Prospective cohort analyzing risk factors for chronic kidney disease progression in children / Coorte prospectiva que analisa os fatores de risco para progressão de doença renal crônica (DRC) em crianças

Abstract Objective: To identify risk factors for chronic kidney disease progression in Brazilian children and to evaluate the interactions between factors. Methods: This was a multicenter prospective cohort in São Paulo, involving 209 children with CKD stages 3-4. The study outcome included: (a) death, (b) start of kidney replacement therapy, (c) eGFR decrease >50% during the followup. Thirteen risk factors were tested using univariate regression models, followed by multivariable Cox regression models. The terms of interaction between the variables showing significant association with the outcome were then introduced to the model. Results: After a median follow-up of 2.5 years (IQR = 1.4-3.0), the outcome occurred in 44 cases (21%): 22 started dialysis, 12 had >50% eGFR decrease, seven underwent transplantation, and three died. Advanced CKD stage at onset (HR = 2.16, CI = 1.14-4.09), nephrotic proteinuria (HR = 2.89, CI = 1.49-5.62), age (HR = 1.10, CI = 1.01-1.17), systolic blood pressure Z score (HR = 1.36, CI = 1.08-1.70), and anemia (HR = 2.60, CI = 1.41-4.77) were associated with the outcome. An interaction between anemia and nephrotic proteinuria at V1 (HR = 0.25, CI = 0.06-1.00) was detected. Conclusions: As the first CKD cohort in the southern hemisphere, this study supports the main factors reported in developed countries with regards to CKD progression, affirming the potential role of treatments to slow CKD evolution. The detected interaction suggests that anemia may be more deleterious for CKD progression in patients without proteinuria and should be further studied.

Resumo Objetivo: Identificar os fatores de risco para progressão da DRC em crianças do Brasil e avaliar as interações entre os fatores. Métodos: Coorte prospectiva multicêntrica em São Paulo, envolvendo 209 crianças com DRC em estágios 3-4. O desfecho do estudo incluiu: a) óbito, b) início da terapia de substituição renal, c) redução de > 50% na taxa estimada de filtração glomerular (eGFR) durante o acompanhamento. Foram testados 13 fatores de risco com o modelo de regressão univariada seguido do modelo de regressão multivariado de Cox. Os termos de interação entre as variáveis mostraram associação significativa e foram introduzidos ao modelo. Resultados: Após média de acompanhamento de 2,5 anos (IIQ = 1,4 a 3,0), 44 casos (21%) apresentaram desfecho: 22 iniciaram diálise, 12 apresentaram redução de > 50% na eGFR, sete foram submetidos a transplante e três morreram. Estágio avançado de DRC no acometimento (RR = 2,16, IC = 1,14-4,09), proteinúria nefrótica (RR = 2,89, IC = 1,49-5,62), idade (RR - 1,10, IC = 1,01-1,17), escore Z da pressão arterial sistólica (RR = 1,36, IC = 1,08-1,70) e anemia (RR = 2,60, IC - 1,41-4,77) foram associados ao resultado. Foi detectada interação entre anemia e proteinúria nefrótica na primeira visita (V1) (RR = 0,25, IC = 0,06-1,00). Conclusões: Como a primeira coorte de DRC no hemisfério sul, este estudo é concordante com os principais fatores relatados em países desenvolvidos com relação à progressão da DRC, afirmando o possível papel dos tratamentos para mostrar a evolução da DRC. A interação detectada sugere que a anemia pode ser mais nociva na progressão da DRC em pacientes sem proteinúria e deve ser ainda mais estudada.

Experimental model of chronic osteomyelitis caused by Leishmania (L) amazonensis.

Experimental animal models have been used for the study of the physiopathogenesis of leishmaniasis, on some occasions with success, while in other situations such as bone alterations that accompany tegumentary leishmaniasis, especially in diffuse cutaneous form (DCL), the mechanisms are still unknown. In the present study, we determined these alterations in an animal model susceptible to Leishmania (L) amazonensis. Amastigotes of L. (L) amazonensis isolated from patients with diffuse cutaneous leishmaniasis (DCL) were inoculated into the hind paws of eight BALB/c mice, macroscopic and histopathological aspects were analyzed. After 90 and 120 days of evolution, histopathological analysis demonstrated a mononuclear cell infiltrate rich in plasma cells and intense parasitism of intra- and extra-medullary macrophages, with areas of bone necrosis and discrete involvement of cartilaginous tissue. The results show that the inflammatory process developed during L. (L) amazonensis infection might cause bone tissue destruction and secondarily affect the joints.