Am J Perinatol 2021; 38(09): 922-929
DOI: 10.1055/s-0039-1701024
Original Article

Acute Kidney Injury in Neonates with Perinatal Asphyxia Receiving Therapeutic Hypothermia

1   Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Demiroglu Bilim University, Istanbul, Turkey
,
Ebru Yucesoy
2   Division of Neonatology, Department of Pediatrics, Sanliurfa Training and Research Hospital, Sanliurfa, Turkey
› Author Affiliations
Funding None.

Abstract

Objective To assess the incidence and severity of acute kidney injury (AKI) and evaluate risk factors that predict AKI in asphyxiated infants receiving therapeutic hypothermia.

Study Design Infants ≥36 weeks' gestation diagnosed with moderate-to-severe perinatal asphyxia and received therapeutic hypothermia were reviewed retrospectively (n = 166). Modified Acute Kidney Injury Network criteria were used to diagnose AKI. The results of infants with AKI were compared with the infants who did not develop AKI.

Results AKI developed in 49 (29.5%) infants, of whom 22 had stage I, 13 had stage II, and 14 had stage III AKI. The overall mortality rate was 15.7% and was significantly higher in infants with AKI when compared with infants without AKI (41 vs. 5%; p < 0.001). Asystole at birth (p = 0.044), placental abruption (p = 0.041), outborn status (p = 0.041), need for vasopressor support (p = 0.031), increased bleeding tendency (p = 0.031), initial lactate level (p = 0.015), and 12-hour lactate level (p = 0.029) were independent risk factors for the development of AKI. Receiver operating characteristic curve analysis demonstrated a good predictive value for initial lactate level (>15 mmol/L), with 69% sensitivity (95% CI: 55–82) and 82% specificity (95% CI: 74–89), and for 12-hour lactate level (>6 mmol/L), with 83.7% sensitivity (95% CI: 70–93) and 73.5% specificity (95% CI: 64.5–81), to predict AKI.

Conclusion AKI is still a common complication of perinatal asphyxia despite treatment with therapeutic hypothermia. Identification of risk factors associated with the development of AKI in asphyxiated infants would be potentially beneficial to reduce morbidity and mortality. Besides perinatal risk factors, initial and 12-hour lactate concentrations can be used for the early prediction of AKI.



Publication History

Received: 31 August 2019

Accepted: 12 December 2019

Article published online:
27 January 2020

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  • References

  • 1 Sharma D, Pandita A, Kumar C. Therapeutic hypothermia in asphyxiated newborn: its applicability, feasibility and accessibility in developing country India: a long way to go. J Neonatal Biol 2014; 3 (05) 111
  • 2 Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS One 2013; 8 (03) e58834
  • 3 Behrman RE, Lees MH, Peterson EN, De Lannoy CW, Seeds AE. Distribution of the circulation in the normal and asphyxiated fetal primate. Am J Obstet Gynecol 1970; 108 (06) 956-969
  • 4 Perlman JM, Tack ED, Martin T, Shackelford G, Amon E. Acute systemic organ injury in term infants after asphyxia. Am J Dis Child 1989; 143 (05) 617-620
  • 5 Karlowicz MG, Adelman RD. Nonoliguric and oliguric acute renal failure in asphyxiated term neonates. Pediatr Nephrol 1995; 9 (06) 718-722
  • 6 Hankins GD, Koen S, Gei AF, Lopez SM, Van Hook JW, Anderson GD. Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstet Gynecol 2002; 99 (5 Pt 1): 688-691
  • 7 Aggarwal A, Kumar P, Chowdhary G, Majumdar S, Narang A. Evaluation of renal functions in asphyxiated newborns. J Trop Pediatr 2005; 51 (05) 295-299
  • 8 Kaur S, Jain S, Saha A. et al. Evaluation of glomerular and tubular renal function in neonates with birth asphyxia. Ann Trop Paediatr 2011; 31 (02) 129-134
  • 9 Sarkar S, Askenazi DJ, Jordan BK. et al. Relationship between acute kidney injury and brain MRI findings in asphyxiated newborns after therapeutic hypothermia. Pediatr Res 2014; 75 (03) 431-435
  • 10 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 (06) 882-888
  • 11 Tanigasalam V, Bhat V, Adhisivam B, Sridhar MG. Does therapeutic hypothermia reduce acute kidney injury among term neonates with perinatal asphyxia?--a randomized controlled trial. J Matern Fetal Neonatal Med 2016; 29 (15) 2545-2548
  • 12 Delbridge MS, Shrestha BM, Raftery AT, El Nahas AM, Haylor JL. The effect of body temperature in a rat model of renal ischemia-reperfusion injury. Transplant Proc 2007; 39 (10) 2983-2985
  • 13 Hasslacher J, Barbieri F, Harler U. et al. Acute kidney injury and mild therapeutic hypothermia in patients after cardiopulmonary resuscitation - a post hoc analysis of a prospective observational trial. Crit Care 2018; 22 (01) 154
  • 14 Selewski DT, Jordan BK, Askenazi DJ, Dechert RE, Sarkar S. Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia. J Pediatr 2013; 162 (04) 725-729
  • 15 Nada A, Bonachea EM, Askenazi DJ. Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med 2017; 22 (02) 90-97
  • 16 Askenazi DJ, Ambalavanan N, Goldstein SL. Acute kidney injury in critically ill newborns: what do we know? What do we need to learn?. Pediatr Nephrol 2009; 24 (02) 265-274
  • 17 Sarafidis K, Tsepkentzi E, Agakidou E. et al. Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol 2012; 27 (09) 1575-1582
  • 18 Karlo J, Bhat BV, Koner BC, Adhisivam B. Evaluation of renal function in term babies with perinatal asphyxia. Indian J Pediatr 2014; 81 (03) 243-247
  • 19 Selewski DT, Charlton JR, Jetton JG. et al. Neonatal acute kidney injury. Pediatrics 2015; 136 (02) e463-e473
  • 20 Kellum JA, Lameire N. KDIGO AKI Guideline Work Group. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1). Crit Care 2013; 17 (01) 204
  • 21 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33 (10) 696-705
  • 22 Thompson CM, Puterman AS, Linley LL. et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr 1997; 86 (07) 757-761
  • 23 Jetton JG, Askenazi DJ. Update on acute kidney injury in the neonate. Curr Opin Pediatr 2012; 24 (02) 191-196
  • 24 Jetton JG, Askenazi DJ. Acute kidney injury in the neonate. Clin Perinatol 2014; 41 (03) 487-502
  • 25 Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 2007; 71 (10) 1028-1035
  • 26 Mehta RL, Kellum JA, Shah SV. et al; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11 (02) R31
  • 27 Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Patil N, Ambalavanan N. Fluid overload and mortality are associated with acute kidney injury in sick near-term/term neonate. Pediatr Nephrol 2013; 28 (04) 661-666
  • 28 Basile DP, Anderson MD, Sutton TA. Pathophysiology of acute kidney injury. Compr Physiol 2012; 2 (02) 1303-1353
  • 29 Saikumar P, Venkatachalam MA. Role of apoptosis in hypoxic/ischemic damage in the kidney. Semin Nephrol 2003; 23 (06) 511-521
  • 30 Deshpande SA, Platt MP. Association between blood lactate and acid-base status and mortality in ventilated babies. Arch Dis Child Fetal Neonatal Ed 1997; 76 (01) F15-F20
  • 31 Singarajah C, Carlson RW. A review of the role of blood lactate measurements in the ICU. J Intensive Care Med 1998; 13: 218-226
  • 32 Zhang Z, Xu X. Lactate clearance is a useful biomarker for the prediction of all-cause mortality in critically ill patients: a systematic review and meta-analysis. Crit Care Med 2014; 42 (09) 2118-2125
  • 33 Duke TD, Butt W, South M. Predictors of mortality and multiple organ failure in children with sepsis. Intensive Care Med 1997; 23 (06) 684-692
  • 34 Manikis P, Jankowski S, Zhang H, Kahn RJ, Vincent JL. Correlation of serial blood lactate levels to organ failure and mortality after trauma. Am J Emerg Med 1995; 13 (06) 619-622
  • 35 Nadeem M, Clarke A, Dempsey EM. Day 1 serum lactate values in preterm infants less than 32 weeks gestation. Eur J Pediatr 2010; 169 (06) 667-670
  • 36 Charpie JR, Dekeon MK, Goldberg CS, Mosca RS, Bove EL, Kulik TJ. Serial blood lactate measurements predict early outcome after neonatal repair or palliation for complex congenital heart disease. J Thorac Cardiovasc Surg 2000; 120 (01) 73-80
  • 37 Grayck EN, Meliones JN, Kern FH, Hansell DR, Ungerleider RM, Greeley WJ. Elevated serum lactate correlates with intracranial hemorrhage in neonates treated with extracorporeal life support. Pediatrics 1995; 96 (5 Pt 1): 914-917
  • 38 Cheung PY, Finer NN. Plasma lactate concentration as a predictor of death in neonates with severe hypoxemia requiring extracorporeal membrane oxygenation. J Pediatr 1994; 125 (5 Pt 1): 763-768
  • 39 Cheung PY, Robertson CMT, Finer NN. Plasma lactate as a predictor of early childhood neurodevelopmental outcome of neonates with severe hypoxaemia requiring extracorporeal membrane oxygenation. Arch Dis Child Fetal Neonatal Ed 1996; 74 (01) F47-F50
  • 40 da Silva S, Hennebert N, Denis R, Wayenberg JL. Clinical value of a single postnatal lactate measurement after intrapartum asphyxia. Acta Paediatr 2000; 89 (03) 320-323
  • 41 Shah S, Tracy M, Smyth J. Postnatal lactate as an early predictor of short-term outcome after intrapartum asphyxia. J Perinatol 2004; 24 (01) 16-20
  • 42 Murray DM, Boylan GB, Fitzgerald AP, Ryan CA, Murphy BP, Connolly S. persistent lactic acidosis in neonatal hypoxic-ischemic encephalopathy correlates with EEG grade and electrographic seizure burden. Arch Dis Child Fetal Neonatal Ed 2008; 93 (03) 183-186
  • 43 Polackova R, Salounova D, Kantor L. Lactate as an early predictor of psychomotor development in neonates with asphyxia receiving therapeutic hypothermia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018; 162 (02) 144-148
  • 44 Chiang MC, Lien R, Chu SM. et al. Serum lactate, brain magnetic resonance imaging and outcome of neonatal hypoxic ischemic encephalopathy after therapeutic hypothermia. Pediatr Neonatol 2016; 57 (01) 35-40
  • 45 Sweetman DU, Onwuneme C, Watson WR, O'Neill A, Murphy JFA, Molloy EJ. Renal function and novel urinary biomarkers in infants with neonatal encephalopathy. Acta Paediatr 2016; 105 (11) e513-e519
  • 46 Abitbol CL, Bauer CR, Montané B, Chandar J, Duara S, Zilleruelo G. Long-term follow-up of extremely low birth weight infants with neonatal renal failure. Pediatr Nephrol 2003; 18 (09) 887-893
  • 47 Mammen C, Al Abbas A, Skippen P. et al. Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study. Am J Kidney Dis 2012; 59 (04) 523-530
  • 48 Jenik AG, Ceriani Cernadas JM, Gorenstein A. et al. A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia. Pediatrics 2000; 105 (04) E45
  • 49 Bakr AF. Prophylactic theophylline to prevent renal dysfunction in newborns exposed to perinatal asphyxia--a study in a developing country. Pediatr Nephrol 2005; 20 (09) 1249-1252
  • 50 Bhat MA, Shah ZA, Makhdoomi MS, Mufti MH. Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial. J Pediatr 2006; 149 (02) 180-184
  • 51 Raina A, Pandita A, Harish R, Yachha M, Jamwal A. Treating perinatal asphyxia with theophylline at birth helps to reduce the severity of renal dysfunction in term neonates. Acta Paediatr 2016; 105 (10) e448-e451
  • 52 Bellos I, Pandita A, Yachha M. Effectiveness of theophylline administration in neonates with perinatal asphyxia: a meta-analysis. J Matern Fetal Neonatal Med 2019; DOI: 10.1080/14767058.2019.1673722.