a cohort study in 444 patients with chronic kidney disease. Nephrol Dial Transplant. 2014;29(2):348–55. doi:10.1093/ndt/gft422Rogacev KS, Pickering JW, Seiler S, Zawada AM, Emrich I, Fliser D et al. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation incorporating both cystatin C and creatinine best predicts individual risk: a cohort study in 444 patients with chronic kidney disease. Nephrol Dial Transplant. 2014;29(2):348–55. doi:10.1093/ndt/gft422Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta. 2015;438:350–357. doi:10.1016/j.cca.2014.08.039Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta. 2015;438:350–357. doi:10.1016/j.cca.2014.08.039Teo BW, Sabanayagam C, Liao J, Toh QC, Saw S, Wong TY et al. Comparison of CKD-EPI cystatin C and creatinine glomerular filtration rate estimation equations in Asian Indians. Int J Nephrol. 2014;2014:746497. doi:10.1155/2014/746497Teo BW, Sabanayagam C, Liao J, Toh QC, Saw S, Wong TY et al. Comparison of CKD-EPI cystatin C and creatinine glomerular filtration rate estimation equations in Asian Indians. Int J Nephrol. 2014;2014:746497. doi:10.1155/2014/746497Ozer BA, Dursun B, Baykal A, Gultekin M, Suleymanlar G. Can cystatin C be a better marker for the early detection of renal damage in primary hypertensive patients? Ren Fail. 2005;27(3):247–53.Ozer BA, Dursun B, Baykal A, Gultekin M, Suleymanlar G. Can cystatin C be a better marker for the early detection of renal damage in primary hypertensive patients? Ren Fail. 2005;27(3):247–53.Palatini P, Benetti E, Zanier A, Santonastaso M, Mazzer A, Cozzio S et al. Cystatin C as predictor of microalbuminuria in the early stage of hypertension. Nephron Clin Pract. 2009;113(4):309– 314. doi:10.1159/000235949Palatini P, Benetti E, Zanier A, Santonastaso M, Mazzer A, Cozzio S et al. Cystatin C as predictor of microalbuminuria in the early stage of hypertension. Nephron Clin Pract. 2009;113(4):309– 314. doi:10.1159/000235949Ezenwaka CE, Idris S, Davis G, Roberts L. Measurement of neutrophil gelatinase-associated lipocalin (NGAL) in patients with non-communicable diseases: any additional benefit? Arch Physiol Biochem. 2016;122(2):70–74. doi: 10.3109/13813455. 2016.1140212Ezenwaka CE, Idris S, Davis G, Roberts L. Measurement of neutrophil gelatinase-associated lipocalin (NGAL) in patients with non-communicable diseases: any additional benefit? Arch Physiol Biochem. 2016;122(2):70–74. doi: 10.3109/13813455. 2016.1140212Кузьмин О. В., Жежа В. В., Белянин В. В., Бучнева Н. В., Ландарь Л. Н., Сердюк С. В. Диагностическая и прогностическая ценность биомаркеров повреждения почечных канальцев NGAL, KIM-1, L-FABP у пациентов с хронической болезнью почек. Нефрология. 2017;21(2):24–32.Kuzmin OB, Zhezha VV, Belaynin VV, Buchneva NV, Landar LN, Serdyuk SV. Diagnostic and prognostic value of renal tubular injury biomarkers NGAL, KIM-1, L-FABP IN chronic kidney disease patients. Nefrologiya = Nephrology. 2017;21(2):24–32. In RussianPrkacin I, Ozvald I, Cavrić G, Balenović D, Bulum T, Flegar-Mestrić Z. Importance of urinary NGAL, serum creatinine standardization and estimated glomerular filtration rate inresistant hypertension. Coll Antropol. 2013;37(3):821–825.Prkacin I, Ozvald I, Cavrić G, Balenović D, Bulum T, Flegar-Mestrić Z. Importance of urinary NGAL, serum creatinine standardization and estimated glomerular filtration rate inresistant hypertension. Coll Antropol. 2013;37(3):821–825.Blázquez-Medela AM, García-Sánchez O, Blanco-Gozalo V, Quiros Y, Montero MJ, Martínez-Salgado C et al. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats. PLoS One. 2014;9(8): e105988. doi:10.1371/journal. pone.0105988. eCollection 2014Blázquez-Medela AM, García-Sánchez O, Blanco-Gozalo V, Quiros Y, Montero MJ, Martínez-Salgado C et al. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats. PLoS One. 2014;9(8): e105988. doi:10.1371/journal. pone.0105988. eCollection 2014Blázquez-Medela AM, García-Sánchez O, Blanco-Gozalo V, Quiros Y, Montero MJ, Martínez-Salgado et al. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats. PLoS One. 2014;9(8): e105988. doi:10.1371/journal.pone. 0105988.Blázquez-Medela AM, García-Sánchez O, Blanco-Gozalo V, Quiros Y, Montero MJ, Martínez-Salgado et al. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats. PLoS One. 2014;9(8): e105988. doi:10.1371/journal.pone. 0105988.Przybylowski P, Malyszko J, Kozlowska S, Malyszko JS. Kidney injury molecule-1 correlates with kidney function in heart allograft recipients. Transplant Proc. 2011;43(8):3061–3. doi:10.1016/j.transproceed.2011.08.049Przybylowski P, Malyszko J, Kozlowska S, Malyszko JS. Kidney injury molecule-1 correlates with kidney function in heart allograft recipients. Transplant Proc. 2011;43(8):3061–3. doi:10.1016/j.transproceed.2011.08.049Ichikawa D, Kamijo-Ikemori A, Sugaya T, Yasuda T, Hoshi- no S, Igarashi-Migitaka J et al. Renal liver-type fatty acid binding protein attenuates angiotensin II-induced renal injury. Hypertension. 2012;60(4):973–80. doi:10.1161/HYPERTENSIONAHA. 112.199828Ichikawa D, Kamijo-Ikemori A, Sugaya T, Yasuda T, Hoshi- no S, Igarashi-Migitaka J et al. Renal liver-type fatty acid binding protein attenuates angiotensin II-induced renal injury. Hypertension. 2012;60(4):973–80. doi:10.1161/HYPERTENSIONAHA. 112.199828Ichikawa D, Kamijo-Ikemori A, Sugaya T, Shibagaki Y, Yasuda T, Katayama K et al. Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation. Am J Physiol Renal Physiol. 2014;306(6): F655–F663. doi:10.1152/ajprenal.00460.2013Ichikawa D, Kamijo-Ikemori A, Sugaya T, Shibagaki Y, Yasuda T, Katayama K et al. Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation. Am J Physiol Renal Physiol. 2014;306(6): F655–F663. doi:10.1152/ajprenal.00460.2013Ichikawa D, Kamijo-Ikemori A, Sugaya T, Shibagaki Y, Yasuda T, Hoshino S et al. Human liver-type fatty acid-binding protein protects against tubulointerstitial injury in aldosterone-induced renal injury. Am J Physiol Renal Physiol. 2015;308(2): F114–F121. doi:10.1152/ajprenal.00469.2014Ichikawa D, Kamijo-Ikemori A, Sugaya T, Shibagaki Y, Yasuda T, Hoshino S et al. Human liver-type fatty acid-binding protein protects against tubulointerstitial injury in aldosterone-induced renal injury. Am J Physiol Renal Physiol. 2015;308(2): F114–F121. doi:10.1152/ajprenal.00469.2014Nakamura T, Inoue T, Sugaya T, Kawagoe Y, Suzuki T, Ueda Y et al. Renoprotective effect of telmisartan in patients with chronic kidney disease. Clin Exp Hypertens. 2008;30(7):662–672. doi:10.1080/10641960802443373Nakamura T, Inoue T, Sugaya T, Kawagoe Y, Suzuki T, Ueda Y et al. Renoprotective effect of telmisartan in patients with chronic kidney disease. Clin Exp Hypertens. 2008;30(7):662–672. doi:10.1080/10641960802443373Nakamura T, Fujiwara N, Kawagoe Y, Sugaya T, Ueda Y, Koide H. Effects of telmisartan and enalapril on renoprotection in patients with mild to moderate chronic kidney disease. Eur J Clin Invest. 2010;40(9):790–796. doi:10.1111/j.1365–2362.2010. 02319.xNakamura T, Fujiwara N, Kawagoe Y, Sugaya T, Ueda Y, Koide H. Effects of telmisartan and enalapril on renoprotection in patients with mild to moderate chronic kidney disease. Eur J Clin Invest. 2010;40(9):790–796. doi:10.1111/j.1365–2362.2010. 02319.xYokoyama T, Kamijo-Ikemori A, Sugaya T, Hoshino S, Yasuda T, Kimura K. Urinary excretion of liver type fatty acid binding protein accurately reflects the degree of tubulointerstitial damage. Am J Pathol. 2009;174(6):2096–2106. doi:10.2353/ajpath. 2009.080780Yokoyama T, Kamijo-Ikemori A, Sugaya T, Hoshino S, Yasuda T, Kimura K. Urinary excretion of liver type fatty acid binding protein accurately reflects the degree of tubulointerstitial damage. Am J Pathol. 2009;174(6):2096–2106. doi:10.2353/ajpath. 2009.080780Tanaka T, Doi K, Maeda-Mamiya R, Negishi K, Portilla D, Sugaya T et al. Urinary L-type fatty acid-binding protein can reflect renal tubulointerstitial injury. Am J Pathol. 2009;174(4):1203–1211. doi:10.2353/ajpath.2009.080511Tanaka T, Doi K, Maeda-Mamiya R, Negishi K, Portilla D, Sugaya T et al. Urinary L-type fatty acid-binding protein can reflect renal tubulointerstitial injury. Am J Pathol. 2009;174(4):1203–1211. doi:10.2353/ajpath.2009.080511

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