Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats
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 o...
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doaj-869486076fbc4543abe91d9933994bf82020-11-25T00:04:00ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2018-10-01510.3389/fmed.2018.00282406289Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized RatsAna Carolina de Bragança0Daniele Canale1Janaína Garcia Gonçalves2Maria Heloisa Massola Shimizu3Antonio Carlos Seguro4Rildo Aparecido Volpini5Laboratorio de Investigacao Medica 12 (LIM12), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilLaboratorio de Investigacao Medica 12 (LIM12), Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilLaboratorio de Investigacao Medica 12 (LIM12), Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilLaboratorio de Investigacao Medica 12 (LIM12), Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilLaboratorio de Investigacao Medica 12 (LIM12), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilLaboratorio de Investigacao Medica 12 (LIM12), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilThe 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 α-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-β1 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.https://www.frontiersin.org/article/10.3389/fmed.2018.00282/fullchronic kidney diseasevitamin D deficiencyfibrosisinflammation5/6 nephrectomyexperimental model |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ana Carolina de Bragança Daniele Canale Janaína Garcia Gonçalves Maria Heloisa Massola Shimizu Antonio Carlos Seguro Rildo Aparecido Volpini |
spellingShingle |
Ana Carolina de Bragança Daniele Canale Janaína Garcia Gonçalves Maria Heloisa Massola Shimizu Antonio Carlos Seguro Rildo Aparecido Volpini Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats Frontiers in Medicine chronic kidney disease vitamin D deficiency fibrosis inflammation 5/6 nephrectomy experimental model |
author_facet |
Ana Carolina de Bragança Daniele Canale Janaína Garcia Gonçalves Maria Heloisa Massola Shimizu Antonio Carlos Seguro Rildo Aparecido Volpini |
author_sort |
Ana Carolina de Bragança |
title |
Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats |
title_short |
Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats |
title_full |
Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats |
title_fullStr |
Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats |
title_full_unstemmed |
Vitamin D Deficiency Aggravates the Renal Features of Moderate Chronic Kidney Disease in 5/6 Nephrectomized Rats |
title_sort |
vitamin d deficiency aggravates the renal features of moderate chronic kidney disease in 5/6 nephrectomized rats |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2018-10-01 |
description |
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 α-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-β1 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. |
topic |
chronic kidney disease vitamin D deficiency fibrosis inflammation 5/6 nephrectomy experimental model |
url |
https://www.frontiersin.org/article/10.3389/fmed.2018.00282/full |
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