Abstract
Acute kidney injury (AKI) is characterized clinically as an abrupt decline in renal function marked by reduced excretion of waste products, disordered electrolytes, and disrupted fluid homeostasis. The recent development of a standardized AKI definition has transformed our understanding of AKI epidemiology and outcomes. We now know that in the short term, children with AKI experience greater morbidity and mortality; additionally, observational studies have established that chronic renal sequelae are far more common after AKI events than previously realized. Many of these studies suggest that patients who develop AKI are at greater risk for the subsequent development of chronic kidney disease (CKD). The goal of this review is to critically evaluate the data regarding the association between AKI and CKD in children. Additionally, we describe best practice approaches for future studies, including the use of consensus AKI criteria, the application of rigorous definitions for CKD and renal sequelae, and the inclusion of non-AKI comparator groups. Finally, based upon existing data, we suggest an archetypal approach to follow-up care for the AKI survivors who may be at greater CKD risk, including children with more severe AKI, those who endure repeated AKI episodes, patients who do not experience full recovery, and those with pre-existing CKD.
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References
Sutherland SM, Byrnes JJ, Kothari M, Longhurst CA, Dutta S, Garcia P, Goldstein SL (2015) AKI in hospitalized children: comparing the pRIFLE, AKIN, and KDIGO definitions. Clin J Am Soc Nephrol 10:554–561
Hui-Stickle S, Brewer ED, Goldstein SL (2005) Pediatric ARF epidemiology at a tertiary care center from 1999 to 2001. Am J Kidney Dis 45:96–101
Williams DM, Sreedhar SS, Mickell JJ, Chan JC (2002) Acute kidney failure: a pediatric experience over 20 years. Arch Pediatr Adolesc Med 156:893–900
Goldstein SL (2011) Acute kidney injury in children: prevention, treatment and rehabilitation. Contrib Nephrol 174:163–172
McGregor TL, Jones DP, Wang L, Danciu I, Bridges BC, Fleming GM, Shirey-Rice J, Chen L, Byrne DW, Van Driest SL (2016) Acute kidney injury incidence in noncritically ill hospitalized children, adolescents, and young adults: a retrospective observational study. Am J Kidney Dis 67:384–390
Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL, Investigators AWARE (2017) Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med 376:11–20
Sutherland SM (2013) AKI in hospitalized children: epidemiology and clinical associations in a national cohort. J Pediatr 8:1661–1669
Alkandari O, Eddington KA, Hyder A, Gauvin F, Ducruet T, Gottesman R, Phan V, Zappitelli M (2011) Acute kidney injury is an independent risk factor for pediatric intensive care unit mortality, longer length of stay and prolonged mechanical ventilation in critically ill children: a two-center retrospective cohort study. Crit Care 15:R146
Chawla LS, Eggers PW, Star RA, Kimmel PL (2014) Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 371:58–66
Chawla LS, Amdur RL, Amodeo S, Kimmel PL, Palant CE (2011) The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 79:1361–1369
Coca SG, Singanamala S, Parikh CR (2012) Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis. Kidney Int 81:442–448
Hsu CY, Hsu RK, Yang J, Ordonez JD, Zheng S, Go AS (2016) Elevated BP after AKI. J Am Soc Nephrol 27:914–923
Mammen C, Al Abbas A, Skippen P, Nadel H, Levine D, Collet JP, Matsell DG (2012) 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 59:523–530
Askenazi DJ, Feig DI, Graham NM, Hui-Stickle S, Goldstein SL (2006) 3-5 year longitudinal follow-up of pediatric patients after acute renal failure. Kidney Int 69:184–189
Menon S, Kirkendall ES, Nguyen H, Goldstein SL (2014) Acute kidney injury associated with high nephrotoxic medication exposure leads to chronic kidney disease after 6 months. J Pediatr 165:522–527
Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, Kurella Tamura M, Feldman HI (2014) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis 63:713–735
Stevens PE, Levin A (2013) Kidney disease: improving global outcomes chronic kidney disease guideline development work group members. Ann Intern Med 158:825–830
Greenberg JH, Zappitelli M, Devarajan P, Thiessen-Philbrook HR, Krawczeski C, Li S, Garg AX, Coca S, Parikh CR, TRIBE-AKI Consortium (2016) Kidney outcomes 5 years after Pediatric cardiac surgery: the TRIBE-AKI study. JAMA Pediatr 170:1071–1078
Goldstein SL, Jaber BL, Faubel S, Chawla LS, Acute Kidney Injury Advisory Group of American Society of Nephrology (2013) AKI transition of care: a potential opportunity to detect and prevent CKD. Clin J Am Soc Nephrol 8:476–483
Silver SA, Goldstein SL, Harel Z, Harvey A, Rompies EJ, Adhikari NK, Acedillo R, Jain AK, Richardson R, Chan CT, Chertow GM, Bell CM, Wald R (2015) Ambulatory care after acute kidney injury: an opportunity to improve patient outcomes. Can J Kidney Health Dis 2:36
Hessey E, Ali R, Dorais M, Morissette G, Pizzi M, Rink N, Jouvet P, Lacroix J, Phan V, Zappitelli M (2017) Renal function follow-up and renal recovery after acute kidney injury in critically ill children. Pediatr Crit Care Med 18:733–740
Wong CJ, Moxey-Mims M, Jerry-Fluker J, Warady BA, Furth SL (2012) CKiD (CKD in children) prospective cohort study: a review of current findings. Am J Kidney Dis 60:1002–1011
Chaturvedi S, Ng KH, Mammen C (2017) The path to chronic kidney disease following acute kidney injury: a neonatal perspective. Pediatr Nephrol 32:227–241
Harer MW, Pope CF, Conaway MR, Charlton JR (2017) Follow-up of acute kidney injury in neonates during childhood years (FANCY): a prospective cohort study. Pediatr Nephrol 32:1067–1076
Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL (2015) Neonatal acute kidney injury. Pediatrics 136:e463–e473
Nada A, Bonachea EM, Askenazi DJ (2017) Acute kidney injury in the fetus and neonate. Semin Fetal Neonatal Med 22:90–97
Venkatachalam MA, Weinberg JM, Kriz W, Bidani AK (2015) Failed tubule recovery, AKI-CKD transition, and kidney disease progression. J Am Soc Nephrol 26:1765–1776
Nath KA (1992) Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 20:1–17
Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumar P, Bidani AK (2010) Acute kidney injury: a springboard for progression in chronic kidney disease. Am J Physiol Renal Physiol 298:F1078–F1094
Nath KA, Croatt AJ, Haggard JJ, Grande JP (2000) Renal response to repetitive exposure to heme proteins: chronic injury induced by an acute insult. Kidney Int 57:2423–2433
Basile DP, Donohoe D, Roethe K, Osborn JL (2001) Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. Am J Physiol Renal Physiol 281:F887–F899
Hsu CY (2012) Yes, AKI truly leads to CKD. J Am Soc Nephrol 23:967–969
Polichnowski AJ, Lan R, Geng H, Griffin KA, Venkatachalam MA, Bidani AK (2014) Severe renal mass reduction impairs recovery and promotes fibrosis after AKI. J Am Soc Nephrol 25:1496–1507
Basile DP, Donohoe DL, Roethe K, Mattson DL (2003) Chronic renal hypoxia after acute ischemic injury: effects of L-arginine on hypoxia and secondary damage. Am J Physiol Renal Physiol 284:F338–F348
Rifkin DE, Coca SG, Kalantar-Zadeh K (2012) Does AKI truly lead to CKD? J Am Soc Nephrol 23:979–984
Ishani A, Xue JL, Himmelfarb J, Eggers PW, Kimmel PL, Molitoris BA, Collins AJ (2009) Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol 20:223–228
Lo LJ, Go AS, Chertow GM, McCulloch CE, Fan D, Ordonez JD, Hsu CY (2009) Dialysis-requiring acute renal failure increases the risk of progressive chronic kidney disease. Kidney Int 76:893–899
Ishani A, Nelson D, Clothier B, Schult T, Nugent S, Greer N, Slinin Y, Ensrud KE (2011) The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med 171:226–233
Thakar CV, Christianson A, Himmelfarb J, Leonard AC (2011) Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus. Clin J Am Soc Nephrol 6:2567–2572
Hsu CY, Chertow GM, McCulloch CE, Fan D, Ordonez JD, Go AS (2009) Nonrecovery of kidney function and death after acute on chronic renal failure. Clin J Am Soc Nephrol 4:891–898
Hsu RK, Hsu CY (2016) The role of acute kidney injury in chronic kidney disease. Semin Nephrol 36:283–292
Hoy WE, White AV, Dowling A, Sharma SK, Bloomfield H, Tipiloura BT, Swanson CE, Mathews JD, McCredie DA (2012) Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life. Kidney Int 81:1026–1032
Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, Salvadori M, Haynes RB, Clark WF (2003) Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA 290:1360–1370
Garg AX, Salvadori M, Okell JM, Thiessen-Philbrook HR, Suri RS, Filler G, Moist L, Matsell D, Clark WF (2008) Albuminuria and estimated GFR 5 years after Escherichia Coli O157 hemolytic uremic syndrome: an update. Am J Kidney Dis 51:435–444
Cooper DS, Claes D, Goldstein SL, Bennett MR, Ma Q, Devarajan P, Krawczeski CD (2016) Follow-up renal assessment of injury long-term after acute kidney injury (FRAIL-AKI). Clin J Am Soc Nephrol 11:21–29
Madsen NL, Goldstein SL, Froslev T, Christiansen CF, Olsen M (2017) Cardiac surgery in patients with congenital heart disease is associated with acute kidney injury and the risk of chronic kidney disease. Kidney Int 92:751–756
Hollander SA, Montez-Rath ME, Axelrod DM, Krawczeski CD, May LJ, Maeda K, Rosenthal DN, Sutherland SM (2016) Recovery from acute kidney injury and CKD following heart transplantation in children, adolescents, and young adults: a retrospective cohort study. Am J Kidney Dis 68:212–218
Mel E, Davidovits M, Dagan O (2014) Long-term follow-up evaluation of renal function in patients treated with peritoneal dialysis after cardiac surgery for correction of congenital anomalies. J Thorac Cardiovasc Surg 147:451–455
Viaud M, Llanas B, Harambat J (2012) Renal outcome in long-term survivors from severe acute kidney injury in childhood. Pediatr Nephrol 27:151–152. Author reply 153
Hoffmeister PA, Hingorani SR, Storer BE, Baker KS, Sanders JE (2010) Hypertension in long-term survivors of pediatric hematopoietic cell transplantation. Biol Blood Marrow Transplant 16:515–524
Buysse CM, Raat H, Hazelzet JA, Hulst JM, Cransberg K, Hop WC, Vermunt LC, Utens EM, Maliepaard M, Joosten KF (2008) Long-term health status in childhood survivors of meningococcal septic shock. Arch Pediatr Adolesc Med 162:1036–1041
Hingorani S, Guthrie KA, Schoch G, Weiss NS, McDonald GB (2007) Chronic kidney disease in long-term survivors of hematopoietic cell transplant. Bone Marrow Transplant 39:223–229
Slack R, Hawkins KC, Gilhooley L, Addison GM, Lewis MA, Webb NJ (2005) Long-term outcome of meningococcal sepsis-associated acute renal failure. Pediatr Crit Care Med 6:477–479
Shaw NJ, Brocklebank JT, Dickinson DF, Wilson N, Walker DR (1991) Long-term outcome for children with acute renal failure following cardiac surgery. Int J Cardiol 31:161–165
Georgaki-Angelaki HN, Steed DB, Chantler C, Haycock GB (1989) Renal function following acute renal failure in childhood: a long term follow-up study. Kidney Int 35:84–89
Kist-van Holthe JE, Bresters D, Ahmed-Ousenkova YM, Goedvolk CA, Abbink FC, Wolterbeek R, Bredius RG, Pauwels EK, van der Heijden AJ (2005) Long-term renal function after hemopoietic stem cell transplantation in children. Bone Marrow Transplant 36:605–610
Greenberg JH, Coca S, Parikh CR (2014) Long-term risk of chronic kidney disease and mortality in children after acute kidney injury: a systematic review. BMC Nephrol 15:184
Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2:1–138
Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM, Subcommittee On Screening and Management Of High Blood Pressure In Children (2017) Clinical practice guideline for screening and Management of High Blood Pressure in children and adolescents. Pediatrics 140(3). https://doi.org/10.1542/peds.2017-3035
Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr (2017) 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and Management of High Blood Pressure in adults: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Hypertension. https://doi.org/10.1161/HYP.0000000000000065
Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL (2007) Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int 71:1028–1035
National Center for Biotechnology Information, U.S. National Library of Medicine (2013) Chapter 1: definition and classification of CKD. Kidney Int Suppl 3(2011):19–62
Brady TM, Schneider MF, Flynn JT, Cox C, Samuels J, Saland J, White CT, Furth S, Warady BA, Mitsnefes M (2012) Carotid intima-media thickness in children with CKD: results from the CKiD study. Clin J Am Soc Nephrol 7:1930–1937
Gerson AC, Wentz A, Abraham AG, Mendley SR, Hooper SR, Butler RW, Gipson DS, Lande MB, Shinnar S, Moxey-Mims MM, Warady BA, Furth SL (2010) Health-related quality of life of children with mild to moderate chronic kidney disease. Pediatrics 125:e349–e357
Hooper SR, Gerson AC, Butler RW, Gipson DS, Mendley SR, Lande MB, Shinnar S, Wentz A, Matheson M, Cox C, Furth SL, Warady BA (2011) Neurocognitive functioning of children and adolescents with mild-to-moderate chronic kidney disease. Clin J Am Soc Nephrol 6:1824–1830
Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2006) Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study. J Pediatr 149:671–675
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1, False; 2, c; 3, d; 4, a; 5, e
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Sigurjonsdottir, V.K., Chaturvedi, S., Mammen, C. et al. Pediatric acute kidney injury and the subsequent risk for chronic kidney disease: is there cause for alarm?. Pediatr Nephrol 33, 2047–2055 (2018). https://doi.org/10.1007/s00467-017-3870-6
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DOI: https://doi.org/10.1007/s00467-017-3870-6