Acute Kidney Injury in Premature, Very Low-Birth-Weight Infants

Abstract

The epidemiology of neonatal acute kidney injury (AKI) is not well established, partly due to lack of a consensus definition. Preterm neonates are likely especially vulnerable to AKI. We performed a retrospective review to assess the incidence of and risk factors for AKI in very low-birth-weight (VLBW), premature infants admitted to a level 4 NICU (2006–2007). AKI was classified using a standardized definition based on changes in serum creatinine (SCr). AKI incidence varied inversely with gestational age (GA): 65% (22–25 weeks), 25% (26–28 weeks), 9% (29–32 weeks) as did severity (p < 0.001). Stage 1 AKI was most common in each cohort. Stages 2 and 3 AKI comprised approximately 60% of AKI in the 22- to 25-week cohort but 20% or less in the older cohorts. By univariate analysis, factors associated with AKI included younger GA, lower BW, lower Apgar scores, hypotension, more frequent treatment with nephrotoxic antimicrobials, longer-duration mechanical ventilation, and higher incidence of patent ductus arteriosus (PDA) requiring treatment. By multiple logistic regression analysis, only GA, hypotension, PDA, and longer duration of mechanical ventilation were independently associated with AKI. AKI was not independently associated with risk of death. Our study suggests that small increases (≥ 0.3 mg/dL) in SCr occur frequently in premature, VLBW infants, and are associated with increased morbidity but not mortality. AKI incidence and severity were highest in the youngest GA cohort. Understanding the epidemiology, risk factors, and impact of neonatal AKI is crucial as long-term premature infant survival continues to improve.

Keywords

neonatal acute kidney injury - creatinine - patent ductus arteriosus

• References

• 1 Bucaloiu ID, Kirchner HL, Norfolk ER, Hartle II JE, Perkins RM. Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 2012; 81 (5) 477-485
• 2 Jones J, Holmen J, De Graauw J, Jovanovich A, Thornton S, Chonchol M. Association of complete recovery from acute kidney injury with incident CKD stage 3 and all-cause mortality. Am J Kidney Dis 2012; 60 (3) 402-408
• 3 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 (4) 523-530
• 4 Viaud M, Llanas B, Harambat J. Renal outcome in long-term survivors from severe acute kidney injury in childhood. Pediatr Nephrol 2012; 27 (1) 151-152 , author reply 153
• 5 Goldstein SL, Devarajan P. Acute kidney injury in childhood: should we be worried about progression to CKD?. Pediatr Nephrol 2011; 26 (4) 509-522
• 6 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 2014; 165 (3) 522-7.e2
• 7 Stapleton FB, Jones DP, Green RS. Acute renal failure in neonates: incidence, etiology and outcome. Pediatr Nephrol 1987; 1 (3) 314-320
• 8 Kellum JA, Lameire N. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO Summary (Part 1). Critical Care 2013; 17: 204
• 9 Selewski DT, Cornell TT, Heung M , et al. Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population. Intensive Care Med 2014; 40 (10) 1481-1488
• 10 Jetton JG, Askenazi DJ. Update on acute kidney injury in the neonate. Curr Opin Pediatr 2012; 24 (2) 191-196
• 11 Askenazi DJ, Ambalavanan N, Hamilton K , et al. Acute kidney injury and renal replacement therapy independently predict mortality in neonatal and pediatric noncardiac patients on extracorporeal membrane oxygenation. Pediatr Crit Care Med 2011; 12 (1) e1-e6
• 12 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 (4) 354-358
• 13 Blinder JJ, Goldstein SL, Lee VV , et al. Congenital heart surgery in infants: effects of acute kidney injury on outcomes. J Thorac Cardiovasc Surg 2012; 143 (2) 368-374
• 14 Gadepalli SK, Selewski DT, Drongowski RA, Mychaliska GB. Acute kidney injury in congenital diaphragmatic hernia requiring extracorporeal life support: an insidious problem. J Pediatr Surg 2011; 46 (4) 630-635
• 15 Shuhaiber J, Thiagarajan RR, Laussen PC, Fynn-Thompson F, del Nido P, Pigula F. Survival of children requiring repeat extracorporeal membrane oxygenation after congenital heart surgery. Ann Thorac Surg 2011; 91 (6) 1949-1955
• 16 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
• 17 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) 3365-3370
• 18 Schwartz GJ, Feld LG, Langford DJ. A simple estimate of glomerular filtration rate in full-term infants during the first year of life. J Pediatr 1984; 104 (6) 849-854
• 19 Gallini F, Maggio L, Romagnoli C, Marrocco G, Tortorolo G. Progression of renal function in preterm neonates with gestational age < or = 32 weeks. Pediatr Nephrol 2000; 15 (1–2) 119-124
• 20 Miall LS, Henderson MJ, Turner AJ , et al. Plasma creatinine rises dramatically in the first 48 hours of life in preterm infants. Pediatrics 1999; 104 (6) e76
• 21 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 (2) R31
• 22 Stevens LA, Levey AS. Measured GFR as a confirmatory test for estimated GFR. J Am Soc Nephrol 2009; 20 (11) 2305-2313
• 23 Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987; 34 (3) 571-590
• 24 Schwartz GJ, Muñoz A, Schneider MF , et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20 (3) 629-637
• 25 Schwartz GJ. Height: the missing link in estimating glomerular filtration rate in children and adolescents. Nephrol Dial Transplant 2014; 29 (5) 944-947
• 26 Myers GL, Miller WG, Coresh J , et al; National Kidney Disease Education Program Laboratory Working Group. Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program. Clin Chem 2006; 52 (1) 5-18
• 27 Schwartz GJ, Kwong T, Erway B , et al. Validation of creatinine assays utilizing HPLC and IDMS traceable standards in sera of children. Pediatr Nephrol 2009; 24 (1) 113-119
• 28 Rodríguez MM, Gómez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 2004; 7 (1) 17-25
• 29 Sutherland MR, Gubhaju L, Moore L , et al. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J Am Soc Nephrol 2011; 22 (7) 1365-1374
• 30 White SL, Perkovic V, Cass A , et al. Is low birth weight an antecedent of CKD in later life? A systematic review of observational studies. Am J Kidney Dis 2009; 54 (2) 248-261
• 31 Grams ME, Matsushita K, Sang Y , et al. Explaining the racial difference in AKI incidence. J Am Soc Nephrol 2014; 25 (8) 1834-1841
• 32 Butler-O'Hara M, D'Angio CT. Risk of persistent renal insufficiency in premature infants following the prenatal use of indomethacin for suppression of preterm labor. J Perinatol 2002; 22 (7) 541-546
• 33 Askenazi DJ, Griffin R, McGwin G, Carlo W, Ambalavanan N. Acute kidney injury is independently associated with mortality in very low birthweight infants: a matched case-control analysis. Pediatr Nephrol 2009; 24 (5) 991-997