A projected cost-utility analysis of avacopan for the treatment of antineutrophil cytoplasmic antibody-associated vasculitis in Spain.

Background: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain.

Methods: A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon.

Defective insulin-stimulated equilibrative nucleoside transporter-2 activity and altered subcellular transporter distribution drive the loss of adenosine homeostasis in diabetic kidney disease progression.

Aim: Progression of diabetic nephropathy (DN) is linked to the dysregulated increase of adenosine and altered signaling properties. A major contribution to the maintenance of physiological extracellular adenosine levels relies on cellular uptake activity through plasma membrane nucleoside transporters. Because kidney cells are responsive to insulin, this study aims to determine how DN affects insulin regulation of the equilibrative nucleoside transporter-2 (ENT2).

From Inflammation to the Onset of Fibrosis through A Receptors in Kidneys from Deceased Donors.

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes.

Seasonal variations in the onset of positive and negative renal ANCA-associated vasculitis in Spain.

Background: The closure of long-standing gaps in our knowledge of aetiological factors behind anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a major challenge. Descriptive and analytical epidemiological studies can improve our understanding of environmental influences. Reported seasonal variations in AAV, mainly related to Wegener's disease, have shown an increasing number of cases in the winter months, which could be related to an extrinsic factor underlying infection.

Rituximab for Steroid-Dependent or Frequently Relapsing Idiopathic Nephrotic Syndrome in Adults: A Retrospective, Multicenter Study in Spain.

Background: Patients with difficult-to-treat idiopathic nephrotic syndrome (INS), steroid-dependent nephrotic syndrome (SDNS), or frequently relapsing nephrotic syndrome (FRNS) require long-term immunosuppressive therapy. Rituximab offers an alternative treatment for patients with disease that has not responded to multiple therapies.

Objective: Our objective was to determine the efficacy and safety of rituximab in adult patients with difficult-to-treat (SDNS or FRNS) INS.

Reduced Adenosine Uptake and Its Contribution to Signaling that Mediates Profibrotic Activation in Renal Tubular Epithelial Cells: Implication in Diabetic Nephropathy.

Altered nucleoside levels may be linked to pathogenic signaling through adenosine receptors. We hypothesized that adenosine dysregulation contributes to fibrosis in diabetic kidney disease. Our findings indicate that high glucose levels and experimental diabetes decreased uptake activity through the equilibrative nucleoside transporter 1 (ENT1) in proximal tubule cells.

HLA-DQA1 and PLA2R1 polymorphisms and risk of idiopathic membranous nephropathy.

Background And Objectives: Single nucleotide polymorphisms (SNPs) within HLA complex class II HLA-DQ α-chain 1 (HLA-DQA1) and M-type phospholipase A2 receptor (PLA2R1) genes were identified as strong risk factors for idiopathic membranous nephropathy (IMN) development in a recent genome-wide association study. Copy number variants (CNVs) within the Fc gamma receptor III (FCGR3) locus have been associated with several autoimmune diseases, but their role in IMN has not been studied. This study aimed to validate the association of HLA-DQA1 and PLA2R1 risk alleles with IMN in a Spanish cohort, test the putative association of FCGR3A and FCGR3B CNVs with IMN, and assess the use of these genetic factors to predict the clinical outcome of the disease.

Adenosine A(2B) receptor-mediated VEGF induction promotes diabetic glomerulopathy.

Diabetic nephropathy ranks as the most devastating kidney disease worldwide. It characterizes in the early onset by glomerular hypertrophy, hyperfiltration and mesangial expansion. Experimental models show that overproduction of vascular endothelial growth factor (VEGF) is a pathogenic condition for podocytopathy; however the mechanisms that regulate this growth factor induction are not clearly identified.

n-3 Fatty acids block TNF-α-stimulated MCP-1 expression in rat mesangial cells.

Monocyte chemoattractant protein 1 (MCP-1) is a CC cytokine that fundamentally contributes to the pathogenesis of inflammatory renal disease. MCP-1 is highly expressed in cytokine-stimulated mesangial cells in vitro and following glomerular injury in vivo. Interventions to limit MCP-1 expression are commonly effective in assorted experimental models.

Signaling pathways modulated by fish oil in salt-sensitive hypertension.

Although many studies have indicated that fish oil (FO) improves cardiovascular risk factors and reduces histopathological manifestations of injury in experimental renal injury models, potential mechanisms underlying this protective effect have not been adequately defined. The objective of this study was to identify potential signaling pathways that confer protection in the Dahl rat model of salt-sensitive hypertension. Male Dahl salt-sensitive rats (n = 10/group) were provided with formulated diets containing 8% NaCl, 20% protein, and 25% FO or 25% corn oil (CO) for 28 days.

TGF-beta1 stimulates monocyte chemoattractant protein-1 expression in mesangial cells through a phosphodiesterase isoenzyme 4-dependent process.

Monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor (TGF)-beta1 are critical mediators of renal injury by promoting excessive inflammation and extracellular matrix deposition, thereby contributing to progressive renal disease. In renal disease models, MCP-1 stimulates the production of TGF-beta1. However, a potential role for TGF-beta1 in the regulation of MCP-1 production by mesangial cells (MCs) has not previously been evaluated.

Differential regulation of mesangial cell mitogenesis by cAMP phosphodiesterase isozymes 3 and 4.

Mesangial cell (MC) mitogenesis is regulated through "negative cross talk" between cAMP-PKA and ERK signaling. Although it is widely accepted that cAMP inhibits mitogenesis through PKA-mediated phosphorylation of Raf-1, recent studies have indicated that cAMP-mediated inhibition of mitogenesis may occur independently of Raf-1 phosphorylation or without inhibiting ERK activity. We previously showed that MCs possess functionally compartmentalized intracellular pools of cAMP that are differentially regulated by cAMP phosphodiesterases (PDE); an intracellular pool directed by PDE3 but not by PDE4 suppresses mitogenesis.

Correlation of quantitative digital image analysis with the glomerular filtration rate in chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is characterized by progressive renal functional loss and histologic abnormalities of one or more tissue compartments. In this study, correlations between histologic abnormalities and graft function [glomerular filtration rate (GFR, measured by iothalamate clearance), serum creatinine (SCr) and urinary protein (UPr)] were investigated using biopsies from 49 patients with newly diagnosed CAN. Extent of tubulointerstitial fibrosis (%TIF), as assessed by a semi-quantitative score, correlated significantly with GFR, SCr and UPr.