Longitudinal monitoring of BKPyV miRNA levels in kidney transplant recipients with BKPyV-related pathology reflects viral DNA levels and remain high in viremia patients after clearance of viral DNA.

Introduction: It is unclear whether polyomavirus BK (BKPyV) microribonucleic acid (miRNA) measurement has additional diagnostic and predictive value in kidney transplant recipients (KTR) as compared to current methods of monitoring BKPyV DNA loads.

Patients And Methods: A retrospective, longitudinal study was performed in 30 KTR with BKPyV viruria (n = 10), BKPyV viremia (n = 10), or BKPyV-associated neuropathy (BKPyVAN) (n = 10). Bkv-miR-B1-3p and 5p and BKPyV DNA load were measured in urine and plasma and compared using receiver operating characteristic (ROC) curves.

Regulatory T cells engineered with TCR signaling-responsive IL-2 nanogels suppress alloimmunity in sites of antigen encounter.

Adoptive cell transfer of ex vivo expanded regulatory T cells (T) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such T therapies to the clinic has been slow. Because T homeostasis is known to require continuous T cell receptor (TCR) ligation and exogenous interleukin-2 (IL-2), some investigators have explored the use of low-dose IL-2 injections to increase endogenous T responses.

Intradialytic Complement Activation Precedes the Development of Cardiovascular Events in Hemodialysis Patients.

Hemodialysis (HD) is a life-saving treatment for patients with end stage renal disease. However, HD patients have markedly increased rates of cardiovascular morbidity and mortality. Previously, a link between the complement system and cardiovascular events (CV-events) has been reported.

The Complement System in Dialysis: A Forgotten Story?

Significant advances have lead to a greater understanding of the role of the complement system within nephrology. The success of the first clinically approved complement inhibitor has created renewed appreciation of complement-targeting therapeutics. Several clinical trials are currently underway to evaluate the therapeutic potential of complement inhibition in renal diseases and kidney transplantation.

A delicate balance between rejection and BK polyomavirus associated nephropathy; A retrospective cohort study in renal transplant recipients.

Background: The immunosuppressive agents mycophenolate acid (MPA) and tacrolimus (Tac) are associated with a higher incidence of BK polyomavirus nephropathy (BKPyVAN). In this observational retrospective cohort study, the frequency of BK polyomavirus (BKPyV) complications over a 24-month period was studied.

Methods: 358 renal transplant recipients (RTR) treated with MPA, with either cyclosporine A (CsA) (CsAM group) or Tac (TacM group) and mostly prednisolone, were included.

Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury.

The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR injury; however, the role of C5aR2 in IR injury is less clear as initial studies proposed the hypothesis that C5aR2 functions as a decoy receptor.

Incidence and outcome of BK polyomavirus infection in a multicenter randomized controlled trial with renal transplant patients receiving cyclosporine-, mycophenolate sodium-, or everolimus-based low-dose immunosuppressive therapy.

Background: It remains unclear whether overall degree of immunosuppression or specific effects of individual immunosuppressive agents are causal for increased occurrence of BK polyomavirus (BKPyV) infection in renal transplant recipients (RTR).

Methods: A prospective, multicenter, open-label randomized controlled trial in 361 de novo RTR was performed. A total of 224 RTR were randomized at 6 months into three treatment groups with dual therapy consisting of prednisolone (Pred) plus either cyclosporine (CsA), mycophenolate sodium (MPS), or everolimus (EVL).

Strong predictive value of mannose-binding lectin levels for cardiovascular risk of hemodialysis patients.

Background: Hemodialysis patients have higher rates of cardiovascular morbidity and mortality compared to the general population. Mannose-binding lectin (MBL) plays an important role in the development of cardiovascular disease. In addition, hemodialysis alters MBL concentration and functional activity.

Human Cytomegalovirus-Encoded Receptor US28 Is Expressed in Renal Allografts and Facilitates Viral Spreading In Vitro.

Background: Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G protein-coupled receptor US28, which scavenges human chemokines and modulates intracellular signaling.

Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis.

Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours.

Assessment of Cotinine Reveals a Dose-Dependent Effect of Smoking Exposure on Long-term Outcomes After Renal Transplantation.

Background: Smoking is a risk factor for poor late outcomes in renal transplant recipients (RTR). Smoking exposure can be assessed by self-report and cotinine measurements. We investigated whether use of cotinine as a biomarker for smoking exposure can serve as an alternative for self-report and to compare associations of smoking exposure by self-report and cotinine with outcomes in RTR and assess dose dependency.

Renal expression of Toll-like receptor 2 and 4: dynamics in human allograft injury and comparison to rodents.

Activation of the innate immunity through Toll-like receptors (TLRs) has been postulated to play an important role in the pathophysiology of renal allograft dysfunction. TLR2 and TLR4 dynamics in different human post-transplant pathological entities has never been studied. Therefore, we evaluated pre- and post-transplantation protein expression of TLR2 and TLR4 in human kidney biopsies.

N-octanoyl dopamine treatment of endothelial cells induces the unfolded protein response and results in hypometabolism and tolerance to hypothermia.

Aim: N-acyl dopamines (NADD) are gaining attention in the field of inflammatory and neurological disorders. Due to their hydrophobicity, NADD may have access to the endoplasmic reticulum (ER). We therefore investigated if NADD induce the unfolded protein response (UPR) and if this in turn influences cell behaviour.

The clinical course of hepatitis E virus infection in patients of a tertiary Dutch hospital over a 5-year period.

Background: Hepatitis E virus (HEV) has long been known as a major cause of acute hepatitis in developing countries with occasional travel-related cases in developed countries, most of them belonging to genotype 1. Currently, genotype 3 HEV is recognized as an emerging public health issue in developed countries and can cause a chronic hepatitis in immunocompromised patients.

Objectives: The aim of this study was to get an overview of the clinical course of HEV infection, from July 2007 to December 2012, and further characterize HEV in patients of the University Medical Center Groningen (UMCG) over a 5-year time period.

The role of diet and physical activity in post-transplant weight gain after renal transplantation.

Background: Long-term survival of renal transplant recipients (RTR) has not improved over the past 20 yr. The question rises to what extent lifestyle factors play a role in post-transplant weight gain and its associated risks after transplantation.

Methods: Twenty-six RTR were measured for body weight, body composition, blood lipids, renal function, dietary intake, and physical activity at six wk, and three, six, and 12 months after transplantation.

Impact of depression on long-term outcome after renal transplantation: a prospective cohort study.

Background: Renal transplantation is the treatment of choice for end stage renal disease. Although there is more depression in wait-listed versus transplant patients, depression persists after transplantation. We investigated the determinants of depression in renal transplantation recipients (RTRs) and the association with cardiovascular (CV) and all-cause-mortality and graft failure.

Novel insights in localization and expression levels of C5aR and C5L2 under native and post-transplant conditions in the kidney.

Aims: The complement system, and especially C5a, plays an important role in the pathophysiology of renal diseases and post-transplant renal injury. The two receptors for C5a are C5a receptor (C5aR) and C5a-like-receptor-2 (C5L2). Only renal C5aR expression has been reported, although exact localization and alterations in expression after transplantation are unknown.

A randomized clinical trial of living donor nephrectomy: a plea for a differentiated appraisal of mini-open muscle splitting incision and hand-assisted laparoscopic donor nephrectomy.

A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini-open muscle splitting incision (MSI) technique and the transperitoneal hand-assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were randomized to MSI or HAL. Primary endpoint was pain experience scored on a visual analogue scale (VAS).

Latent cytomegalovirus infection is an independent risk factor for late graft failure in renal transplant recipients.

Background: Cytomegalovirus (CMV) is a risk factor for rejection and mortality soon after renal transplantation. Little is known about its consequences longer after transplantation. We prospectively investigated whether latent CMV infection is a risk factor for graft failure and mortality long after transplantation.

Smoking is a risk factor for graft failure and mortality after renal transplantation.

Background: Smoking in renal transplant recipients (RTR) is an acknowledged cardiovascular risk factor. It is, however, unclear whether smoking also increases the risk of graft failure (GF).

Method: In this study, we prospectively assessed the association of current smoking versus past and never smoking with GF and mortality in 604 RTR (age 51.

Long-term health and work outcomes of renal transplantation and patterns of work status during the end-stage renal disease trajectory.

Introduction: The aim of this study was to examine the health- and work outcomes of renal transplant recipients long-term after transplantation as well as the pattern of work status, work ability and disability benefits during the end-stage renal disease (ESRD) trajectory that precedes transplantation.

Methods: 34 transplant recipients completed interviews 3, 13 months and >6 years posttransplantation. Health status (SF-36), work ability (WAI), and fatigue (CIS) were assessed by questionnaires, clinical data were derived from medical charts, and data on functional limitations were extracted from the social security system database.

Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.

Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together.

Renal function equations before and after living kidney donation: a within-individual comparison of performance at different levels of renal function.

Background And Objectives: The Modification of Diet in Renal Disease (MDRD) study equation and the Cockcroft-Gault (CG) equation perform poorly in the (near-) normal range of GFR. Whether this is due to the level of GFR as such or to differences in individual characteristics between healthy individuals and patient with chronic kidney disease (CKD) is unknown.

Design, Setting, Participants, & Measurements: We evaluated the performance of MDRD, CG per BSA (CG/(BSA)) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations compared with measured GFR (mGFR; I-iothalamate) at 4 months before and 2 months after donation in 253 consecutive living kidney donors.