{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:03:12Z","timestamp":1792803792204,"version":"4.5.0"},"reference-count":122,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T00:00:00Z","timestamp":1644969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mahidol University \u2013 Basic Research Fund: fiscal year 2021","award":["(FRB640032) (Contract No. BRF1-A42\/ 2564)"],"award-info":[{"award-number":["(FRB640032) (Contract No. BRF1-A42\/ 2564)"]}],"id":[{"id":"https:\/\/ror.org\/01znkr924","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Mahidol University \u2013 Basic Research Fund: fiscal year 2022","award":["(FRB650007\/ 0185) (Contract No. BRF1-062\/ 2565)"],"award-info":[{"award-number":["(FRB650007\/ 0185) (Contract No. BRF1-062\/ 2565)"]}],"id":[{"id":"https:\/\/ror.org\/01znkr924","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Health System Research Institute (HRSI) \u2013 Flagship Project Fund: fiscal year 2020","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Leptospirosis is a zoonotic and waterborne disease worldwide. It is a neglected infectious disease caused by Leptospira spp., as well as a reemerging disease and global public health problem with respect to morbidity and mortality both in humans and animals. Leptospirosis emerges as a leading cause of acute febrile illness along with hepatorenal injury in many countries, including Thailand. While most affected persons are symptomatic in acute disease, which is always difficult to differentiate from other tropical diseases, there is growing evidence of subtle manifestations that cause unrecognized chronic symptoms. The kidney is one of the common organs affected by Leptospires. Although acute kidney injury in the spectrum of interstitial nephritis is a well-described characteristic in severe leptospirosis, chronic kidney disease from leptospirosis is widely discussed. Early recognition of severe leptospirosis leads to reduce morbidity and mortality. Thus, in this review, we highlight the spectrum of characteristics involved in leptospirosis kidney disease and the use of serologic and molecular methods, as well as the treatments of severe leptospirosis.<\/jats:p>","DOI":"10.3390\/cells11040698","type":"journal-article","created":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T20:26:41Z","timestamp":1645043201000},"page":"698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Going Micro in Leptospirosis Kidney Disease"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2965-146X","authenticated-orcid":false,"given":"Wiwat","family":"Chancharoenthana","sequence":"first","affiliation":[{"name":"Tropical Nephrology Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand"},{"name":"Tropical Immunology and Translational Research Unit, Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence on Translational Research in Inflammatory and Immunology (CETRII), Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3969-7792","authenticated-orcid":false,"given":"Marcus J.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand"},{"name":"Department of Intensive Care, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands"},{"name":"Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford OX3 7LG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen M.","family":"Dondorp","sequence":"additional","affiliation":[{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand"},{"name":"Department of Intensive Care, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands"},{"name":"Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford OX3 7LG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1179\/136485910X12851868779867","article-title":"Emerging tropical diseases in Australia. Part 1. Leptospirosis","volume":"104","author":"Tulsiani","year":"2010","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hinjoy, S., Kongyu, S., Doung-Ngern, P., Doungchawee, G., Colombe, S.D., Tsukayama, R., and Suwancharoen, D. (2019). Environmental and behavioral risk factors for severe leptospirosis in Thailand. Trop. Med. Infect. Dis., 4.","DOI":"10.3390\/tropicalmed4020079"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.31128\/AFP-07-17-4286","article-title":"Leptospirosis: An important zoonosis acquired through work, play and travel","volume":"47","author":"Lau","year":"2018","journal-title":"Aust. J. Gen. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1080\/00480169.1980.34688","article-title":"Leptospirosis and other infections of Battus rattus and Rattus norvegicus","volume":"28","author":"Carter","year":"1980","journal-title":"N. Z. Vet. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/sj.ki.5000119","article-title":"Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane proteins in proximal tubule cells","volume":"69","author":"Yang","year":"2006","journal-title":"Kidney Int."},{"key":"ref_6","first-page":"199","article-title":"Leptospirosis diagnosis: Competancy of various laboratory tests","volume":"8","author":"Budihal","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Costa, F., Hagan, J.E., Calcagno, J., Kane, M., Torgerson, P., Martinez-Silveira, M.S., Stein, C., Abela-Ridder, B., and Ko, A.I. (2015). Global morbidity and mortality of leptospirosis: A systematic Review. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003898"},{"key":"ref_8","unstructured":"Hinjoy, S. (2021, November 01). Epidemiology of Leptospirosis from Thai National Disease Surveillance System, 2003\u20132012. Outbreak, Surveillance, and Investigation Reports (OSIR). Available online: http:\/\/www.osirjournal.net\/index.php\/osir\/article\/view\/38."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Torgerson, P.R., Hagan, J.E., Costa, F., Calcagno, J., Kane, M., Martinez-Silveira, M.S., Goris, M.G., Stein, C., Ko, A.I., and Abela-Ridder, B. (2015). Global burden of leptospirosis: Estimated in terms of disability adjusted life years. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004122"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1016\/S0140-6736(12)61728-0","article-title":"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: A systematic analysis for the Global Burden of Disease Study 2010","volume":"380","author":"Lozano","year":"2012","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/S0272-6386(97)90091-3","article-title":"Leptospirosis: An ignored cause of acute renal failure in Taiwan","volume":"30","author":"Yang","year":"1997","journal-title":"Am. J. Kidney Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1097\/SHK.0b013e3182594ad7","article-title":"Early identification of leptospirosis as an ignored cause of multiple organ dysfunction syndrome","volume":"38","author":"Yang","year":"2012","journal-title":"Shock"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/ncpneph0326","article-title":"Renal dysfunction in leptospirosis: A view from the tropics","volume":"2","author":"Sitprija","year":"2006","journal-title":"Nat. Clin. Pract. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.5414\/CN108865","article-title":"Acute kidney injury in leptospirosis: The Kidney Disease Improving Global Outcomes (KDIGO) criteria and mortality","volume":"86","author":"Teles","year":"2016","journal-title":"Clin. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/0974-777X.127941","article-title":"Studying risk factors associated with human leptospirosis","volume":"6","author":"Kamath","year":"2014","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.4269\/ajtmh.2010.09-0239","article-title":"Travel-related leptospirosis in Israel: A nationwide study","volume":"82","author":"Leshem","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1159\/000185943","article-title":"Acute renal failure of leptospirosis: Nonoliguric and hypokalemic forms","volume":"55","author":"Seguro","year":"1990","journal-title":"Nephron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1638\/2009-0197.1","article-title":"Vasculitis secondary to presumptive leptospirosis treated with long-term corticosteroids in a captive lesser kudu (Tragelaphus imberbis australis)","volume":"41","author":"Fogelberg","year":"2010","journal-title":"J. Zoo. Wildl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1995-7645(11)60041-2","article-title":"Two uncommon manifestations of leptospirosis: Sweet\u2019s syndrome and central nervous system vasculitis","volume":"4","author":"George","year":"2011","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1752-1947-8-150","article-title":"Myocarditis, pancreatitis, polyarthritis, mononeuritis multiplex and vasculitis with symmetrical peripheral gangrene of the lower extremities as a rare presentation of leptospirosis: A case report and review of the literature","volume":"8","author":"Panagopoulos","year":"2014","journal-title":"J. Med. Case Rep."},{"key":"ref_21","first-page":"229","article-title":"Leptospirosis with acute renal failure and vasculitis: A case report","volume":"34","author":"Kudu","year":"2018","journal-title":"Arch. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/ndt\/14.1.193","article-title":"Leptospirosis associated with hypokalaemia and thick ascending limb dysfunction","volume":"14","author":"Lin","year":"1999","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1590\/S1413-86702008000300016","article-title":"Renal involvement in leptospirosis\u2014New insights into pathophysiology and treatment","volume":"12","author":"Cerqueira","year":"2008","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s00428-010-0894-8","article-title":"Acute kidney injury in human leptospirosis: An immunohistochemical study with pathophysiological correlation","volume":"456","author":"Araujo","year":"2010","journal-title":"Virchows Arch."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/ncpneph0695","article-title":"Altered fluid, electrolyte and mineral status in tropical disease, with an emphasis on malaria and leptospirosis","volume":"4","author":"Sitprija","year":"2008","journal-title":"Nat. Clin. Pract. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"F586","DOI":"10.1152\/ajprenal.00102.2006","article-title":"Leptospirosis leads to dysregulation of sodium transporters in the kidney and lung","volume":"292","author":"Andrade","year":"2007","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1093\/ndt\/gfh452","article-title":"Reduced renal Na+-K+-Cl- co-transporter activity and inhibited NKCC2 mRNA expression by Leptospira shermani: From bedside to bench","volume":"19","author":"Wu","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1093\/ndt\/gfm698","article-title":"Renal magnesium wasting and tubular dysfunction in leptospirosis","volume":"23","author":"Khositseth","year":"2008","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00574","DOI":"10.1016\/j.idcr.2019.e00574","article-title":"Unusual presentation of urban leptospirosis complicated by a septic shock","volume":"17","author":"Farooqui","year":"2019","journal-title":"IDCases"},{"key":"ref_30","first-page":"817414","article-title":"Severe leptospirosis with multiple organ failure successfully treated by plasma exchange and high-volume hemofiltration","volume":"2011","author":"Bourquin","year":"2011","journal-title":"Case Rep. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1099\/00222615-9-2-149","article-title":"The route of entry of leptospires into the kidney tubule","volume":"9","author":"Marshall","year":"1976","journal-title":"J. Med. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1097\/01.ASN.0000022007.91733.62","article-title":"The Leptospira outer membrane protein LipL32 induces tubulointerstitial nephritis-mediated gene expression in mouse proximal tubule cells","volume":"13","author":"Yang","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_33","first-page":"e00700","article-title":"Lactobacillus rhamnosus L34 attenuates gut translocation-induced bacterial sepsis in murine models of leaky gut","volume":"86","author":"Panpetch","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ondee, T., Gillen, J., Visitchanakun, P., Somparn, P., Issara-Amphorn, J., Dang Phi, C., Chancharoenthana, W., Gurusamy, D., Nita-Lazar, A., and Leelahavanichkul, A. (2019). Lipocalin-2 (Lcn-2) attenuates polymicrobial sepsis with LPS preconditioning (LPS tolerance) in FcGRIIb deficient lupus mice. Cells, 8.","DOI":"10.3390\/cells8091064"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1681\/ASN.V11112017","article-title":"Leptospira outer membrane protein activates NF-kappaB and downstream genes expressed in medullary thick ascending limb cells","volume":"11","author":"Yang","year":"2000","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1128\/IAI.68.4.2276-2285.2000","article-title":"The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection","volume":"68","author":"Haake","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0378-1119(00)00293-6","article-title":"Identification and partial characterization of a novel hemolysin from Leptospira interrogans serovar lai","volume":"254","author":"Lee","year":"2000","journal-title":"Gene"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.micinf.2018.01.010","article-title":"Leptospira interrogans infection leads to IL-1\u03b2 and IL-18 secretion from a human macrophage cell line through reactive oxygen species and cathepsin B mediated-NLRP3 inflammasome activation","volume":"20","author":"Li","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nri1997","article-title":"Inflammasome adaptors and sensors: Intracellular regulators of infection and inflammation","volume":"7","author":"Mariathasan","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, H., Wu, Y., Ojcius, D.M., Yang, X.F., Zhang, C., Ding, S., Lin, X., and Yan, J. (2012). Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-\u03baB signaling pathways. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042266"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2923072","DOI":"10.1155\/2019\/2923072","article-title":"Roles of inflammasomes in inflammatory kidney diseases","volume":"2019","author":"Fan","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/sj.ki.5002393","article-title":"Leptospirosis renal disease: Understanding the initiation by Toll-like receptors","volume":"72","author":"Yang","year":"2007","journal-title":"Kidney Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S465","DOI":"10.1086\/431998","article-title":"Prevention of lymphocyte apoptosis\u2014A potential treatment of sepsis?","volume":"41","author":"Hotchkiss","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Raffray, L., Giry, C., Vandroux, D., Kuli, B., Randrianjohany, A., Pequin, A.M., Renou, F., Jaffar-Bandjee, M.C., and Gasque, P. (2016). Major neutrophilia observed in acute phase of human leptospirosis is not associated with increased expression of granulocyte cell activation markers. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165716"},{"key":"ref_45","first-page":"EC21","article-title":"Serial changes in complete blood counts in patients with leptospirosis: Our experience","volume":"11","author":"Adiga","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1681\/ASN.2006020159","article-title":"Leptospiral outer membrane protein induces extracellular matrix accumulation through a TGF-beta1\/Smad-dependent pathway","volume":"17","author":"Tian","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1128\/IAI.01287-09","article-title":"Leptospira santorosai Serovar Shermani detergent extract induces an increase in fibronectin production through a Toll-like receptor 2-mediated pathway","volume":"79","author":"Tian","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fanton d\u2019Andon, M., Quellard, N., Fernandez, B., Ratet, G., Lacroix-Lamand\u00e9, S., Vandewalle, A., Boneca, I.G., Goujon, J.M., and Werts, C. (2014). Leptospira Interrogans induces fibrosis in the mouse kidney through Inos-dependent, TLR- and NLR-independent signaling pathways. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002664"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Carrillo-Larco, R.M., Altez-Fernandez, C., Acevedo-Rodriguez, J.G., Ortiz-Acha, K., and Ugarte-Gil, C. (2019). Leptospirosis as a risk factor for chronic kidney disease: A systematic review of observational studies. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007458"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Herath, N.J., Kularatne, S.A., Weerakoon, K.G., Wazil, A., Subasinghe, N., and Ratnatunga, N.V. (2014). Long term outcome of acute kidney injury due to leptospirosis? A longitudinal study in Sri Lanka. BMC Res. Notes, 7.","DOI":"10.1186\/1756-0500-7-398"},{"key":"ref_51","first-page":"65","article-title":"Leptospirosis in humans","volume":"387","author":"Haake","year":"2015","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1111\/j.1365-3083.2010.02505.x","article-title":"Leptospirosis: Aspects of innate immunity, immunopathogenesis and immune evasion from the complement system","volume":"73","author":"Fraga","year":"2011","journal-title":"Scand. J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Reis, E.A., Hagan, J.E., Ribeiro, G.S., Teixeira-Carvalho, A., Martins-Filho, O.A., Montgomery, R.R., Shaw, A.C., Ko, A.I., and Reis, M.G. (2013). Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002457"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cyto.2011.01.014","article-title":"Serum TNF-\u03b1, sTNFR1, IL-6, IL-8 and IL-10 levels in Weil\u2019s syndrome","volume":"54","author":"Kyriakidis","year":"2011","journal-title":"Cytokine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3389\/fimmu.2016.00623","article-title":"Complement evasion by pathogenic Leptospira","volume":"7","author":"Fraga","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.molimm.2013.05.222","article-title":"Human complement control and complement evasion by pathogenic microbes\u2014Tipping the balance","volume":"56","author":"Zipfel","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1128\/IAI.01310-08","article-title":"Immune evasion of Leptospira species by acquisition of human complement regulator C4BP","volume":"77","author":"Barbosa","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2009.07.005","article-title":"Complement and immune defense: From innate immunity to human diseases","volume":"126","author":"Zipfel","year":"2009","journal-title":"Immunol. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1128\/IAI.02844-14","article-title":"Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA","volume":"83","author":"Miragaia","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3389\/fmicb.2017.00958","article-title":"Pathogenic leptorspira secreted proteases target the membrane attack complex: A potential role for thermolysin in complement inhibition","volume":"8","author":"Amamura","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1128\/IAI.01282-09","article-title":"Leptospiral endostatin-like protein A is a bacterial cell surface receptor for human plasminogen","volume":"78","author":"Verma","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1099\/mic.0.000217","article-title":"Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation","volume":"162","author":"Siqueira","year":"2016","journal-title":"Microbiology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bj.2019.12.002","article-title":"Leptospirosis is an invasive infectious and systemic inflammatory disease","volume":"43","author":"Sun","year":"2020","journal-title":"Biomed. J."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Scharrig, E., Carestia, A., Ferrer, M.F., C\u00e9dola, M., Pretre, G., Drut, R., Picardeau, M., Schattner, M., and G\u00f3mez, R.M. (2015). Neutrophil extracellular traps are involved in the innate immune response to infection with Leptospira. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003927"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41426-018-0135-9","article-title":"A novel Fas-binding outer membrane protein and lipopolysaccharide of Leptospira interrogans induce macrophage apoptosis through the Fas\/FasL-caspase-8\/-3 pathway","volume":"7","author":"Du","year":"2018","journal-title":"Emerg. Microbes Infect."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Garcia, L.E., de Ara\u00fajo Junior, E.C., Melo, L.M., Bragato, J.P., Peir\u00f3, J.R., F\u00e9lix de Lima, V.M., Marinho, M., Arnold, D.R., and Lopes, F.L. (2018). Characterization of the microtranscriptome of macrophages infected with virulent, attenuated and saprophyte strains of Leptospira spp.. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006621"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Silva, P., Lauretti-Ferreira, F., Caldas de Lima, M., Lima, S.S., Covarrubias, A.E., De Franco, M., Carvalho, E., Ho, P.L., da Costa, R., and Martins, E. (2019). Phagocytosis of Leptospira by leukocytes from mice with different susceptibility to leptospirosis and possible role of chemokines. BMC Microbiol., 19.","DOI":"10.1186\/s12866-018-1371-9"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.jiph.2018.10.137","article-title":"Diagnostic accuracy of rapid diagnostic tests for the early detection of leptospirosis","volume":"12","author":"Alia","year":"2019","journal-title":"J. Infect. Public Health"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rubbo, P.A., Soup\u00e9-Gilbert, M.E., Golongba, D.M., Mbombo, F., Girault, D., Nakoun\u00e9, E., Lombart, J.P., Breurec, S., and Goarant, C. (2018). Evidence of human leptospirosis cases in a cohort of febrile patients in Bangui, Central African Republic: A retrospective study, 2012\u20132015. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3298-z"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1016\/j.vaccine.2017.08.067","article-title":"DNA vaccines against leptospirosis: A literature review","volume":"35","author":"Silveira","year":"2017","journal-title":"Vaccine"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lin, X., Xiao, G., Luo, D., Kong, L., Chen, X., Sun, D., and Yan, J. (2016). Chimeric epitope vaccine against Leptospira interrogans infection and induced specific immunity in guinea pigs. BMC Microbiol., 16.","DOI":"10.1186\/s12866-016-0852-y"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"103984","DOI":"10.1016\/j.dci.2020.103984","article-title":"Goat \u03b3\u03b4 T cell subpopulations defined by WC1 expression, responses to pathogens and cytokine production","volume":"118","author":"Yirsaw","year":"2021","journal-title":"Dev. Comp. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Ferrer, M.F., Scharrig, E., Alberdi, L., Cedola, M., Pretre, G., Drut, R., Song, W.C., and Gomez, R.M. (2014). Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102860"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1128\/CVI.00397-15","article-title":"Specific CD4+ T-cell reactivity and cytokine release in different clinical presentations of leptospirosis","volume":"22","author":"Volz","year":"2015","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fcimb.2018.00204","article-title":"Leptospirosis pathophysiology: Into the storm of cytokines","volume":"8","author":"Cagliero","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diagmicrobio.2013.09.012","article-title":"Rapid tests for diagnosis of leptospirosis: Current tools and emerging technologies","volume":"78","author":"Picardeau","year":"2014","journal-title":"Diag. Microbiol. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1128\/CMR.14.2.296-326.2001","article-title":"Leptospirosis","volume":"14","author":"Levett","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_78","unstructured":"Faine, S., and World Health Organization (1982). Guidelines for the Control of Leptospirosis, WHO. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/37219."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0034-5288(18)31716-8","article-title":"Dihydrostreptomycin treatment of bovine carriers of Leptospira interrogans serovar Hardjo","volume":"39","author":"Ellis","year":"1985","journal-title":"Res. Vet. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"9620","DOI":"10.1038\/s41598-020-66526-4","article-title":"Isolation and propagation of leptospires at 37 \u00b0C directly from the mammalian host","volume":"10","author":"Hornsby","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3201\/eid1903.111260","article-title":"Human leptospirosis trends, the Netherlands, 1925\u20132008","volume":"19","author":"Goris","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1056\/NEJMoa1401268","article-title":"Actionable diagnosis of neuroleptospirosis by next-generation sequencing","volume":"370","author":"Wilson","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Villumsen, S., Pedersen, R., Krogfelt, K.A., and Jensen, J.S. (2010). Expanding the diagnostic use of PCR in leptospirosis: Improved method for DNA extraction from blood cultures. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012095"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.femsle.2005.06.011","article-title":"A rapid and quantitative method for the detection of Leptospira species in human leptospirosis","volume":"249","author":"Merien","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3389\/fmicb.2020.00457","article-title":"A Validated multiplex real-time PCR assay for the diagnosis of infectious Leptospira spp.: A novel assay for the detection and differentiation of strains from both pathogenic groups I and II","volume":"11","author":"Lanka","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.diagmicrobio.2013.12.009","article-title":"Evaluation of nested polymerase chain reaction for the early detection of Leptospira spp. DNA in serum samples from patients with leptospirosis","volume":"78","author":"Blanco","year":"2014","journal-title":"Diag. Microbiol. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1139\/w06-027","article-title":"Nested polymerase chain reaction for detection of pathogenic leptospires","volume":"52","author":"Jouglard","year":"2006","journal-title":"Can. J. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Gasem, M.H., Hadi, U., Alisjahbana, B., Tjitra, E., Hapsari, M., Lestari, E.S., Aman, A.T., Lokida, D., Salim, G., and Kosasih, H. (2020). Leptospirosis in Indonesia: Diagnostic challenges associated with atypical clinical manifestations and limited laboratory capacity. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-4903-5"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Widiasih, D.A., Lindahl, J.F., Artama, W.T., Sutomo, A.H., Kutanegara, P.M., Mulyani, G.T., Widodo, E., Djohan, T.S., and Unger, F. (2021). Leptospirosis in ruminants in Yogyakarta, Indonesia: A serological survey with mixed methods to identify risk factors. Trop. Med. Infect. Dis., 6.","DOI":"10.3390\/tropicalmed6020084"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1128\/JCM.00481-12","article-title":"A new loop-mediated isothermal amplification method for rapid, simple, and sensitive detection of Leptospira spp. in urine","volume":"50","author":"Koizumi","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.4269\/ajtmh.20-1518","article-title":"Next-generation sequencing analysis of pathogenic leptospira: A way forward for understanding infectious disease dynamics in low\/middle-income, disease-endemic settings","volume":"104","author":"Agampodi","year":"2021","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jmii.2013.03.001","article-title":"Laboratory diagnosis of leptospirosis: A challenge","volume":"46","author":"Musso","year":"2013","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_93","first-page":"184","article-title":"Overview of laboratory methods to diagnose Leptospirosis and to identify and to type leptospires","volume":"20","author":"Marquez","year":"2017","journal-title":"Int. Microbiol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Goris, M.G., Leeflang, M.M., Loden, M., Wagenaar, J.F., Klatser, P.R., Hartskeerl, R.A., and Boer, K.R. (2013). Prospective evaluation of three rapid diagnostic tests for diagnosis of human leptospirosis. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002290"},{"key":"ref_95","unstructured":"(2022, February 01). OiE Terrestrial Manual. Chapter 3.1.12. Leptospirosis. Available online: https:\/\/www.oie.int\/fileadmin\/Home\/fr\/Health_standards\/tahm\/3.01.12_LEPTO.pdf."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1128\/jcm.32.8.1894-1898.1994","article-title":"Detection of leptospires in urine by PCR for early diagnosis of leptospirosis","volume":"32","author":"Bal","year":"1994","journal-title":"J. Clin. Microbiol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ganoza, C.A., Matthias, M.A., Saito, M., Cespedes, M., Gotuzzo, E., and Vinetz, J.M. (2010). Asymptomatic renal colonization of humans in the peruvian Amazon by Leptospira. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000612"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Sukmark, T., Lumlertgul, N., Peerapornratana, S., Khositrangsikun, K., Tungsanga, K., Sitprija, V., Srisawat, N., and Thai-Lepto AKI study group (2018). Thai-Lepto-on-admission probability (THAI-LEPTO) score as an early tool for initial diagnosis of leptospirosis: Result from Thai-Lepto AKI study group. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006319"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1097\/01.qco.0000178824.05715.2c","article-title":"Leptospirosis","volume":"18","author":"McBride","year":"2005","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1086\/513767","article-title":"Leptospirosis: Prognostic factors associated with mortality","volume":"25","author":"Dupont","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"14630","DOI":"10.1038\/s41598-021-94073-z","article-title":"The role of leptospiremia and specific immune response in severe leptospirosis","volume":"11","author":"Limothai","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/S0140-6736(99)80012-9","article-title":"Urban epidemic of severe leptospirosis in Brazil. Salvador Leptospirosis Study Group","volume":"354","author":"Ko","year":"1999","journal-title":"Lancet"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.4269\/ajtmh.1983.32.1464","article-title":"Thrombocytopenia and renal failure in leptospirosis","volume":"32","author":"Raoult","year":"1983","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Yang, H.L., Jiang, X.C., Zhang, X.Y., Li, W.J., Hu, B.Y., Zhao, G.P., and Guo, X.K. (2006). Thrombocytopenia in the experimental leptospirosis of guinea pig is not related to disseminated intravascular coagulation. BMC Infect. Dis., 6.","DOI":"10.1186\/1471-2334-6-19"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1080\/20477724.2020.1799605","article-title":"Kidney biomarkers in tropical infections: An update","volume":"114","author":"Duarte","year":"2020","journal-title":"Pathog. Glob. Health"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.2215\/CJN.11261210","article-title":"Urinary biomarkers and renal recovery in critically ill patients with renal support","volume":"6","author":"Srisawat","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Srisawat, N., Praditpornsilpa, K., Patarakul, K., Techapornrung, M., Daraswang, T., Sukmark, T., Khositrangsikun, K., Fakthongyoo, A., Oranrigsupak, P., and Praderm, L. (2015). Neutrophil gelatinase associated lipocalin (NGAL) in leptospirosis acute kidney injury: A multicenter study in Thailand. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143367"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/msb.2011.37","article-title":"Absolute quantification of microbial proteomes at different states by directed mass spectrometry","volume":"7","author":"Schmidt","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Panich, T., Chancharoenthana, W., Somparn, P., Issara-Amphorn, J., Hirankarn, N., and Leelahavanichkul, A. (2017). Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury. BMC Nephrol., 18.","DOI":"10.1186\/s12882-016-0415-3"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1086\/375226","article-title":"Ceftriaxone compared with sodium penicillin G for treatment of severe leptospirosis","volume":"36","author":"Panaphut","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_111","first-page":"CD008264","article-title":"Antibiotics for leptospirosis","volume":"2","author":"Coldren","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1097\/CCM.0000000000005357","article-title":"Executive summary: Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock 2021","volume":"49","author":"Evans","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1093\/bja\/aev222","article-title":"Decrease in pulse pressure and stroke volume variations after mini-fluid challenge accurately predicts fluid responsiveness","volume":"115","author":"Mallat","year":"2015","journal-title":"Br. J. Anaesth."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1097\/CCM.0b013e31824e1a1f","article-title":"Fluid balance and outcome in acute kidney injury: Is fluid really the best medicine?","volume":"40","author":"Murugan","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1097\/00024382-199805000-00009","article-title":"Etiology of metabolic acidosis during saline resuscitation in endotoxemia","volume":"9","author":"Kellum","year":"1998","journal-title":"Shock"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1056\/NEJMra1309483","article-title":"Lactic acidosis","volume":"371","author":"Kraut","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_117","first-page":"303","article-title":"Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis","volume":"18","author":"Hoste","year":"2005","journal-title":"J. Nephrol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"739","DOI":"10.2215\/CJN.00680207","article-title":"Door-to-dialysis time and daily hemodialysis in patients with leptospirosis: Impact on mortality","volume":"2","author":"Andrade","year":"2007","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/1744-9987.12016","article-title":"Enhanced vascular endothelial growth factor and inflammatory cytokine removal with online hemodiafiltration over high-flux hemodialysis in sepsis-related acute kidney injury patients","volume":"17","author":"Chancharoenthana","year":"2013","journal-title":"Ther. Apher. Dial."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1056\/NEJMoa020074","article-title":"Hemofiltration and peritoneal dialysis in infection-associated acute renal failure in Vietnam","volume":"347","author":"Phu","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.3748\/wjg.v25.i28.3684","article-title":"Acute kidney injury spectrum in patients with chronic liver disease: Where do we stand?","volume":"25","author":"Chancharoenthana","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"R23","DOI":"10.1186\/cc11188","article-title":"Hepatorenal syndrome: The 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group","volume":"16","author":"Nadim","year":"2012","journal-title":"Crit. Care"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/4\/698\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:20:58Z","timestamp":1760134858000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/4\/698"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,16]]},"references-count":122,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["cells11040698"],"URL":"https:\/\/doi.org\/10.3390\/cells11040698","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,16]]}}}