RESUMO
Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum. Clinically, VL evolves with systemic impairment, immunosuppression and hyperactivation with hypergammaglobulinemia. Although renal involvement has been recognized, a dearth of understanding about the underlying mechanisms driving acute kidney injury (AKI) in VL remains. We aimed to evaluate the involvement of immunoglobulins (Igs) and immune complexes (CIC) in the occurrence of AKI in VL patients. Fourteen VL patients were evaluated between early treatment and 12 months post-treatment (mpt). Anti-Leishmania Igs, CIC, cystatin C, C3a and C5a were assessed and correlated with AKI markers. Interestingly, high levels of CIC were observed in VL patients up to 6 mpt. Concomitantly, twelve patients met the criteria for AKI, while high levels of cystatin C were observed up to 6 mpt. Plasmatic cystatin C was positively correlated with CIC and Igs. Moreover, C5a was correlated with cystatin C, CIC and Igs. We did not identify any correlation between amphotericin B use and kidney function markers in VL patients, although this association needs to be further explored in subsequent studies. Our data reinforce the presence of an important renal function impairment during VL, suggesting the involvement of Igs, CIC, and C5a in this clinical condition.
Assuntos
Injúria Renal Aguda , Complexo Antígeno-Anticorpo , Leishmaniose Visceral , Humanos , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/sangue , Injúria Renal Aguda/sangue , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/parasitologia , Masculino , Feminino , Complexo Antígeno-Anticorpo/sangue , Adulto , Biomarcadores/sangue , Pessoa de Meia-Idade , Cistatina C/sangue , Adolescente , Adulto Jovem , Anfotericina B/uso terapêutico , Leishmania infantum/imunologiaRESUMO
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Assuntos
Humanos , Masculino , Adulto , Injúria Renal Aguda/patologia , Plasmodium malariae/isolamento & purificação , Malária/complicações , Injúria Renal Aguda/parasitologia , Malária/tratamento farmacológico , Malária/microbiologia , Injúria Renal Aguda/diagnóstico , Rim/parasitologia , BiópsiaRESUMO
Abstract INTRODUCTION Renal damage is a consequence of severe malaria, and is generally caused by sequestration of Plasmodium falciparum -infected erythrocytes in the renal microcirculation, which leads to obstruction, hypoxia, and ischemia. This triggers high mobility group box 1 (HMGB1) to send a danger signal through toll-like receptors 2 and 4. This signal up-regulates inducible nitric oxide (iNOS) and nitrotyrosine to re-perfuse the tissue, and also increases heat shock protein 70 (HSP70) expression. As no study has examined the involvement of intracellular secondary molecules in this setting, the present study compared the renal expressions of HSP70, HMGB1, iNOS, and nitrotyrosine between mice suffered from severe malaria and normal mice. METHODS C57BL/6 mice were divided into an infected group (intraperitoneal injection of 10 6 P. berghei ANKA) and a non-infected group. Renal damage was evaluated using hematoxylin eosin staining, and immunohistochemistry was used to evaluate the expressions of HSP70, HMGB1, iNOS, and nitrotyrosine. RESULTS Significant inter-group differences were observed in the renal expressions of HSP70, HMGB1, and iNOS (p=0.000, Mann-Whitney test), as well as nitrotyrosine (p=0.000, independent t test). The expressions of HSP70 and HMGB1 were strongly correlated (p=0.000, R=1.000). No correlations were observed between iNOS and HMGB, HMGB1 and nitrotyrosine, HSP70 and nitrotyrosine, or iNOS and nitrotyrosine. CONCLUSIONS It appears that HMGB1, HSP70, iNOS, and nitrotyrosine play roles in the renal damage that is observed in mice with severe malaria. Only HSP70 expression is strongly correlated with the expression of HMGB1.