Relationship between STAT6 and chronic kidney injury in dogs with Visceral Leishmaniasis

Abstract

In Visceral Leishmaniasis (LV), the parasite Leishmania infantum chagasi infects the vertebrate hosts by means of the vector (Lutzomyia longipalpis), the dogs being the main domestic reservoirs of the disease, besides being a source of infection for man. In dogs, clinical signs include skin lesions (alopecia, desquamation, ulcers, crusting), progressive thinning of cachexia, onychogrifosis, generalized lymphadenomegaly. The spleen, liver, and bone marrow are the primary targets for systemic infection. Renal involvement is common, even in apparently healthy animals with no changes in serum urea and creatinine levels. The evolution of renal injury results in chronic renal failure and death may be secondary to the severity of the lesions. In man, the transcription factor STAT6 was related to a protective effect of the tubules and renal interstitium against injuries, stimulating the production of extracellular matrix and renal fibrosis. Therefore, the objective of this study is to evaluate the intensity of STAT6 marking in the kidney of infected dogs and to compare this finding with renal interstitial fibrosis and with the intensity of the tubulointerstitial and glomerular inflammatory processes. The macrophage density positive for Leishmania sp. will also be compared to these findings. For this, the parasite load and STAT6 detection will be evaluated by immunohistochemistry in 25 naturally infected dogs from the endemic area for LV and in 5 control animals from non-endemic areas. Expression of ±-SMA (alpha smooth muscle actin) will be evaluated because of its relation to fibrosis. The intensity of glomerulonephritis (PAS) and renal fibrosis (Masson's trichrome) will be evaluated by scores. With the results of this study it will be possible to verify if the aggravation of the chronic kidney disease would be related to these parameters.