Pathogenesis of renal disease in leptospirosis: Clinical and experimental studies

Sitprija, Visith; Pipatanagul, Vichitra; Mertowidjojo, Koesoemowardojo; Boonpucknavig, Vijitr; Boonpucknavig, S

doi:10.1038/ki.1980.95

Cited by 101 publications

(75 citation statements)

References 20 publications

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“…Indeed, several studies on animals (22)(23)(24)(25) as well as humans (26)(27)(28) have demonstrated the presence of leptospirae and/or leptospira antigens in diseased tissues. The presence of GLP itself in these tissues was also detected immunologically during experimental leptospirosis (23).…”

Section: Discussionmentioning

confidence: 99%

Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin

Younes-Ibrahim¹,

Buffin-Meyer²,

Cheval³

et al. 1997

Braz J Med Biol Res

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On the basis of our report that a glycolipoprotein fraction (GLP) extracted from Leptospira interrogans contains a potent inhibitor of renal Na,K-ATPase, we proposed that GLP-induced inhibition of Na,K-ATPase might be the primary cellular defect in the physiopathology of leptospirosis. The present study was designed to test this hypothesis by determining whether or not 1) GLP inhibits all the isoforms of Na,K-ATPase which are expressed in the tissues affected by leptospirosis, 2) Na,K-ATPase from leptospirosis-resistant species, such as the rat, is sensitive to GLP, 3) GLP inhibits Na,K-ATPase from intact cells, and 4) GLP inhibits ouabain-sensitive H,K-ATPase. The results indicate that in the rabbit, a leptospirosis-sensitive species, GLP inhibits with similar efficiency (apparent IC 50 : 120-220 µg protein GLP/ml) all isoforms of Na,K-ATPase known to be expressed in target tissues for the disease. Na,K-ATPase from rat kidney displays a sensitivity to GLP similar to that of the rabbit kidney enzyme (apparent IC 50 : 25-80 and 50-150 µg protein GLP/ml for rat and rabbit, respectively), indicating that resistance to the disease does not result from the resistance of Na,K-ATPase to GLP. GLP also reduces ouabain-sensitive rubidium uptake in rat thick ascending limbs (pmol mm -1 min -1 ± SEM; control: 23.8 ± 1.8; GLP, 88 µg protein/ml: 8.2 ± 0.9), demonstrating that it is active in intact cells. Finally, GLP had no demonstrable effect on renal H,K-ATPase activity, even on the ouabain-sensitive form, indicating that the active principle of GLP is more specific for Na,K-ATPase than ouabain itself. Although the hypothesis remains to be demonstrated in vivo, the present findings are compatible with the putative role of GLP-induced inhibition of Na,KATPase as an initial mechanism in the physiopathology of leptospirosis.

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Section: Discussionmentioning

confidence: 99%

Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin

Younes-Ibrahim¹,

Buffin-Meyer²,

Cheval³

et al. 1997

Braz J Med Biol Res

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“…5,6 Interstitial nephritis is the main pathological finding in patients with leptospirosis, even in those without AKI. 7,8 Leptospira or its fragments can be found in renal tubules and interstitium. 9 Observational studies have indicated that Leptospira spread through the hematogenous route to the kidney, circulate to peritubular capillaries, migrate to the interstitium and renal tubule, and finally, remain in the proximal tubular lumen.…”

Section: Introductionmentioning

confidence: 99%

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Libório¹,

Braz²,

Seguro³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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Abstract. Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P 0.001) and syndecan-1 (73.7 ± 15.9 versus 21.2 ± 7.9 ng/mL, P 0.001) compared with exposed controls. Patients with leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinaseassociated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKIassociated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage.

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“…23 , bem como a de seus componentes. Estes poderiam incluir produtos de síntese bacteriana ou corresponder a substâncias liberadas durante sua lise 229 .…”

Section: Resultsunclassified

“…Estudos clínicos e anátomo-patológicos da leptospirose têm sugerido que as lesões ou as disfunções orgânicas possam ser causadas pela ação direta das leptospiras, por toxinas elaboradas por essas bactérias ou liberadas durante a sua lise 2,4,5,6,9,10,11,23,29. Diversas tentativas de isolamento e caracterização de possíveis fatores tó-xicos, foram realizadas por STALHEIM 24 , MIL-LER e cols.…”

Section: Introductionunclassified

Glicolipoproteína de Leptospira interrogans sorogrupo icterohaemorrhagiae: distribuição em fígado e rim de cobaias experimentalmente infectadas

Santos

Sakata

Yasuda

et al. 1989

Rev. Inst. Med. trop. S. Paulo

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RESUMOAcredita-se que as lesões teciduais na leptospirose possam decorrer da ação direta das leptospiras, de toxinas sintetizadas ou liberadas durante sua lise. O presente estudo visou a extração quimica da glicolipoproteína (GLP) da leptospira, a produção de anti-soro anti-GLP e a avaliação de sua distribuição em cortes de fígado e rim de cobaias inoculadas e sacrificadas em estudo seqüencial diário até o 6? dia de infecçâo, correspondente ao pico da doença. Procurou-se também correlacionar a expressão tecidual da GLP com o grau de lesões locais, em busca de novos subsídios para a compreensão da patogenia da leptospirose. A QLP foi detectada em fígado e rim de 2 dentre 6 cobaias no 5? dia e em todas as 6 no 6? dia de infecção, sob a forma de grânulos no citoplasma de macrófagos, livres no interstício ou acolados à membrana de células endoteliais e parenquimatosas, especialmente nas regiões mais lesadas. A cronologia do aparecimento da GLP e sua distribuição sugerem tratar-se de produto de lise de leptospiras fagocitadas por macrófagos e que esta substância, conquanto não comprovada como iniciadora das lesões, associa-se a seu agravamento nas etapas mais avançadas da leptospirose.IMTERMOS. Glicolipoproteína; Leptospirose; Imunohistoquímica. INTRODUÇÃOEstudos clínicos e anátomo-patológicos da leptospirose têm sugerido que as lesões ou as disfunções orgânicas possam ser causadas pela ação direta das leptospiras, por toxinas elaboradas por essas bactérias ou liberadas durante a sua lise 2,4,5,6,9,10,11,23,29. Diversas tentativas de isolamento e caracterização de possíveis fatores tó-xicos, foram realizadas por STALHEIM 24 , MIL-LER e cols.* JACKSON & ZEY 16 , KNIGHT e cols. 17 e FAINE e cols. ,5 . A ação citotóxica do sorotipo pomona sobre cultura âe fibroblastos foi demonstrada por YAM e cols. 28 , sem entretanto caracterizar a natureza química responsá-vel por essa atividade tóxica. Já, VINH e cols. 27 extrairam do sorotipo Copenhagen!, tanto de cepas virulentas quanto de cepas avirulentas, uma glicolipoproteína (GLP) de efeito citotóxico sobre fibroblastos de camundongos e sugeriram ser o componente lipídico dessa GLP o fator responsável por essa toxicidade.(1) Divisão de Patologia, Instituto

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Pathogenesis of renal disease in leptospirosis: Clinical and experimental studies

Cited by 101 publications

References 20 publications

Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin

Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin

Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Glicolipoproteína de Leptospira interrogans sorogrupo icterohaemorrhagiae: distribuição em fígado e rim de cobaias experimentalmente infectadas

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