Produção Nacional
Flaviviruses and Kidney Diseases
2019; Elsevier BV; Volume: 26; Issue: 3 Linguagem: Inglês
10.1053/j.ackd.2019.01.002
ISSN1548-5609
Autores Tópico(s)Malaria Research and Control
ResumoThe genus Flavivirus comprises approximately 73 viruses, which share several common aspects, such as dimension, structure, nucleic acid properties, and shape in electronic microscopy. Global incidence of flavivirus infection increased dramatically over the last decades, causing large outbreaks in several areas of the world. These viruses are expanding from endemic tropical and subtropical areas to previously nonendemic areas, affecting and causing diseases in millions of individuals worldwide and posing a formidable challenge to public health in several countries. The majority of clinically significant flavivirus-associated infections are mosquito borne (arboviruses—acronym for ARthropod-BOrne VIRUSES), such as dengue, yellow fever, Japanese encephalitis, Zika, and West Nile fever. Most diseases caused by flaviviruses are asymptomatic or manifest as self-limited, mild, undifferentiated febrile diseases. In a limited number of cases, these diseases may evolve to severe inflammatory, multisystem diseases, causing high morbidity and mortality. Some flaviviruses have been consistently identified in kidney tissue and urine and have been clinically associated with kidney diseases. In this review, we will provide an overview of the epidemiology, risk factors, kidney pathology, etiopathogenesis, and outcomes of acute and chronic kidney syndromes associated with dengue, yellow fever, Zika, and West Nile virus disease. The genus Flavivirus comprises approximately 73 viruses, which share several common aspects, such as dimension, structure, nucleic acid properties, and shape in electronic microscopy. Global incidence of flavivirus infection increased dramatically over the last decades, causing large outbreaks in several areas of the world. These viruses are expanding from endemic tropical and subtropical areas to previously nonendemic areas, affecting and causing diseases in millions of individuals worldwide and posing a formidable challenge to public health in several countries. The majority of clinically significant flavivirus-associated infections are mosquito borne (arboviruses—acronym for ARthropod-BOrne VIRUSES), such as dengue, yellow fever, Japanese encephalitis, Zika, and West Nile fever. Most diseases caused by flaviviruses are asymptomatic or manifest as self-limited, mild, undifferentiated febrile diseases. In a limited number of cases, these diseases may evolve to severe inflammatory, multisystem diseases, causing high morbidity and mortality. Some flaviviruses have been consistently identified in kidney tissue and urine and have been clinically associated with kidney diseases. In this review, we will provide an overview of the epidemiology, risk factors, kidney pathology, etiopathogenesis, and outcomes of acute and chronic kidney syndromes associated with dengue, yellow fever, Zika, and West Nile virus disease. Clinical Summary•The genus Flavivirus, family Flaviviridae, comprises approximately 73 viruses. The majority of the clinically significant infections caused by flaviviruses have mosquito as the vector, usually Aedes spp. or Culex spp.•The global incidence of flavivirus infection increased dramatically over the last few decades, with large outbreaks in several areas of the world. Currently, some flaviviruses, such as dengue, yellow fever, Zika, and West Nile, cause diseases that affect millions of individuals worldwide, representing a formidable challenge to public health in low- and middle-income countries.•Dengue, yellow fever, Zika, and West Nile flaviviruses have been consistently identified in kidney tissue and urine of infected animals and humans and have been clinically associated with acute and chronic kidney diseases, contributing to worse outcomes.•The kidney abnormalities associated with these viruses include hematuria, proteinuria, electrolyte abnormalities, hemolytic uremic syndrome, glomerulopathies, and acute and chronic kidney injury. The available information on kidney pathology shows acute structural injuries in epithelial tubular cells, interstitial edema and inflammatory cell infiltration, glomerulonephritis, and thrombotic microangiopathy. •The genus Flavivirus, family Flaviviridae, comprises approximately 73 viruses. The majority of the clinically significant infections caused by flaviviruses have mosquito as the vector, usually Aedes spp. or Culex spp.•The global incidence of flavivirus infection increased dramatically over the last few decades, with large outbreaks in several areas of the world. Currently, some flaviviruses, such as dengue, yellow fever, Zika, and West Nile, cause diseases that affect millions of individuals worldwide, representing a formidable challenge to public health in low- and middle-income countries.•Dengue, yellow fever, Zika, and West Nile flaviviruses have been consistently identified in kidney tissue and urine of infected animals and humans and have been clinically associated with acute and chronic kidney diseases, contributing to worse outcomes.•The kidney abnormalities associated with these viruses include hematuria, proteinuria, electrolyte abnormalities, hemolytic uremic syndrome, glomerulopathies, and acute and chronic kidney injury. The available information on kidney pathology shows acute structural injuries in epithelial tubular cells, interstitial edema and inflammatory cell infiltration, glomerulonephritis, and thrombotic microangiopathy. The genus Flavivirus, family Flaviviridae, comprises approximately 73 viruses with numerous common aspects, such as dimension, structure, nucleic acid properties, and shape in electron microscopy. These viruses are composed of an approximately 10 to 11 kilobase, single-stranded, positive sense RNA genome packaged in a virion constituted by a spherical nucleocapsid protein core enveloped in an icosahedral membrane. Most of these viruses are transmitted by bites of arthropods, specifically mosquitoes or tick vectors, and thus are generically termed arboviruses (acronym for ARthropod-BOrne VIRUSES).1Daep C.A. Muñoz-Jordán J.L. Eugenin E.A. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.J Neurovirol. 2014; 20: 539-560Google Scholar, 2Holbrook M.R. Historical Perspectives on flavivirus Research.Viruses. 2017; 9: E97Google Scholar, 3Solomon T. Mallewa M. Dengue and other emerging flaviviruses.J Infect. 2001; 42: 104-115Abstract Full Text PDF PubMed Scopus (150) Google Scholar Flavivirus presumably originated from a common ancestor in Africa 85, 000 to 120, 000 years ago, which was subsequently divided into mosquito- and tick-borne flaviviruses and efficiently evolved, rapidly spreading and filling new ecological niches.4Pettersson J.H. Fiz-Palacios O. Dating the origin of the genus Flavivirus in the light of Beringian biogeography.J Gen Virol. 2014; 95: 1969-1982Google Scholar Flaviviruses infect birds and a variety of mammalian hosts, including humans, nonhuman primates, horses, pigs, and so forth. Approximately half of the identified flaviviruses can cause human diseases, and few are relevant human pathogens. Nevertheless, this relatively small number of medically important flaviviruses cause diseases that affect millions of individuals worldwide. The vast majority of the clinically significant flavivirus-associated infections are mosquito borne, such as dengue, yellow fever (YF), Japanese encephalitis, Zika, and West Nile fever (WNF). Culex spp–infected mosquitoes usually transmit neurotropic viruses (Japanese encephalitis, West Nile neuroinvasive disease [WNND]), whereas Aedes spp–infected mosquitoes are more associated with viscerotropic, systemic, and/or hemorrhagic diseases (dengue, YF). Clinically significant tick-borne infections are more rare and usually associated with neurological syndromes, although hemorrhagic manifestations have also been described. Most diseases caused by flaviviruses are asymptomatic or manifest as self-limited, oligosymptomatic, mild, undifferentiated febrile diseases. Symptoms, when present, generally begin seven days after the bite and can last up to 14 days. In a limited number of cases, ranging from 5% to 30% depending on the specific flavivirus, the infection may evolve to a severe inflammatory multisystem disease, carrying high morbidity and mortality (Table 1).1Daep C.A. Muñoz-Jordán J.L. Eugenin E.A. Flaviviruses, an expanding threat in public health: focus on dengue, West Nile, and Japanese encephalitis virus.J Neurovirol. 2014; 20: 539-560Google Scholar, 2Holbrook M.R. Historical Perspectives on flavivirus Research.Viruses. 2017; 9: E97Google Scholar, 3Solomon T. Mallewa M. Dengue and other emerging flaviviruses.J Infect. 2001; 42: 104-115Abstract Full Text PDF PubMed Scopus (150) Google Scholar, 5Hidalgo J. Richards G.A. Jiménez J.I.S. Baker T. Amin P. Viral hemorrhagic fever in the tropics: report from the task force on tropical diseases by the world Federation of Societies of intensive and critical care medicine.J Crit Care. 2017; 42: 366-372Crossref PubMed Scopus (21) Google ScholarTable 1Virus Characteristics, Vectors, Hosts, Geographic Distribution, Estimation of Global Burden of Patients, Clinical Presentation, and Vaccines in Dengue, Yellow Fever, Zika, and West Nile FlavivirusesDengueYellow FeverZikaWest NileVirusFour serotypes (a fifth serotype described in Borneo)One serotypeTwo virus lineages (African and Asian)Two virus lineages (lineage 1 and lineage 2)Main mosquito vector genusAedesHaemagogus, Aedes, SabethesAedesCulexRelevant hostsHumansNonhuman primates/humansNonhuman primates/humansBirdsGeographic distributionMostly Latin America, Africa, South and Southeast Asia, and Oceania. Spreading to North America and Europe. Present in more than 128 countries.Africa (34 countries); Central and South America (13 countries)American continents, Africa, Asia; vector-borne transmission present in more than 84 countriesNorth America, Africa, the Middle East, Europe, Asia, OceaniaEstimated burden/year390 million (96 million symptomatic) worldwide8000 to 200,000 (90% in Africa) worldwideJanuary 2015 to March 2017, 754,460 suspected and laboratory-confirmed cases reported in the American continents1503 cases reported in 11 European countries in 2018; 48,183 cases reported from 1999 to 2017 in the USAClinical picture"Flu-like" to severe multisystem disease"Flu-like" to fulminating multisystem diseaseSymptomatic ("flu-like" disease) in 20% to 25% of the cases. Neurological abnormalities described in severe cases.80% asymptomatic, 20% "flu-like" symptoms to serious neuroinvasive diseaseVaccineIn developmentLive attenuated virus (YFV 17D)NoNo Open table in a new tab The global incidence of flavivirus infection has increased continuously and noticeably over the last few decades, with reports of large outbreaks in several areas of the world.10Proenca-Modena J.L. Milanez G.P. Costa M.L. Judice C.C. Maranhão Costa F.T. Zika virus: lessons learned in Brazil.Microbes Infect. 2018; 20: 661-669Crossref PubMed Scopus (20) Google Scholar, 11Moreira-Soto A. Torres M.C. Lima de Mendonça M.C. et al.Evidence for multiple sylvatic transmission cycles during the 2016-2017 yellow fever virus outbreak, Brazil.Clin Microbiol Infect. 2018; 24: 1019.e1-1019.e4Abstract Full Text Full Text PDF Scopus (48) Google Scholar, 6Leta S. Beyene T.J. De Clercq E.M. Amenu K. Kraemer M.U.G. Revie C.W. Global risk mapping for major diseases transmitted by Aedes aegypti and Aedes albopictus.Int J Infect Dis. 2018; 67: 25-35Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar, 7Brito C.A. Cordeiro M.T. One year after the Zika virus outbreak in Brazil: from hypotheses to evidence.Rev Soc Bras Med Trop. 2016; 49: 537-543Google Scholar, 8Guo C. Zhou Z. Wen Z. et al.Global epidemiology of dengue outbreaks in 1990-2015: a systematic review and Meta-analysis.Front Cell Infect Microbiol. 2017; 7: 317Crossref PubMed Scopus (177) Google Scholar, 9Rezende I.M. Sacchetto L. Munhoz de Mello É. et al.Persistence of yellow fever virus outside the Amazon basin, causing epidemics in Southeast Brazil, from 2016 to 2018.Plos Negl Trop Dis. 2018; 12: e0006538Google Scholar These diseases are also expanding from the tropical and subtropical areas, where they were typically endemic, to previously nonendemic areas (Table 1).12Petersen L.R. Marfin A.A. Shifting epidemiology of Flaviviridae.J Trav Med. 2005; 12: S3-S11PubMed Google Scholar, 13Arboviral Diseases - United States, 2017.MMWR Morb Mortal Wkly Rep. 2018; 67: 1137-1142Google Scholar, 14McGibbon E. Moy M. Vora N.M. et al.Epidemiological characteristics and Laboratory findings of Zika virus cases in New York city, January 1, 2016-June 30, 2017.Vector Borne Zoonotic Dis. 2018; 18: 382-389Google Scholar, 15Barzon L. Ongoing and emerging arbovirus threats in Europe.J Clin Virol. 2018; 107: 38-47Crossref PubMed Scopus (75) Google Scholar These changes in flavivirus epidemiology are related to the lack of health investment in the control of the vectors, increased business and tourism travel, immigration waves, world climate warming, deforestation, and unplanned, rapid urbanization.16Tabachnick W.J. Climate change and the arboviruses: lessons from the Evolution of the dengue and yellow fever viruses.Annu Rev Virol. 2016; 3: 125-145Google Scholar, 17Fuller T.L. Calvet G. Genaro Estevam C. et al.Behavioral, climatic, and environmental risk factors for Zika and Chikungunya virus infections in Rio de Janeiro, Brazil, 2015-16.PLoS One. 2017; 12: e0188002Google Scholar Some flaviviruses have been consistently identified in kidney tissue and urine of infected animals and humans and have been clinically associated with kidney diseases (Table 2).18Burdmann E.A. Jha V. Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.Kidney Int. 2017; 91: 1033-1046Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 19Barzon L. Pacenti M. Palù G. West Nile virus and kidney disease.Expert Rev Anti Infect Ther. 2013; 11: 479-487Google Scholar In this review, we will provide an overview of the epidemiology, risk factors, etiopathogenesis, kidney pathology, and outcomes of acute and chronic kidney syndromes associated with dengue, YF, Zika, and WNF viruses.Table 2Kidney Clinical Forms and Kidney Histology Associated With Infection by Dengue, Yellow Fever, Zika, and West Nile FlavivirusesFlavivirusesClinical Manifestation of the Kidney DiseaseKidney Structural LesionDengueAKI; serum electrolyte abnormalities; hematuria; nephrotic and nonnephrotic proteinuria; glomerulopathies; HUS; worsening of kidney function in CKD patients and renal transplant recipients; late development of CKD?ATN; acute tubule epithelial cell lesions; tubular and glomerular hemorrhage; interstitial edema and inflammation; glomerular congestion; hypertrophy and hyperplasia of mesangial and endothelial cells; focal thickening of the GBM; crescentic GN; diffuse proliferative GN; IgA nephropathy; peritubular capillary congestion and TMA.Yellow feverAKI; oliguria; elevation of blood urea nitrogen and serum creatinine; proteinuria; hematuria.Proliferation of mesangial cells; swelling of endothelial cells; glomerular fibrinogen deposits; interstitial and tubular cell edema; bile staining granular and hyaline casts at distal tubules.∗In monkeys.ATN with protein and hemoglobin casts; interstitial nephritis; and glomerular injury.ZikaNot yet described.Apoptosis of renal proximal tubular cells of mice in vivo and of humans in vitro.West NileAKI (rare); associated with late development of CKD.Fibrin thrombi in the small vessels; †In a diabetic and hypertensive patient.sclerotic glomeruli with mesangial matrix expansion, tubular cell degeneration and regeneration, mild interstitial lymphocytic infiltrate, and marked arteriosclerosis.Abbreviations: AKI, acute kidney injury; ATN, acute tubular necrosis; CKD, chronic kidney disease; GBM, glomerular basement membrane; GN, glomerulonephritis; HUS, hemolytic uremic syndrome; TMA, thrombotic microangiopathy.∗ In monkeys.† In a diabetic and hypertensive patient. Open table in a new tab Abbreviations: AKI, acute kidney injury; ATN, acute tubular necrosis; CKD, chronic kidney disease; GBM, glomerular basement membrane; GN, glomerulonephritis; HUS, hemolytic uremic syndrome; TMA, thrombotic microangiopathy. Dengue is globally the most clinically relevant arthropod-borne viral infection, currently posing a formidable challenge to public health in 128 countries, mainly in the tropical and subtropical areas.18Burdmann E.A. Jha V. Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.Kidney Int. 2017; 91: 1033-1046Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 20Oliveira J.F. Burdmann E.A. Dengue-associated acute kidney injury.Clin Kidney J. 2015; 8: 681-685Google Scholar The numbers that attest dengue importance are staggering: four billion individuals are considered to be at risk, and the burden of infections is estimated at 390 million/year, with 96 million patients manifesting clinical signs and symptoms. The projected annual economic burden of dengue reaches US $8.9 billion.21Bhatt S. Gething P.W. Brady O.J. et al.The global distribution and burden of dengue.Nature. 2013; 496: 504-507Crossref PubMed Scopus (5725) Google Scholar, 22Shepard D.S. Undurraga E.A. Halasa Y.A. Stanaway J.D. The global economic burden of dengue: a systematic analysis.Lancet Infect Dis. 2016; 16: 935-941Abstract Full Text Full Text PDF PubMed Scopus (368) Google Scholar Dengue epidemiology is inseparable from vector etiology. Infected female mosquitoes of the genus Aedes, specifically Aedes aegypti and Aedes albopictus, can transmit four serotypes of dengue flavivirus (a 5th serotype was described in Borneo).23Guzman M.G. Harris E. Dengue.Lancet. 2015; 385: 453-465Abstract Full Text Full Text PDF PubMed Scopus (766) Google Scholar, 24Normile D. Tropical medicine. Surprising new dengue virus throws a spanner in disease control efforts.Science. 2013; 342: 415Google Scholar These mosquitoes have intensively spread globally and adapted to urban and domestic locations, with an extraordinary efficiency. Dengue clinical presentation is extremely variable. Most cases are clinically unapparent or manifest as subclinical or self-limited febrile viral diseases characterized by an unspecific clinical picture that may comprise abrupt onset of high fever, intense headache, retroorbital pain, weakness, severe muscle and articular pain, cutaneous exanthema, anorexia, nausea, vomiting, and diarrhea. A minority of cases evolve to critical multisystem disease, with hemorrhage, hemodynamic instability, and high lethality.18Burdmann E.A. Jha V. Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.Kidney Int. 2017; 91: 1033-1046Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 20Oliveira J.F. Burdmann E.A. Dengue-associated acute kidney injury.Clin Kidney J. 2015; 8: 681-685Google Scholar, 23Guzman M.G. Harris E. Dengue.Lancet. 2015; 385: 453-465Abstract Full Text Full Text PDF PubMed Scopus (766) Google Scholar, 25World Health OrganizationDengue: Guidelines for Diagnosis, Treatment, Prevention and Control. New edition. World Health Organization, Geneva2009Google Scholar Several clinical forms of kidney involvement have been associated with dengue, including acute kidney injury (AKI), serum electrolyte abnormalities, hematuria, nephrotic and nonnephrotic proteinuria, glomerulopathies, hemolytic uremic syndrome, and worsening of kidney function in chronic kidney disease (CKD) patients and renal transplant recipients.18Burdmann E.A. Jha V. Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.Kidney Int. 2017; 91: 1033-1046Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 20Oliveira J.F. Burdmann E.A. Dengue-associated acute kidney injury.Clin Kidney J. 2015; 8: 681-685Google Scholar, 26Gurugama P. Jayarajah U. Wanigasuriya K. Wijewickrama A. Perera J. Seneviratne S.L. Renal manifestations of dengue virus infections.J Clin Virol. 2018; 101: 1-6Crossref PubMed Scopus (20) Google Scholar, 27Mallhi T.H. Khan A.H. Adnan A.S. Sarriff A. Khan Y.H. 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These abnormalities consist of acute tubular necrosis, cortical tubular hemorrhage, interstitial edema and inflammatory cell infiltration, glomerular hemorrhage, glomerular congestion, hypertrophy and hyperplasia of mesangial and endothelial cells and focal thickening of the glomerular basement membrane in children, pauci-immune crescentic glomerulonephritis, lupus-like diffuse proliferative glomerulonephritis, reversible IgA nephropathy, peritubular capillary congestion, and thrombotic microangiopathy.36Boonpucknavig V. Bhamarapravati N. Boonpucknavig S. Futrakul P. Tanpaichitr P. Glomerular changes in dengue hemorrhagic fever.Arch Pathol Lab Med. 1976; 100: 206-212Google Scholar, 37Upadhaya B.K. Sharma A. Khaira A. Dinda A.K. Agarwal S.K. Tiwari S.C. Transient IgA nephropathy with acute kidney injury in a patient with dengue fever.Saudi J Kidney Dis Transpl. 2010; 21: 521-525Google Scholar, 38Rajadhyaksha A. Mehra S. Dengue fever evolving into systemic lupus erythematosus and lupus nephritis: a case report.Lupus. 2012; 21: 999-1002Google Scholar, 39Lizarraga K.J. Florindez J.A. Daftarian P. et al.Anti-GBM disease and ANCA during dengue infection.Clin Nephrol. 2015; 83: 104-110Google Scholar, 40Bhargava V. Gupta P. Kauntia R. Bajpai G. Dengue fever-induced thrombotic microangiopathy: an Unusual cause of renal failure.Indian J Nephrol. 2017; 27: 321-323PubMed Google Scholar, 41Nieto-Ríos J.F. Álvarez Barreneche M.F. Penagos S.C. Bello Márquez D.C. Serna-Higuita L.M. Ramírez Sánchez I.C. Successful treatment of thrombotic microangiopathy associated with dengue infection: a case report and literature review.Transpl Infect Dis. 2018; 20: e12824Google Scholar, 43Mohsin N. Mohamed E. Gaber M. Obaidani I. Budruddin M. Al Busaidy S. Acute tubular necrosis associated with non-hemorrhagic Dengue fever: a case report.Ren Fail. 2009; 31: 736-739Google Scholar, 44Repizo L.P. Malheiros D.M. Yu L. Barros R.T. 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Infection of young adult mice with dengue virus type 2.Trans R Soc Trop Med Hyg. 1981; 75: 647-653Google Scholar, 48Barreto D.F. Takiya C.M. Paes M.V. et al.Histopathological aspects of Dengue-2 virus infected mice tissues and complementary virus isolation.J Submicrosc Cytol Pathol. 2004; 36: 121-130Google Scholar Dengue is a complex clinical situation in which hypovolemia, hypotension, and dehydration can coexist in a setting of a systemic inflammatory storm with marked presence of viruses in kidney tissue, making the patient particularly vulnerable to AKI. Estimation of the frequency of AKI in dengue is based mainly on retrospective studies. There is a wide variation, from approximately 1% to 36%, which depends on the specific population assessed, the severity of disease, the criteria used for the diagnosis of AKI, and the time for evaluation of the kidney function.18Burdmann E.A. Jha V. Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.Kidney Int. 2017; 91: 1033-1046Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 20Oliveira J.F. Burdmann E.A. Dengue-associated acute kidney injury.Clin Kidney J. 2015; 8: 681-685Google Scholar, 26Gurugama P. Jayarajah U. Wanigasuriya K. Wijewickrama A. Perera J. Seneviratne S.L. Renal manifestations of dengue virus infections.J Clin Virol. 2018; 101: 1-6Crossref PubMed Scopus (20) Google Scholar, 27Mallhi T.H. Khan A.H. Adnan A.S. Sarriff A. Khan Y.H. Jummaat F. Incidence, characteristics and risk factors of acute kidney injury among dengue patients: a retrospective analysis.PLoS One. 2015; 10: e0138465Crossref PubMed Scopus (45) Google Scholar, 28Mallhi T.H. Khan A.H. Sarriff A. Adnan A.S. Khan Y.H. Jummaat F. Defining acute kidney injury in dengue viral infection by conventional and novel classification systems (AKIN and RIFLE): a comparative analysis.Postgrad Med J. 2016; 92: 78-86Google Scholar, 29Nair J.J. Bhat A. Prabhu M.V. A clinical study of acute kidney injury in tropical acute febrile illness.J Clin Diagn Res. 2016; 10: OC01-OC05PubMed Google Scholar Several risk factors for dengue-associated AKI have been identified, including hypoalbuminemia, increased hepatic enzymes, reduced serum bicarbonate, simultaneous infection with bacteria or other viruses, sepsis, multiple organ failure, use of vasopressor or inotropic drugs, use of nephrotoxic drugs, severity of dengue infection, rhabdomyolysis, diabetes mellitus as comorbidity, older age, obesity, and late hospitalization.18Burdmann E.A. Jha V. Acute kidney injury due to tropical infectious diseases and animal venoms: a tale of 2 continents.Kidney Int. 2017; 91: 1033-1046Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 20Oliveira J.F. Burdmann E.A. Dengue-associated acute kidney injury.Clin Kidney J. 2015; 8: 681-685Google Scholar, 26Gurugama P. Jayarajah U. Wanigasuriya K. Wijewickrama A. Perera J. Seneviratne S.L. Renal manifestations of dengue virus infections.J Clin Virol. 2018; 101: 1-6Crossref PubMed Scopus (20) Google Scholar, 27Mallhi T.H. Khan A.H. Adnan A.S. Sarriff A. Khan Y.H. Jummaat F. Incidence, characteristics and risk factors of acute kidney injury among d
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