Blood pressure changes after renal denervation are more pronounced in women and nondiabetic patients: findings from the Austrian Transcatheter Renal Denervation Registry.

Objectives: Three recently published sham-controlled studies proved the efficacy of renal denervation (RDN) in hypertensive patients. The study presented here analyzed a nationwide multicentre registry database to clarify which patient subgroups benefit most from radiofrequency RDN.

Methods: This is a post hoc analysis from the multicentre Austrian Transcatheter Renal Denervation Registry hosted by the Austrian Society of Hypertension.

Computational Drug Screening Identifies Compounds Targeting Renal Age-associated Molecular Profiles.

Aging is a major driver for chronic kidney disease (CKD) and the counterbalancing of aging processes holds promise to positively impact disease development and progression. In this study we generated a signature of renal age-associated genes (RAAGs) based on six different data sources including transcriptomics data as well as data extracted from scientific literature and dedicated databases. Protein abundance in renal tissue of the 634 identified RAAGs was studied next to the analysis of affected molecular pathways.

Effect of cyclosporine, tacrolimus and sirolimus on cellular senescence in renal epithelial cells.

Introduction: In transplantation medicine calcineurin inhibitors (CNI) still represent the backbone of immunosuppressive therapy. The nephrotoxic potential of the CNI Cyclosporine A (CsA) and Tacrolimus (FK506) is well recognized and CNI not only have been linked with toxicity, but also with cellular senescence which hinders parenchymal tissue regeneration and thus may prime kidneys for subsequent insults. To minimize pathological effects on kidney grafts, alternative immunosuppressive agents like mTOR inhibitors or the T-cell co-stimulation blocker Belatacept have been introduced.

Metallothioneins and renal ageing.

Background: Human lifespan is increasing continuously and about one-third of the population >70 years of age suffers from chronic kidney disease. The pathophysiology of the loss of renal function with ageing is unclear.

Methods: We determined age-associated gene expression changes in zero-hour biopsies of deceased donor kidneys without laboratory signs of impaired renal function, defined as a last serum creatinine >0.

Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing.

Introduction: Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.

Methodology: The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease.

Influence of the delivery modus on subpopulations and replication of lymphocytes in mothers and newborns.

Background: Several studies reported that the mode of delivery may induce changes to the immune system. Our hypothesis was that the delivery mode may influence mainly the naive T cell subpopulation.

Aims: Particular focus was set on the proportions and peripheral replicative history of naive T cells and cord blood serum concentrations of IL-7, a cytokine involved in peripheral naive T cell homeostasis.

Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506) induced TGF-β-like effects, manifested by increased expression of NAD(P)H-oxidase 4 (Nox4), transgelin, tropomyosin 1, and procollagen α1(V) mRNA after three days.

Effect of different immunosuppressive drugs on immune cells from young and old healthy persons.

Background: Life expectancy, as well as the average age of patients undergoing solid organ transplantation, increases constantly. Consequently, immunosuppressive therapy is no longer limited to young organ recipients.

Objective: Here, we investigate how different types of immunosuppressive therapy, namely the calcineurin inhibitors cyclosporin A and tacrolimus, as well as the mTOR inhibitor rapamycin, affect the function of immune cells in young and elderly persons.

How immunosuppressive therapy affects T cells from kidney transplanted patients of different age: the role of latent cytomegalovirus infection.

The average age of patients receiving renal transplantation is increasing as programmes have been established which support the donation of organs from elderly donors to older recipients. Little is known about the effect of immunosuppressive therapy on the immune system of older patients. In this study, T cell function and the composition of the T cell repertoire were analysed in immunosuppressed renal transplant recipients of different age and cytomegalovirus (CMV) status in comparison to age- and CMV-matched controls.

Lower CD28+ T cell proportions were associated with CMV-seropositivity in patients with Hashimoto's thyroiditis.

Background: Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto's thyroiditis (HT, n = 18) and healthy controls (HC, n = 70).

Methods: Proportions of peripheral T cells were investigated by flow cytometry.

Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria.

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post-transplant serum creatinine when compared to "Gold Standard" clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function.

Increased replication of CD4+ naive T cells and changes in T cell homeostasis in a case of acute exacerbation of juvenile idiopathic arthritis: a case comparison study.

Introduction: Juvenile idiopathic arthritis is a heterogeneous T cell-mediated autoimmune disease with symptoms of premature aging of the immune system (immunosenescence). The present work is an investigation of immunosenescence parameters, such as quantity of naive and CD28- T cells, T cell receptor excision circles, relative telomere length and alterations of peripheral T cell replication, and was performed via comparison of a case of acute exacerbation of juvenile idiopathic arthritis against six patients with juvenile idiopathic arthritis with disease remission and six age-matched healthy donors over a follow-up course of 12 months.

Case Presentation: Phenotypical T cell characterization and intracellular interferon γ, tumor necrosis factor α, and interleukin 2 production were studied in peripheral blood mononuclear cells from seven patients with juvenile idiopathic arthritis and six healthy control donors, with findings determined by flow cytometry.

Maternal cigarette smoking and its effect on neonatal lymphocyte subpopulations and replication.

Background: Significant immunomodulatory effects have been described as result of cigarette smoking in adults and pregnant women. However, the effect of cigarette smoking during pregnancy on the lymphocyte subpopulations in newborns has been discussed, controversially.

Methods: In a prospective birth cohort, we analyzed the peripheral lymphocyte subpopulations of smoking (SM) and non-smoking mothers (NSM) and their newborns and the replicative history of neonatal, mostly naive CD4 + CD45RA + T cells by measurements of T-cell-receptor-excision-circles (TRECs), relative telomere lengths (RTL) and the serum cytokine concentrations.

Pathfinder cells provide a novel therapeutic intervention for acute kidney injury.

Pathfinder cells (PCs) are a novel class of adult-derived cells that facilitate functional repair of host tissue. We used rat PCs to demonstrate that they enable the functional mitigation of ischemia reperfusion (I/R) injury in a mouse model of renal damage. Female C57BL/6 mice were subjected to 30 min of renal ischemia and treated with intravenous (i.

Elevated proportions of recent thymic emigrants in children and adolescents with type 1 diabetes.

It is unclear, whether pediatric patients with type 1 diabetes (T1DM) show immunological alterations typically found in autoimmune conditions resembling immune dysfunction of the thymus, such as decrease of naïve T cells, lower T cell receptor excision circle (TREC) numbers, telomeric erosion, and diminished interleukin-7 (IL-7) levels. Furthermore, it is unknown, whether long-term therapy with insulin, a thymic growth factor, interferes with these changes. Therefore, the aim of this study was to analyze the quantity of the naïve T cell subset and its TREC content, relative telomere length (RTL) of naïve T cells, and peripheral IL-7 levels in patients with recent-onset T1DM (n = 5), long-standing T1DM (n = 33), and age-matched healthy donors (HD) (n = 37).

Impact of anemia on aortic pulse wave velocity in hemodialysis patients.

Background: Recent studies indicate an increased mortality of anemic patients with renal failure when near-normal hemoglobin levels are aimed for by treatment with erythropoiesis stimulating agents. Aortic pulse wave velocity (aPWV) is a strong predictor of all-cause and cardiovascular mortality in patients with end-stage renal disease. The relationships between aPWV, hemoglobin levels and erythropoiesis stimulating agent dosage have not been evaluated to date.

Serum hepcidin concentration in chronic haemodialysis patients: associations and effects of dialysis, iron and erythropoietin therapy.

Background: Hepcidin, a liver-derived peptide induced by iron overload and inflammation, is a major regulator of iron homeostasis. As hepcidin decreases gastrointestinal iron absorption and recirculation from monocytes, over-expression is associated with the development of anaemia.

Methods: We studied the associations between circulating hepcidin levels and various laboratory parameters related to anaemia and/or inflammation in 20 patients on chronic haemodialysis.

Biomarkers of aging with prognostic and predictive value in non-oncological diseases.

In this review we discuss the current knowledge on Biomarkers of Aging (BoAs) in the context of human diseases and their value as predictive or prognostic markers. The vast majority of studies using BoAs in a clinical context have been undertaken by determining telomere length in peripheral blood mononuclear cells (PBMCs), whereas the expression of cell cycle inhibitors and an increase in advanced glycation end products (AGEs) have rarely been used. Here we summarize the impact of BoAs on non-oncological, hematological, cardiovascular, metabolic, renal and neurological diseases, as well as on overall survival.

Calcineurin inhibitor-based immunosuppressive therapy, donor age, and long-term outcome after kidney transplantation.

Background: It is unclear whether the choice of maintenance immunosuppression modulates the negative effect of advanced donor age on outcome after renal transplantation.

Methods: All 1829 patients who received their first transplant between 1990 and 2003 at the Vienna Medical Centre and had a functioning graft after 90 days were studied. At this time point, 1587 received calcineurin inhibitors (CNI+), 242 did not (CNI-).

Kidney fusion anomalies revisited: clinical and radiological analysis of 209 cases of crossed fused ectopia and horseshoe kidney.

Objective: To analyse the morphological appearance of horseshoe kidneys (HKs) and crossed fused ectopia (CFE) and to assess the frequency and clinical significance of associated anomalies and diseases.

Patients And Methods: The findings and images of 209 patients with fused kidneys (FKs) were reviewed; in all, 244 scans from computed tomography (CT), 233 ultrasonograms and 89 micturition cysto-urethrograms, urograms, magnetic resonance images and angiograms were taken.

Results: HKs (found in one of 474 abdominal CT scans) and CFEs (found in one of 3078 CT scans) showed a high variability of vasculature that could not be classified.

Premature aging of the immune system in children with juvenile idiopathic arthritis.

Objective: Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity.

Markers of cellular senescence in zero hour biopsies predict outcome in renal transplantation.

Although chronological donor age is the most potent predictor of long-term outcome after renal transplantation, it does not incorporate individual differences of the aging-process itself. We therefore hypothesized that an estimate of biological organ age as derived from markers of cellular senescence in zero hour biopsies would be of higher predictive value. Telomere length and mRNA expression levels of the cell cycle inhibitors CDKN2A (p16INK4a) and CDKN1A (p21WAF1) were assessed in pre-implantation biopsies of 54 patients and the association of these and various other clinical parameters with serum creatinine after 1 year was determined.

Indications for a disturbed peripheral T-cell homeostasis in juvenile idiopathic arthritis (JIA): absent expansion of CD28 T-cells and no decrease of naive T-cells in cytomegalovirus-positive patients with JIA.

Objective: To investigate the influence of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on CD28-expressing T-cell subpopulations and replicative senescence of naive T-cells as a marker for aging of the immune system in children with juvenile ideopathic arthritis (JIA).

Methods: T-cell subpopulations were analyzed from 24 patients with JIA and 61 healthy age-matched controls by fluorescence activated cell sorting. Relative telomere length (RTL) in CD4+CD28+CD45RA+ (naive) T-cells was measured by quantitative polymerase chain reaction.