Acute kidney injury in Ugandan children with severe malaria is associated with long-term behavioral problems


Autoři: Meredith R. Hickson aff001;  Andrea L. Conroy aff002;  Paul Bangirana aff003;  Robert O. Opoka aff004;  Richard Idro aff004;  John M. Ssenkusu aff006;  Chandy C. John aff002
Působiště autorů: Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America aff001;  Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, Indiana, United States of America aff002;  Department of Psychiatry, Makerere University of School of Medicine, Kampala, Uganda aff003;  Department of Paediatrics and Child Health, Makerere University School of Medicine, Kampala, Uganda aff004;  Centre of Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom aff005;  Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda aff006
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226405

Souhrn

Background

Acute kidney injury (AKI) is a risk factor for neurocognitive impairment in severe malaria (SM), but the impact of AKI on long-term behavioral outcomes following SM is unknown.

Methods

We conducted a prospective study on behavioral outcomes of Ugandan children 1.5 to 12 years of age with two forms of severe malaria, cerebral malaria (CM, n = 226) or severe malarial anemia (SMA, n = 214), and healthy community children (CC, n = 173). AKI was defined as a 50% increase in creatinine from estimated baseline. Behavior and executive function were assessed at baseline and 6, 12, and 24 months later using the Child Behavior Checklist and Behavior Rating Inventory of Executive Function, respectively. Age-adjusted z-scores were computed for each domain based on CC scores. The association between AKI and behavioral outcomes was evaluated across all time points using linear mixed effect models, adjusting for sociodemographic variables and disease severity.

Results

AKI was present in 33.2% of children with CM or SMA at baseline. Children ≥6 years of age with CM or SMA who had AKI on admission had worse scores in socio-emotional function in externalizing behaviors (Beta (95% CI), 0.52 (0.20, 0.85), p = 0.001), global executive function (0.48 (0.15, 0.82), p = 0.005) and behavioral regulation (0.66 (0.32, 1.01), p = 0.0002) than children without AKI. There were no behavioral differences associated with AKI in children <6 years of age.

Conclusions

AKI is associated with long-term behavioral problems in children ≥6 years of age with CM or SMA, irrespective of age at study enrollment.

Klíčová slova:

Behavior – Cerebral malaria – Cognitive impairment – Creatinine – Children – Kidneys – Malaria – Metacognition


Zdroje

1. Lu C, Black MM, Richter LM. Risk of poor development in young children in low-income and middle-income countries: an estimation and analysis at the global, regional, and country level. The Lancet Global Health. 2016;4(12):e916–e22. doi: 10.1016/S2214-109X(16)30266-2 27717632

2. McCoy DC, Peet ED, Ezzati M, Danaei G, Black MM, Sudfeld CR, et al. Early Childhood Developmental Status in Low- and Middle-Income Countries: National, Regional, and Global Prevalence Estimates Using Predictive Modeling. PLoS Med. 2016;13(6):e1002034. doi: 10.1371/journal.pmed.1002034 27270467; PubMed Central PMCID: PMC4896459.

3. Walker SP, Wachs TD, Gardner JM, Lozoff B, Wasserman GA, Pollitt E, et al. Child development: risk factors for adverse outcomes in developing countries. Lancet. 2007;369(9556):145–57. doi: 10.1016/S0140-6736(07)60076-2 17223478.

4. John CC, Bangirana P, Byarugaba J, Opoka RO, Idro R, Jurek AM, et al. Cerebral malaria in children is associated with long-term cognitive impairment. Pediatrics. 2008;122(1):e92–9. doi: 10.1542/peds.2007-3709 18541616; PubMed Central PMCID: PMC2607241.

5. Bangirana P, Opoka RO, Boivin MJ, Idro R, Hodges JS, Romero RA, et al. Severe malarial anemia is associated with long-term neurocognitive impairment. Clin Infect Dis. 2014;59(3):336–44. Epub 2014/04/29. doi: 10.1093/cid/ciu293 24771329; PubMed Central PMCID: PMC4155441.

6. Plewes K, Royakkers AA, Hanson J, Hasan MM, Alam S, Ghose A, et al. Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria. Malar J. 2014;13:91. doi: 10.1186/1475-2875-13-91 24618154; PubMed Central PMCID: PMC3995633.

7. Conroy AL, Hawkes M, Elphinstone RE, Morgan C, Hermann L, Barker KR, et al. Acute Kidney Injury Is Common in Pediatric Severe Malaria and Is Associated With Increased Mortality. Open Forum Infect Dis. 2016;3(2):ofw046. doi: 10.1093/ofid/ofw046 27186577; PubMed Central PMCID: PMC4866565.

8. von Seidlein L, Olaosebikan R, Hendriksen IC, Lee SJ, Adedoyin OT, Agbenyega T, et al. Predicting the clinical outcome of severe falciparum malaria in african children: findings from a large randomized trial. Clin Infect Dis. 2012;54(8):1080–90. Epub 2012/03/14. doi: 10.1093/cid/cis034 22412067; PubMed Central PMCID: PMC3309889.

9. Jallow M, Casals-Pascual C, Ackerman H, Walther B, Walther M, Pinder M, et al. Clinical features of severe malaria associated with death: a 13-year observational study in the Gambia. PLoS One. 2012;7(9):e45645. doi: 10.1371/journal.pone.0045645 23029157; PubMed Central PMCID: PMC3460946.

10. Kapoor K, Gupta S. Malarial acute kidney injury in a paediatric intensive care unit. Trop Doct. 2012;42(4):203–5. doi: 10.1258/td.2012.120196 22869838.

11. Imani PD, Odiit A, Hingorani SR, Weiss NS, Eddy AA. Acute kidney injury and its association with in-hospital mortality among children with acute infections. Pediatr Nephrol. 2013;28(11):2199–206. doi: 10.1007/s00467-013-2544-2 23872929.

12. Waller D, Krishna S, Crawley J, Miller K, Nosten F, Chapman D, et al. Clinical features and outcome of severe malaria in Gambian children. Clin Infect Dis. 1995;21(3):577–87. doi: 10.1093/clinids/21.3.577 8527547.

13. Dondorp A, Nosten F, Stepniewska K, Day N, White N, South East Asian Quinine Artesunate Malaria Trial g. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet. 2005;366(9487):717–25. doi: 10.1016/S0140-6736(05)67176-0 16125588.

14. Conroy AL, Opoka RO, Bangirana P, Idro R, Ssenkusu JM, Datta D, et al. Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria. BMC Med. 2019.

15. Trang TT, Phu NH, Vinh H, Hien TT, Cuong BM, Chau TT, et al. Acute renal failure in patients with severe falciparum malaria. Clin Infect Dis. 1992;15(5):874–80. Epub 1992/11/01. doi: 10.1093/clind/15.5.874 1445988.

16. Anand S, Bitton A, Gaziano T. The gap between estimated incidence of end-stage renal disease and use of therapy. PLoS One. 2013;8(8):e72860. doi: 10.1371/journal.pone.0072860 24023651; PubMed Central PMCID: PMC3758352.

17. World Health Organization. Severe Malaria. Trop Med Int Health. 2014;19:7–131. doi: 10.1111/tmi.12313_2 25214480.

18. Nsobya SL, Parikh S, Kironde F, Lubega G, Kamya MR, Rosenthal PJ, et al. Molecular evaluation of the natural history of asymptomatic parasitemia in Ugandan children. J Infect Dis. 2004;189(12):2220–6. doi: 10.1086/421281 15181569.

19. KDIGO. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;Supplement(2):1–138.

20. Bangirana P, John CC, Idro R, Opoka RO, Byarugaba J, Jurek AM, et al. Socioeconomic predictors of cognition in Ugandan children: implications for community interventions. PLoS One. 2009;4(11):e7898. doi: 10.1371/journal.pone.0007898 19936066; PubMed Central PMCID: PMC2774512.

21. Caldwell BM BR. Home Inventory Administration Manual (3rd ed.). Little Rock, AR: University of Arkansas; 2001.

22. Gerson AC, Butler R, Moxey-Mims M, Wentz A, Shinnar S, Lande MB, et al. Neurocognitive outcomes in children with chronic kidney disease: Current findings and contemporary endeavors. Ment Retard Dev Disabil Res Rev. 2006;12(3):208–15. doi: 10.1002/mrdd.20116 17061289.

23. Achenbach TM, Ruffle TM. The Child Behavior Checklist and related forms for assessing behavioral/emotional problems and competencies. Pediatr Rev. 2000;21(8):265–71. doi: 10.1542/pir.21-8-265 10922023.

24. Gioia G, Espy KA., Isquith PK. Behavior Rating Inventory of Executive Function®—Preschool Version (BRIEF®-P). 16204 North Florida Avenue, Lutz, Florida: Psychological Assessment Resources, Inc. (PAR); 1996.

25. Ssenkusu JM, Hodges JS, Opoka RO, Idro R, Shapiro E, John CC, et al. Long-term Behavioral Problems in Children With Severe Malaria. Pediatrics. 2016;138(5):e20161965. doi: 10.1542/peds.2016-1965 27940786; PubMed Central PMCID: PMC5079082 conflicts of interest to disclose.

26. Helbok R, Kendjo E, Issifou S, Lackner P, Newton Charles R, Kombila M, et al. The Lambaréné Organ Dysfunction Score (LODS) Is a Simple Clinical Predictor of Fatal Malaria in African Children. The Journal of Infectious Diseases. 2009;200(12):1834–41. doi: 10.1086/648409 19911989.

27. Conroy AL, Hawkes M, Hayford K, Namasopo S, Opoka RO, John CC, et al. Prospective validation of pediatric disease severity scores to predict mortality in Ugandan children presenting with malaria and non-malaria febrile illness. Crit Care. 2015;19:47. Epub 2015/04/17. doi: 10.1186/s13054-015-0773-4 25879892; PubMed Central PMCID: PMC4339236.

28. Conroy AL, Opoka RO, Bangirana P, Idro R, Ssenkusu JM, Datta D, et al. Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria. BMC Med. 2019;17(1):98. doi: 10.1186/s12916-019-1332-7 31109328; PubMed Central PMCID: PMC6528242.

29. Gerstein ED, Pedersen YAA, Crnic KA, Ryu E, Baker BL, Blacher J. Developmental risk and young children's regulatory strategies: predicting behavior problems at age five. J Abnorm Child Psychol. 2011;39(3):351–64. doi: 10.1007/s10802-010-9471-5 21107675; PubMed Central PMCID: PMC3586735.

30. Baker BL, McIntyre LL, Blacher J, Crnic K, Edelbrock C, Low C. Pre-school children with and without developmental delay: behaviour problems and parenting stress over time. J Intellect Disabil Res. 2003;47(4–5):217–30. doi: 10.1046/j.1365-2788.2003.00484.x 12787154

31. Greenough WT, Black JE, Wallace CS. Experience and brain development. Child Dev. 1987;58(3):539–59. 3038480.

32. Bronfenbrenner U. Toward an experimental ecology of human development. Am Psychol. 1977;32(7):513–31.

33. Maulik PK, Darmstadt GL. Childhood disability in low- and middle-income countries: overview of screening, prevention, services, legislation, and epidemiology. Pediatrics. 2007;120 Suppl 1(Supplement 1):S1–55. doi: 10.1542/peds.2007-0043B 17603094.

34. Kristensen K, Omagor-Loican M, Onen N, Okot D. Opportunities for inclusion? The education of learners with special educational needs and disabilities in special schools in Uganda. British Journal of Special Education. 2006;33(3):139–47. doi: 10.1111/j.1467-8578.2006.00429.x

35. Nguansangiam S, Day NP, Hien TT, Mai NT, Chaisri U, Riganti M, et al. A quantitative ultrastructural study of renal pathology in fatal Plasmodium falciparum malaria. Trop Med Int Health. 2007;12(9):1037–50. Epub 2007/09/19. doi: 10.1111/j.1365-3156.2007.01881.x 17875015.

36. Milner DA Jr., Whitten RO, Kamiza S, Carr R, Liomba G, Dzamalala C, et al. The systemic pathology of cerebral malaria in African children. Front Cell Infect Microbiol. 2014;4:104. doi: 10.3389/fcimb.2014.00104 25191643; PubMed Central PMCID: PMC4139913.

37. Hanson J, Lee SJ, Hossain MA, Anstey NM, Charunwatthana P, Maude RJ, et al. Microvascular obstruction and endothelial activation are independently associated with the clinical manifestations of severe falciparum malaria in adults: an observational study. BMC Med. 2015;13:122. doi: 10.1186/s12916-015-0365-9 26018532; PubMed Central PMCID: PMC4453275.

38. Barber BE, Grigg MJ, Piera KA, William T, Cooper DJ, Plewes K, et al. Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury. Emerg Microbes Infect. 2018;7(1):106. Epub 2018/06/07. doi: 10.1038/s41426-018-0105-2 29872039; PubMed Central PMCID: PMC5988665.

39. Nongnuch A, Panorchan K, Davenport A. Brain-kidney crosstalk. Crit Care. 2014;18(3):225. doi: 10.1186/cc13907 25043644; PubMed Central PMCID: PMC4075125.

40. Kinsey GR, Li L, Okusa MD. Inflammation in acute kidney injury. Nephron Exp Nephrol. 2008;109(4):e102–7. Epub 09/18. doi: 10.1159/000142934 18802372; PubMed Central PMCID: PMC2614446.

41. Andres-Hernando A, Dursun B, Altmann C, Ahuja N, He Z, Bhargava R, et al. Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy. Nephrol Dial Transplant. 2012;27(12):4339–47. Epub 07/09. doi: 10.1093/ndt/gfs256 22778179; PubMed Central PMCID: PMC3520082.

42. Fitzgerald JC, Basu RK, Akcan-Arikan A, Izquierdo LM, Pineres Olave BE, Hassinger AB, et al. Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability. Crit Care Med. 2016;44(12):2241–50. doi: 10.1097/CCM.0000000000002007 27513354; PubMed Central PMCID: PMC5267552.

43. Mammen C, Al Abbas A, Skippen P, Nadel H, Levine D, Collet JP, 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):523–30. doi: 10.1053/j.ajkd.2011.10.048 22206744.

44. Calderon-Margalit R, Golan E, Twig G, Leiba A, Tzur D, Afek A, et al. History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease. N Engl J Med. 2018;378(5):428–38. doi: 10.1056/NEJMoa1700993 29385364.

45. Familiar I, Ruisenor-Escudero H, Giordani B, Bangirana P, Nakasujja N, Opoka R, et al. Use of the Behavior Rating Inventory of Executive Function and Child Behavior Checklist in Ugandan Children with HIV or a History of Severe Malaria. J Dev Behav Pediatr. 2015;36(4):277–84. doi: 10.1097/DBP.0000000000000149 25738440; PubMed Central PMCID: PMC4414719.


Článek vyšel v časopise

PLOS One


2019 Číslo 12