Efficacy and Safety of Roxadustat in Patients with CKD: Pooled Analysis by Baseline Inflammation Status.

: Inflammation may contribute to hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) and is often present in patients with chronic kidney disease (CKD). Roxadustat is approved in multiple countries for the treatment of anemia of CKD. This pooled analysis evaluated the efficacy and safety of roxadustat in patients with dialysis-dependent (DD) or non-dialysis-dependent (NDD) CKD by inflammation status.

The Early Diagnosis and Treatment of Chronic Renal Insufficiency.

Background: Chronic renal insufficiency (CRI) is becoming more common and has an increasing impact on public health. In Germany, approximately one in ten adults has CRI. Its most serious consequence is generally not the development of end-stage renal failure, but rather the markedly increased cardiovascular risk as kidney function declines.

[Autosomal polycystic kidney disease].

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic kidney disease. The clinical course is highly variable, association to certain genetic mutations only weak. Great progress has been made in recent years in determining the pathophysiology of the disease.

Antitumoral effects of calcitriol in basal cell carcinomas involve inhibition of hedgehog signaling and induction of vitamin D receptor signaling and differentiation.

Activation of the Hedgehog (Hh)-signaling pathway due to deficiency in the Hh receptor Patched1 (Ptch) is the pivotal defect leading to formation of basal cell carcinoma (BCC). Recent reports provided evidence of Ptch-dependent secretion of vitamin D(3)-related compound, which functions as an endogenous inhibitor of Hh signaling by repressing the activity of the signal transduction partner of Ptch, Smoothened (Smo). This suggests that Ptch-deficient tumor cells are devoid of this substance, which in turn results in activation of Hh-signaling.

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID).

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.

Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases.

Fibrosis and evidence for epithelial-mesenchymal transition in the kidneys of patients with staghorn calculi.

Objectives: • To quantify fibrotic lesions in renal tissues obtained from patients with large calculi and to evaluate association with renal function. • Presence of epithelial-mesenchymal transition (EMT) in stone-containing renal tissues was investigated.

Patients, Subjects And Methods: • In all, 50 patients with nephrolithiasis with large calculi and matched healthy controls (37) were recruited.

The role of bone morphogenetic protein-5 (BMP-5) in human nephrosclerosis.

Background: Bone morphogenetic protein-5 (BMP-5) has been shown to be essential for nephrogenesis. Its role in adult kidney and in patients with hypertensive nephrosclerosis is still unknown.

Methods: BMP-5 expression was evaluated by immunostaining and real-time PCR in tissue samples from normal and nephrosclerotic human kidneys.

Fulminant plasmapheresis-refractory thrombotic microangiopathy associated with advanced gastric cancer.

We report a case of a 27-year-old female with thrombotic microangiopathy as an initial presentation of an unexpected disseminated gastric carcinoma. Based on clinical features and laboratory findings, thrombotic thrombocytopenic purpura (TTP) was diagnosed and plasma exchange started. However, she had responded poorly to plasmapheresis, developed multiorgan failure and died 72 h after admission.

Retrospective analysis of long-term lipid apheresis at a single center.

We retrospectively analyzed 10 906 lipid apheresis sessions (heparin-induced lipoprotein precipitation, direct adsorption of lipoproteins, double filtration plasmapheresis, dextran sulfate adsorption, and immunoadsorption) in 38 patients who were consecutively treated in our department during the last 20 years. The incidences of major cardiovascular events (MACE) (death, cerebrovascular accident, myocardial infarction, limb amputation, and renal vascular involvement) were taken separately as primary end-points or as a combined end-point. The time-course of secondary end-points (coronary and extracranial status of arteries, left ventricular function, occlusive artery disease, and calculated glomerular filtration rate [cGFR]) were also evaluated, as well as the extent of the reduction in plasma lipids and lipoproteins and the incidence of therapy associated side-effects.

Pathogenesis of tubulointerstitial fibrosis in chronic allograft dysfunction.

The term chronic allograft nephropathy (CAN) was originally coined in 1991 to replace chronic rejection which was used too generalized. However, the revised Banff classification, published in 2007, eliminated the term CAN again because it was felt that the term was used too broadly and prevented the search for the underlying cause. Interstitial fibrosis and tubular atrophy are integral parts of chronic allograft dysfunction and represent in the new classification a separate entity with or without the identification of a specific etiology.

Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure.

Background: The chemokine/chemokine receptor pair CX(3)C-L/CX(3)C-R is suspected to play a role in renal fibrogenesis. The aim of this study was to investigate their function in an animal model of slowly progressive chronic renal failure.

Methods: Functional data were analysed in folic acid nephropathy (FAN) at different time points (up to day 142 after induction).

The CX(3)C-chemokine fractalkine in kidney diseases.

The chemokine CX(3)C-L/FKN is expressed in both soluble and transmembrane/mucin hybrid forms, thus combining chemoattractant functions together with receptor/adhesion molecule properties. In contrast to other chemokine receptors, CX(3)C-R is expressed not only on lymphoid cell populations, but also on several intrinsic cells including tubular epithelial cells and renal fibroblasts where it regulates various aspects of cell viability, matrix synthesis and degradation, migration, inflammation as well as oxidative stress. In the kidney, the chemokines/receptor pair has been shown to play a role in nephrogenesis as well as in the pathogenesis primary and secondary nephropathies.

Prenatal dexamethasone exposure does not alter blood pressure and nephron number in the young adult marmoset monkey.

The influence of prenatal factors on the development of arterial hypertension has gained considerable interest in recent years. Prenatal dexamethasone exposure was found to induce hypertension and to alter nephron number and size in rodents and sheep. However, it is not clear whether these findings are applicable to nonhuman primates.

Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells.

Neuropilin-1 (NRP1) and neuropilin-2 (NRP2) are transmembrane glycoproteins with large extracellular domains that interact with class 3 semaphorins, vascular endothelial growth factor (VEGF) family members, and ligands, such as hepatocyte growth factor, platelet-derived growth factor BB, transforming growth factor-beta1 (TGF-beta1), and fibroblast growth factor2 (FGF2). Neuropilins (NRPs) have been implicated in tumor growth and vascularization, as novel mediators of the primary immune response and in regeneration and repair; however, their role in renal pathophysiology is largely unknown. Here, we report upregulation of tubular and interstitial NRP2 protein expression in patients with focal segmental glomerulosclerosis (FSGS).

Renal fibrosis is attenuated by targeted disruption of KCa3.1 potassium channels.

Proliferation of interstitial fibroblasts is a hallmark of progressive renal fibrosis commonly resulting in chronic kidney failure. The intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) has been proposed to promote mitogenesis in several cell types and contribute to disease states characterized by excessive proliferation.

The role of FGF-2 in renal fibrogenesis.

Basic fibroblast growth factor (FGF-2) is a pleiotropic cytokine which exerts its effects via four different high affinity receptors (FGFR-1 to -4) which function as protein tyrosine kinases. In the kidney, FGF-2 is expressed in epithelial cells already during fetal development. During later stages, expression of the cytokine can be found in distal tubular epithelial cells, glomerular cells and few interstitial cells.

Role of basic fibroblast growth factor (FGF-2) in diabetic nephropathy and mechanisms of its induction by hyperglycemia in human renal fibroblasts.

Basic fibroblast growth factor (FGF-2) plays a role in renal fibrogenesis, although its potential implications for tubulointerstitial involvement in diabetic nephropathy are unknown. We evaluated the expression of FGF-2 in kidney biopsies from patients with diabetic nephropathy and studied the mechanisms of its induction in human renal fibroblasts under hyperglycemia. Tubulointerstitial expression of FGF-2 was significantly upregulated in diabetic nephropathy compared with control kidneys with a good correlation to the degree of the injury.