The DNA damage response pathway regulates the expression of the immune checkpoint CD47.

CD47 is a cell surface ligand expressed on all nucleated cells. It is a unique immune checkpoint protein acting as "don't eat me" signal to prevent phagocytosis and is constitutively overexpressed in many tumors. However, the underlying mechanism(s) for CD47 overexpression is not clear.

Impact of tozinameran (BNT162b2) mRNA vaccine on kidney transplant and chronic dialysis patients: 3-5 months follow-up.

Background: Determining the humoral immunogenicity of tozinameran (BNT162b2) in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, may guide risk assessment and changes in vaccination policy.

Methods: In a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody responses to vaccine or infection, and infection rate during follow-up.

The Effect of a 26-Hour Fast in Living Kidney Donors.

Background: Living kidney donation is widely practiced, and short- and long-term outcomes are acceptable. Within the living kidney donor population there are unique ethnic groups who practice customs that affect kidney function. In Judaism, Yom Kippur (Day of Atonement) is a 25- to 26-hour fast practiced yearly.

Practical recommendations for kidney transplantation in the COVID-19 pandemic.

Kidney transplantation at the time of a global viral pandemic has become challenging in many aspects. Firstly, we must reassess deceased donor safety (for the recipient) especially in communities with a relatively high incidence of coronavirus disease 19 (COVID-19). With respect to elective live donors, if one decides to do them at all, similar considerations must be made that may impose undue hardship on the donor.

Toxicology and Pharmacokinetic Studies in Mice and Nonhuman Primates of the Nontoxic, Efficient, Targeted Hexameric FasL: CTLA4-FasL.

Cytotoxic T-lymphocyte antigen 4 (CTLA4)-FasL, a homo-hexameric signal converter protein, is capable of inducing robust apoptosis in malignant cells of the B-cell lineage expressing its cognate B7 and Fas targets, while sparing nonmalignant ones. This fusion protein's striking proapoptotic efficacy stems from its complementary abilities to coordinately activate apoptotic signals and abrogate antiapoptotic ones. A limiting factor in translating FasL or Fas receptor agonists into the clinic has been lethal hepatotoxicity.

Ambulatory monitoring unmasks hypertension among kidney transplant patients: single center experience and review of the literature.

Background: Disagreements between clinic and ambulatory blood pressure (BP) measurements are well-described in the general population. Though hypertension is frequent in renal transplant recipients, only a few studies address the clinic-ambulatory discordance in this population. We aimed to describe the difference between clinic and ambulatory BP in kidney transplant patients at our institution.

Access-related infections in two haemodialysis units: results of a nine-year intervention and surveillance program.

Background: Access-related infections are a major cause of morbidity and mortality in haemodialysis patients. Our goal was to decrease the rate of these infections by implementing an intervention and surveillance program.

Methods: This intervention took place in two haemodialysis units (Units A and B) and was a joint effort by the haemodialysis staff and the unit for infection prevention and control.

Fn14·TRAIL fusion protein is oligomerized by TWEAK into a superefficient TRAIL analog.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates specific anti-cancer activity, but insufficient efficacy in patients. A fusion protein Fn14·TRAIL, that combines soluble TRAIL molecule with a specific TWEAK receptor Fn14, is a better apoptosis-inducer for hepatocellular carcinomas than soluble TRAIL. However, Fn14·TRAIL does not effectively induce apoptosis in tumors of the lymphoid origin.

Age limitation for organ transplantation: the Israeli example.

In 2013 the Israeli Ministry of Health appointed a public committee to examine the policy of placing an age limitation on candidates listed for organ transplantation. The committee rejected the use of an age limit criterion for listing candidates for transplantation and recommended to abolish it. However, opinions differed regarding the use of recipients’ age in shaping a fair organ allocation policy.

Implementation of guidelines for metabolic syndrome control in kidney transplant recipients: results at a single center.

Background: Cardiovascular disease is a leading cause of death among kidney transplant recipients. Metabolic syndrome increases the risk for cardiovascular events and decreases graft survival. Lately, guidelines for management of the metabolic syndrome, primarily hypertension, diabetes mellitus (DM) and hypercholesterolemia have dramatically changed in an attempt to decrease cardiovascular risks among kidney transplant recipients.

Highly efficient, in-vivo Fas-mediated apoptosis of B-cell lymphoma by hexameric CTLA4-FasL.

Non-Hodgkin lymphomas (NHLs) account for 4% of all malignancies. 5-year survival rate increased to 50% with new treatment modalities, however there is need for new effective treatment for the more aggressive, relapsing forms. Recently, CTLA4-FasL, that can bind to B7 and Fas receptor (Fas), was shown to induce robust apoptosis of cell lines originating from B cell lymphomas expressing both B7 and Fas, by activating pro-apoptotic signals in parallel to abrogating anti-apoptotic ones.

Serum vitamin D levels in kidney transplant recipients: the importance of an immunosuppression regimen and sun exposure.

Background: Vitamin D deficiency was shown to be prevalent among renal transplant recipients in northern countries, but little is known regarding risk factors.

Objectives: To test vitamin D levels in kidney transplant recipients residing closer to the equator, compare them to levels in liver transplant recipients and hemodialysis patients, and identify possible risk factors.

Methods: In a cross-sectional study 103 kidney transplant recipients, 27 liver transplant recipients and 50 hemodialysis patients followed at our institute were tested for vitamin D levels.

Fn14•TRAIL effectively inhibits hepatocellular carcinoma growth.

Background: New strategies for the treatment of hepatocellular carcinoma (HCC) are needed, given that currently available chemotherapeutics are inefficient. Since tumor growth reflects the net balance between pro-proliferative and death signaling, agents shifting the equilibrium toward the latter are of considerable interest. The TWEAK:Fn14 signaling axis promotes tumor cell proliferation and tumor angiogenesis, while TRAIL:TRAIL-receptor (TRAIL-R) interactions selectively induce apoptosis in malignant cells.

Heart rate response to blood pressure variations: sympathetic activation versus baroreflex response in patients with end-stage renal disease.

Background: Continuous systolic blood pressure (SBP) and interbeat intervals (IBI) recordings reveal sequences of consecutive beats in which SBP and heart rate change in opposite direction, representing negative feedback baroreflex mechanisms, as well as sequences in which SBP and heart rate change in the same direction (non-baroreflex), believed to represent feedforward control mechanisms. The present study was undertaken to assess the relationship between baroreflex and non-baroreflex sequences in end stage renal insufficiency.

Methodology/principal Findings: Continuous beat-to-beat SBP and IBI monitoring was performed in patients on chronic hemodialysis (HD, n=72), in age-matched patients after renal transplantation (TX, n=41) and healthy (control) individuals (C, n=34).

Amelioration of autoimmune neuroinflammation by the fusion molecule Fn14·TRAIL.

Background: Multiple sclerosis (MS) is a, T cell-mediated autoimmune disease, the management of which remains challenging. The recently described fusion protein, Fn14·TRAIL, combining the extracellular domain of Fn14 (capable of blocking the pro-inflammatory TWEAK ligand) fused to the extracellular domain of the TRAIL ligand (capable of sending apoptotic signals through its receptors on activated inflammatory cells) was designed to modulate the immune system as an anti-inflammatory agent. The present study explores the efficacy of this purified protein as an anti-inflammatory agent, using the animal model of MS - experimental autoimmune encephalomyelitis (EAE).

CD40·FasL and CTLA-4·FasL fusion proteins induce apoptosis in malignant cell lines by dual signaling.

Evolution of apoptosis resistance in both lymphoma and leukemia cells is well documented, and induction of apoptosis in malignant cells is a major goal of cancer therapy. Up-regulation of anti-apoptotic signals is one of the mechanisms whereby resistance to apoptosis emerges. We have previously described the fusion proteins CD40·FasL and CTLA-4·FasL, which are formed from two functional membrane proteins and induce apoptosis of activated T cells.

Human erythropoietin gene therapy for patients with chronic renal failure.

Gene therapy holds a major promise. However, until now, this promise was fulfilled only in few cases, in rare genetic diseases. One very common clinical condition is anemia.

Regulation of NaPi-IIa mRNA and transporter protein in chronic renal failure: role of parathyroid hormone (PTH) and dietary phosphate (Pi).

Chronic renal failure (CRF) is associated with a high fractional phosphate excretion (FEPi), secondary hyperparathyroidism, and resistance to parathyroid hormone (PTH). This study was undertaken to characterize the role of PTH and dietary Pi in the regulation of PTH/PTH-related peptide receptor (PTHrP-R) mRNA and NaPi-IIa mRNA and protein in CRF. The following groups of rats were studied: (1) sham-operated (control); (2) CRF: 6 weeks after 5/6 nephrectomy (NPX); (3) NPX and parathyroidectomy (NPX + PTX); (4) NPX rats fed a low-Pi diet (NPX + LP); (5) sham-operated rats fed a low-Pi diet (control + LP); (6) sham-operated after PTX (control + PTX).

Sensing phosphate across the kingdoms.

Purpose Of Review: The present review summarizes recent findings that may help in understanding how the cell senses changes in serum phosphate.

Recent Findings: The sensing of phosphate determines the organism's response to change in supply of this essential nutrient. Phosphate depletion or surfeit results in homeostatic responses that involve changes in transcription, transcript stability, transporter recruitment or breakdown, and cell replication.

CTLA-4. FasL induces alloantigen-specific hyporesponsiveness.

The APC:T cell interface can be effectively targeted with immunotherapeutic proteins. We previously described a unique trans signal converter protein, CTLA-4. Fas ligand (FasL), that has the inherent capacities to tether the T cell inhibitor FasL (CD95 ligand) to the surfaces of B7 (CD80 and CD86)-positive APC (via CTLA-4:B7 interaction), and in so doing, to simultaneously interfere with B7-to-CD28 T cell activation signals.