Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats

Autor(es)

de Braganca, Ana Carolina ^[1] ; Canale, Daniele ^[2] ; Goncalves, Janaina Garcia ^[2] ; Massola Shimizu, Maria Heloisa ^[2] ; Seguro, Antonio Carlos ^[1] ; Volpini, Rildo Aparecido ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, LIM12, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, LIM12, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MEDICINE; v. 5, OCT 10 2018.
• Citações Web of Science: 3

Resumo

The pathogenesis of chronic kidney disease (CKD) involves a very complex interaction between hemodynamic and inflammatory processes, leading to glomerular/vascular sclerosis, and fibrosis formation with subsequent evolution to end-stage of renal disease. Despite efforts to minimize the progression of CKD, its incidence and prevalence continue to increase. Besides cardiovascular diseases and infections, several studies demonstrate that vitamin D status could be considered as a non-traditional risk factor for the progression of CKD. Therefore, we investigated the effects of vitamin D deficiency (VDD) in the course of moderate CKD in 5/6 nephrectomized rats (Nx). Adult male Wistar rats underwent Sham surgery or Nx and were subdivided into the following four groups: Sham, receiving standard diet (Sham); Sham VDD, receiving vitamin D-free diet (VDD); Nx, receiving standard diet (Nx); and VDD+Nx, receiving vitamin D-free diet (VDD+Nx). Sham or Nx surgeries were performed 30 days after standard or vitamin D-free diets administration. After validation of vitamin D depletion, we considered only Nx and VDD+Nx groups for the following studies. Sixty days after surgeries, VDD+Nx rats exhibited hypertension, a greater decline in renal function and plasma FGF-23 levels, renal hypertrophy, as well as higher plasma levels of PTH and aldosterone. In addition, those animals presented more significant chronic tubulointerstitial changes (cortical interstitial expansion/inflammation/fibrosis), higher expression of collagen IV, fibronectin and alpha-smooth muscle actin, and lower expressions of JG12 and M2 macrophages. Also, VDD+Nx rats had greater infiltration of inflammatory cells (M1 macrophages and T-cells). Such changes were accompanied by higher expression of TGF-beta 1 and angiotensinogen and decreased expression of VDR and Klotho protein. Our observations indicate that vitamin D deficiency impairs the renal function and worsens the renovascular and morphological changes, aggravating the features of moderate CKD in 5/6 nephrectomized rats. (AU)

• Processo FAPESP: 10/52294-0 - Avaliação do papel da vitamina D na evolução da lesão renal aguda pós-isquêmica
• Beneficiário: Rildo Aparecido Volpini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/05513-1 - Avaliação dos eventos envolvidos nas alterações renais associadas aos modelos experimentais de injúria renal aguda isquêmica, nefrectomia 5/6 e nefrotoxicidade por Anfotericina B: influência da deficiência de vitamina D
• Beneficiário: Rildo Aparecido Volpini
• Modalidade de apoio: Auxílio à Pesquisa - Regular