Abstract
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.
Highlights
The incidence and prevalence of chronic kidney disease (CKD) have been increasing over the years [1]
Our inulin clearance studies showed that renal ablation led to an impaired renal function, evidenced by glomerular filtration rate (GFR) compared to subdivided the animals into groups: (Sham) rats
Our GFR and mean arterial pressure (MAP) results indicate that vitamin D deficiency is an aggravating factor concerning renal function recovery and blood pressure control
Summary
The incidence and prevalence of chronic kidney disease (CKD) have been increasing over the years [1]. The set of those features evolves to end-stage renal disease (ESRD) [1]. It has been shown that the mortality of patients with CKD is directly related to renal function deterioration associated with cardiovascular/hemodynamic diseases and infections [2, 3]. These major risk factors account for only half of the causes of mortality [2, 3]. Early intervention against risk factors during the course of CKD is crucial to avoid the progression of the disease
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