Application of biological markers of kidney injury for prognosis of long-term adverse outcomes in patients with ST-segment elevation myocardial infarction

   Objective: To study the prognostic significance of serum NGAL (sNGAL) and cystatin C in the acute phase of ST-segment elevation myocardial infarction (STEMI) in the late disease period.
   Material and Methods: 357 patients with STEMI, admitted to hospital within 24 h of symptom onset, were included in the study. Serum creatinine levels with the calculation of glomerular filtration rate (GFR) using the MDRD as well as levels of sNGAL and cystatin C were measured on day 1 and 12–14.

   Results: All patients were divided into 2 groups according to their estimated GFR: with and without renal dysfunction (RD), defined as a decrease of GFR < 60 ml/min/1.73 m². Within 3 years of follow-up, the composite endpoint (CEP) were assessed (CEP – death + non-fatal cardiovascular events). The ROC curve analysis was used to determine the thresholds for every biomarker, involved in the CEP development: NGAL (≥ 1.25 ng / ml) and cystatin C (≥ 1.9 mg / l). On day 12–14 of hospitalization elevated NGAL ≥ 1.25 ng / mL was associated with a 3-fold increased risk for adverse cardio vascular events in a 3-year follow up after STEMI; whereas, elevated cystatin C ≥ 1.9 mg/l –
with a 2-fold increased risk for the CEP, and signs of RD, found in patients before the discharge from the hospital, – with a 1.5-fold increased cardiovascular risk. The model considering an increase of NGAL over 1.25 ng / l has the highest prognostic value, while the models based on the levels
of cystatin C and GFR are of equal prognostic value.

   Conclusion: The most promising issue in the prognosis of long-term adverse outcomes in patients with STEMI may be considered the assessment of RD using new biomarkers such as sNGAL.

1. Сыркин А. Л. Острый коронарный синдром / А. Л. Сыркин, Н. А. Новикова, С. А. Терехин. – М.: МИА, 2010. – 440 с.

2. Herzog C. A., Asinger R. W., Berger A. K. et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO) // Kidney Int. 2011. Vol. 80, N 6. P. 572–572.

3. Мензоров М. В. Сложности диагностики острого повреждения почек у больных инфарктом миокарда с подъемом сегмента ST / М. В. Мензоров [и др.] // Терапевт. арх. – 2014. – Т. 86, № 4. – С. 25–30.

4. Liu X. L., Wang Z. J., Yang Q. et al. Plasma neutrophilgelatinase-associated lipocalin and cystatin C could early diagnosecontrast-induced acute kidney injury in patients with renal insufficiency undergoing an elective percutaneous coronary intervention // Chin. Med. J. (Engl.). 2012. Vol. 125, N 6. P. 1051–1056.

5. Функциональное состояние почек и прогнозирование сердечно-сосудистого риска / Рекомендации разработаны Комитетом экспертов Всероссийского научного общества кардиологов и научным обществом нефрологов России // Кардиоваскулярная терапия и профилактика. – 2008. – Т. 7, № 6 (прил. 3). – С. 1–20.

6. Parikh C. R., Devarajan P. New biomarkers of acute kidney injury // Crit. Care Med. 2008. Vol. 36, N 4 (suppl.). P. 159–165.

7. Schneider A. G., Bellomo R. Acute kidney injury: new studies // Intensive Care Med. 2013. Vol. 39. P. 569–571.

8. Вельков В. В. NGAL – «ренальный тропонин»: ранний маркер острого повреждения почек / В. В. Вельков. – Пущино: ЗАО «ДИАКОН», 2011. – 55 с.

9. Bolignano D., Coppolino G., Lacquaniti A., Buemi M. From kidney to cardiovascular diseases: NGAL as a biomarker beyond the confines of nephrology // Eur. J. Clin. Invest. 2010. Vol. 40, N 3. P. 273–276.

10. Bolignano D., Donato V., Coppolino G. et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage // Am. J. Kidney Dis. 2008. Vol. 52. P. 595–605.

11. Shaker O., El-Shehaby A., El-Khatib M. Early diagnostic markers for contrast nephropathy in patients undergoing coronary angiography // Angiology. 2010. Vol. 61, N 8. P. 731–736.

12. Chew J. S. C., Saleem M., Florkowski C. M., George P. M. Cystatin C – a paradigm of evidence based labo ratory medicine // Clin. Biochem. Rev. 2008. Vol. 29. P. 47–62.

13. Шафранская К. С. Роль цистатина С в прогнозировании риска развития неблагоприятных исходов коронарного шунтирования в госпитальном периоде / К. С. Шафранская [и др.] // Рос. кардиол. журн. – 2013. – № 3. – С. 45–50.

14. Lodh M., Parida A., Sanyal J., Ganguly A. Cystatin С in acute coronary syndrome // eJIFCC. 2013. Vol. 24, N 2. URL: http://www.ifcc.org/media/231296/05_Lodh.pdf (date accessed: 22.03.2014).

15. Donadio C. Effect of glomerular filtration rate impairment on diagnostic performance of neutrophil gelatinase-associated lipocalin and B-type natriuretic peptide as markers of acute cardiac and renal failure in chronic kidney disease patients // Critical Care. 2014. Vol. 18. Р. 12. URL: https://pubmed.ncbi.nlm.nih.gov/24581340/ (date accessed: 22. 04. 2014).

16. Lindberg S., Pedersen S. H., Mogelvang R. et al. Prognostic utility of neutrophil gelatinase-associated lipocalin in predicting mortality and cardiovascular events in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention // JACC. 2012. Vol. 60, N 4. P. 339–345.

17. Еkerblom A., Wallentin L., Siegbahn A. et al. Cystatin C and estimated glomerular filtration rate as predictors for adverse outcome in patients with ST-elevation and non-ST-elevation acute coronary syndromes: results from the platelet inhibition and patient outcomes study // Clin. Chem. 2012. Vol. 58. P. 190–199.

18. Luc G., Bard J. M., Lesueur C. et al. Plasma cystatin-C and development of coronary heart disease: The PRIME Study // Atherosclerosis. 2006. Vol. 185, N 2. P. 375–378.

19. Vieira C., Nabais S., Ramos V. et al. Multimarker approach with cystatin C, N-terminal pro-brain natriuretic peptide, C-reactive protein and red blood cell distribution width in risk stratification of patients with acute coronary syndromes // Rev. Port. Cardiol. 2014. Vol. 33, N 3. P. 127–136.

20. Jernberg T., Lindahl B., James S. et al. A novel predictor of outcome in suspected or confirmed non-ST-elevation acute coronary syndrome // Circulation.2004. Vol. 110. P. 2342–2348.