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

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.

Vitamin D deficiency is a potential risk factor for lipid Amphotericin B nephrotoxicity

“…Inulin clearance values represent the mean of three periods. Blood and urine inulin were determined by the anthrone method, and the GFR data is expressed as ml/min/100g BW [12].…”

“…In addition, hypovitaminosis D has been associated with the arising of hypertension, development of cardiovascular disease, diabetes mellitus and the aggravation of chronic kidney disease (CKD) [9–11]. These effects could also reflect on a worse prognosis in cases of acute kidney injury (AKI) [12,13] and drug-induced nephrotoxicity [14].…”

Effect of Low and High Doses of Vitamin D on Sreptozotocin-induced Diabetic Nephropathy in Adult Male Albino Rats: Histological and Immunohistochemical Sudy

“…In 2018, de Braganca et al submitted that Vitamin D deficiency provoked the immunostainings for both fibronectin and collagen IV markers and aggravated both renal inflammation and fibrosis. The conclusion that, vitamin D deficiency donated a prohibitive illustration of fibronectin and collagen IV [35] . STZ treated (Group II) rats illustrated in electron microscopic results, cytoplasmic vacuolations and destructed mitochondria of proximal convoluted tubule.…”

VDR inhibits NLRP3 signal in lupus nephritis by competitively binding with importin 4 to suppress NF-κB nuclear translocation

“…Vitamin D receptor (VDR) is an ancient nuclear receptor, vitamin D (VD) de ciency is implicated in various diseases, including SLE/LN [12]. VDR plays critical roles in transcriptional regulation, immunity, in ammation and proliferation, it relates with chronic tubulointerstitial changes, such as, cortical interstitial expansion, in ammation and brosis [13]. VDR signaling reduces in ammation by suppressing in ammatory signaling pathway, promoting anti-in ammatory cytokines secretion and regulating T-cell different [14,15].…”