Top

Published in:

18-10-2021 | Acute Kidney Injury | Original Article

Low albumin levels are independently associated with neonatal acute kidney injury: a report from AWAKEN Study Group

Authors: Arwa Nada, David Askenazi, Juan C. Kupferman, Maroun Mhanna, John D. Mahan, Louis Boohaker, Linzi Li, Russell L. Griffin, the AWAKEN Collaborative

Published in: Pediatric Nephrology | Issue 7/2022

Abstract

Background

Data from adult and pediatric literature have shown an association between albumin levels and AKI. Whether hypoalbuminemia and neonatal AKI are associated has not been studied.

Methods

We evaluated the association of albumin with early (during the first postnatal week) and late (after the first postnatal week) AKI for 531 neonates from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database and for 3 gestational age (GA) subgroups: < 29, 29 to < 36, and ≥ 36 weeks GA.

Results

Low albumin levels were associated with increased odds of neonatal AKI; for every 0.1 g/dL decrease in albumin, the odds of late AKI increased by 12% on continuous analysis. After adjustment for potential confounders, neonates with albumin values in the lowest quartiles (< 2.2 g/dL) had an increased odds of early [Adjusted Odd Ratio (AdjOR) 2.5, 95% CI = 1.1–5.3, p < 0.03] and late AKI [AdjOR 13.4, 95% CI = 3.6–49.9, p < 0.0001] compared to those with albumin in the highest quartile (> 3.1 g/dL). This held true for albumin levels 2.3 to 2.6 g/dL for early [AdjOR 2.5, 95% CI = 1.2–5.5, p < 0.02] and late AKI [AdjOR 6.4, 95% CI = 1.9–21.6, p < 0.01]. Albumin quartiles of (2.7 to 3.0 g/dL) were associated with increased odds of late AKI. Albumin levels of 2.6 g/dL and 2.4 g/dL best predicted early (AUC = 0.59) and late AKI (AUC = 0.64), respectively. Analysis of albumin association with AKI by GA is described.

Conclusions

Low albumin levels are independently associated with early and late neonatal AKI. Albumin could be a potential modifiable risk factor for neonatal AKI.

Jetton JG, Guillet R, Askenazi DJ, Dill L, Jacobs J, Kent AL et al (2016) Assessment of worldwide acute kidney injury epidemiology in neonates: design of a retrospective cohort study. Front Pediatr 4:68PubMedPubMedCentralCrossRef

Askenazi DJ, Koralkar R, Hundley HE, Montesanti A, Patil N, Ambalavanan N (2013) Fluid overload and mortality are associated with acute kidney injury in sick near-term/term neonate. Pediatr Nephrol 28:661–666PubMedCrossRef

Bolat F, Comert S, Bolat G, Kucuk O, Can E, Bulbul A et al (2013) Acute kidney injury in a single neonatal intensive care unit in Turkey. World J Pediatr 9:323–329PubMedCrossRef

Cataldi L, Leone R, Moretti U, De Mitri B, Fanos V, Ruggeri L et al (2005) Potential risk factors for the development of acute renal failure in preterm newborn infants: a case-control study. Arch Dis Child Fetal Neonatal Ed 90:F514-519PubMedPubMedCentralCrossRef

Cuzzolin L, Fanos V, Pinna B, di Marzio M, Perin M, Tramontozzi P et al (2006) Postnatal renal function in preterm newborns: a role of diseases, drugs and therapeutic interventions. Pediatr Nephrol 21:931–938PubMedCrossRef

Koralkar R, Ambalavanan N, Levitan EB, McGwin G, Goldstein S, Askenazi D (2011) Acute kidney injury reduces survival in very low birth weight infants. Pediatr Res 69:354–358PubMedCrossRef

Selewski DT, Jordan BK, Askenazi DJ, Dechert RE, Sarkar S (2013) Acute kidney injury in asphyxiated newborns treated with therapeutic hypothermia. J Pediatr 162:725–729PubMedCrossRef

Selewski DT, Akcan-Arikan A, Bonachea EM, Gist KM, Goldstein SL, Hanna M et al (2019) The impact of fluid balance on outcomes in critically ill near-term/term neonates: a report from the AWAKEN study group. Pediatr Res 85:79–85PubMedCrossRef

Jetton JG, Boohaker LJ, Sethi SK, Wazir S, Rohatgi S, Soranno DE et al (2017) Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health 1:184–194PubMedPubMedCentralCrossRef

10.

Charlton JR, Boohaker L, Askenazi D, Brophy PD, Fuloria M, Gien J et al (2019) Late onset neonatal acute kidney injury: results from the AWAKEN Study. Pediatr Res 85:339–348PubMedCrossRef

11.

Charlton JR, Boohaker L, Askenazi D, Brophy P, D’Angio C, Fuloria M, Gien J, Griffin R, Hingorani S, Ingraham S, Mian A, Ohls R, Rastogi S, Rhee C, Revenis M, Sarkar S, Smith A, Starr M, Kent A, Neonatal Kidney Collaborative (NKC) (2019) Incidence and risk factors of early onset neonatal AKI. Clin J Am Soc Nephrol 14:184–195PubMedPubMedCentralCrossRef

12.

Iacobelli S, Bonsante F, Lacoutiere C, Ferdynus C, Cottenet J, Binquet C et al (2012) Hypoproteinemia on the first day of life and adverse outcome in very preterm infants admitted to the neonatal intensive care unit. J Perinatol 32:520–524PubMedCrossRef

13.

Iacobelli S, Bonsante F, Quantin C, Robillard PY, Binquet C, Gouyon JB (2013) Total plasma protein in very preterm babies: prognostic value and comparison with illness severity scores. PLoS ONE 8:e62210PubMedPubMedCentralCrossRef

14.

Atkinson SDTD, Tunell WP (1989) Hypoalbuminemia may predispose infants to necrotizing enterocolitis. J Pediatr Surg 24:674–676PubMedCrossRef

15.

Torer B, Hanta D, Yapakci E, Gokmen Z, Parlakgumus A, Gulcan H et al (2016) Association of serum albumin level and mortality in premature infants. J Clin Lab Anal 30:867–872PubMedPubMedCentralCrossRef

16.

Shao M, Wang S, Parameswaran PK (2017) Hypoalbuminemia: a risk factor for acute kidney injury development and progression to chronic kidney disease in critically ill patients. Int Urol Nephrol 49:295–302PubMedCrossRef

17.

Giacobbe DR, di Masi A, Leboffe L, Del Bono V, Rossi M, Cappiello D et al (2018) Hypoalbuminemia as a predictor of acute kidney injury during colistin treatment. Sci Rep 8:11968PubMedPubMedCentralCrossRef

18.

Chawla LS, Abell L, Mazhari R, Egan M, Kadambi N, Burke HB et al (2005) Identifying critically ill patients at high risk for developing acute renal failure: a pilot study. Kidney Int 68:2274–2280PubMedCrossRef

19.

Lang J, Scherzer R, Tien PC, Parikh CR, Anastos K, Estrella MM et al (2014) Serum albumin and kidney function decline in HIV-infected women. Am J Kidney Dis 64:584–591PubMedPubMedCentralCrossRef

20.

Wiedermann CJ, Wiedermann W, Joannidis M (2010) Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies. Intensive Care Med 36:1657–1665PubMedPubMedCentralCrossRef

21.

Wiedermann CJ, Wiedermann W, Joannidis M (2017) Causal relationship between hypoalbuminemia and acute kidney injury. World J Nephrol 6:176–187PubMedPubMedCentralCrossRef

22.

Lian D, Guo-Huang H, Meng J, Cheng-Liang Z, Yan-Ying D (2018) Association of hypoalbuminemia with acute kidney injury in children after cardiac surgery. Chin J Contemp Pediatr 20:475–480

23.

Khwaja A (2012) KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract 120:c179-184PubMed

24.

Jetton JG, Askenazi DJ (2014) Acute kidney injury in the neonate. Clin Perinatol 41:487–502PubMedCrossRef

25.

Zappitelli M, Ambalavanan N, Askenazi DJ, Moxey-Mims MM, Kimmel PL, Star RA et al (2017) Developing a neonatal acute kidney injury research definition: a report from the NIDDK neonatal AKI workshop. Pediatr Res 82:569–573PubMedCrossRef

26.

Nada A, Askenazi D, Boohaker LJ, Li L, Mahan JD, Charlton J et al (2021) Low hemoglobin levels are independently associated with neonatal acute kidney injury: a report from the AWAKEN Study Group. Pediatr Res 89:922–931PubMedCrossRef

27.

Malhotra K, Axisa B (2009) Low plasma albumin linked to fluid overload in postoperative epidural patients. Ann R Coll Surg Engl 91:703–707PubMedPubMedCentralCrossRef

28.

Selewski DT, Gist KM, Nathan AT, Goldstein SL, Boohaker LJ, Akcan-Arikan A, Bonachea EM, Hanna M, Joseph C, Mahan JD, Mammen C, Nada A, Reidy K, Staples A, Wintermark P, Griffin R, Askenazi DJ, Guillet R, Neonatal Kidney Collaborative (2020) The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group. Pediatr Res 87:550–557. https://doi.org/10.1038/s41390-019-0579-1CrossRefPubMed

29.

Ruopp MD, Perkins NJ, Whitcomb BW, Schisterman EF (2008) Youden Index and optimal cut-point estimated from observations affected by a lower limit of detection. Biom J 50:419–430PubMedPubMedCentralCrossRef

30.

Watchko JF, Spitzer AR, Clark RH (2017) Prevalence of hypoalbuminemia and elevated bilirubin/albumin ratios in a large cohort of infants in the Neonatal Intensive Care Unit. J Pediatr 188:280–286PubMedCrossRef

31.

Jardine LA, Jenkins-Manning S, Davies MW (2004) Albumin infusion for low serum albumin in preterm newborn infants. Cochrane Database Syst Rev 3:CD004208

32.

Greenough A, Emery E, Hird MF, Gamsu HR (1993) Randomised controlled trial of albumin infusion in ill preterm infants. Eur J Pediatr 152:157–159PubMedCrossRef

33.

Ferah O, Akbulut A, Acik ME, Gokkaya Z, Acar U, Yenidunya O et al (2019) Acute kidney injury after pediatric liver transplantation. Transplant Proc 51:2486–2491PubMedCrossRef

34.

Duan Y, Jin D, Xu Y, Tong W, Hu P (2019) Risk factors and prognosis of acute kidney injury in children with sepsis in pediatric intensive care unit. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 31:1004–1007PubMed

35.

Kongsayreepong S, Nitikaroon P (2013) Early acute kidney injury in postoperative severe sepsis/septic shock admitting to general surgical intensive care unit. Intensive Care Med 39:S266

36.

Shum HP, Kong HH, Chan KC, Yan WW, Chan TM (2016) Septic acute kidney injury in critically ill patients—a single-center study on its incidence, clinical characteristics, and outcome predictors. Ren Fail 38:706–716PubMedCrossRef

37.

Gameiro J, Goncalves M, Pereira M, Rodrigues N, Godinho I, Neves M et al (2018) Obesity, acute kidney injury and mortality in patients with sepsis: a cohort analysis. Ren Fail 40:120–126PubMedPubMedCentralCrossRef

38.

Kwon JA, Lee JE, Huh W, Peck KR, Kim YG, Kim DJ et al (2010) Predictors of acute kidney injury associated with intravenous colistin treatment. Int J Antimicrob Agents 35:473–477PubMedCrossRef

39.

Gamba G, Contreras AM, Cortés J, Nares F, Santiago Y, Espinosa A, Bobadilla J, Jiménez Sánchez G, López G, Valadez A et al (1990) Hypoalbuminemia as a risk factor for amikacin nephrotoxicity. Rev Invest Clin 42:204–209PubMed

40.

Lee EH, Baek SH, Chin JH, Choi DK, Son HJ, Kim WJ et al (2012) Preoperative hypoalbuminemia is a major risk factor for acute kidney injury following off-pump coronary artery bypass surgery. Intensive Care Med 38:1478–1486PubMedCrossRef

41.

Findik O, Aydin U, Baris O, Parlar H, Alagoz GA, Ata Y et al (2016) Preoperative low serum albumin levels increase the requirement of renal replacement therapy after cardiac surgery. Heart Surg Forum 19:E123-127PubMedCrossRef

42.

Kim WH, Park MH, Kim HJ, Lim HY, Shim HS, Sohn JT et al (2015) Potentially modifiable risk factors for acute kidney injury after surgery on the thoracic aorta: a propensity score matched case-control study. Medicine (Baltimore) 94:e273CrossRef

43.

Go PH, Hodari A, Nemeh HW, Borgi J, Lanfear DE, Williams CT et al (2015) Effect of preoperative albumin levels on outcomes in patients undergoing left ventricular device implantation. ASAIO J 61:734–737PubMedCrossRef

44.

Murat SN, Kurtul A, Yarlioglues M (2015) Impact of serum albumin levels on contrast-induced acute kidney injury in patients with acute coronary syndromes treated with percutaneous coronary intervention. Angiology 66:732–737PubMedCrossRef

45.

Lee EH, Kim WJ, Kim JY, Chin JH, Choi DK, Sim JY et al (2016) Effect of exogenous albumin on the incidence of postoperative acute kidney injury in patients undergoing off-pump coronary artery bypass surgery with a preoperative albumin level of less than 4.0 g/dl. Anesthesiology 124:1001–1011PubMedCrossRef

46.

Lang J, Katz R, Ix JH, Gutierrez OM, Peralta CA, Parikh CR et al (2018) Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders. Nephrol Dial Transplant 33:986–992PubMedCrossRef

47.

Margarson MP, Soni N (1998) Serum albumin: touchstone or totem? Anaesthesia 53:789–803PubMedCrossRef

48.

Nicholson JP, Wolmarans MR, Park GR (2000) The role of albumin in critical illness. Br J Anaesth 85:599–610PubMedCrossRef

49.

Iglesias J, Abernethy VE, Wang Z, Lieberthal W, Koh JS, Levine JS (1999) Albumin is a major serum survival factor for renal tubular cells and macrophages through scavenging of ROS. Am J Physiol 277:F711–F722PubMed

50.

Kaufmann MA, Castelli I, Pargger H, Drop LJ (1995) Nitric oxide dose-response study in the isolated perfused rat kidney after inhibition of endothelium- derived relaxing factor synthesis: the role of serum albumin. J Pharmacol Exp Ther 273:855–862PubMed

51.

Roche M, Rondeau P, Singh NR, Tarnus E, Bourdon E (2008) The antioxidant properties of serum albumin. FEBS Lett 582:1783–1787PubMedCrossRef

52.

Dixon R, Brunskill NJ (1999) Activation of mitogenic pathways by albumin in kidney proximal tubule epithelial cells: implications for the pathophysiology of proteinuric states. J Am Soc Nephrol 10:1487–1497PubMedCrossRef

53.

Curry S (2009) Lessons from the crystallographic analysis of small molecule binding to human serum albumin. Drug Metab Pharmacokinet 24:342–357PubMedCrossRef

54.

Engelman DT, Watanabe M, Maulik N, Cordis GA, Engelman RM, Rousou JA et al (1995) L-arginine reduces endothelial inflammation and myocardial stunning during ischemia/reperfusion. Ann Thorac Surg 60:1275–1281PubMedCrossRef

55.

Hall JE, Coleman TG, Guyton AC, Kastner PR, Granger JP (1981) Control of glomerular filtration rate by circulating angiotensin II. Am J Physiol 241:R190-197PubMed

56.

Walther CP, Gutierrez OM, Cushman M, Judd SE, Lang J, McClellan W et al (2018) Serum albumin concentration and risk of end-stage renal disease: the REGARDS study. Nephrol Dial Transplant 33:1770–1777PubMedCrossRef

Title: Low albumin levels are independently associated with neonatal acute kidney injury: a report from AWAKEN Study Group
Authors: Arwa Nada
David Askenazi
Juan C. Kupferman
Maroun Mhanna
John D. Mahan
Louis Boohaker
Linzi Li
Russell L. Griffin
the AWAKEN Collaborative
Publication date: 18-10-2021
Publisher: Springer Berlin Heidelberg
Keywords: Acute Kidney Injury
Acute Kidney Injury
Published in: Pediatric Nephrology / Issue 7/2022
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-021-05295-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Low albumin levels are independently associated with neonatal acute kidney injury: a report from AWAKEN Study Group

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 7/2022

Whole exome sequencing identifies monogenic forms of nephritis in a previously unsolved cohort of children with steroid-resistant nephrotic syndrome and hematuria

Hematuria and proteinuria in a 14-year-old boy on anti-tubercular treatment: Questions

Monogenic forms of low-renin hypertension: clinical and molecular insights

How immunosuppressive drugs may directly target podocytes in glomerular diseases

Specific immune biomarker monitoring in two children with severe IgA nephropathy and successful therapy with immunoadsorption in a rapidly progressive case

Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes