Pediatric medicine is growing in complexity and an increasing number of children with co-morbidities are exposed to potential renal damage. Initially ill-defined and thought to be mostly a transient phenomenon in children, acute kidney injury (AKI) has now emerged as a complex clinical syndrome independently associated with increased mortality and morbidity, including the development of chronic renal sequelae. Recent advances in molecular nephrology have better elucidated the early phase of AKI, where evidence of renal tissue damage is associated with adverse outcomes even without decrease in glomerular filtration rate, illustrating the flaws of the old paradigm based solely on an insensitive filtration marker, the serum creatinine. Prevention, prompt evaluation and early interventions are of essence to decrease AKI incidence and severity. Emerging data reveal that AKI is commonly encountered in hospitalized children, especially critically ill ones, hence the importance for all clinicians to be able to identify high risk patients, recognize AKI early and be comfortable with the initial medical management. In recent years, significant advances have been made in AKI definition and prediction, allowing early preventive measures in high risk children that are now proven to reduce AKI incidence. This review covers recent advances in the diagnosis, risk stratification, prevention and management of AKI in children.
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Sutherland SM, Ji J, Sheikhi FH, et al. AKI in hospitalized children: epidemiology and clinical associations in a national cohort. Clin J Am Soc Nephrol. 2013;8:1661–9.
Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL. Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med [Internet]. 2017;376:11–20. Available at: http://www.nejm.org/doi/10.1056/NEJMoa1611391.
McGregor TL, Jones DP, Wang L, et al. Acute kidney injury incidence in noncritically ill hospitalized children, adolescents, and young adults: a retrospective observational study. Am J Kidney Dis. 2016;67:384–90.
Lameire N, Van Biesen W, Vanholder R. Epidemiology of acute kidney injury in children worldwide, including developing countries. Pediatr Nephrol. 2017;32:1301–14.
Kwiatkowski DM, Sutherland SM. Acute kidney injury in pediatric patients. Best Pract Res Clin Anaesthesiol [Internet]. 2017;31:427–39. Available at:. https://doi.org/10.1016/j.bpa.2017.08.007.
Chawla LS, Bellomo R, Bihorac A, et al. Acute kidney disease and renal recovery: consensus report of the acute disease quality initiative (ADQI) 16 workgroup. Nat Rev Nephrol [Internet]. 2017;13:241–57. Available at: https://doi.org/10.1038/nrneph.2017.2.
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 [Internet]. 2012;59:523–30. Available at:. https://doi.org/10.1053/j.ajkd.2011.10.048.
Madsen NL, Goldstein SL, Frøslev T, Christiansen CF, Olsen M. Cardiac surgery in patients with congenital heart disease is associated with acute kidney injury and the risk of chronic kidney disease. Kidney Int [Internet]. 2017;92:751–6. Available at:. https://doi.org/10.1016/j.kint.2017.02.021.
Menon S, Kirkendall ES, Nguyen H, Goldstein SL. Acute kidney injury associated with high nephrotoxic medication exposure leads to chronic kidney disease after 6 months. J Pediatr [Internet]. 2014;165:522–7.e2. Available at:. https://doi.org/10.1016/j.jpeds.2014.04.058.
Kidney Disease: Improving Global Outcome (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guidelines for acute kidney injury. Kidney Int Suppl [Internet]. 2012;2:138. Available at: https://linkinghub.elsevier.com/retrieve/pii/S2157171615310406.
Kellum J, Sileanu F, Murugan R, Lucko N, Shaw A, Clermont G. Classifying AKI by urine output versus serum creatinine level. J Am Soc Nephrol. 2015;26:2231–8.
Hoste L, Dubourg L, Selistre L, et al. A new equation to estimate the glomerular filtration rate in children, adolescents and young adults. Nephrol Dial Transplant [Internet]. 2014;29:1082–91. Available at: https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gft277.
Roy J-P, Johnson C, Towne B, et al. Use of height-independent baseline creatinine imputation method with renal angina index. Pediatr Nephrol [Internet]. 2019. Available at: http://link.springer.com/10.1007/s00467-019-04294-8.
Hessey E, Ali R, Dorais M, et al. Evaluation of height-dependent and height-independent methods of estimating baseline serum creatinine in critically ill children. Pediatr Nephrol. 2017;32:1953–62.
Basu RK, Kaddourah A, Goldstein SL, et al. Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study. Lancet Child Adolesc Heal [Internet]. 2017;4642:1–9. Available at: http://linkinghub.elsevier.com/retrieve/pii/S2352464217301815.
Desanti De Oliveira B, Xu K, Shen TH, et al. Molecular nephrology: types of acute tubular injury. Nat Rev Nephrol 2019; in press.
Perazella MA, Coca SG. Traditional urinary biomarkers in the assessment of hospital-acquired AKI. Clin J Am Soc Nephrol. 2012;7:167–74.
Ishizaki Y, Isozaki-Fukuda Y, Kojima T, Sasai M, Matsuzaki S, Kobayashi Y. Evaluation of diagnostic criteria of acute renal failure in premature infants. Acta Paediatr Jpn Overseas Ed Australia. 1993;35:311–5.
Goldstein SL, Mottes T, Simpson K, et al. A sustained quality improvement program reduces nephrotoxic medication-associated acute kidney injury. Kidney Int [Internet]. 2016;90:212–21. Available at: https://doi.org/10.1016/j.kint.2016.03.031.
Moffett BS, Goldstein SL. Acute kidney injury and increasing nephrotoxic-medication exposure in noncritically-ill children. Clin J Am Soc Nephrol. 2011;6:856–63.
Filho LT, Grande AJ, Colonetti T, Della ÉSP, da Rosa MI. Accuracy of neutrophil gelatinase-associated lipocalin for acute kidney injury diagnosis in children: systematic review and meta-analysis. Pediatr Nephrol. 2017;32:1979–88.
Su LJ, Li YM, Kellum JA, Peng ZY. Predictive value of cell cycle arrest biomarkers for cardiac surgery-associated acute kidney injury: a meta-analysis. Br J Anaesth. 2018;121:350–7.
Rossaint J, Schmidt C, Stege D, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury after pediatric cardiac surgery. PLoS One. 2014;9:e110865.
Griffin BR, Gist KM, Faubel S. Current status of novel biomarkers for the diagnosis of acute kidney injury: a historical perspective. J Intensive Care Med [Internet]. 2019;088506661882453. Available at: http://www.ncbi.nlm.nih.gov/pubmed/30654681%0A http://journals.sagepub.com/doi/10.1177/0885066618824531.
Levey AS, Inker LA. Assessment of glomerular filtration rate in health and disease: a state of the art review. Clin Pharmacol Ther. 2017;102:405–19.
Basu RK, Zappitelli M, Brunner L, et al. Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Kidney Int. 2013;85:659–67.
Cruz DN, Ferrer-Nadal A, Piccinni P, et al. Utilization of small changes in serum creatinine with clinical risk factors to assess the risk of AKI in critically lll adults. Clin J Am Soc Nephrol [Internet]. 2014;9:663–72. Available at: http://cjasn.asnjournals.org/cgi/doi/10.2215/CJN.05190513.
Menon S, Goldstein SL, Mottes 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;31:586–94.
Chawla LS, Davison DL, Brasha-Mitchell E, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care [Internet]. 2013;17:R207. Available at: http://ccforum.com/content/17/5/R207.
Lumlertgul N, Peerapornratana S, Trakarnvanich T, et al. Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial). Crit Care. 2018;22:1–9.
Penk J, Gist KM, Wald EL, et al. Furosemide response predicts acute kidney injury in children after cardiac surgery. J Thorac Cardiovasc Surg. 2019;157:2444–51.
Göcze I, Jauch D, Götz M, et al. Biomarker-guided intervention to prevent acute kidney injury after major surgery. Ann Surg. 2018;267:1013–20.
Downes KJ, Cowden C, Laskin BL, et al. Association of acute kidney injury with concomitant vancomycin and piperacillin/tazobactam treatment among hospitalized children. JAMA Pediatr [Internet]. 2017;19146:e173219. Available at: http://jamanetwork.com/journals/jamapediatrics/fullarticle/2654886.
Petejova N, Martinek A, Zadrazil J, Teplan V. Acute toxic kidney injury. Ren Fail [Internet]. 2019;41:576–94. Available at: https://doi.org/10.1080/0886022X.2019.1628780.
Jones GL, Will A, Jackson GH, Webb NJA, Rule S, Committee B. Guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2015;169:661–71.
Michelsen J, Cordtz J, Liboriussen L, et al. Prevention of rhabdomyolysis-induced acute kidney injury – a DASAIM/DSIT clinical practice guideline. Acta Anaesthesiol Scand. 2019;63:576–86.
Hammond DA, Lam SW, Rech MA, et al. Balanced crystalloids versus saline in critically ill adults: a systematic review and meta-analysis. Ann Pharmacother. 2019;1060028019866420.
Semler MW, Self WH, Rice TW. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018;378:1951.
Self WH, Semler MW, Wanderer JP, et al. Balanced crystalloids versus saline in noncritically ill adults. N Engl J Med. 2018;378:819–28.
Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Engl J Med. 2018;378:603–14.
Devarajan P. Prevention and management of acute kidney injury (acute renal failure) in children [Internet]. UpToDate. 2019. Available at: https://www.uptodate.com. Accessed 1st Aug 2019.
Pierce B, Bole I, Patel V, Brown DL. Clinical outcomes of remote ischemic preconditioning prior to cardiac surgery: a meta-analysis of randomized controlled trials. J Am Heart Assoc. 2017;6:1–14.
Zarbock A, Kellum JA, Van Aken H, et al. Long-term effects of remote ischemic preconditioning on kidney function in high-risk cardiac surgery patients: follow-up results from the renalRIP trial. Anesthesiology. 2017;126:787–98.
Xia T, Li Z, Zhou Y, et al. Remote ischemic preconditioning upregulates microRNA-21 to protect the kidney in children with congenital heart disease undergoing cardiopulmonary bypass. Pediatr Nephrol. 2017;33:911–9.
Raina R, Sethi SK, Wadhwani N, Vemuganti M, Krishnappa V, Bansal SB. Fluid overload in critically ill children. Front Pediatr [Internet]. 2018;6:306. Available at: https://www.frontiersin.org/article/10.3389/fped.2018.00306/full.
Sethi SK, Maxvold N, Bunchman T, Jha P, Kher V, Raina R. Nutritional management in the critically ill child with acute kidney injury : a review. Pediatr Nephrol. 2017;32:589–601.
Conflict of Interest
Dr. Devarajan is a co-inventor on submitted patents for the use of NGAL as a biomarker for kidney injury.
Source of Funding
Work quoted in this review that was completed in the authors’ laboratory was funded by grants fromthe NIH(P50DK096418).
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Roy, JP., Devarajan, P. Acute Kidney Injury: Diagnosis and Management. Indian J Pediatr 87, 600–607 (2020). https://doi.org/10.1007/s12098-019-03096-y
- Acute kidney injury
- Acute renal failure
- Renal angina