Correctional health care and Australian prisoners as recipients of kidney transplants: Legal and ethical issues.

AIM: This research aims to examine the legal and ethical issues surrounding Australia prisoners as potential kidney transplant recipients. METHODS: Examination of relevant statutory and common law including human rights law, state and territory corrections legislation and negligence law. Ethical principles considered, particularly in regards to practical and logistical considerations including adequate delivery of transplantation medical care and implications on the broader organ donation program. Approaches in the United States of America and United Kingdom are compared with the Australian approach. RESULTS: Prisoners are more likely than non-incarcerated individuals to have chronic medical conditions. For most people with kidney failure, kidney transplantation improves both quality of life and life expectancy compared with dialysis therapy. Prisoners have a right to access reasonable medical care under state-based corrections legislation, which is underpinned by human rights law and ethical principles, primarily beneficence, transparency and justice. The right of prisoners to receive reasonable medical care likely extends to ensuring prisoners with kidney failure are considered for kidney transplantation and waitlisted if medically appropriate. Social factors and logistical factors can be relevant when considering eligibility for transplantation as they can relate to a person's ability to comply with medical therapy. Additionally, organ allocation decisions can be emotive, and a decision to offer a kidney transplant to a prisoner may generate significant negative publicity. CONCLUSION: Prisoners with kidney failure should be considered for kidney transplantation. Logistical barriers, such as guard availability, should be addressed by state departments responsible for prisoner health.

Impact of chronic kidney disease on illness perceptions, coping, self-efficacy, psychological distress and quality of life.

Chronic kidney disease (CKD) negatively impacts psychological well-being and quality of life (QoL). Underpinned by the Common Sense Model (CSM), this study evaluated the potential mediating role of self-efficacy, coping styles and psychological distress on the relationship between illness perceptions and QoL in patients living with CKD. Participants were 147 people with stage 3-5 kidney disease. Measures included eGFR, illness perceptions, coping styles, psychological distress, self-efficacy and QoL. Correlational analyses were performed, followed by regression modelling. Poorer QoL was associated with greater distress, engagement in maladaptive coping, poorer illness perceptions and lower self-efficacy. Regression analysis revealed that illness perceptions predicted QoL, with psychological distress acting as a mediator. The proportion of variance explained was 63.8%. These findings suggest that psychological interventions are likely to enhance QoL in CKD, if they target the mediating psychological processes associated with illness perceptions and psychological distress.

A psychosocial intervention for individuals with advanced chronic kidney disease: A feasibility randomized controlled trial.

AIM: The current study evaluated the feasibility and preliminary efficacy of a psychosocial intervention, the Kidney Optimal Health Program, in reducing symptoms of depression and anxiety in individuals with advanced chronic kidney disease. METHODS: Patients with stage 4 or 5 chronic kidney disease were randomized to either a nine-session psychosocial intervention programme or usual care. Feasibility was assessed through recruitment and retention rates and programme acceptability. Participants completed assessments of depression, anxiety and psychosocial health at baseline and at 3-, 6- and 12-month follow-up. A repeated-measures analysis of variance was used to compare groups on outcomes over time. RESULTS: One hundred and twenty-eight patients were screened for eligibility; 84 consented to participant and were randomized to receive the intervention (N = 42) or usual care (N = 42). 27 (32.1%) participants withdrew prior to baseline assessment. Of those who completed the baseline assessment (N = 57), trial retention was high (75.4% at 3-month, 80.7% at 6-month and 70.2% at 12-month follow-up). Participants reported high levels of programme acceptability. The patients who completed the intervention (N = 17) demonstrated significantly decreased depression at 12-month follow-up compared to the usual care group (N = 13). CONCLUSION: The results support the feasibility of the Kidney Optimal Health Program intervention in recruitment, retention and programme acceptability with an improved screening protocol. Preliminary support is provided for improvement in depressive symptoms in patients with advanced chronic kidney disease. Further investigation through a fully powered randomized controlled trial is warranted.

Cocaine-associated atypical haemolytic uraemic syndrome in a genetically susceptible individual.

Atypical haemolytic uraemic syndrome (aHUS) is a severe, life-threatening condition that requires early recognition and urgent treatment. In aHUS rare genetic variants in CFH, CFI, CD46, C3 and CFB predispose to complement over activation. This case describes a case of aHUS in which there was a strong temporal association between disease onset and the use of smoked cocaine. The patient was found to have a rare genetic variant in the CFI gene which may have been unmasked by first-time exposure to cocaine. The patient stabilized and improved with early administration of eculizumab, supporting the notion of an underlying immunological pathogenesis and the importance of early intervention.

Regulated necrosis in kidney ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process that is triggered when an organ undergoes a transient reduction or cessation of blood flow, followed by re-establishment of perfusion. In the clinical setting, IRI contributes to significant acute kidney injury, patient morbidity and mortality, and adverse outcomes in transplantation. Tubular cell death by necrosis and apoptosis is a central feature of renal IRI. Recent research has challenged traditional views of cell death by identifying new pathways in which cells die in a regulated manner but with the morphologic features of necrosis. This regulated necrosis (RN) takes several forms, with necroptosis and ferroptosis being the best described. The precise mechanisms and relationships between the RN pathways in renal IRI are currently the subject of active research. The common endpoint of RN is cell membrane rupture, resulting in the release of cytosolic components with subsequent inflammation and activation of the immune system. We review the evidence and mechanisms of RN in the kidney following renal IRI, and discuss the use of small molecule inhibitors and genetically modified mice to better understand this process and guide potentially novel therapeutic interventions.

Antigen-specific CD4+ CD25+ T cells induced by locally expressed ICOS-Ig: the role of Foxp3, Perforin, Granzyme B and IL-10 - an experimental study.

We have previously reported that ICOS-Ig expressed locally by a PIEC xenograft induces a perigraft cellular accumulation of CD4+ CD25+ Foxp3+ T cells and specific xenograft prolongation. In the present study we isolated and purified CD4+ CD25+ T cells from ICOS-Ig secreting PIEC grafts to examine their phenotype and mechanism of xenograft survival using knockout and mutant mice. CD4+ CD25+ T cells isolated from xenografts secreting ICOS-Ig were analysed by flow cytometry and gene expression by real-time PCR. Regulatory function was examined by suppression of xenogeneic or allogeneic primed CD4 T cells in vivo. Graft prolongation was shown to be dependent on a pre-existing Foxp3+ Treg, IL-10, perforin and granzyme B. CD4+ CD25+ Foxp3+ T cells isolated from xenografts secreting ICOS-Ig demonstrated a phenotype consistent with nTreg but with a higher expression of CD275 (ICOSL), expression of CD278 (ICOS) and MHC II and loss of CD73. Moreover, these cells were functional and specifically suppressed xenogeinic but not allogeneic primed T cells in vivo.

Lifetime risk of end-stage kidney disease in living donors for paediatric kidney transplant recipients in Australia and New Zealand - a retrospective study.

Living kidney donors (LKD) for paediatric kidney transplant recipients (KTR) have a heightened motivation to donate for emotional reasons and the clear health benefits to the KTR. We hypothesized that the cohort of LKD for paediatric KTR (LKD-P) includes motivated young parents with a higher lifetime end-stage kidney disease (ESKD) risk compared to adult KTR (LKD-A). Data from the Australia and New Zealand Dialysis and Transplant LKD Registry (2004-2015) was analysed to compare baseline characteristics and predonation ESKD risk in LKD-P (n = 315) versus LKD-A (n = 3448). LKD-P were younger (median age 42 vs. 50 years; P < 0.001) and had a marginally higher lifetime ESKD risk (median 0.44% vs. 0.40%; P < 0.01), with a similar proportion of LKD exceeding 1% risk threshold (5.4% vs. 5.6%; P = NS). Compared to grandparents as LKD-P, parents (median age 41 vs. 59 years; P < 0.001) had a higher lifetime ESKD (0.44% vs. 0.25%; P < 0.001). Although unique benefits to paediatric KTR justify the minor increase in lifetime ESKD risk in young parents, carefully selected grandparents are an alternative LKD-P option, allowing parents to donate for subsequent transplants.

Effect of haemodialysis and residual renal function on serum levels of galectin-3, B-type natriuretic peptides and cardiac troponin T.

AIM: Levels of plasma markers of myocardial fibrosis (galectin-3), stretch (B-type natriuretic peptide (BNP)) and injury (high-sensitivity troponin T (hs-TnT)) are affected by haemodialysis, residual renal function (RRF) and cardiac pathology. We aimed to determine the association of RRF, urine output and haemodialysis itself on cardiac biomarkers in haemodialysis patients. METHODS: Adult haemodialysis patients underwent venesection pre- and post-haemodialysis then echocardiography and inter-dialytic urine collection to calculate RRF (mL/min per 1.73m2 ) and urine output (mL/day). Galectin-3, BNP-32, NT-ProBNP and hs-TnT levels were compared across tertiles of echocardiographic parameters, RRF and urine output using the non-parametric test for trend across ordered groups. RESULTS: Twenty-three patients (17 male) with mean age 67.7±13.8 years and median (interquartile range) dialysis duration 13.6 (9.8-19.1) months participated. Galectin-3 was substantially lower following haemodialysis: 55 ng/mL (47-70) versus 23 ng/mL (19-27, P < 0.001), but other biomarkers changed little. By increasing RRF tertile, post-dialysis galectin-3 was 32.6 ng/mL (23.7-36.6), 21.9 ng/mL (19.0-23.2) and 19.0 ng/mL (16.9-21.0, P = 0.001); NT-ProBNP was 10 192 ng/L (2303-21 504), 2037 ng/L (1224-10 795) and 1481 ng/L (172-2890, P = 0.016). Results were similar for daily urine volume, but measured echocardiographic parameters were not associated with biomarker concentrations. CONCLUSION: Plasma concentration of galectin-3 is reduced by the haemodialysis procedure. Lower RRF and urine volume are strongly associated with higher levels of galectin-3 and NT-Pro-BNP. These associations are important to the clinical interpretation of these biomarker levels in haemodialysis patients.

Perioperative risk assessment for successful kidney transplant in leigh syndrome: a case report.

BACKGROUND: Leigh syndrome (LS) is a rare neurodegenerative mitochondrial disorder which typically presents in childhood but has a varied clinical course. Renal involvement such as proximal tubulopathy in patients with mitochondrial disorders has been described. However, end stage renal disease (ESRD) is uncommon and literature regarding patients undergoing kidney transplantation is limited. Successful deceased donor renal transplant has not been previously described in a patient with Leigh Syndrome. CASE PRESENTATION: We report a 21-year-old Han Chinese man who presented with limb weakness and unsteady gait, which progressed rapidly over a period of months until he was wheelchair-bound. He subsequently developed ESRD and was commenced on hemodialysis. Investigations revealed a m.13513G > A mutation with clinical and radiological features consistent with LS. His mitochondrial disease stabilised and he underwent a multidisciplinary assessment for deceased donor kidney transplantation to identify and minimise the LS-associated perioperative risks and potential negative effects of immunosuppressants on his LS. Successful kidney transplantation followed with excellent graft function three and a half years post-transplant and improvement in the patient's physical function. CONCLUSION: This case highlights the importance of careful pre-transplant perioperative risk assessment and post-transplant care in a rare and heterogeneous neurological disease to achieve an ultimately excellent clinical outcome. To our knowledge, this is the first report of successful deceased donor kidney transplant in a patient with known LS.

Carvedilol and Cardiac Biomarkers in Dialysis Patients: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND/AIMS: Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients. METHODS: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo. Serum and plasma were collected before the run-in, then 6 and 12 months post-randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT-ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and galectin-3. Left ventricular global longitudinal strain (GLS) was measured by echocardiography at baseline. RESULTS: Seventy-two participants were recruited of whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS (Spearman's rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median change scores from baseline to 12 months did not differ significantly between participants with complete biomarker data randomized to carvedilol (n=15) or placebo (n=16) for any biomarkers. CONCLUSIONS: NT-proBNP and hs-TnT were associated with GLS. However, changes in levels of the biomarkers from baseline to 12 months were not different between groups randomized to carvedilol and placebo.

The ß-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) Feasibility Study: A Randomized Controlled Trial.

BACKGROUND: ß-Blocking agents reduce cardiovascular mortality in patients with heart disease, but their potential benefit in dialysis patients is unclear. We aimed to determine the feasibility of a randomized controlled trial (RCT). STUDY DESIGN: Pilot RCT. SETTING & PARTICIPANTS: Patients who received dialysis for 3 or more months and were 50 years or older (or ≥18 years with diabetes or cardiovascular disease) were recruited from 11 sites in Australia and New Zealand. We aimed to recruit 150 participants. INTERVENTION: After a 6-week run-in with the ß-blocker carvedilol, we randomly assigned participants to treatment with carvedilol or placebo for 12 months. OUTCOMES & MEASUREMENTS: The prespecified primary outcome was the proportion of participants who tolerated carvedilol, 6.25mg, twice daily during the run-in period. After randomization, we report participant withdrawal and the incidence of intradialytic hypotension (IDH). RESULTS: Of 1,443 patients screened, 354 were eligible, 91 consented, and 72 entered the run-in stage. 49 of 72 run-in participants (68%; 95% CI, 57%-79%) achieved the primary outcome. 5 of the 23 withdrawals from run-in were attributable to bradycardia or hypotension. After randomization, 10 of 26 allocated to carvedilol and 4 of 23 allocated to placebo withdrew. 4 participants randomly assigned to carvedilol withdrew because of bradycardia or hypotension. Overall, there were 4 IDH events per 100 hemodialysis sessions; in participants allocated to carvedilol versus placebo, respectively, there were 7 versus 2 IDH events per 100 hemodialysis sessions (P=0.1) in the 2 weeks immediately following a dose increase and 4 versus 3 IDH events per 100 hemodialysis sessions after no dose increase (P=0.7). LIMITATIONS: Unable to recruit planned sample size. CONCLUSIONS: Recruiting patients receiving dialysis to an RCT of ß-blocker versus placebo will prove challenging. Possible solutions include international collaboration and exploring novel trial designs such as a registry-based RCT.

Application of an epitope-based allocation system in pediatric kidney transplantation.

Donor-recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope-based allocation approach to prospectively exclude donors with high-level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m2 , no episodes of rejection, and time to transplant 6.55 months. HLA-A, HLA-B, HLA-DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope-based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow-up and larger numbers, but has the potential to reduce anti-HLA sensitization and improve both graft survival and opportunities for future retransplantation.

Microvascular Disease After Renal Transplantation.

BACKGROUND/AIMS: Individuals who reach end-stage kidney disease (CKD5) have a high risk of vascular events that persists even after renal transplantation. This study compared the prevalence and severity of microvascular disease in transplant recipients and patients with CKD5. METHODS: Individuals with a renal transplant or CKD5 were recruited consecutively from renal clinics, and underwent bilateral retinal photography (Canon CR5-45, Canon). Their retinal images were deidentified and reviewed for hypertensive/microvascular signs by an ophthalmologist and a trained grader (Wong and Mitchell classification), and for vessel caliber at a grading centre using a computer-assisted method and Knudtson's modification of the Parr-Hubbard formula. RESULTS: Ninety-two transplant recipients (median duration 6.4 years, range 0.8 to 28.8) and 70 subjects with CKD5 were studied. Transplant recipients were younger (p<0.001), with a higher eGFR (p< 0.001), but were just as likely to have a moderate-severe hypertensive/microvascular retinopathy (46/92, 50%) as subjects with CKD5 (38/70, 54%; OR 0.84, CI 0.45 to 1.57, p=0.64), and had similar mean arteriole and venular calibres (135.1 ± 7.5 µm and 137.9 ± 14.9 µm, p=0.12; and 199.1 ± 17.8 µm and 202.4 ± 27.8 µm, p=0.36, respectively). Arteriole and venular caliber were not different in nine patients examined before and after transplantation (p=0.62 and p=0.11, respectively). CONCLUSIONS: Hypertensive/microvascular disease occurred just as often and was generally as severe in transplant recipients and subjects with CKD5. Microvascular disease potentially contributes to increased cardiac events post-transplantation.

The rationale and design of the Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study.

AIMS: The Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study aims to determine the feasibility of a large-scale randomized controlled trial with clinical endpoints comparing the beta-blocking agent carvedilol with placebo in patients receiving dialysis. METHODS: The BLOCADE Feasibility Study is a randomized, double-blind, placebo-controlled, parallel group feasibility study comparing the beta-blocking agent carvedilol with placebo. Patients receiving dialysis for ≥3 months and who are aged ≥50 years, or who are ≥18 years and have diabetes or cardiovascular disease, were eligible. The primary outcome was the proportion of participants who complete a 6-week run-in phase in which all participants received carvedilol titrated from 3.125 mg twice daily to 6.25 mg twice daily. Other measures included how many patients are screened, the proportion recruited, the overall recruitment rate, the proportion of participants who remain on study drug for 12 months and the incidence of intra-dialytic hypotension while on randomized treatment. RESULTS: The BLOCADE Feasibility Study commenced recruiting in May 2011 and involves 11 sites in Australia and New Zealand. CONCLUSIONS: The BLOCADE Feasibility Study will inform the design of a larger clinical endpoint study to determine whether beta-blocking agents provide benefit to patients receiving dialysis, and define whether such a study is feasible.

Angiotensin-converting enzyme 2 activity in patients with chronic kidney disease.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of the renin-angiotensin system that counteracts the adverse effects of angiotensin II. In heart failure patients, elevated plasma ACE2 activity predicted adverse events and greater myocardial dysfunction. We aimed to describe plasma ACE2 activity and its clinical associations in patients with kidney disease. METHODS: Patients recruited from a single centre comprised of chronic kidney disease Stage III/IV (CKD), haemodialysis patients and kidney transplant recipients (KTRs). Plasma ACE2 enzyme activity was measured using a fluorescent substrate assay in plasma, collected at baseline and stored at -80°C. Linear regression was performed in both males and females separately to determine the covariates associated with log-transformed ACE2. RESULTS: The median (interquartile range) plasma ACE2 activity in pmol/mL/min was 15.9 (8.4-26.1) in CKD (n = 59), 9.2 (3.9-18.2) in haemodialysis (n = 100) and 13.1 (5.7-21.9) in KTR (n = 80; P < 0.01). In male haemodialysis patients, ACE2 activity was 12.1 (6.8-19.6) compared with 4.4 (2.5-10.3) in females (P < 0.01). Log-transformed ACE2 plasma activity was associated with post-haemodialysis systolic blood pressure in females [ß-coefficient 0.04, 95% confidence interval (95% CI) 0.01-0.06, P = 0.006]. In males, log-transformed ACE2 plasma activity was associated with B-type natriuretic peptide (ß-coefficient 0.39, 95% CI 0.19-0.60, P < 0.001). Plasma ACE2 activity was not associated with mortality. CONCLUSIONS: Plasma ACE2 activity is reduced in haemodialysis patients compared with CKD patients, and in female haemodialysis patients compared with male. The different associations of plasma ACE2 activity between male and female haemodialysis patients indicate that the role of ACE2 in cardiovascular disease may differ by gender.

Enteric-coated mycophenolate sodium in combination with full dose or reduced dose cyclosporine, basiliximab and corticosteroids in Australian de novo kidney transplant patients.

AIM: Cyclosporine (CsA), dosed to achieve C2 targets, has been shown to provide safe and efficacious immunosuppression when used with a mycophenolate and steroids for de novo kidney transplant recipients. This study examined whether use of enteric-coated mycophenolate sodium (EC-MPS) together with basiliximab and steroids would enable use of CsA dosed to reduced C2 targets in order to achieve improved graft function. METHODS: Twelve-month, prospective, randomized, open-label trial in de novo kidney transplant recipients in Australia. Seventy-five patients were randomized to receive either usual exposure (n = 33) or reduced exposure (n = 42) CsA, EC-MPS 720 mg twice daily, basiliximab and corticosteroids. RESULTS: There was no significant difference in mean Cockcroft-Gault CrCl (creatinine clearance) (60.2 ± 17.6 mL/min per 1.73 m(2) vs 63.2 ± 24.3, P = 0.64 for usual versus reduced exposure respectively) at 6 months. There was no significant difference between treatment groups in the incidence of treatment failure defined as biopsy proven acute rejection, graft loss or death (secondary endpoint: 30.3% full exposure vs 35.7% reduced exposure). At 12 months the incidence of overall adverse events was the same in both groups. CONCLUSION: This exploratory study suggests de novo renal transplant patients can safely receive a treatment regimen of either full or reduced exposure CsA in combination with EC-MPS, corticosteroids and basiliximab, with no apparent difference in efficacy or graft function during the first year after transplant.

Challenges of Glycemic Control in People With Diabetes and Advanced Kidney Disease and the Potential of Automated Insulin Delivery.

Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease in the world. It is known that maintaining optimal glycemic control can slow the progression of CKD. However, the failing kidney impacts glucose and insulin metabolism and contributes to increased glucose variability. Conventional methods of insulin delivery are not well equipped to adapt to this increased glycemic lability. Automated insulin delivery (AID) has been established as an effective treatment in patients with type 1 diabetes mellitus, and there is emerging evidence for their use in type 2 diabetes mellitus. However, few studies have examined their role in diabetes with concurrent advanced CKD. We discuss the potential benefits and challenges of AID use in patients with diabetes and advanced CKD, including those on dialysis.

Dynamics of necroptosis in kidney ischemia-reperfusion injury.

Necroptosis, a pathway of regulated necrosis, involves recruitment and activation of RIPK1, RIPK3 and MLKL, leading to cell membrane rupture, cell death and release of intracellular contents causing further injury and inflammation. Necroptosis is believed to play an important role in the pathogenesis of kidney ischemia-reperfusion injury (IRI). However, the dynamics of necroptosis in kidney IRI is poorly understood, in part due to difficulties in detecting phosphorylated MLKL (pMLKL), the executioner of the necroptosis pathway. Here, we investigated the temporal and spatial activation of necroptosis in a mouse model of unilateral warm kidney IRI, using a robust method to stain pMLKL. We identified the period 3-12 hrs after reperfusion as a critical phase for the activation of necroptosis in proximal tubular cells. After 12 hrs, the predominant pattern of pMLKL staining shifted from cytoplasmic to membrane, indicating progression to the terminal phase of necroptotic cell death. Mlkl-ko mice exhibited reduced kidney inflammation at 12 hrs and lower serum creatinine and tubular injury at 24 hrs compared to wild-type littermates. Interestingly, we observed increased apoptosis in the injured kidneys of Mlkl-ko mice, suggesting a relationship between necroptosis and apoptosis in kidney IRI. Together, our findings confirm the role of necroptosis and necroinflammation in kidney IRI, and identify the first 3 hrs following reperfusion as a potential window for targeted treatments.

Challenges in blood pressure measurement in patients treated with maintenance hemodialysis.

The association between blood pressure and cardiovascular outcomes in patients undergoing hemodialysis remains controversial. This may relate in part to the technique and device used and the timing of the blood pressure measurement in relation to the hemodialysis procedure. Emerging evidence indicates that standardized hemodialysis unit blood pressure measurements or measurements obtained at home, either by the patient or using an ambulatory blood pressure monitor, may offer advantages over routine hemodialysis unit blood pressure measurements for determining cardiovascular risk and treatment. This review discusses the available evidence and implications for clinicians and clinical trials.