Neutrophil lymphocyte ratio and severity of acute kidney injury in septic children

Nurul Huda Kowita; Nora Sovira; Mulya Safri; Jufitriani Ismy; Syafruddin Haris; Heru Noviat Herdata; Bakhtiar Bakhtiar

doi:10.14238/pi63.6.2023.492-8

Nurul Huda Kowita Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital Banda Aceh, Aceh
Nora Sovira Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital Banda Aceh, Aceh
Mulya Safri Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital Banda Aceh, Aceh
Jufitriani Ismy Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital Banda Aceh, Aceh
Syafruddin Haris Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital Banda Aceh, Aceh
Heru Noviat Herdata Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital Banda Aceh, Aceh
Bakhtiar Bakhtiar Department of Child Health, Medical Faculty of Syiah Kuala University/Dr. Zainoel Abidin General Hospital Banda Aceh, Aceh

DOI: https://doi.org/10.14238/pi63.6.2023.492-8

Keywords: sepsis; acute kidney injury; neutrophil-lymphocyte ratio; pelod-2 score; children; mortality

Abstract

Background Acute kidney injury (AKI) in sepsis is associated with an inflammatory process in kidney microcirculation and may increase morbidity and mortality in children. The neutrophil lymphocyte ratio (NLR) is an inflammatory biomarker of the inflammatory process in sepsis.

Objective To determine the role of NLR in predicting the severity of AKI and to describe the demographic and laboratory characteristics, as they relate to outcomes of pediatric patients with AKI and sepsis.

Methods This cross-sectional study was conducted in the PICU at Dr. Zainoel Abidin General Hospital (RSUDZA), Banda Aceh, Aceh. Medical record data were obtained from critically ill children with sepsis and AKI. Chi-square test was used to compare the proportions of each variable. We also calculated odds ratios to evaluate the AKI severity, PELOD-2 score, and patient outcomes. Spearman's analysis was used to look for a possible correlation between NLR and AKI severity in septic children.

Results Seventy-one subjects with sepsis and AKI were included. Subject characteristics were as follows: 63.4% males, 63.4% < 1 year of age, 56.3% with respiratory problems as a primary disease, 38% with AKI injury stage, and 54.9% subjects with PELOD-2 score ?10. There was no significant correlation between AKI severity and mortality (OR 3.04; 95%CI 0.990 to 9.378; P=0.052). Subjects with a PELOD-2 score ?10 had a 47.6 times higher chance of mortality in septic children with AKI compared to those with PELOD-2 scores <10. There was no correlation between NLR and AKI severity (r=0.019; P=0.878).

Conclusion There is no correlation between NLR and AKI severity. Sepsis accompanied by AKI may increase the risk of mortality in children. Septic children with more severe AKI tends to be less survive.

References

Kementerian Kesehatan Republik Indonesia. Keputusan Menteri Kesehatan Republik Indonesia Nomor Hk.01.07/Menkes/4722/2021 tentang Pedoman Nasional Pelayanan Kedokteran Tata Laksana Sepsis pada Anak. [cited 2022 May 15 ]. Available from https://yankes.kemkes.go.id/unduhan/fileunduhan_1681539780_895283.pdf.
2. Kumar G, Kumar N, Taneja A, Kaleekal T, Tarima S, McGinley E, et al. Nationwide trends of severe sepsis in the 21st century (2000-2007). Chest. 2011;140:1223–31. DOI: https://doi.org/10.1378/chest.110352.
3. Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of pediatric and neonatal sepsis: a systematic review. Lancer Respir Med. 2018;6:223-30. DOI: https://doi.org/10.1016/S2213-2600(18)30063-8
4. Hadinegoro SRS, Chairulfatah A, Latief A, Pudjiadi AH, Malisie ririe F, Alam A. Diagnosis and management of sepsis in children. Jakarta: Indonesian Pediatric Association; 2016. p. 1-42.
5. Majumdar A. Sepsis-induced acute kidney injury. Indian J Crit Care Med. 2010;14:14-21. DOI: https://doi.org/10.4103/0972-5229.63031
6. Fitzgerald JC, Basu R, Akcan-Arikan A, Izquierdo LM, Olave BEP, Hassinger AB, et al. Acute kidney injury in pediatric severe sepsis, an independent risk factor for death and new disability. Crit Care Med. 2016;44:2241-50. DOI: https://doi.org/10.1097/CCM.00000000000020077. Ostermann M, Liu K. Pathophysiology of AKI. Best Pract Res Clin Anaesthesiol. 2017;31:305–14. DOI: https://doi.org/10.1016/j.bpa.2017.09.001
8. Mårtensson J, Bellomo R. Pathophysiology of septic acute kidney injury. Contrib Nephrol. 2016;187:36–46. DOI: https://doi.org/10.1159/000442363
9. Chmielewski PP, Strzelec B. Elevated leukocyte count as a haringer of systemic inflammation, disease progression, and poor prognosis: a review. Folia Morphol. 2018;77:171-8. DOI: https://doi.org/10.5603.FM.a2017.0101.
10. Yudhantari DGA, Somasetia DH, Fadlyana E, Setiabudi D. Neutrophil-lymphocyte count ratio correlation to procalcitonin and PELOD-2 score in pediatric sepsis. Paediatr Indones. 2021;61:211–6. DOI: https://doi.org/10.14238/pi61.4.2021.211-6.
11. Natasukma YL, Pudjiastuti, Martuti S. Peran delta neutrophil index sebagai prediktor sepsis pada anak Sari Pediatr. 2019;21:115-20. DOI: https://doi.org/10.14328/sp21.2.2019.115-20.
12. Alfeilat MA, Slotki I, Shavit L. Single emergency room measurement of neutrophil/lymphocyte ratio for early detection of acute kidney injury (AKI). Intern Emerg Med. 2018;13:717–25. DOI: https://doi.org/10.1007/s11739-017-1715-8.
13. Yilmaz H, Cakmak M, Inan O, Darcin T, Akcay A. Can neutrophil-lymphocyte ratio be independent risk factor for predicting acute kidney injury in patients with severe sepsis? Ren Fail. 2015;37:225–9. DOI: https://doi.org/10.3109/0886022X.2014.982477.
14. Kana S, Ganesh RN, Surendran D, Kulkarni RG, Bobbili RK, Jeby JO. Urine microscopy and neutrophil lymphocyte ratio are early predictors of acute kidney injury in patients with urinary tract infection. Asian J Urol. 2021;8:220-6. DOI: https://doi.org/10.1016/j.ajur.2020.01.002.
15. Bu X, Zhang L, Chen P, Wu X. Relation of neutrophil-to-lymphocyte ratio to acute kidney injury in patients with sepsis and septic shock: A retrospective study. Int Immunipharmacol. 2019;10:372-7. DOI: https://doi.org.10.1016/j.intimp.2019.02.043.
16. Xie T, Xin Qi, Chen R, Zhang X, Zhang F, Ren H, et al. Clinical value of prognostic nutritional index and neutrophil-to-lymphocyte ratio in prediction of the development of sepsis-induced kidney injury. Dis Markers. 2022;2022:1-9.
17. Nilawati G.. Kejadian acute kidney injury dengan kriteria pRIFLE pada Unit Perawatan Intensif Anak Rumah Sakit Sanglah DenpasarSari Pediatr. 2012;14:158–61. DOI: https://doi.org/10.14238/sp14.3.2012.158-61.18. Aygün F, Durak C, Varol F, Çoku?ra? H, Camc?o?lu Y, Çam H. Evaluation of complete blood count parameters for diagnosis in children with sepsis in the pediatric intensive care unit. J Pediatr Inf. 2020;14:e55–e62. DOI: https://doi.org/10.5578/ced.68886.
19. Ghuman AK, Newth CJL, Khemani RG. Impact of gender on sepsis mortality and severity of illness for prepubertal and postpubertal children. J Pediatr. 2013;163:835-40. DOI: https://doi.org/10.1016/j.jpeds.2013.04.018.
20. Suari NMR, Latief A, Pudjiadi AH. New PELOD-2 cut-off score for predicting death in children with sepsis. Paediatr Indones. 2021;61:39–45. DOI:https://doi.org/10.14238/pi61.1.2021.39-45.
21. Zhong X, Ma A, Zhang Z, Liu Y, Liang G. Neutrophil-to-lymphocyte ratio as a predictive marker for severe pediatric sepsis. Transl Pediatr. 2021;10:657–65. DOI: https://doi.org/10.21037/tp-21-47..
22. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2–8. DOI: https://doi.org/10.1097/01.PCC.0000149131.72248.E6
23. Aulia M, Triratna S, Iriani Y, Bakri A, Saputra I. Pediatric sofa score for detecting sepsis in children. Paediatr Indones. 2021;61:1–7. DOI:https://doi.org/10.14238/pi61.1.2021.1-7.
24. Fitzgerald JC, Ross ME, Thomas NJ, Weiss SL, Balamuth F, Anderson AH. Risk factors and inpatient outcomes associated with acute kidney injury at pediatric severe sepsis presentation. Pediatr Nephrol. 2018;33:1781–90. DOI: https://doi.org/10.1007/s00467-018-39981-8 .
25. Wulandari A, Pudjiastuti P, Martuti S. Severe sepsis criteria, PELOD-2, and pSOFA as predictors of mortality in critically ill children with sepsis. Paediatr Indones. 2019;59:318–24. DOI: https://doi.org/10.14238/pi59.6.2019.318-24.
26. Riyuzo MC, Silveira LV de A, Macedo CS, Fioretto JR. Predictive factors of mortality in pediatric patients with acute renal injury associated with sepsis. J Pediatr (Rio J). 2017;93:28–34. DOI: https://doi.org/10.1016.j.jped.2016.04.006.
27. Li K, Peng Y, Yan R, Song W, Peng X, Ni X. Age-dependent changes of total and differential white blood cell counts in children. Chin Med J. 2020;133:1900-7. DOI: https/doi.org/10.1097/ CM9.0000000000000854.
28. Moosmann J, Krusemark A, Dittrich S, Ammer T, Rauh M, Woelfle J, et al. Age-and sex-spesific pediatric reference intervals for neutrophil-to-lymphocyte ratio, lympocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio. Int J Lab Hematol. 2011;44:296-301. DOI: hhtps://doi.org/10.1111/ijlh.13768.
29. Kimball R, Shachar E, Eyerly-Webb S, Patel DM, Spader H. Using the neutrophil-to-lymphocyte ratio to predict outcomes in pediatric patients with traumatic brain injury. Clin Neurol Neurosurg. 2020;193:105772. DOI: https://doi.org/10.1016/j.clineuro.2020.105772.
30. Liu Y, Zheng J, Zhang D, Jing L. Neutrophil-lympocyte ratio and plasma lactate predict 28-day mortality in patients with sepsis. J Clin Lab Anal.209;33:1-6 DOI: https://doi.org/10.1002/jcla.22942.
31. Alatas H, Laksmi E. Acute Kidney Injury. In: Rachmadi D , Sekarwana N, Hilmanto D, Garna H, editors. Pediatric nephrology textbook. 3rd ed. Jakarta: Indonesian Pediatrician Association; 2017. p. 589-608.
32. Ciccia E, Devarajan P. Pediatric acute kidney injury: prevalence, impact, and management challenges. Int J Nephrol Renovasc Dis. 2017;10:77–84. DOI: https://doi.org/10.2147/IJNRD.S103785.
33. Umbro I, Gentile G, Tinti F, Muiesan P, Paola A. Recent advances in pathophysiology and biomarkers of sepsis-induced acute kidney injury. J Infect. 2016;72:131-42. DOI: https://doi.org/10.1016/j.jinf.2015.11.008.
34. Odum JD, Wong HR, Stanski NL. A precision medicine approach to biomarker utilization in pediatric sepsis-associated acute kidney injury. Front Pediatr. 2021;9:632248. DOI: https://doi.org/10.3389/fped.2021.632248.
35. Weiss SL, Balamuth F, Thurm CW, Downes KJ, Fitzgerald JC, Laskin BL. Major adverse kidney events in pediatric sepsis. Clin J Am Soc Nephrol. 2019;14:664–72. DOI: https://doi.org/10.2215/CJN.12201018.
36. Vera R, Triratna S, Bahrun D, Theodorus. Hubungan acute kidney injury dan skor pelod pada pasien penyakit kritis. Sari Pediatr. 2013;15:181–5. DOI: https://doi.org/10.14238/sp15.3.2013.181-5.