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ISSN (Online): 1875-6336

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Renal Involvement in Pediatric Patients with COVID-19: An Up-to-date Review

Author(s): Yuri Márcio Campos, André Luís Vieira Drumond, Mariane de Matos Gamonal, Milena Pereira Parreira and Ana Cristina Simões e Silva*

Volume 17, Issue 4, 2021

Published on: 24 September, 2021

Page: [253 - 263] Pages: 11

DOI: 10.2174/1573396317666210924121550

Price: $65

Abstract

Background: In pediatric patients, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has been mostly associated with mild symptoms. However, as in adults, renal involvement has been reported in children and adolescents with Coronavirus Disease 2019 (COVID-19).

Objective: This review aimed to report data about renal involvement in pediatric COVID-19 patients. The focuses were on the pathophysiology of acute kidney injury in Pediatric Inflammatory Multisystem Syndrome Temporally Associated (PIMS-TS) with SARS-CoV-2 and the possible impact of SARS-CoV-2 infection upon kidney function, as well as data concerning patients with previous kidney diseases, including Nephrotic Syndrome and Chronic Renal Disease. The implications for COVID-19 outcomes in pediatric patients were also discussed.

Methods: This integrative review searched for articles on renal involvement in pediatric COVID-19 patients. The databases evaluated were PubMed and Scopus.

Results: The emergence of PIMS-TS with SARS-CoV-2 has shown that pediatric patients are at risk of severe COVID-19, with multi-organ involvement and dysfunction. In addition to intense inflammation, several systems are affected in this syndrome, collectively creating a combination of factors that results in acute kidney injury. Several studies have proposed that kidney cells, including the podocytes, might be at risk of direct infection by SARS-CoV-2, as high levels of ACE2, the virus receptor, are expressed on the membrane of such cells. Some cases of glomerular diseases triggered by SARS-CoV-2 infection and relapses of previous renal diseases have been reported.

Conclusion: Further studies are necessary to establish risk factors for renal involvement in pediatric COVID-19 and to predict disease outcomes.

Keywords: COVID-19, SARS-CoV-2, pediatrics, children, kidney, acute kidney injury, nephrotic syndrome, chronic kidneydisease.

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[1]
Felsenstein S, Hedrich CM. COVID-19 in children and young people. Lancet Rheumatol 2020; 2(9): e514-6.
[http://dx.doi.org/10.1016/S2665-9913(20)30212-5] [PMID: 32838308]
[2]
Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection in children and adolescents. JAMA Pediatr 2020; 174(9): 882-9.
[http://dx.doi.org/10.1001/jamapediatrics.2020.1467] [PMID: 32320004]
[3]
Götzinger F, Santiago-García B, Noguera-Julián A, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health 2020; 4(9): 653-61.
[http://dx.doi.org/10.1016/S2352-4642(20)30177-2] [PMID: 32593339]
[4]
Gupta A, Madhavan MV, Sehgal K, et al. Extrapulmonary manifestations of COVID-19. Nat Med 2020; 26(7): 1017-32.
[http://dx.doi.org/10.1038/s41591-020-0968-3] [PMID: 32651579]
[5]
Naicker S, Yang CW, Hwang SJ, Liu BC, Chen JH, Jha V. The novel coronavirus 2019 epidemic and kidneys. Kidney Int 2020; 97(5): 824-8.
[http://dx.doi.org/10.1016/j.kint.2020.03.001] [PMID: 32204907]
[6]
Cheng Y, Luo R, Wang K, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020; 97(5): 829-38.
[http://dx.doi.org/10.1016/j.kint.2020.03.005] [PMID: 32247631]
[7]
Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int 2020; 98(1): 209-18.
[http://dx.doi.org/10.1016/j.kint.2020.05.006] [PMID: 32416116]
[8]
Ahmed M, Advani S, Moreira A, et al. Multisystem inflammatory syndrome in children: A systematic review. EClinicalMedicine 2020; 26: 100527.
[http://dx.doi.org/10.1016/j.eclinm.2020.100527] [PMID: 32923992]
[9]
Cheung EW, Zachariah P, Gorelik M, et al. Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. JAMA 2020; 324(3): 294-6.
[http://dx.doi.org/10.1001/jama.2020.10374] [PMID: 32511676]
[10]
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 395(10237): 1607-8.
[http://dx.doi.org/10.1016/S0140-6736(20)31094-1] [PMID: 32386565]
[11]
Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020; 395(10239): 1771-8.
[http://dx.doi.org/10.1016/S0140-6736(20)31103-X] [PMID: 32410760]
[12]
Moraleda C, Serna-Pascual M, Soriano-Arandes A, et al. Multi-inflammatory syndrome in children related to severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in Spain. Clin Infect Dis 2021; 72(9): e397-401.
[http://dx.doi.org/10.1093/cid/ciaa1042] [PMID: 32710613]
[13]
Feldstein LR, Rose EB, Horwitz SM, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020; 383(4): 334-46.
[http://dx.doi.org/10.1056/NEJMoa2021680] [PMID: 32598831]
[14]
HAN Archive - 00432 | Health Alert Network (HAN). Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). 2020. Available from: https://emergency.cdc.gov/han/2020/han00432.asp
[15]
Stewart DJ, Hartley JC, Johnson M, Marks SD, du Pré P, Stojanovic J. Renal dysfunction in hospitalised children with COVID-19. Lancet Child Adolesc Health 2020; 4(8): e28-9.
[http://dx.doi.org/10.1016/S2352-4642(20)30178-4] [PMID: 32553126]
[16]
Derespina KR, Kaushik S, Plichta A, et al. Clinical manifestations and outcomes of critically ill children and adolescents with Coronavirus disease 2019 in New York City. J Pediatr 2020; 226: 55-63.
[http://dx.doi.org/10.1016/j.jpeds.2020.07.039] [PMID: 32681989]
[17]
Deep A, Upadhyay G, du Pré P, et al. Acute kidney injury in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome Coronavirus-2 pandemic: Experience from PICUs across the United Kingdom. Crit Care Med 2020; 48(12): 1809-18.
[http://dx.doi.org/10.1097/CCM.0000000000004662] [PMID: 33044282]
[18]
Toubiana J, Poirault C, Corsia A, et al. Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study. BMJ 2020; 369: m2094.
[http://dx.doi.org/10.1136/bmj.m2094] [PMID: 32493739]
[19]
Takasu O, Gaut JP, Watanabe E, et al. Mechanisms of cardiac and renal dysfunction in patients dying of sepsis. Am J Respir Crit Care Med 2013; 187(5): 509-17.
[http://dx.doi.org/10.1164/rccm.201211-1983OC] [PMID: 23348975]
[20]
Brun C, Munck O. Lesions of the kidney in acute renal failure following shock. Lancet 1957; 272(6969): 603-7.
[http://dx.doi.org/10.1016/S0140-6736(57)91069-3] [PMID: 13407077]
[21]
Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet 2019; 394(10212): 1949-64.
[http://dx.doi.org/10.1016/S0140-6736(19)32563-2] [PMID: 31777389]
[22]
Bonventre JV, Yang L. Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 2011; 121(11): 4210-21.
[http://dx.doi.org/10.1172/JCI45161] [PMID: 22045571]
[23]
Puelles VG, Lütgehetmann M, Lindenmeyer MT, et al. Multiorgan and renal tropism of SARS-CoV-2. N Engl J Med 2020; 383(6): 590-2.
[http://dx.doi.org/10.1056/NEJMc2011400] [PMID: 32402155]
[24]
Wang B, Luo Q, Zhang W, et al. The involvement of chronic kidney disease and acute kidney injury in disease severity and mortality in patients with COVID-19: A meta-analysis. Kidney Blood Press Res 2020; 1-14.
[http://dx.doi.org/10.1159/000512211] [PMID: 33352576]
[25]
Deep A, Bansal M, Ricci Z. Acute kidney injury and special considerations during renal replacement therapy in children with coronavirus disease-19: Perspective from the critical care nephrology section of the European society of paediatric and neonatal intensive care. Blood Purif 2021; 50(2): 150-60.
[PMID: 32663827]
[26]
Pousa PA, Mendonça TSC, Oliveira EA, Simões-E-Silva AC. Extrapulmonary manifestations of COVID-19 in children: a comprehensive review and pathophysiological considerations. J Pediatr (Rio J) 2021; 97(2): 116-39.
[http://dx.doi.org/10.1016/j.jped.2020.08.007] [PMID: 32980319]
[27]
Pan XW, Xu D, Zhang H, Zhou W, Wang LH, Cui XG. Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis. Intensive Care Med 2020; 46(6): 1114-6.
[http://dx.doi.org/10.1007/s00134-020-06026-1] [PMID: 32236644]
[28]
Costa LB, Perez LG, Palmeira VA, et al. Insights on SARS-CoV-2 molecular interactions with the renin-angiotensin system. Front Cell Dev Biol 2020; 8: 559841.
[http://dx.doi.org/10.3389/fcell.2020.559841] [PMID: 33042994]
[29]
Simões E Silva AC, Lanza K, Palmeira VA, Costa LB, Flynn JT. 2020 update on the renin-angiotensin-aldosterone system in pediatric kidney disease and its interactions with coronavirus. Pediatr Nephrol 2021; 36(6): 1407-26.
[http://dx.doi.org/10.1007/s00467-020-04759-1] [PMID: 32995920]
[30]
Vieira C, Nery L, Martins L, Jabour L, Dias R, Simões E Silva AC. Downregulation of membrane-bound angiotensin converting enzyme 2 (ACE2) receptor has a pivotal role in COVID-19 immunopathology. Curr Drug Targets 2021; 22(3): 254-81.
[http://dx.doi.org/10.2174/1389450121666201020154033] [PMID: 33081670]
[31]
Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int 2020; 98(1): 219-27.
[http://dx.doi.org/10.1016/j.kint.2020.04.003] [PMID: 32327202]
[32]
Joannidis M, Forni LG, Klein SJ, et al. Lung-kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup. Intensive Care Med 2020; 46(4): 654-72.
[http://dx.doi.org/10.1007/s00134-019-05869-7] [PMID: 31820034]
[33]
Ronco C, Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol 2020; 16(6): 308-10.
[http://dx.doi.org/10.1038/s41581-020-0284-7] [PMID: 32273593]
[34]
Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet 2020; 395(10235): 1517-20.
[http://dx.doi.org/10.1016/S0140-6736(20)30920-X] [PMID: 32311318]
[35]
Peerapornratana S, Manrique-Caballero CL, Gómez H, Kellum JA. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int 2019; 96(5): 1083-99.
[http://dx.doi.org/10.1016/j.kint.2019.05.026] [PMID: 31443997]
[36]
Lu X, Zhang L, Du H, et al. SARS-CoV-2 infection in children. N Engl J Med 2020; 382(17): 1663-5.
[http://dx.doi.org/10.1056/NEJMc2005073] [PMID: 32187458]
[37]
Whittaker E, Bamford A, Kenny J, et al. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020; 324(3): 259-69.
[http://dx.doi.org/10.1001/jama.2020.10369] [PMID: 32511692]
[38]
Chuang GT, Tsai IJ, Lin MT, Chang LY. Acute kidney injury in patients with Kawasaki disease. Pediatr Res 2016; 80(2): 224-7.
[http://dx.doi.org/10.1038/pr.2016.81] [PMID: 27064240]
[39]
Glanzmann C, Frey B, Vonbach P, Meier CR. Drugs as risk factors of acute kidney injury in critically ill children. Pediatr Nephrol 2016; 31(1): 145-51.
[http://dx.doi.org/10.1007/s00467-015-3180-9] [PMID: 26260379]
[40]
Chen PS, Chi H, Huang FY, Peng CC, Chen MR, Chiu NC. Clinical manifestations of Kawasaki disease shock syndrome: a case-control study. J Microbiol Immunol Infect 2015; 48(1): 43-50.
[http://dx.doi.org/10.1016/j.jmii.2013.06.005] [PMID: 23927822]
[41]
Godfred-Cato S, Bryant B, Leung J, et al. COVID-19: Associated multisystem inflammatory syndrome in children — United States, March–July 2020. MMWR Morb Mortal Wkly Rep 2020; 69(32): 1074-80.
[http://dx.doi.org/10.15585/mmwr.mm6932e2] [PMID: 32790663]
[42]
Riollano-Cruz M, Akkoyun E, Briceno-Brito E, et al. Multisystem inflammatory syndrome in children related to COVID-19: A New York City experience. J Med Virol 2021; 93(1): 424-33.
[http://dx.doi.org/10.1002/jmv.26224] [PMID: 32584487]
[43]
Miller J, Cantor A, Zachariah P, Ahn D, Martinez M, Margolis KG. Gastrointestinal symptoms as a major presentation component of a novel multisystem inflammatory syndrome in children that is related to Coronavirus disease 2019: A single center experience of 44 cases. Gastroenterology 2020; 159(4): 1571-1574.e2.
[http://dx.doi.org/10.1053/j.gastro.2020.05.079] [PMID: 32505742]
[44]
Grimaud M, Starck J, Levy M, et al. Acute myocarditis and multisystem inflammatory emerging disease following SARS-CoV-2 infection in critically ill children. Ann Intensive Care 2020; 10(1): 69.
[http://dx.doi.org/10.1186/s13613-020-00690-8] [PMID: 32488505]
[45]
Liu L, Wei Q, Lin Q, et al. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 2019; 4(4): e123158.
[http://dx.doi.org/10.1172/jci.insight.123158] [PMID: 30830861]
[46]
Capone CA, Subramony A, Sweberg T, et al. Characteristics, cardiac involvement, and outcomes of multisystem inflammatory syndrome of childhood associated with severe acute respiratory syndrome Coronavirus 2 infection. J Pediatr 2020; 224: 141-5.
[http://dx.doi.org/10.1016/j.jpeds.2020.06.044] [PMID: 32553873]
[47]
Mamishi S, Movahedi Z, Mohammadi M, et al. Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran. Epidemiol Infect 2020; 148: e196.
[http://dx.doi.org/10.1017/S095026882000196X] [PMID: 32854812]
[48]
Esper F, Shapiro ED, Weibel C, Ferguson D, Landry ML, Kahn JS. Association between a novel human coronavirus and Kawasaki disease. J Infect Dis 2005; 191(4): 499-502.
[http://dx.doi.org/10.1086/428291] [PMID: 15655771]
[49]
Noval Rivas M, Arditi M. Kawasaki disease: pathophysiology and insights from mouse models. Nat Rev Rheumatol 2020; 16(7): 391-405.
[http://dx.doi.org/10.1038/s41584-020-0426-0] [PMID: 32457494]
[50]
Viner RM, Whittaker E. Kawasaki-like disease: emerging complication during the COVID-19 pandemic. Lancet 2020; 395(10239): 1741-3.
[http://dx.doi.org/10.1016/S0140-6736(20)31129-6] [PMID: 32410759]
[51]
Watanabe T. Kidney and urinary tract involvement in kawasaki disease. Int J Pediatr 2013; 2013: 831834.
[http://dx.doi.org/10.1155/2013/831834] [PMID: 24288547]
[52]
Menikou S, Langford PR, Levin M. Kawasaki disease: The role of immune complexes revisited. Front Immunol 2019; 10: 1156.
[http://dx.doi.org/10.3389/fimmu.2019.01156] [PMID: 31263461]
[53]
Levin M, Holland PC, Nokes TJ, et al. Platelet immune complex interaction in pathogenesis of Kawasaki disease and childhood polyarteritis. Br Med J (Clin Res Ed) 1985; 290(6480): 1456-60.
[http://dx.doi.org/10.1136/bmj.290.6480.1456] [PMID: 3922532]
[54]
Consiglio CR, Cotugno N, Sardh F, et al. The immunology of multisystem inflammatory syndrome in children with COVID-19. Cell 2020; 183(4): 968-981.e7.
[http://dx.doi.org/10.1016/j.cell.2020.09.016] [PMID: 32966765]
[55]
Dimitrijevic ZM, Salinger-Martinovic SS, Jankovic RJ, Mitic BP. Elevated serum ferritin levels are predictive of renal function recovery among patients with acute kidney injury. Tohoku J Exp Med 2019; 248(2): 63-71.
[http://dx.doi.org/10.1620/tjem.248.63] [PMID: 31178527]
[56]
Bjornstad EC, Krallman KA, Askenazi D, Zappitelli M, Goldstein SL, Basu RK. Preliminary assessment of acute kidney injury in critically ill children associated with SARS-CoV-2 infection. Clin J Am Soc Nephrol 2021; 16(3): 446-8.
[http://dx.doi.org/10.2215/CJN.11470720] [PMID: 33144276]
[57]
Tonial CT, Garcia PCR, Schweitzer LC, et al. Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis. J Pediatr (Rio J) 2017; 93(3): 301-7.
[http://dx.doi.org/10.1016/j.jped.2016.08.006] [PMID: 28126563]
[58]
Gross O, Moerer O, Weber M, Huber TB, Scheithauer S. COVID-19-associated nephritis: early warning for disease severity and complications? Lancet 2020; 395(10236): e87-8.
[http://dx.doi.org/10.1016/S0140-6736(20)31041-2] [PMID: 32423587]
[59]
Kari JA, Shalaby MA, Albanna AS, Alahmadi TS, Alherbish A, Alhasan KA. Acute kidney injury in children with COVID-19: a retrospective study. BMC Nephrol 2021; 22(1): 202.
[http://dx.doi.org/10.1186/s12882-021-02389-9] [PMID: 34059010]
[60]
Wang X, Chen X, Tang F, et al. Be aware of acute kidney injury in critically ill children with COVID-19. Pediatr Nephrol 2021; 36(1): 163-9.
[http://dx.doi.org/10.1007/s00467-020-04715-z] [PMID: 32844290]
[61]
Shah SA, Carter HP. New-onset nephrotic syndrome in a child associated with COVID-19 infection. Front Pediatr 2020; 8: 471.
[http://dx.doi.org/10.3389/fped.2020.00471] [PMID: 32974243]
[62]
Alvarado A, Franceschi G, Resplandor E, Sumba J, Orta N. COVID-19 associated with onset nephrotic syndrome in a pediatric patient: coincidence or related conditions? Pediatr Nephrol 2021; 36(1): 205-7.
[http://dx.doi.org/10.1007/s00467-020-04724-y] [PMID: 32852576]
[63]
Enya T, Sugimoto K. SARS-CoV-2 infection associated with the recurrence of nephrotic syndrome in a Japanese boy. Pediatr Nephrol 2021; 36(1): 209-9.
[http://dx.doi.org/10.1007/s00467-020-04782-2] [PMID: 32990810]
[64]
Andolino TP, Reid-Adam J. Nephrotic syndrome. Pediatr Rev 2015; 36(3): 117-25.
[http://dx.doi.org/10.1542/pir.36-3-117] [PMID: 25733763]
[65]
Harambat J, Allard L, Godron-Dubrasquet A. Relapse rate of nephrotic syndrome in the time of COVID-19. Pediatr Nephrol 2021; 36(1): 211-2.
[http://dx.doi.org/10.1007/s00467-020-04814-x] [PMID: 33123772]
[66]
Molloy EJ, Bearer CF. COVID-19 in children and altered inflammatory responses. Pediatr Res 2020; 88(3): 340-1.
[http://dx.doi.org/10.1038/s41390-020-0881-y] [PMID: 32244248]
[67]
Waterer GW, Rello J. Steroids and COVID-19: We need a precision approach, not one size fits all. Infect Dis Ther 2020; 9(4): 701-5.
[http://dx.doi.org/10.1007/s40121-020-00338-x] [PMID: 32936438]
[68]
Melgosa M, Madrid A, Alvárez O, et al. SARS-CoV-2 infection in Spanish children with chronic kidney pathologies. Pediatr Nephrol 2020; 35(8): 1521-4.
[http://dx.doi.org/10.1007/s00467-020-04597-1] [PMID: 32435879]
[69]
Marlais M, Wlodkowski T, Vivarelli M, et al. The severity of COVID-19 in children on immunosuppressive medication. Lancet Child Adolesc Health 2020; 4(7): e17-8.
[http://dx.doi.org/10.1016/S2352-4642(20)30145-0] [PMID: 32411815]
[70]
Angeletti A, Drovandi S, Sanguineri F, et al. COVID-19 in children with nephrotic syndrome on Anti-CD20 chronic immunosuppression. Clin J Am Soc Nephrol 2020; 15(10): 1494-5.
[http://dx.doi.org/10.2215/CJN.06400420] [PMID: 32718953]
[71]
Lipsitch M, Swerdlow DL, Finelli L. Defining the epidemiology of COVID-19 — Studies needed. N Engl J Med 2020; 382(13): 1194-6.
[http://dx.doi.org/10.1056/NEJMp2002125] [PMID: 32074416]
[72]
Plumb L, Benoy-Deeney F, Casula A, et al. COVID-19 in children with chronic kidney disease: findings from the UK renal registry. Arch Dis Child 2021; 106(3): e16.
[http://dx.doi.org/10.1136/archdischild-2020-319903] [PMID: 32709685]
[73]
Munro APS, Faust SN. Children are not COVID-19 super spreaders: time to go back to school. Arch Dis Child 2020; 105(7): 618-9.
[http://dx.doi.org/10.1136/archdischild-2020-319474] [PMID: 32371442]
[74]
Mastrangelo A, Morello W, Vidal E, et al. Impact of COVID-19 pandemic in children with CKD or immunosuppression. Clin J Am Soc Nephrol 2021; 16(3): 449-51.
[http://dx.doi.org/10.2215/CJN.13120820] [PMID: 33318026]
[75]
Shen Q, Wang M, Che R, et al. Consensus recommendations for the care of children receiving chronic dialysis in association with the COVID-19 epidemic. Pediatr Nephrol 2020; 35(7): 1351-7.
[http://dx.doi.org/10.1007/s00467-020-04555-x] [PMID: 32333285]

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