The implications of donor-recipient size mismatch in renal transplantation.

Introduction: Transplanting kidneys small for recipient's size results in inferior graft function. Body surface area (BSA) is related to kidney size. We used the BSA index (BSAi) (Donor BSA/Recipient BSA) to assess whether the renal graft size is sufficient for the recipient.

Ex vivo delivery of Mirococept: A dose-finding study in pig kidney after showing a low dose is insufficient to reduce delayed graft function in human kidney.

The complement system plays a pivotal role in the pathogenesis of ischemia-reperfusion injury in solid organ transplantation. Mirococept is a potent membrane-localizing complement inhibitor that can be administered ex vivo to the donor kidney prior to transplantation. To evaluate the efficacy of Mirococept in reducing delayed graft function (DGF) in deceased donor renal transplantation, we undertook the efficacy of mirococept (APT070) for preventing ischaemia-reperfusion injury in the kidney allograft (EMPIRIKAL) trial (ISRCTN49958194).

Hypoperfusion warm ischaemia time in renal transplants from donors after circulatory death.

Background: The donor hypoperfusion phase before asystole in renal transplants from donors after circulatory death (DCD) has been considered responsible for worse outcomes than those from donors after brain death (DBD).

Methods: We included 10 309 adult renal transplants (7128 DBD and 3181 DCD; 1 January 2010-31 December 2016) from the UK Transplant Registry. We divided DCD renal transplants into groups according to hypoperfusion warm ischaemia time (HWIT).

UK renal transplant outcomes in low and high BMI recipients: the need for a national policy.

Introduction: We assessed the effect of recipient body mass index (BMI) on the outcomes of renal transplantation and the management of obese patients with end-stage renal disease across the UK.

Methods: We analyzed data of 25539 adult renal transplants (2007-2016) from the UK Transplant Registry. Patients were divided in BMI groups [underweight: < 18.

Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples.

Background: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage.

Methods: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study.

Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study.

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2-11.

Chronic histological changes in deceased donor kidneys at implantation do not predict graft survival: a single-centre retrospective analysis.

The use of preimplantation kidney biopsies (PIKBs) to aid deceased donor kidney utilization decisions is controversial. Outcomes of transplants that had been biopsied after the decision had been made to implant were analysed, in order to determine the association between chronic histological changes at implantation and graft outcomes. A retrospective analysis of transplants between the year range 2006-2015 was performed.

Outcomes in Third and Fourth Kidney Transplants Based on the Type of Donor.

Background: An increasing number of patients are requiring multiple retransplants. We assessed outcomes of third and fourth kidney transplants, to aid decision making on the most suitable donor type.

Methods: Data were collected retrospectively for 2561 transplants, including 69 third and 8 fourth, performed from 2000 to 2017.

A double-blind randomised controlled investigation into the efficacy of Mirococept (APT070) for preventing ischaemia reperfusion injury in the kidney allograft (EMPIRIKAL): study protocol for a randomised controlled trial.

Background: Delayed graft function (DGF) is traditionally defined as the requirement for dialysis during the first week after transplantation. DGF is a common complication of renal transplantation, and it negatively affects short- and long-term graft outcomes. Ischaemia reperfusion injury (IRI) is a prime contributor to the development of DGF.

Successful medical treatment of emphysematous pyelonephritis in chronic hemodialysis.

Emphysematous pyelonephritis (EPN) is a life-threatening renal infection caused by gas-producing bacteria and fungi. It usually occurs in patients with diabetes and patients with urinary tract obstruction. A combination of systemic antibiotics, percutaneous catheter drainage, or open nephrectomy is typically required to achieve cure.

Perioperative administration of high-dose recombinant human erythropoietin for delayed graft function prevention in kidney transplantation: a meta-analysis.

Delayed graft function (DGF) due to ischemia-reperfusion injury is a major early complication of kidney transplantation (KT). Recombinant human erythropoietin (rHuEPO) has been shown to exert nephroprotective action in animal models. We conducted a meta-analysis to explore the impact of rHuEPO on DGF in KT.

Effect of Smad pathway activation on podocyte cell cycle regulation: an immunohistochemical evaluation.

Background: Mature podocytes are in cell cycle arrest and their inability to proliferate successfully is a consequence of negative cell-cycle regulators' expression, such as p57. Phosphorylated smad2/smad3 (pSmad2/3) is an intracellular heteromeric mediator of transforming growth factor beta (TGF-β) signals and, together with co-activators such as P300, regulates gene transcription, including cell cycle regulator proteins.

Methods: In order to investigate Smad pathway activation and podocyte cell cycle regulation in glomerular injury, we studied the glomerular immunohistochemical expression of p57, pSmad2/3 and P300 in samples from 67 patients with various types of glomerulonephritis (GN) and 10 normal kidney tissue specimens.

Statins in chronic kidney disease and kidney transplantation.

HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular (CV) outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their pleiotropic effects statins have been shown to reduce inflammation, alleviate oxidative stress, modify the immunologic responses, improve endothelial function and suppress platelet aggregation.

Dyslipidemia, statins, and CKD patients' outcomes - review of the evidence in the post-sharp era.

Hyperlipidemia in the general population is strongly associated with an increased incidence of major adverse cardiovascular (CV) events (MACE). It is well established that HMG-CoA reductase inhibitors (statins) reduce CV and all-cause mortality in the general population, as well as in patients with CV disease (CVD). However, such a finding has not been definitively confirmed in patients with chronic kidney disease (CKD).

Long-term safety and efficacy of renin-angiotensin blockade in atherosclerotic renal artery stenosis.

Purpose: The activation of the renin-angiotensin-aldosterone system caused by renal ischaemia in atherosclerotic renal artery stenosis (ARAS) may be responsible for serious cardiovascular and renal consequences. The aim of the study was to assess the long-term safety, tolerability and outcomes of the use of angiotensin I-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients with ARAS.

Methods: Thirty-six patients with angiographically defined ARAS (managed either with revascularization or only with medical treatment) were prospectively assessed for the safety, tolerability and outcomes of the use of ACEis or ARBs.

Statins and prostate cancer: molecular and clinical aspects.

The field of the potential applications of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) beyond their unambiguous cardiovascular beneficial effects is steadily increasing. In this regard, statins have also been shown to possess anti-inflammatory, immunomodulatory, antioxidant and growth inhibitory properties. Regarding their role in carcinogenesis, both preclinical and clinical studies report conflicting results.

Impaired desensitization of a human polymorphic α2B-adrenergic receptor variant enhances its sympatho-inhibitory activity in chromaffin cells.

Background: α2-adrenergic receptors (ARs) mediate many cellular actions of epinephrine and norepinephrine and inhibit their secretion from adrenal chromaffin cells. Like many other G-protein coupled receptors (GPCRs), they undergo agonist-dependent phopshorylation and desensitization by GPCR Kinases (GRKs), a phenomenon recently shown to play a major role in the sympathetic overdrive that accompanies and aggravates chronic heart failure. A deletion polymorphism in the human α2B-AR gene (Glu301-303) causes impaired agonist-promoted receptor phosphorylation and desensitization in heterologous cell lines.

Transcription factor Sp1 expression is upregulated in human glomerulonephritis: correlation with pSmad2/3 and p300 expression and renal injury.

Background: Sp1 is a ubiquitous transcription factor that mediates the fibrogenic factor transforming growth factor beta (TGF-beta) signals through cooperation with Smad proteins. The transcriptional coactivator p300 is also suggested to play a role in Smad signal transduction.

Methods: We investigated the immunohistochemical expression of Sp1 as well as the expression of pSmad2/3 and the coactivator p300 in 157 renal biopsy specimens from patients with various types of glomerulonephritis (GN).

Anaemia, microcytosis and sirolimus--is iron the missing link?

Background: Sirolimus (SRL) has been implicated in the causation of post-transplantation anaemia (PTA). It also induces profound red blood cell (RBC) microcytosis, which is poorly understood.

Methods: We conducted a retrospective study of SRL-induced anaemia and microcytosis [mean corpuscular volume (MCV) <80 fl] with specific reference to iron homeostasis in 93 renal transplant patients treated with SRL for at least 3 months.

The role of statins in chronic kidney disease (CKD): friend or foe?

The effects of statins in chronic kidney disease (CKD) are incompletely understood. To date, no clinical trial has provided definitive evidence that cholesterol lowering treatments reduce cardiovascular morbidity and mortality in CKD patients. Moreover, existing preclinical data suggest both a renoprotective effect of statins (highlighted by reduction in the rate of the decline of GFR and reduction of proteinuria) and a harmful effect (mainly by accelerating renal fibrosis) in the long-term management of patients with CKD.