Download PDF
J Pediatr Infect Dis 2016; 11(03): 55-64
DOI: 10.1055/s-0036-1597299
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Sepsis and Neonatal Acute Kidney Injury

A. Nillsen
1   Department of Neonatology, Centenary Hospital for Women and Children, Canberra Hospital, Woden, Australia
,
Alison L. Kent
1   Department of Neonatology, Centenary Hospital for Women and Children, Canberra Hospital, Woden, Australia
2   Department of Neonatology, Australian National University Medical School, Canberra, Australia
› Author Affiliations
Further Information

Publication History

03 August 2016

02 September 2016

Publication Date:
19 December 2016 (online)

    Permissions and Reprints

Abstract

Although the neonatal period is only the first 28 days of life, it accounts globally for in excess of 40% of deaths of children younger than 5 years of age. Sepsis is an important contributor to this burden of neonatal death as well as disease. Sepsis is in addition a leading cause of acute kidney injury (AKI) in neonates. Neonatal AKI independently contributes toward mortality and morbidity with neonates dying because of AKI. The neonates' response to sepsis and AKI is complicated by hemodynamic instability from cardiac and intrapulmonary shunts as well as immature renal function. This review article will examine the at-risk neonatal populations, causes of and risk factors for neonatal sepsis, pathophysiology, fluid overload, prevention, and global perspectives.

Keywords

neonate - acute kidney injury - sepsis - preterm
 

  • References

  • 1 Liu L, Johnson HL, Cousens S. , et al; Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 379 9832 2151-2161
    CrossrefPubMedGoogle Scholar
  • 2 Liu L, Oza S, Hogan D. , et al. Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 2015; 385 9966 430-440
    CrossrefPubMedGoogle Scholar
  • 3 Libório AB, Branco KM, Torres de Melo Bezerra C. Acute kidney injury in neonates: from urine output to new biomarkers. BioMed Res Int 2014; 2014: 601568
    PubMedGoogle Scholar
  • 4 Kriplani DS, Sethna CB, Leisman DE, Schneider JB. Acute kidney injury in neonates in the PICU. Pediatr Crit Care Med 2016; 17 (04) e159-e164
    CrossrefPubMedGoogle Scholar
  • 5 Blencowe H, Cousens S, Oestergaard MZ. , et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 2012; 379 9832 2162-2172
    CrossrefPubMedGoogle Scholar
  • 6 Chang HH, Larson J, Blencowe H. , et al; Born Too Soon preterm prevention analysis group. Preventing preterm births: analysis of trends and potential reductions with interventions in 39 countries with very high human development index. Lancet 2013; 381 9862 223-234
    CrossrefPubMedGoogle Scholar
  • 7 Shane AL, Stoll BJ. Neonatal sepsis: progress towards improved outcomes. J Infect 2014; 68 (Suppl. 01) S24-S32
    CrossrefPubMedGoogle Scholar
  • 8 Askenazi DJ, Morgan C, Goldstein SL. , et al. Strategies to improve the understanding of long-term renal consequences after neonatal acute kidney injury. Pediatr Res 2016; 79 (03) 502-508
    CrossrefPubMedGoogle Scholar
  • 9 Hanna MH, Askenazi DJ, Selewski DT. Drug-induced acute kidney injury in neonates. Curr Opin Pediatr 2016; 28 (02) 180-187
    CrossrefPubMedGoogle Scholar
  • 10 Osathanondh V, Potter EL. Development of human kidney as shown by microdissection. III. Formation and interrelationship of collecting tubules and nephrons. Arch Pathol 1963; 76: 290-302
    PubMedGoogle Scholar
  • 11 Black MJ, Sutherland MR, Gubhaju L, Kent AL, Dahlstrom JE, Moore L. When birth comes early: effects on nephrogenesis. Nephrology (Carlton) 2013; 18 (03) 180-182
    CrossrefPubMedGoogle Scholar
  • 12 DeFreitas MJ, Seeherunvong W, Katsoufis CP. , et al. Longitudinal patterns of urine biomarkers in infants across gestational ages. Pediatr Nephrol 2016; 31 (07) 1179-1188
    CrossrefPubMedGoogle Scholar
  • 13 Bertram JF, Douglas-Denton RN, Diouf B, Hughson MD, Hoy WE. Human nephron number: implications for health and disease. Pediatr Nephrol 2011; 26 (09) 1529-1533
    CrossrefPubMedGoogle Scholar
  • 14 Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 2012; 120 (04) c179-c184
    CrossrefPubMedGoogle Scholar
  • 15 Jetton JG, Guillet R, Askenazi DJ. , et al; Neonatal Kidney Collaborative. Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: design of a retrospective cohort study. Front Pediatr 2016; 4: 68
    PubMedGoogle Scholar
  • 16 Momtaz HE, Sabzehei MK, Rasuli B, Torabian S. The main etiologies of acute kidney injury in the newborns hospitalized in the neonatal intensive care unit. J Clin Neonatol 2014; 3 (02) 99-102
    CrossrefPubMedGoogle Scholar
  • 17 El-Badawy AA, Makar S, Abdel-Razek AR, Abd Elaziz D. Incidence and risk factors of acute kidney injury among the critically ill neonates. Saudi J Kidney Dis Transpl 2015; 26 (03) 549-555
    CrossrefPubMedGoogle Scholar
  • 18 Duzova A, Bakkaloglu A, Kalyoncu M. , et al; Turkish Society for Pediatric Nephrology Acute Kidney Injury Study Group. Etiology and outcome of acute kidney injury in children. Pediatr Nephrol 2010; 25 (08) 1453-1461
    CrossrefPubMedGoogle Scholar
  • 19 Youssef D, Abd-Elrahman H, Shehab MM, Abd-Elrheem M. Incidence of acute kidney injury in the neonatal intensive care unit. Saudi J Kidney Dis Transpl 2015; 26 (01) 67-72
    CrossrefPubMedGoogle Scholar
  • 20 Vachvanichsanong P, McNeil E, Dissaneevate S, Dissaneewate P, Chanvitan P, Janjindamai W. Neonatal acute kidney injury in a tertiary center in a developing country. Nephrol Dial Transplant 2012; 27 (03) 973-977
    CrossrefPubMedGoogle Scholar
  • 21 Askenazi DJ, Koralkar R, Hundley HE. , et al. Urine biomarkers predict acute kidney injury in newborns. J Pediatr 2012; 161 (02) 270-5.e1
    CrossrefPubMedGoogle Scholar
  • 22 Smertka M, Wroblewska J, Suchojad A. , et al. Serum and urinary NGAL in septic newborns. BioMed Res Int 2014; 2014: 717318
    PubMedGoogle Scholar
  • 23 Weintraub AS, Connors J, Carey A, Blanco V, Green RS. The spectrum of onset of acute kidney injury in premature infants less than 30 weeks gestation. J Perinatol 2016; 36 (06) 474-480
    CrossrefPubMedGoogle Scholar
  • 24 Filler G, Guerrero-Kanan R, Alvarez-Elías AC. Assessment of glomerular filtration rate in the neonate: is creatinine the best tool?. Curr Opin Pediatr 2016; 28 (02) 173-179
    CrossrefPubMedGoogle Scholar
  • 25 Alge JL, Arthur JM. Biomarkers of AKI: a review of mechanistic relevance and potential therapeutic implications. Clin J Am Soc Nephrol 2015; 10 (01) 147-155
    CrossrefPubMedGoogle Scholar
  • 26 Zhou M, Cheng S, Yu J, Lu Q. Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis. PLoS One 2015; 10 (05) e0127170
    CrossrefPubMedGoogle Scholar
  • 27 Wynn JL, Wong HR, Shanley TP, Bizzarro MJ, Saiman L, Polin RA. Time for a neonatal-specific consensus definition for sepsis. Pediatr Crit Care Med 2014; 15 (06) 523-528
    CrossrefPubMedGoogle Scholar
  • 28 Wynn JL. Defining neonatal sepsis. Curr Opin Pediatr 2016; 28 (02) 135-140
    CrossrefPubMedGoogle Scholar
  • 29 Vergnano S, Sharland M, Kazembe P, Mwansambo C, Heath PT. Neonatal sepsis: an international perspective. Arch Dis Child Fetal Neonatal Ed 2005; 90 (03) F220-F224
    CrossrefPubMedGoogle Scholar
  • 30 Obiero CW, Seale AC, Berkley JA. Empiric treatment of neonatal sepsis in developing countries. Pediatr Infect Dis J 2015; 34 (06) 659-661
    CrossrefPubMedGoogle Scholar
  • 31 Edmond K, Zaidi A. New approaches to preventing, diagnosing, and treating neonatal sepsis. PLoS Med 2010; 7 (03) e1000213
    CrossrefPubMedGoogle Scholar
  • 32 Zea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr 2015; 61 (01) 1-13
    CrossrefPubMedGoogle Scholar
  • 33 van Herk W, Stocker M, van Rossum AM. Recognising early onset neonatal sepsis: an essential step in appropriate antimicrobial use. J Infect 2016; 72: S77-S82
    CrossrefPubMedGoogle Scholar
  • 34 Doi K. Role of kidney injury in sepsis. J Intensive Care 2016; 4: 17
    CrossrefPubMedGoogle Scholar
  • 35 Gomez H, Ince C, De Backer D. , et al. A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock 2014; 41 (01) 3-11
    PubMedGoogle Scholar
  • 36 Honore PM, Jacobs R, Hendrickx I. , et al. Prevention and treatment of sepsis-induced acute kidney injury: an update. Ann Intensive Care 2015; 5 (01) 51
    CrossrefPubMedGoogle Scholar
  • 37 Zarbock A, Gomez H, Kellum JA. Sepsis-induced acute kidney injury revisited: pathophysiology, prevention and future therapies. Curr Opin Crit Care 2014; 20 (06) 588-595
    CrossrefPubMedGoogle Scholar
  • 38 Prowle JR, Bellomo R. Sepsis-associated acute kidney injury: macrohemodynamic and microhemodynamic alterations in the renal circulation. Semin Nephrol 2015; 35 (01) 64-74
    CrossrefPubMedGoogle Scholar
  • 39 Langenberg C, Bellomo R, May C, Wan L, Egi M, Morgera S. Renal blood flow in sepsis. Crit Care 2005; 9 (04) R363-R374
    CrossrefPubMedGoogle Scholar
  • 40 Kluckow M. Use of ultrasound in the haemodynamic assessment of the sick neonate. Arch Dis Child Fetal Neonatal Ed 2014; 99 (04) F332-F337
    CrossrefPubMedGoogle Scholar
  • 41 Maddens B, Vandendriessche B, Demon D. , et al. Severity of sepsis-induced acute kidney injury in a novel mouse model is age dependent. Crit Care Med 2012; 40 (09) 2638-2646
    CrossrefPubMedGoogle Scholar
  • 42 Seely KA, Holthoff JH, Burns ST. , et al. Hemodynamic changes in the kidney in a pediatric rat model of sepsis-induced acute kidney injury. Am J Physiol Renal Physiol 2011; 301 (01) F209-F217
    CrossrefPubMedGoogle Scholar
  • 43 Abitbol CL, DeFreitas MJ, Strauss J. Assessment of kidney function in preterm infants: lifelong implications. Pediatr Nephrol 2016; 31: 1-10
    CrossrefPubMedGoogle Scholar
  • 44 Emlet DR, Shaw AD, Kellum JA. Sepsis-associated AKI: epithelial cell dysfunction. Semin Nephrol 2015; 35 (01) 85-95
    CrossrefPubMedGoogle Scholar
  • 45 Awad H, el-Safty I, el-Barbary M, Imam S. Evaluation of renal glomerular and tubular functional and structural integrity in neonates. Am J Med Sci 2002; 324 (05) 261-266
    CrossrefPubMedGoogle Scholar
  • 46 Garg PM, Tatum R, Ravisankar S, Shekhawat PS, Chen YH. Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins. Pediatr Res 2015; 78 (05) 527-532
    CrossrefPubMedGoogle Scholar
  • 47 Claud EC. Neonatal necrotizing enterocolitis -inflammation and intestinal immaturity. Antiinflamm Antiallergy Agents Med Chem 2009; 8 (03) 248-259
    CrossrefPubMedGoogle Scholar
  • 48 Hsieh EM, Hornik CP, Clark RH, Laughon MM, Benjamin Jr DK, Smith PB. ; Best Pharmaceuticals for Children Act—Pediatric Trials Network. Medication use in the neonatal intensive care unit. Am J Perinatol 2014; 31 (09) 811-821
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Diaz Heijtz R. Fetal, neonatal, and infant microbiome: perturbations and subsequent effects on brain development and behavior. Semin Fetal Neonatal Med 2016; 21 (06) 410-417
    CrossrefPubMedGoogle Scholar
  • 50 Turta O, Rautava S. Antibiotics, obesity and the link to microbes - what are we doing to our children?. BMC Med 2016; 14: 57
    CrossrefPubMedGoogle Scholar
  • 51 Azad MB, Bridgman SL, Becker AB, Kozyrskyj AL. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int J Obes 2014; 38 (10) 1290-1298
    CrossrefPubMedGoogle Scholar
  • 52 Cotten CM. Adverse consequences of neonatal antibiotic exposure. Curr Opin Pediatr 2016; 28 (02) 141-149
    Google Scholar
  • 53 Arikan AA, Zappitelli M, Goldstein SL, Naipaul A, Jefferson LS, Loftis LL. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med 2012; 13 (03) 253-258
    CrossrefPubMedGoogle Scholar
  • 54 Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int 2012; 2 (Suppl): 1-141
    CrossrefPubMedGoogle Scholar
  • 55 Wang N, Jiang L, Zhu B, Wen Y, Xi XM. ; Beijing Acute Kidney Injury Trial (BAKIT) Workgroup. Fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study. Crit Care 2015; 19: 371
    CrossrefPubMedGoogle Scholar
  • 56 Bouchard J, Soroko SB, Chertow GM. , et al; Program to Improve Care in Acute Renal Disease (PICARD) Study Group. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 2009; 76 (04) 422-427
    CrossrefPubMedGoogle Scholar
  • 57 Cerda J, Sheinfeld G, Ronco C. Fluid overload in critically ill patients with acute kidney injury. Blood Purif 2010; 29 (04) 331-338
    CrossrefPubMedGoogle Scholar
  • 58 Soler YA, Nieves-Plaza M, Prieto M, García-De Jesús R, Suárez-Rivera M. Pediatric risk, injury, failure, loss, end-stage renal disease score identifies acute kidney injury and predicts mortality in critically ill children: a prospective study. Pediatr Crit Care Med 2013; 14 (04) e189-e195
    CrossrefPubMedGoogle Scholar
  • 59 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
    CrossrefPubMedGoogle Scholar
  • 60 Sutherland SM, Zappitelli M, Alexander SR. , et al. Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry. Am J Kidney Dis 2010; 55 (02) 316-325
    CrossrefPubMedGoogle Scholar
  • 61 Butcher BW, Liu KD. Fluid overload in AKI: epiphenomenon or putative effect on mortality?. Curr Opin Crit Care 2012; 18 (06) 593-598
    CrossrefPubMedGoogle Scholar
  • 62 Rinke ML, Chen AR, Bundy DG. , et al. Implementation of a central line maintenance care bundle in hospitalized pediatric oncology patients. Pediatrics 2012; 130 (04) e996-e1004
    CrossrefPubMedGoogle Scholar
  • 63 AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2014; (04) CD005496
    PubMedGoogle Scholar
  • 64 Ohlsson A, Lacy JB. Intravenous immunoglobulin for suspected or proven infection in neonates. Cochrane Database Syst Rev 2015; (03) CD001239
    PubMedGoogle Scholar
  • 65 Carr R, Modi N, Doré C. G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev 2003; 3 (03) CD003066
    PubMedGoogle Scholar
  • 66 Kylat RI, Ohlsson A. Recombinant human activated protein C for severe sepsis in neonates. Cochrane Database Syst Rev 2012; (04) CD005385
    PubMedGoogle Scholar
  • 67 Shah PS, Kaufman DA. Antistaphylococcal immunoglobulins to prevent staphylococcal infection in very low birth weight infants. Cochrane Database Syst Rev 2009; (02) CD006449
    PubMedGoogle Scholar
  • 68 Pammi M, Brocklehurst P. Granulocyte transfusions for neonates with confirmed or suspected sepsis and neutropenia. Cochrane Database Syst Rev 2011; (10) CD003956
    PubMedGoogle Scholar
  • 69 Yoshida S, Martines J, Lawn JE. , et al; neonatal health research priority setting group. Setting research priorities to improve global newborn health and prevent stillbirths by 2025. J Glob Health 2016; 6 (01) 010508
    PubMedGoogle Scholar
  • 70 Reilly R, Evans K, Gomersall J. , et al. Effectiveness, cost effectiveness, acceptability and implementation barriers/enablers of chronic kidney disease management programs for Indigenous people in Australia, New Zealand and Canada: a systematic review of mixed evidence. BMC Health Serv Res 2016; 16: 119
    CrossrefPubMedGoogle Scholar
  • 71 Hoy WE, Samuel T, Mott SA. , et al. Renal biopsy findings among Indigenous Australians: a nationwide review. Kidney Int 2012; 82 (12) 1321-1331
    CrossrefPubMedGoogle Scholar
  • 72 Hoy WE, Hughson MD, Kopp JB, Mott SA, Bertram JF, Winkler CA. APOL1 risk alleles are associated with exaggerated age-related changes in glomerular number and volume in African-American adults: an autopsy study. J Am Soc Nephrol 2015; 26 (12) 3179-3189
    CrossrefPubMedGoogle Scholar
  • 73 Genovese G, Friedman DJ, Ross MD. , et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010; 329 5993 841-845
    CrossrefPubMedGoogle Scholar
  • 74 White A, Wong W, Sureshkumur P, Singh G. The burden of kidney disease in indigenous children of Australia and New Zealand, epidemiology, antecedent factors and progression to chronic kidney disease. J Paediatr Child Health 2010; 46 (09) 504-509
    CrossrefPubMedGoogle Scholar
  • 75 Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 2012; 81 (05) 442-448
    CrossrefPubMedGoogle Scholar
  • 76 Askenazi DJ, Feig DI, Graham NM, Hui-Stickle S, Goldstein SL. 3-5.  year longitudinal follow-up of pediatric patients after acute renal failure. Kidney Int 2006; 69 (01) 184-189
    CrossrefPubMedGoogle Scholar
  • 77 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
    CrossrefPubMedGoogle Scholar
  • 78 Koralkar R, Ambalavanan N, Levitan EB, McGwin G, Goldstein S, Askenazi D. Acute kidney injury reduces survival in very low birth weight infants. Pediatr Res 2011; 69 (04) 354-358
    CrossrefPubMedGoogle Scholar
  • 79 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
    CrossrefPubMedGoogle Scholar
  • 80 Charlton JR, Portilla D, Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant 2014; 29 (07) 1301-1311
    CrossrefPubMedGoogle Scholar
  • 81 Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol 2008; 48: 463-493
    CrossrefPubMedGoogle Scholar
  • 82 de Geus HR, Betjes MG, Bakker J. Biomarkers for the prediction of acute kidney injury: a narrative review on current status and future challenges. Clin Kidney J 2012; 5 (02) 102-108
    CrossrefPubMedGoogle Scholar
  • 83 El-Achkar TM, Wu XR. Uromodulin in kidney injury: an instigator, bystander, or protector?. Am J Kidney Dis 2012; 59 (03) 452-461
    CrossrefPubMedGoogle Scholar
  • 84 Schreiber R, Wolpin J, Koren G. Determinants of aciclovir-induced nephrotoxicity in children. Paediatr Drugs 2008; 10 (02) 135-139
    CrossrefPubMedGoogle Scholar
  • 85 Gunness P, Aleksa K, Bend J, Koren G. Acyclovir-induced nephrotoxicity: the role of the acyclovir aldehyde metabolite. Transl Res 2011; 158 (05) 290-301
    CrossrefPubMedGoogle Scholar
  • 86 Chai LY, Netea MG, Tai BC. , et al. An elevated pro-inflammatory cytokine response is linked to development of amphotericin B-induced nephrotoxicity. J Antimicrob Chemother 2013; 68 (07) 1655-1659
    CrossrefPubMedGoogle Scholar
  • 87 Mingeot-Leclercq MP, Tulkens PM. Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 1999; 43 (05) 1003-1012
    PubMedGoogle Scholar
  • 88 Topham JC, Murgatroyd LB, Jones DV, Goonetilleke UR, Wright J. Safety evaluation of meropenem in animals: studies on the kidney. J Antimicrob Chemother 1989; 24 (Suppl A ): 287-306
    CrossrefPubMedGoogle Scholar
  • 89 Bamgbola O. Review of vancomycin-induced renal toxicity: an update. Ther Adv Endocrinol Metab 2016; 7 (03) 136-147
    CrossrefPubMedGoogle Scholar