Serum KIM-1 and Cystatin Levels as the Predictors of Acute Kidney Injury in Asphyxiated Neonates

Document Type : Original Article


1 Department of Pediatrics, School of Medicine, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pediatrics, School of Medicine, Al Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Pediatrics, School of Medicine, Kidney Diseases Research Center, Imam Hossein Children’s Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Pediatrics, Isfahan University of Medical Sciences, Isfahan, Iran

5 Department of Social Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Asphyxia may lead to serious complications, among which acute kidney injury (AKI) is the most common. Early diagnosis of AKI can help prevent impaired acid-base, fluid, and electrolyte balance that may lead to life-threatening complications. This study aimed to evaluate the effect of kidney injury molecule-1 (KIM-1) and cystatin-C in the early diagnosis of AKI among asphyxiated neonates.
Methods: This case-control study was conducted on 45 asphyxiated neonates, 24 of whom were in the control group and 23 cases were in the case group. Creatinine (Cr), KIM-1, and cystatin-C were measured for participants within 8 h and 4 days after birth and compared between case and control groups.
Results: The mean level of Cr-Standardized KIM-1 measured within 8 h and 4 days after birth was significantly higher in the case group, compared to the control group (P-value<0.05). The mean level of Cr-Standardized cysteine, only 4 days after birth, was significantly higher in the case group, compared to the control group (P-value<0.05). A receiver operating characteristic (ROC) curve analysis demonstrated that between the two biomarkers with two measurements, the KIM-1 Cr-Standardized within 4 days had the highest area under the curve (AUC) (0.751, 95% CI: 0.597-0.905). Moreover, the results of ROC curve analysis showed that Cr-Standardized KIM-1 within 4 days after birth with a critical value of >0.67 ng/ml allowed to predict kidney failure in newborns with 57.1‌% sensitivity and 86.4‌% specificity.
Conclusion: The findings of the present study show that high-specificity KIM-1 is a good biomarker for the early detection of acute renal failure in asphyxiated infants; however, similar expectations cannot exist with regards to cystatin-C for at least the first 8 h after birth.


  1. Aslam HM, Saleem S, Afzal R, Iqbal U, Saleem SM, Shaikh MW, Shahid N, et al. Risk factors of birth asphyxia. Ital J Pediatr. 2014;40(1):1-9.
  2. Hakobyan M, Dijkman KP, Laroche S, Naulaers G, Rijken M, Steiner K, van Straaten HL, Swarte RM, Ter Horst HJ, Zecic A, Zonnenberg IA, et al. Outcome of infants with therapeutic hypothermia after perinatal asphyxia and early-onset sepsis. Neonatology. 2019;115(2):127-33.
  3. Sendeku FW, Azeze GG, Fenta SL. Perinatal asphyxia and its associated factors in Ethiopia: a systematic review and meta-analysis. BMC pediatrics. 2020;20(1):1-1.
  4. Odd D, Heep A, Luyt K, Draycott T. Hypoxic-ischemic brain injury: Planned delivery before intrapartum events. J Neonatal-Perinat. 2017;10(4):347-53.
  5. Alonso-Spilsbury M, Mota-Rojas D, Villanueva-García D, Martínez-Burnes J, Orozco H, Ramírez-Necoechea R, Mayagoitia AL, Trujillo ME, et al. Perinatal asphyxia pathophysiology in pig and human: a review. Anim Reprod Sci. 2005;90(1-2):1-30.
  6. Popescu MR, Panaitescu AM, Pavel B, Zagrean L, Peltecu G, Zagrean AM, et al. Getting an early start in understanding perinatal asphyxia impact on the cardiovascular system. Front Pedlatr. 2020;8:68.
  7. Durkan AM, Alexander RT. Acute kidney injury post neonatal asphyxia. J Pediatr. 2011;158(2):e29-33.
  8. Saboute M, Parvini B, Khalessi N, Kalbassi Z, Kalani M. The prevalence of acute kidney injury
    in neonates with asphyxia. Pediatr Nephrol. 2016;4(1):30-2.
  9. Gallo D, de Bijl-Marcus KA, Alderliesten T, Lilien M, Groenendaal F. Early acute kidney injury in preterm and term neonates: Incidence, outcome, and associated clinical features. Neonatology. 2021;
  10. Srisawat N, Kellum JA. The role of biomarkers in acute kidney injury. Crit Care Clin. 2020;36(1):
  11. Stevens LA, Levey AS. Measurement of kidney function. Med Clin North Am. 2005;89(3):457–473.
  12. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, MaQ, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005;365(9466):1231–1238.
  13. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT. Association between increases in urinary neutrophil gelatinase–associated lipocalin and acute renal dysfunction after adult cardiac surgery. The Journal of the American Society of Anesthesiologists. 2006;105(3):485-91.
  14. Dent CL, Ma Q, Dastrala S, Bennett M, Mitsnefes MM, Barasch J, Devarajan P, et al. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care . 2007;11(6):1-8.
  15. Oncel MY, Canpolat FE, Arayici S, Alyamac Dizdar E, Uras N, Oguz SS. Urinary markers of acute kidney injury in newborns with perinatal asphyxia. Ren Fail.2016;38(6):882-8.
  16. Sweetmann DU, Molloy EJ. Biomarkers of acute kidney injury in neonatal encephalopathy. Eur J Pediatr. 2013;172:305–16.
  17. Selewski DT,Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ,Kent AL, et al. Neonatal acute kidney injury. Pediatrics, 2015,136(2): e463-e473.‏
  18. Chaturvedi SH, Farmer T, KAPKE Gordon F. Assay validation for KIM-1: human urinary renal dysfunction biomarker. Int J Biol Sci. 2009;5(2):
  19. Vaidya 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.
  20. Genc G, Ozkaya O, Avci B, Aygun C, Kucukoduk S. Kidney injury molecule-1 as a promising biomarker for acute kidney injury in premature babies. Am J Perinatol. 2013;30(3):245-52.
  21. Liangos O, Perianayagam MC, Vaidya VS, Wald WHR, Tighiouart H, MacKinnon RW, Li L, S Balakrishnan V, J G Pereira B, Bonventre JV, L Jaber B, et al. Urinary N-acetyl-β-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol.2007;18(3):904-912. ‏
  22. Khreba Nora A, Abdelsalam M, Wahab AM, Sanad M, Elhelaly R, Adel M, El-kannishy GH, et al. Kidney injury molecule 1 (KIM-1) as an early predictor for acute kidney injury in post-cardiopulmonary bypass (CPB) in open heart surgery patients. Int J Nephrol. 2019;2019:1-6.
  23. Chaturvedi S, Farmer T, Gordon FK. Assay validation for KIM-1: human urinary renal dysfunction biomarker. Int J Biol Sci. 2009;5(2):12834-.‏
  24. BONVENTRE, Joseph V. Kidney Injury Molecule‐1 (KIM‐1): a specific and sensitive biomarker of kidney injury. Scand. J Clin Lab Invest. 2008; 68.sup241: 78-83. ‏
  25. Li Y, Fu C, Zhou X, Xiao Z, Zhu X, Jin M, et al. Urine interleukin-18 and cystatin-C as biomarkers of acute kidney injury in critically ill neonates. Pediatr Nephrol. 2012;27(5):851-60.
  26. Askenazi David J, Montesanti A, Hundley H, Koralkar R, Pawar P,Shuaib F, Liwo A,Devarajan P, Amvalabalan N, et al. Urine biomarkers predict acute kidney injury and mortality in very low birth weight infants. J Pediatr. 2011;159(6): 907-912.