APPLYING OF URINE BIOMARKERS NGAL AND KIM-1 FOR EARLY DETECTION OF RENAL PROXIMAL TUBULAR DAMAGE IN PATIENTS WITH ARTERIAL HYPERTENSION

THE AIM: to investigate the possibility of the use of urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin) and KIM-1 (kidney injury molecule-1) for early detection of damage to proximal tubules (PT) and tubulointerstitium in nondiabetic hypertensive patients with CKD stage 2.

PATIENTS AND METHODS. The research involved 60 patients (16 men and 44 women, mean age 60,4±8,37 years) with primary and nephrogenic hypertension, which were divided into 3 groups: 1 gr. with GFR>85 ml/min/1,73 m2 ), 2 gr. with GFR 60-74 ml/min/1,73 m2 ), and 3 gr. with GFR<60 ml/min/1,73 m2 ), The control group consisted 15 normotensive individuals (6 men and 9 women, mean age 49,8±9,68 years) without overt signs of kidney and cardiovascular diseases. All patients carried out a comprehensive survey with determination the content of urine NGAL («Human NGAL ELISA kit») and KIM-1 («Human KIM-1 Immunoassay ELISA»).

RESULTS. Increased NGAL content In the urine of patients 2 and 3 gr. were identified respectively in 2,62 and 7,22 times compared with the control group. Augmentation the concentration of KIM-1 in the urine of the same patients groups was respectively 2,12 and 3,14 times. Similar results were obtained in a selected group (n = 30) of hypertensive patients with chronic heart failure with preserved ejection fraction. Urinary NGAL concentration in the group of patients with mild renal dysfunction (GFR 67,2±5,93 ml/min/1,73 m2 ) was higher than the comparison group data in 2,36 times, and in the patients with severe renal impairment (GFR 53,6±6,67 ml/min/1,73 m2 ) – to 9,09 times (p < 0,05). Similar data growth KIM-1 content in the urine of the patients with CHFpEF were respectively 1,84 and 6,87 times (p < 0,05).

CONCLUSION. Urinary NGAL increase by more than 2,5 times and increase urinary KIM-1 more than 2 times compared with normal values can be diagnostic marker of early damage of PT and tubulointerstitium in nondiabetic hypertensive patients with stage 2 CKD. 

1. Ощепкова ЕВ, Долгушева ЮА, Жернакова ЮВ и др. Распространенность нарушения функции почек при артериальной гипертонии (по данным эпидемиологического исследования ЭССЕ-РФ). Системные гипертензии 2015; 12 (3): 19-24 [Oschepkova EV, Dolgusheva YuA, Zhernakova YuV et al. Rasprostranennost narusheniya funktsii pochek pri arterialnoy gipertonii (po dannyim epidemiologicheskogo issledovaniya ESSERF). Sistemnyie gipertenzii 2015; 12 (3): 19-24]

2. Zhang JH, Xu Y, Chen XH et al. The predictive value of mild renal insufficiency on the prognosis of patients with acute coronary syndrome. Zhonghua Nei Ke Za Zhi 2013; 52 (12): 1033-101036

3. Кузьмин ОБ, Жежа ВВ, Белянин ВВ, Бучнева НВ. Раннее повреждение почек у больных артериальной гипертензией: прогностическое значение и подходы к нефропротективной терапии. Артериальная гипертензия 2016; 22 (5): 519-527 [Kuz’min OB, Zhezha VV, Belyanin VV, Buchneva NV. Ranneye povrezhdeniye pochek u bolnykh s arterialnoy gipertenziyey: prognosticheskoye znacheniye i podkhody k nephroprotectivnoy terapii. Arterialnaya gipertenziya 2016; 22 (5): 519-527] doi: 10.18705/1607-419X-2016-22-5-519-527

4. McCullough PA, Shaw AD, Haase M et al. Diagnosis of acute kidney injury using functional and injury biomarkers: workgroup statements from the tenth Acute Dialysis Quality Initiative Сonsensus Сonference. Contrib Nephrol 2013; 182: 13-29 doi: 10.1059/000349963

5. Смирнов АВ, Добронравов ВА, Румянцев АШ и др. Национальные рекомендации. Острое повреждение почек: основные принципы диагностики, профилактики и терапии. Часть 1. Нефрология 2016; 20 (1): 79-104 [Smirnov AV, Dobronravov VA, Rumyantsev ASh i dr. Natsionalnyye recomendatsii. Ostroye povrezhdeniye pochek: Osnovnyye printsipy diagnostiki, profilactiki i terapii. Nefrologiya 2016; 20 (1): 79-104]

6. Пролетов ЯЮ, Саганова ЕС, Смирнов АВ. Биомаркеры в диагностике острого повреждения почек. Сообщение 1. Нефрология 2014; 18(4): 25-35 [Proletov YaYu, Saganova ES, Smirnov AV. Biomarkery v diagnostike ostrogo povrezhdenija pochek. Soobshhenie 1. Nefrologiya 2014; 18 (4): 25-35]

7. Моисеев ВС, Мухин НА, Смирнов АВ и др. Сердечно-сосудистый риск и хроническая болезнь почек: стратегии кардио-нефропротекции. Клиническая фармакология и терапия 2014; 23 (3): 4-27 [Moiseev VS, Muhin NA, Smirnov AV i dr. Nacional’nye rekomendacii. Serdechno-sosudistyj risk i chronicheskaya bolezn’ pochek: strategii kardio-nefroprotekcii. Klinicheskaya farmakologiya i terapiya 2014; 23 (3): 4-27]

8. Cheng RK, Cox M, Neely ML et al. Outcomes in patients with heart failure with preserved, borderline and reduced ejection fraction in Medicare population. Am Heart J 2014; 168 (5): 721-730. doi: 10.1016/j.ahj.2014.07.008

9. Lin HY, Hwang DY, Lee SC et al. Urinary neutrophil gelatinase-associated lipocalin and clinical outcomes in chronic kidney disease patients. Clin Chem Lab Med 2015; 53 (1): 73-83 doi: 10.1515/ccim-2014-0647

10. Hasegawa M, Ishii J, Katagawa F et al. Urinary neutrophil gelatinase-associated lipocalin as a predictor of cardiovascular events in patients with chronic kidney disease. Heart Vessels 2015; 30 (1): 81-88 doi: 10.1007/s00380-013-0454-7

11. Liu KD, Yang W, Go AS et al. Urine neutrophil gelatinaseassociated lipocalin and risk cardiovascular disease and death in CKD: results from the Chronic Renal Insufficiency Cohort (CRIS) study. Am J Kidney Dis 2015; 65 (2): 267-274 doi: 10.1053/j.ajkd.2014.07.025

12. Damman K, Veldhuisen DJ, Navis G et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL), a marker tubular damage, is increased in patients with chronic heart failure. Eur J Heart Fail. 2008; 10 (10): 997-1000 doi: 10.1016/j.ejheart.2008.07.01

13. Peters HP, Waanders F, Meijer E et al. High urinary excretion of kidney injury molecule-1 is an independent predictor for end-stage renal disease in patients with IgA nephropathy. Nephrol Dial Transplant 2011; 26 (11): 3581-3588 doi: 10.1093/ndt/gfr135

14. Damman K, Masson S, Hillege HL et al. Tubular damage and worsening renal function in chronic heart failure. JACC Heart Fail 2013; 1 (5): 417-425 doi: 10.1016/j.jchf.2013.05.007

15. Кузьмин ОБ, Белянин ВВ, Жежа ВВ. Легкая дисфункция почек у больных сердечной недостаточностью: доклинические признаки и их прогностическое значение. Журнал Сердечная недостаточность 2014; 15 (2): 126-131 [Kuz’min OB, Belyanin VV, Zhezha VV. Legkaya disfunctsiya pochek u bolnyih serdechnouy nedostatochnotyu: doklinicheskie priznaki i ih prognosticheskoe znachenie. Zhurnal Serdechnaya nedostatochnost 2014; 15 (2): 126-131]

16. Hosohata K, Yoshioka D, Tanaka A et al. 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.2015.103