Skip to main content

The Evolution of Acute Kidney Injury Research Over the Past Two Decades

  • Chapter
  • First Online:
Critical Care Nephrology and Renal Replacement Therapy in Children
  • 1341 Accesses

Abstract

The recognition that patients are dying from and not with acute kidney injury has prompted a transformation in clinical, basic, and translational acute kidney injury research over the past two decades. Initial work described the single-center epidemiology and associated outcomes for children with acute kidney injury who required support with renal replacement therapy. More recent study focuses on risk stratification, discovery validation, and incorporation of novel biomarkers into the prediction of acute kidney injury and description of its course. Finally, two large multicenter and multinational studies of pediatric and neonatal acute kidney injury demonstrate the irrefutable incremental risk conferred by pediatric acute kidney injury and morbidity and mortality across the spectrum of pediatric critical illness. All of these advancements were made possible by development of a standardized multidimensional definition of acute kidney injury development and severity. The evolution of pediatric acute kidney injury research in the past two decades provides the foundation necessary and optimism for the future to improve outcomes for the critically ill child with or at risk for acute kidney injury.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sutherland SM, Byrnes JJ, Kothari M, Longhurst CA, Dutta S, Garcia P, et al. AKI in hospitalized children: comparing the pRIFLE, AKIN, and KDIGO definitions. Clin J Am Soc Nephrol. 2015;10(4):554–61.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Akcan-Arikan A, Gebhard DJ, Arnold MA, Loftis LL, Kennedy CE. Fluid overload and kidney injury score: a multidimensional real-time assessment of renal disease burden in the critically ill patient. Pediatr Crit Care Med. 2017;18(6):524–30.

    Article  PubMed  Google Scholar 

  3. Basu RK, Zappitelli M, Brunner L, Wang Y, Wong HR, Chawla LS, et al. Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Kidney Int. 2014;85(3):659–67.

    Article  PubMed  Google Scholar 

  4. Alge JL, Arthur JM. Biomarkers of AKI: a review of mechanistic relevance and potential therapeutic implications. Clin J Am Soc Nephrol. 2015;10(1):147–55.

    Article  CAS  PubMed  Google Scholar 

  5. Sutherland SM, Goldstein SL, Alexander SR. The prospective pediatric continuous renal replacement therapy (ppCRRT) registry: a critical appraisal. Pediatr Nephrol. 2014;29(11):2069–76.

    Article  PubMed  Google Scholar 

  6. Bunchman TE, McBryde KD, Mottes TE, Gardner JJ, Maxvold NJ, Brophy PD. Pediatric acute renal failure: outcome by modality and disease. Pediatr Nephrol. 2001;16(12):1067–71.

    Article  CAS  PubMed  Google Scholar 

  7. Ronco C, Garzotto F, Brendolan A, Zanella M, Bellettato M, Vedovato S, et al. Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM). Lancet. 2014;383(9931):1807–13.

    Article  PubMed  Google Scholar 

  8. Coulthard MG, Crosier J, Griffiths C, Smith J, Drinnan M, Whitaker M, et al. Haemodialysing babies weighing <8 kg with the Newcastle infant dialysis and ultrafiltration system (Nidus): comparison with peritoneal and conventional haemodialysis. Pediatr Nephrol. 2014;29(10):1873–81.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Goldstein SL, Currier H, Graf C, Cosio CC, Brewer ED, Sachdeva R. Outcome in children receiving continuous venovenous hemofiltration. Pediatrics. 2001;107(6):1309–12.

    Article  CAS  PubMed  Google Scholar 

  10. Symons JM, Chua AN, Somers MJ, Baum MA, Bunchman TE, Benfield MR, et al. Demographic characteristics of pediatric continuous renal replacement therapy: a report of the prospective pediatric continuous renal replacement therapy registry. Clin J Am Soc Nephrol. 2007;2(4):732–8.

    Article  Google Scholar 

  11. Gillespie RS, Seidel K, Symons JM. Effect of fluid overload and dose of replacement fluid on survival in hemofiltration. Pediatr Nephrol. 2004;19(12):1394–9.

    Article  PubMed  Google Scholar 

  12. Foland JA, Fortenberry JD, Warshaw BL, Pettignano R, Merritt RK, Heard ML, et al. Fluid overload before continuous hemofiltration and survival in critically ill children: a retrospective analysis. Crit Care Med. 2004;32(8):1771–6.

    Article  PubMed  Google Scholar 

  13. Goldstein SL, Somers MJ, Brophy PD, Bunchman TE, Baum M, Blowey D, et al. The prospective pediatric continuous renal replacement therapy (ppCRRT) registry: design, development and data assessed. Int J Artif Organs. 2004;27(1):9–14.

    Article  CAS  PubMed  Google Scholar 

  14. Kellum JA, Angus DC. Patients are dying of acute renal failure. Crit Care Med. 2002;30(9):2156–7.

    Article  PubMed  Google Scholar 

  15. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16(11):3365–70.

    Article  PubMed  Google Scholar 

  16. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the acute Dialysis quality initiative (ADQI) group. Crit Care. 2004;8(4):R204–12.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 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):1–138.

    Google Scholar 

  19. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294(7):813–8.

    Article  CAS  PubMed  Google Scholar 

  20. Hui-Stickle S, Brewer ED, Goldstein SL. Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001. Am J Kidney Dis. 2005;45(1):96–101.

    Article  Google Scholar 

  21. Vachvanichsanong P, Dissaneewate P, Lim A, McNeil E. Childhood acute renal failure: 22-year experience in a university hospital in southern Thailand. Pediatrics. 2006;118(3):e786–91.

    Article  PubMed  Google Scholar 

  22. Moghal NE, Brocklebank JT, Meadow SR. A review of acute renal failure in children: incidence, etiology and outcome. Clin Nephrol. 1998;49(2):91–5.

    PubMed  CAS  Google Scholar 

  23. 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):1028–35.

    Article  CAS  Google Scholar 

  24. Plotz FB, Bouma AB, van Wijk JA, Kneyber MC, Bokenkamp A. Pediatric acute kidney injury in the ICU: an independent evaluation of pRIFLE criteria. Intensive Care Med. 2008;34(9):1713–7.

    Article  PubMed  Google Scholar 

  25. Slater MB, Anand V, Uleryk EM, Parshuram CS. A systematic review of RIFLE criteria in children, and its application and association with measures of mortality and morbidity. Kidney Int. 2012;81(8):791–8.

    Article  PubMed  Google Scholar 

  26. Basu RK, Kaddourah A, Terrell T, Mottes T, Arnold P, Jacobs J, et al. Assessment of worldwide acute kidney injury, renal angina and epidemiology in critically ill children (AWARE): study protocol for a prospective observational study. BMC Nephrol. 2015;16:24.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, Investigators A. Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med. 2017;376(1):11–20.

    Article  PubMed  Google Scholar 

  28. 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(2):265–74.

    Article  PubMed  Google Scholar 

  29. Jetton JG, Guillet R, Askenazi DJ, Dill L, Jacobs J, Kent AL, et al. Assessment of worldwide acute kidney injury epidemiology in neonates: design of a Retrospective Cohort Study. Front Pediatr. 2016;4:68.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jetton JG, Boohaker LJ, Sethi SK, Wazir S, Rohatgi S, Soranno DE, et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health. 2017;1(3):184–94.

    Article  PubMed  Google Scholar 

  31. Blinder JJ, Goldstein SL, Lee VV, Baycroft A, Fraser CD, Nelson D, et al. Congenital heart surgery in infants: effects of acute kidney injury on outcomes. J Thorac Cardiovasc Surg. 2012;143(2):368–74.

    Article  PubMed  Google Scholar 

  32. Chiravuri SD, Riegger LQ, Christensen R, Butler RR, Malviya S, Tait AR, et al. Factors associated with acute kidney injury or failure in children undergoing cardiopulmonary bypass: a case-controlled study. Paediatr Anaesth. 2011;21(8):880–6.

    Article  PubMed  Google Scholar 

  33. Toth R, Breuer T, Cserep Z, Lex D, Fazekas L, Sapi E, et al. Acute kidney injury is associated with higher morbidity and resource utilization in pediatric patients undergoing heart surgery. Ann Thorac Surg. 2012;93(6):1984–90.

    Article  PubMed  Google Scholar 

  34. Zarbock A, Kellum JA, Schmidt C, Van Aken H, Wempe C, Pavenstadt H, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA. 2016;315(20):2190–9.

    Article  CAS  PubMed  Google Scholar 

  35. Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122–33.

    Article  PubMed  Google Scholar 

  36. Krawczeski CD, Goldstein SL, Woo JG, Wang Y, Piyaphanee N, Ma Q, et al. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;58(22):2301–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kwiatkowski DM, Menon S, Krawczeski CD, Goldstein SL, Morales DL, Phillips A, et al. Improved outcomes with peritoneal dialysis catheter placement after cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg. 2015;149(1):230–6.

    Article  PubMed  Google Scholar 

  38. Kwiatkowski DM, Goldstein SL, Cooper DS, Nelson DP, Morales DL, Krawczeski CD. Peritoneal Dialysis vs furosemide for prevention of fluid overload in infants after cardiac surgery: a randomized clinical trial. JAMA Pediatr. 2017;171(4):357–64.

    Article  PubMed  Google Scholar 

  39. Menon S, Goldstein SL, Mottes T, Fei L, Kaddourah A, Terrell T, et al. Urinary biomarker incorporation into the renal angina index early in intensive care unit admission optimizes acute kidney injury prediction in critically ill children: a prospective cohort study. Nephrol Dial Transplant. 2016;31(4):586–94.

    Article  CAS  PubMed  Google Scholar 

  40. Basu RK, Wang Y, Wong HR, Chawla LS, Wheeler DS, Goldstein SL. Incorporation of biomarkers with the renal angina index for prediction of severe AKI in critically ill children. Clin J Am Soc Nephrol. 2014;9(4):654–62.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005;365(9466):1231–8.

    Article  CAS  Google Scholar 

  42. Basu RK, Wong HR, Krawczeski CD, Wheeler DS, Manning PB, Chawla LS, et al. Combining functional and tubular damage biomarkers improves diagnostic precision for acute kidney injury after cardiac surgery. J Am Coll Cardiol. 2014;64(25):2753–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43(11):1551–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stuart L. Goldstein .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Goldstein, S.L. (2018). The Evolution of Acute Kidney Injury Research Over the Past Two Decades. In: Deep, A., Goldstein, S. (eds) Critical Care Nephrology and Renal Replacement Therapy in Children. Springer, Cham. https://doi.org/10.1007/978-3-319-90281-4_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90281-4_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90280-7

  • Online ISBN: 978-3-319-90281-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics