Disfunção renal em pacientes com leishmaniose tegumentar americana antes e após o uso do antimoniato de meglumina

• Ano de defesa: 2011
• Autor(a) principal: Oliveira, Rodrigo Alves de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Palavras-chave em Português: Leishmaniose Cutânea; Insuficiência Renal Crônica; Transtornos Urinários
• Link de acesso: http://www.repositorio.ufc.br/handle/riufc/12259

Leishmaniasis is an infectious, non-contagious zoonotic disease for which humans are incidental hosts. Various types of kidney injury have been reported in cases of visceral leishmaniasis. The renal dysfunction seen in ACL has been attributed to the use of antimonials. Objectives. To determine whether ACL itself and its specific treatment can cause renal dysfunction, we evaluated ACL patients before and after to the initiation of treatment. Patients and methods. This was a controlled, observational prospective study, conducted in the city of Barbalha, state of Ceara, Brazil, between July 2008 and August 2009. The study group comprised 37 patients diagnosed with ACL based on clinical, epidemiological, serological and histopathological criteria, as well as on Montenegro skin test results. Before and after specific treatment, glomerular and renal tubular function were tested, and the results were compared with those obtained from 10 control subjects. Urine and plasma osmolality (Uosm and Posm) were tested before and after administration of DDAVP (intranasal, after a 12-h fast), before and after specific treatment. Plasma bicarbonate (Pbic), urinary pH (UpH) and plasma pH (PpH) were evaluated before and after oral administration of CaCl2 (acidification test), before and after specific treatment. The following urinary exosomes were quantified before specific treatment: AQP2; NHE3; NKCC2 H-ATPase and pendrin. Results. Mean age was 35.6 12 years in the study group and 32.2 ± 11.7 years in the control group. The study group comprised 19 men and 26 non-whites. All patients had cutaneous ACL (mean disease duration, 28.5 ± 20.6 days). Of the 37 patients, 27 had a single skin lesion, 7 had 2-4 lesions, and 3 had >4 lesions. Significant glomerular dysfunction wasn´t shown neither before, nor after specific treatment (plasma creatinine, 0.81 0.16 mg/dl; ClCr, 109 31 ml/min). Urinary concentrating defect was identified based on the post-test U/Posm ratio (<2.8) in 27 patients before treatment and in 31 patients after treatment (77% vs 88%, p=NS) and post-test Uosm (<700 mOsm/kg) in 22 (63%). Significant difference in U/Posm ratio in T4 wasn´t shown between before and after treatment (2.19 ± 0.73 vs 1.95 ± 0.73, p=NS. There was no statistical difference between the pre-and post-test osmolality values (539 43 vs. 618 34 mOsm/kg). Urinary expression of AQP2 was significantly lower in patients than in controls (99.5 0.5 vs. 38.5 12%, p=0.006), whereas that of NKCC2 was significantly higher (102 2.5 vs. 147 12%, p=0.02). Urinary acidification defect (post-test UpH >5.5) was detected in 15 patients before specific treatment and in 6 patients after treatment (40% vs 16%, p=0.012). Pre-test Pbic was <21 mEq/L in 12 patients (32.5%), and pre-test PpH was <7.35 in 14 (38%). Expression of NHE3 was significantly higher in the patients than in the controls (100 0.6 vs. 176 15%, p=0.015), as was that of H-ATPase (98 0.2 vs. 190 8%, p=0.04) and pendrin (176 ± 15 vs. 100 ± 0.6%, P = 0.015). Conclusion. ACL can cause assimptomatic tubular dysfunction. It is likely that the urinary concentrating defect observed in patients with ACL is caused by downregulation of AQP2 expression, and that the increased NKCC2 expression represents a compensatory mechanism. The greater expression of NHE3 and H-ATPase might represent another compensatory mechanism to pendrin expression increase, since ACL patients also presented urinary acidification defect.