Vascular permeability increase and cell influx are phenomena independent of gait disturbance. Neutrophils do not seem to contribute to development of gait disturbance in Zy arthritis. Sensitization of specific pain receptors in periarticular rather than in synovial tissue is responsible for gait disturbance in Zy-induced arthritis.

EMT occurs in response to a number of stresses conditions as mechanical stretch, cancer, hypoxia, oxidative stress (ROS), among others. EMT describes a phenotypical change induced in epithelial cells. It is characterized by increases in motility, extracellular matrix synthesis, proliferation, and invasiveness. The present study analyzed if oxalate ions (Ox) could induce EMT in IMCD cells. Ox (0.5 mM) and transforming growth factor beta (TGF-β1 20 ng/mL) exposition during 48 hours increased migration and invasiveness, increased mesenchymal marker expression (Vimentin, alpha-smooth muscle actin: α-SMA, TGF-β1) and decreased epithelial marker expression (E-cadherin). IMCD stimulated with Ox and TGF-β1 and then exposed to the osteogenic medium during 15 days significantly increased early osteogenic markers (RUNX-2 and Alkaline Phosphatase) expression. Hyperoxaluric mice fed with trans-4-hydroxy-L-proline (HPL) presented calcium oxalate crystal excretion, increased in TGF-β1 expression and collagen fibers deposition and increased early osteogenic markers (RUNX-2 and Alkaline Phosphatase) at 60 days. Our in vitro and in vivo results suggest that oxalate induces EMT in inner medulla collecting duct cells and it may be involved in fibrotic tissue development, osteogenic differentiation and calcium crystal production both implicated in nephrolithiasis.

Several studies have demonstrated an important association between altered lipid metabolism and the development of kidney injury because of a high-fat diet. Fructose is also closely associated with renal injury. We opted for a combination of fructose and saturated fats in a diet (DH) that is a model known to induce renal damage in order to evaluate whether soy isoflavones could have promising use in the treatment of renal alterations. After two months of ingestion, there was an expansion of visceral fat, which was associated with long-term metabolic disorders, such as sustained hyperglycemia, insulin resistance, polyuria, dyslipidemia, and hypertension. Additionally, we found a decrease in renal blood flow and an increase in renal vascular resistance. Biochemical markers of chronic kidney disease were detected; there was an infiltration of inflammatory cells with an elevated expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β), the activation of the renin–angiotensin system, and oxidative/nitrosative stress. Notably, in rats exposed to the DH diet for 120 days, the concomitant treatment with isoflavones after 60 days was able to revert metabolic parameters, renal alterations, and oxidative/nitrosative stress. The beneficial effects of isoflavones in the kidney of the obese rats were found to be mediated by expression of peroxisome proliferator-activated receptor gamma (PPAR-γ).

Hypertension and Diabetes mellitus are the two main causes of chronic kidney disease that culminate in the final stage of kidney disease. Since these two risk factors are common and can overlap, new approaches to prevent or treat them are needed. Macitentan (MAC) is a new non-selective antagonist of the endothelin-1 (ET-1) receptor. This study aimed to evaluate the effect of chronic blockade of ET-1 receptor with MAC on the alteration of renal function observed in hypertensive and hyperglycemic animals. Genetically hypertensive rats were divided into control hypertensive (HT-CTL) group, hypertensive and hyperglycemic (HT+DIAB) group, and hypertensive and hyperglycemic group that received 25 mg/kg macitentan (HT-DIAB+MAC25) via gavage for 60 days. Kidney function and parameters associated with oxidative and nitrosative stress were evaluated. Immunohistochemistry for neutrophil gelatinase-associated lipocalin (NGAL), ET-1, and catalase in the renal cortex was performed. The HT+DIAB group showed a decrease in kidney function and an increase in NGAL expression in the renal cortex, as well as an increase in oxidative stress. MAC treatment was associated with attenuated ET-1 and NGAL production and increases in antioxidant defense (catalase expression) and nitric oxide production. In addition, MAC prevented an increase in oxidant injury (as measured by urinary hydroperoxide and lipid peroxidation), thus improving renal function. Our results suggest that the antioxidant effect of the ET-1 receptor antagonist MAC is involved in the improvement of kidney function observed in hypertensive and hyperglycemic rats.