Using Information Available at the Time of Donor Offer to Predict Kidney Transplant Survival Outcomes: A Systematic Review of Prediction Models.

Statistical models that can predict graft and patient survival outcomes following kidney transplantation could be of great clinical utility. We sought to appraise existing clinical prediction models for kidney transplant survival outcomes that could guide kidney donor acceptance decision-making. We searched for clinical prediction models for survival outcomes in adult recipients with single kidney-only transplants. Models that require information anticipated to become available only after the time of transplantation were excluded as, by that time, the kidney donor acceptance decision would have already been made. The outcomes of interest were all-cause and death-censored graft failure, and death. We summarised the methodological characteristics of the prediction models, predictive performance and risk of bias. We retrieved 4,026 citations from which 23 articles describing 74 models met the inclusion criteria. Discrimination was moderate for all-cause graft failure (C-statistic: 0.570-0.652; Harrell's C: 0.580-0.660; AUC: 0.530-0.742), death-censored graft failure (C-statistic: 0.540-0.660; Harrell's C: 0.590-0.700; AUC: 0.450-0.810) and death (C-statistic: 0.637-0.770; Harrell's C: 0.570-0.735). Calibration was seldom reported. Risk of bias was high in 49 of the 74 models, primarily due to methods for handling missing data. The currently available prediction models using pre-transplantation information show moderate discrimination and varied calibration. Further model development is needed to improve predictions for the purpose of clinical decision-making. Systematic Review Registration: https://osf.io/c3ehp/l.

Transplantation of a Gitelman Syndrome Kidney Ameliorates Hypertension: A Case Report.

Gitelman syndrome is caused by inactivating mutations of the gene that encodes the renal sodium/chloride cotransporter (NCC; encoded by SLC12A3), resulting in hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Renal salt wasting commonly provokes mild hypotension. The paucity of previous kidney transplants from donors with known tubulopathies suggests that such conditions may be considered contraindications to donation. A 76-year-old man received a live unrelated kidney transplant from a donor with known Gitelman syndrome secondary to a pathogenic mutation of SLC12A3. Immediate graft function preceded the emergence of the Gitelman syndrome biochemical phenotype and blood pressure subsequently improved. The recipient developed unexpected hyponatremia. Potential causes are discussed, including the possibility that it paralleled the physiologic changes seen in the high-volume state of thiazide-induced hyponatremia. Transplanted kidneys are subject to nephrotoxicity from the use of calcineurin inhibitors. Acquired Gitelman syndrome may confer a potential long-term advantage to the recipient through both improved blood pressure control and protection against the calcineurin inhibitor-induced side-effect profile caused by NCC overactivation. Both the donor and recipient remain well. In conclusion, Gitelman syndrome need not preclude kidney donation and transference of the phenotype may have benefits for the recipient.

Designing lightweight neutron absorbing composites using a comprehensive absorber areal density metric.

Efforts to lightweight neutron absorbing composites are limited by incomplete understandings of the interaction between absorbing particles and their matrices. In this study, analytical models and a more physically representative simulation evaluated the penalty to neutron absorbing performance due to neutron channeling between large absorbing particles. Models and simulation agreed that B4C particles smaller than 100µm and especially those smaller than 10µm did not cause excessive neutron channeling. A more comprehensive neutron absorbing composite design metric - boron-10 equivalent areal density, which considers the particle size penalty and the matrix contribution to absorptivity - was introduced and used to estimate lightweighting via matrix substitution. Calculations using this new metric showed that a non-absorbing Mg matrix reduced mass by up to 35% over Al, constrained by the difference in mass density, while an absorbing Mg-Li matrix reduced mass by up to 60%, exceeding the difference in mass densities alone. Measurement of apparent absorber areal density through two experimental techniques - foil activation and direct counting - validated estimated absorber areal density as a neutron absorbing composite design metric. This updated understanding of the particle size penalty, newly introduced design metric, and experimental validation demonstrate a path to lightweight neutron absorbing composites.

BAI1 localizes AMPA receptors at the cochlear afferent post-synaptic density and is essential for hearing.

Type I spiral ganglion neurons (SGNs) convey sound information to the central auditory pathway by forming synapses with inner hair cells (IHCs) in the mammalian cochlea. The molecular mechanisms regulating the formation of the post-synaptic density (PSD) in the SGN afferent terminals are still unclear. Here, we demonstrate that brain-specific angiogenesis inhibitor 1 (BAI1) is required for the clustering of AMPA receptors GluR2-4 (glutamate receptors 2-4) at the PSD. Adult Bai1-deficient mice have functional IHCs but fail to transmit information to the SGNs, leading to highly raised hearing thresholds. Despite the almost complete absence of AMPA receptor subunits, the SGN fibers innervating the IHCs do not degenerate. Furthermore, we show that AMPA receptors are still expressed in the cochlea of Bai1-deficient mice, highlighting a role for BAI1 in trafficking or anchoring GluR2-4 to the PSDs. These findings identify molecular and functional mechanisms required for sound encoding at cochlear ribbon synapses.

Consensus guidelines for the safe prescription and administration of oral bowel-cleansing agents.

Oral bowel-cleansing preparations are used before colonic surgery and endoscopic and radiological assessment of the intestine to minimise faecal contamination. In February 2009, the UK National Patient Safety Agency issued a Rapid Response Report highlighting the potential risk of harm associated with the use of these preparations and instructing local NHS Trusts to implement safeguards to reduce this risk. This guidance has been prepared to help NHS Trusts to respond to these concerns, as the risk of complications is influenced by both individual patient risk factors and the choice of bowel preparation, for which definitive guidance was not previously available. This document provides an outline of the different available oral bowel-cleansing agents and the complications that may arise. This is followed by recommendations for their use in different patient groups and circumstances. The recommendations are based on consensus between the authors, each of whom circulated drafts to members of their specialist society. The evidence for these recommendations has been assessed using the modified GRADE system. The recommendations cover the choice, administration and complications (relative and absolute) of the different oral bowel-cleansing agents, with specific guidance provided for different patient groups.

An external validation of the Kidney Donor Risk Index in the UK transplant population in the presence of semi-competing events.

BACKGROUND: Transplantation represents the optimal treatment for many patients with end-stage kidney disease. When a donor kidney is available to a waitlisted patient, clinicians responsible for the care of the potential recipient must make the decision to accept or decline the offer based upon complex and variable information about the donor, the recipient and the transplant process. A clinical prediction model may be able to support clinicians in their decision-making. The Kidney Donor Risk Index (KDRI) was developed in the United States to predict graft failure following kidney transplantation. The survival process following transplantation consists of semi-competing events where death precludes graft failure, but not vice-versa. METHODS: We externally validated the KDRI in the UK kidney transplant population and assessed whether validation under a semi-competing risks framework impacted predictive performance. Additionally, we explored whether the KDRI requires updating. We included 20,035 adult recipients of first, deceased donor, single, kidney-only transplants between January 1, 2004, and December 31, 2018, collected by the UK Transplant Registry and held by NHS Blood and Transplant. The outcomes of interest were 1- and 5-year graft failure following transplantation. In light of the semi-competing events, recipient death was handled in two ways: censoring patients at the time of death and modelling death as a competing event. Cox proportional hazard models were used to validate the KDRI when censoring graft failure by death, and cause-specific Cox models were used to account for death as a competing event. RESULTS: The KDRI underestimated event probabilities for those at higher risk of graft failure. For 5-year graft failure, discrimination was poorer in the semi-competing risks model (0.625, 95% CI 0.611 to 0.640;0.611, 95% CI 0.597 to 0.625), but predictions were more accurate (Brier score 0.117, 95% CI 0.112 to 0.121; 0.114, 95% CI 0.109 to 0.118). Calibration plots were similar regardless of whether the death was modelled as a competing event or not. Updating the KDRI worsened calibration, but marginally improved discrimination. CONCLUSIONS: Predictive performance for 1-year graft failure was similar between death-censored and competing event graft failure, but differences appeared when predicting 5-year graft failure. The updated index did not have superior performance and we conclude that updating the KDRI in the present form is not required.

A universal stress protein upregulated by hypoxia has a role in Burkholderia cenocepacia intramacrophage survival: Implications for chronic infection in cystic fibrosis.

Universal stress proteins (USPs) are ubiquitously expressed in bacteria, archaea, and eukaryotes and play a lead role in adaptation to environmental conditions. They enable adaptation of bacterial pathogens to the conditions encountered in the human niche, including hypoxia, oxidative stress, osmotic stress, nutrient deficiency, or acid stress, thereby facilitating colonization. We previously reported that all six USP proteins encoded within a low-oxygen activated (lxa) locus in Burkholderia cenocepacia showed increased abundance during chronic colonization of the cystic fibrosis (CF) lung. However, the role of USPs in chronic cystic fibrosis infection is not well understood. Structural modeling identified surface arginines on one lxa-encoded USP, USP76, which suggested it mediated interactions with heparan sulfate. Using mutants derived from the B. cenocepacia strain, K56-2, we show that USP76 is involved in host cell attachment. Pretreatment of lung epithelial cells with heparanase reduced the binding of the wild-type and complement strains but not the Δusp76 mutant strain, indicating that USP76 is directly or indirectly involved in receptor recognition on the surface of epithelial cells. We also show that USP76 is required for growth and survival in many conditions associated with the CF lung, including acidic conditions and oxidative stress. Moreover, USP76 also has a role in survival in macrophages isolated from people with CF. Overall, while further elucidation of the exact mechanism(s) is required, we can conclude that USP76, which is upregulated during chronic infection, is involved in bacterial survival within CF macrophages, a hallmark of Burkholderia infection.

Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask.

Background: Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen prior to the procedure ("preoxygenation") decreases the risk of hypoxemia during intubation. Research Question: Whether preoxygenation with noninvasive ventilation prevents hypoxemia during tracheal intubation of critically ill adults, compared to preoxygenation with oxygen mask, remains uncertain. Study Design and Methods: The PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) is a prospective, multicenter, non-blinded randomized comparative effectiveness trial being conducted in 7 emergency departments and 17 intensive care units across the United States. The trial compares preoxygenation with noninvasive ventilation versus oxygen mask among 1300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask prior to induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 minutes after intubation. Enrollment began on 10 March 2022 and is expected to conclude in 2023. Interpretation: The PREOXI trial will provide important data on the effectiveness of noninvasive ventilation and oxygen mask preoxygenation for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan prior to the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial. Clinical trial registration number: NCT05267652.

Catastrophic Fibromuscular Dysplasia Presenting with Concomitant Bilateral Renal Infarction, Vertebral Artery Dissection, and Mesenteric Ischaemia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic, non-inflammatory disorder of the arterial wall muscular layer which can lead to arterial stenosis, occlusion, and dissection. Clinical presentations of FMD vary depending on the arterial territories involved, often leading to diagnostic challenges. This case report describes an exceptionally unusual presentation of FMD, not previously described, affecting a previously fit and well 37-year-old female presenting with bilateral renal infarction, sequential vertebral artery dissections, mesenteric ischaemia, and the requirement for continued renal replacement. This report highlights how unusual presentations of FMD can mask the underlying diagnosis. Early consideration of FMD in a differential diagnosis can guide an effective management strategy, including appropriate imaging and multi-speciality involvement.

The follow-up of renal transplant recipients by telephone consultation: three years experience from a single UK renal unit.

Although telephone consulting is increasingly used by clinicians seeking to balance rising caseloads, heightened patient expectation and the desire to ensure continued improvements in the quality, convenience and accessibility of the care they provide, its use to provide care to renal transplant recipients has not previously been described. Climate change is a major global public health threat. However, the provision of healthcare itself has a significant environmental impact. A transformation to lower carbon clinical care must be achieved without detriment to the quality of the patient care. This article reports the use of telephone consultation clinics to provide follow-up to renal transplant recipients over a three-year period. The benefits of this service to patients, providers and the environment are outlined, the existing literature regarding the provision of virtual care to patients with kidney disease is reviewed, and the possibilities of more widespread adoption are discussed.

Hypertension awareness, treatment, and control in adults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: A low rate of blood pressure control has been reported in patients with chronic kidney disease (CKD). These data were derived from population-based samples with a low rate of CKD awareness. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: Data from the baseline visit of the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,612) were analyzed. Participants with an estimated glomerular filtration rate of 20-70 mL/min/1.73 m(2) were identified from physician offices and review of laboratory databases. OUTCOMES: Prevalence and awareness of hypertension, treatment patterns, control rates, and factors associated with hypertension control. MEASUREMENTS: Following a standardized protocol, blood pressure was measured 3 times by trained staff, and hypertension was defined as systolic blood pressure > or =140 mm Hg and/or diastolic blood pressure > or =90 mm Hg and/or self-reported antihypertensive medication use. Patients' awareness and treatment of hypertension were defined using self-report, and 2 levels of hypertension control were evaluated: systolic/diastolic blood pressure <140/90 and <130/80 mm Hg. RESULTS: The prevalence of hypertension was 85.7%, and 98.9% of CRIC participants were aware of this diagnosis and 98.3% were treated with medications, whereas 67.1% and 46.1% had hypertension controlled to <140/90 and <130/80 mm Hg, respectively. Of CRIC participants with hypertension, 15%, 25%, 26%, and 32% were using 1, 2, 3, and > or =4 antihypertensive medications, respectively. After multivariable adjustment, older patients, blacks, and those with higher urinary albumin excretion were less likely, whereas participants using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were more likely to have controlled their hypertension to <140/90 and <130/80 mm Hg. LIMITATIONS: Data were derived from a single study visit. CONCLUSIONS: Despite almost universal hypertension awareness and treatment in this cohort of patients with CKD, rates of hypertension control were suboptimal.

Clinical transformation: the key to green nephrology.

Climate change represents a major global public health threat. The very provision of healthcare itself has a significant untoward effect on the environment, to which kidney care is likely to contribute disproportionately. In this article we describe the four principles we believe will underpin a successful transformation to lower carbon kidney care: disease prevention, patient empowerment, lean service delivery and the preferential use of low-carbon technologies. We illustrate their application and their co-benefits, such as improvements in patient care and reductions in cost, with examples.

Addison's disease presenting with acute kidney injury.

This lesson describes a case of Addison's disease presenting with acute kidney injury. The condition is briefly reviewed and a number of learning points are highlighted for clinicians encountering similar presentations.

Cardiac arrest secondary to type 2 Kounis syndrome resulting from urticaria and angioedema.

A 43-year-old man with no cardiac history presented with chest pain followed by cardiac arrest. He was successfully defibrillated and underwent primary percutaneous coronary angioplasty to a culprit coronary artery lesion. He later re-presented with a diffuse urticarial rash and lip swelling, reporting that these symptoms had been present for 4 weeks before his cardiac arrest and voicing concern that a further cardiac arrest may be imminent. A diagnosis of post-viral or idiopathic autoimmune urticaria and angioedema was made. Given the absence of cardiac symptoms before the development of the rash, it was hypothesised that coronary artery spasm precipitated by histamine release due to his dermatological condition contributed to his myocardial infarction and cardiac arrest. The final diagnosis was therefore cardiac arrest secondary to type II Kounis syndrome, resulting from idiopathic autoimmune or post-viral urticaria and angioedema.

Delayed Presentation of Urinoma Following Renal Transplant Biopsy: A Case Report.

A urinoma is an unusual complication following renal transplant biopsy that can easily be missed or mistaken for a hematoma. In addition to trauma to the renal collecting system, a degree of urinary tract obstruction is required for urine to leak into the surrounding tissues and form a urinoma, which can in turn cause pressure on surrounding structures. This case report describes a patient who developed ipsilateral leg swelling several months after a renal transplant biopsy. Imaging demonstrated a perirenal transplant fluid collection, which biochemical analysis confirmed to be urine. This was successfully managed with percutaneous nephrostomy and antegrade ureteric stent insertion. The fluid collection persisted as a seroma however, and the patient proceeded to have peritoneal fenestration and marsupialization surgery. To our knowledge, this is the first reported case of urinoma complicating a renal transplant biopsy. This case highlights a diagnosis that can be easily missed and is therefore a potential pitfall for clinicians.

A Case of Abulia From Left Middle Cerebral Artery Stroke in an Adolescent Treated Successfully With Short Duration Olanzapine.

INTRODUCTION: Abulia is defined as a pathological state of amotivation, apathy, and global absence of willpower. It presents with a challenging array of overlapping symptoms, making effective identification and treatment difficult. CASE PRESENTATION: We describe the first known report of an adolescent with a ventricular assist device who developed abulia following a left middle cerebral artery (MCA) stroke who responded successfully to treatment with olanzapine. DISCUSSION: The neurobiological etiology of abulia is still unclear but is postulated to be related to deficits in the dopaminergic reward circuitry in the frontal-subcortical-mesolimbic regions. There have been reports of poststroke patients with abulia being treated by modulating this dopamine circuitry and in some cases with short-term low-dose olanzapine. CONCLUSION: Further research is needed to develop a better understanding of the pathophysiology of abulia leading to more effective treatment algorithms including more specific diagnostic tools and effective pharmacological interventions.

The involvement of the low-oxygen-activated locus of Burkholderia cenocepacia in adaptation during cystic fibrosis infection.

Chronic infection with opportunistic pathogens including Burkholderia cepacia complex (Bcc) is a hallmark of cystic fibrosis (CF). We investigated the adaptive mechanisms facilitating chronic lung infection in sequential Bcc isolates from two siblings with CF (P1 and P2), one of whom also experienced intermittent blood-stream infections (P2). We previously showed increased lung cell attachment with colonisation time in both P1 and P2. WGS analysis confirmed that the isolates are closely related. Twelve genes showed three or more mutations, suggesting these were genes under selection. Single nucleotide polymorphisms (SNVs) in 45 regulatory genes were also observed. Proteomic analysis showed that the abundance of 149 proteins increased over 61-months in sputum isolates, and both time- and source-related alterations in protein abundance between the second patient's isolates. A consistent time-dependent increase in abundance of 19 proteins encoded by a low-oxygen-activated (lxa) locus was observed in both sets of isolates. Attachment was dramatically reduced in a B. cenocepacia K56-2Δlxa-locus deletion mutant, further indicating that it encodes protein(s) involved in host-cell attachment. Time-related changes in virulence in Galleria mellonella or motility were not observed. We conclude that the lxa-locus, associated with anoxic persistence in vitro, plays a role in host-cell attachment and adaptation to chronic colonization in the hypoxic niche of the CF lung.