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Mutant EZH2 Drives Follicular Lymphoma by simply Changing B-cell Dependencies.
In a groundbreaking meeting, leading global kidney disease organizations came together in the fall of 2020 as an International Home Dialysis Roundtable (IHDR) to address strategies to increase access to and uptake of home dialysis, both peritoneal dialysis and home hemodialysis. This challenge has become urgent in the wake of the coronavirus disease 2019 (COVID-19) pandemic, during which patients with advanced kidney disease, who are more susceptible to viral infections and severe complications, must be able to safely physically distance at home. To boost access to home dialysis on a global scale, IHDR members committed to collaborate, through the COVID-19 public health emergency and beyond, to promote uptake of home dialysis on a broad scale. Their commitments included increasing the reach and influence of key stakeholders with policy makers, building a cooperative of advocates and champions for home dialysis, working together to increase patient engagement and empowerment, and sharing intelligence about policy, education, and other programs so that such efforts can be operationalized globally. In the spirit of international cooperation, IHDR members agreed to document, amplify, and replicate established efforts shown to improve access to home dialysis and support new policies that facilitate access through procedures, innovation, and reimbursement.Individuals receiving long-term hemodialysis are at increased risk of developing cardiovascular disease (CVD). Traditional cardiovascular risk factors do not fully explain the high CVD risk in this population. GLX351322 mouse During hemodialysis, blood interacts with the biomaterials of the hemodialysis circuit. This interaction can activate the complement system and the factor XII-driven contact system. FXII activation triggers both the intrinsic pathway of coagulation and the kallikrein-kinin pathway, resulting in thrombin and bradykinin production, respectively. The complement system plays a key role in the innate immune response, but also contributes to the pathogenesis of numerous disease states. Components of the complement pathway, including mannose binding lectin and C3, are associated with CVD risk in people with end-stage kidney disease (ESKD). Both the complement system and the factor XII-driven contact coagulation system mediate proinflammatory and procoagulant responses that could contribute to or accelerate CVD in hemodialysis recipents. This review summarizes what is already known about hemodialysis-mediated activation of the complement system and in particular the coagulation contact system, emphasizing the potential role these systems play in the identification of new biomarkers for CVD risk stratification and the development of potential therapeutic targets or innovative therapies that decrease CVD risk in ESKD patients.Small-scale trials in patients with chronic kidney disease (CKD) 3-5 have shown that hypobicarbonatemic metabolic acidosis promotes progression of CKD. Accordingly, the 2012 KDIGO (Kidney Disease Improving Global Outcomes) guideline suggests base administration to patients with CKD when serum bicarbonate concentration ([HCO3-]) is less then 22 mEq/L (~15% of non-dialysis-dependent patients with CKD). However, individuals with milder CKD largely maintain serum [HCO3-] within the normal range (eubicarbonatemia) and yet can manifest hydrogen ion (H+) retention. Limited data in eubicarbonatemic patients with CKD 2 suggest that base administration ameliorates CKD progression. Furthermore, most patients with moderate and advanced CKD maintain a normal serum [HCO3-], and of those, the vast majority most likely harbor masked H+ retention. The present review probes this expanded concept of metabolic acidosis of CKD the eubicarbonatemic H+ retention or subclinical metabolic acidosis of CKD. It focuses on the high prevalence of the entity, its pathophysiologic features, its clinical course, and recent work on potential biomarkers of the condition. Further, it puts forward the urgent task of investigating definitively whether treatment with alkali of eubicarbonatemic H+ retention delays CKD progression. If proven true, such knowledge would trigger a paradigm shift in the indication for alkali therapy in CKD.
Chronic kidney disease (CKD) is common but often goes unrecorded.

Cross-sectional.

Military Health System (MHS) beneficiaries aged 18 to 64 years who received care during fiscal years 2016 to2018.

Age, sex, active duty status, race, diabetes, hypertension, and numbers of kidney test results.

We defined CKD by
(
) code and/or a positive result on a validatedelectronic phenotype that uses estimatedglomerular filtration rate and measures of proteinuria with evidence of chronicity. Wedefined coded CKD by the presence of an
code. We defined uncoded CKD byapositive e-phenotype result without an
code.

We compared coded and uncoded populations using 2-tailed
tests (continuous variables) and Pearson χ
test for independence (categorical variables).

The MHS population included 3,330,893 beneficiaries. Prevalence of CKD was 3.2%, based on
code and/or positive e-phenotype result. Of those identified with CKD, 63% were uncoded. Compared with beneficiaries with coded CKD, those with uncoded CKore likely to be coded, suggesting that clinicians may be missing CKD in groups traditionally considered lower risk, potentially resulting in suboptimal care.
Patient awareness of disease is the first step toward effective management and disease control. Awareness of chronic kidney disease (CKD) has consistently been shown to be low, but studies estimating patient awareness of CKD have used different methods. We sought to determine whether the estimated prevalence of CKD awareness differed by the wording used to ascertain awareness or by setting characteristics.

Systematic review and meta-analysis.

Adults with CKD not receiving dialysis.

We included studies that estimated CKD awareness, determined CKD status by laboratory criteria, and provided the exact question wording used to ascertain awareness.

2 reviewers independently extracted data for each study; discordance was resolved by a third independent reviewer.

Mixed-effects models were used to calculate pooled CKD awareness estimates and 95% CIs.

32 studies were included. Publication year ranged from 2004 to 2017, with study populations ranging from 107 to 28,923 individuals. CKD awareness in indiviost effectively surveil and leverage CKD awareness to improve management and disease control.
Digital health system tools to support shared decision making and preparation for kidney replacement treatments for patients with chronic kidney disease (CKD) are needed.

Descriptive study of the implementation of digital infrastructure to support a patient-centered health system intervention.

4 CKD clinics within a large integrated health system.

We developed an integrated suite of digital engagement tools to support patients' shared decision making and preparation for kidney failure treatments. Tools included an automated CKD patient registry and risk prediction algorithm within the electronic health record (EHR) to identify and prioritize patients in need of nurse case management to facilitate shared decision making and preparation for kidney replacement treatments, an electronic patient-facing values clarification tool, a tracking application to document patients' preparation for treatments, and an EHR work flow to broadcast patients' treatment preferences to all health care providers.

Uptake annts.

This work was supported through a Patient-Centered Outcomes Research Institute (PCORI) Project Program Award (IHS-1409-20967).

ClinicalTrials.gov NCT02722382.
ClinicalTrials.gov NCT02722382.
Neighborhood socioeconomic status (SES) and health insurance status may be important upstream social determinants of chronic kidney disease (CKD), but their relationship remains unclear. The aim of this study was to determine whether neighborhood SES and individual-level health insurance status were independently associated with CKD prevalence.

Observational study using electronic health records (EHRs).

EHRs of patients (n=185,269) seen at a health care system in the 7-county Minneapolis/St Paul area (2017-2018).

Census tract neighborhood SES measures (median value of owner-occupied housing units [wealth], percentage of residents aged>25 years with bachelor's degree or higher [education]) and individual-level health insurance status (aged<65 years Medicaid vs other insurance;≥65 years Medicare vs Medicare and supplemental insurance plan) were obtained from the American Community Survey and EHR data. Neighborhood SES was operationalized into quartiles, comparing low (first quartile) versus high (iated with prevalence of CKD in the fully adjusted model.

One health care system and selection bias.

Living in low neighborhood SES as defined by wealth and education and having Medicaid for patients younger than 65 years were associated with higher CKD prevalence.
Living in low neighborhood SES as defined by wealth and education and having Medicaid for patients younger than 65 years were associated with higher CKD prevalence.
Urinary biomarker concentrations are frequently indexed to urinary creatinine (Ucr) concentration in spot samples to account for urine dilution; however, this may introduce biases. We evaluated whether indexing versus adjusting urinary biomarker concentrations for Ucr concentration altered their associations with outcomes.

Observational cohort.

We analyzed data from 2,360 Systolic Blood Pressure Intervention Trial (SPRINT) participants with estimated glomerular filtration rates<60mL/min/1.73m
and urinary albumin (UAlb) and 8 urinary kidney tubule biomarkers measured at baseline.

The primary outcome was a composite of cardiovascular disease events; secondary outcomes were all-cause mortality and a composite of kidney outcomes (50% estimated glomerular filtration rate decline, end-stage kidney disease, or transplantation).

We used Cox proportional hazards regression to examine the associations of 1/Ucr with outcomes and compared the associations of UAlb and 8 individual urinary tubule biomarkers dently associated with cardiovascular events in trial participants with chronic kidney disease. Indexing versus adjusting for 1/Ucr does not significantly change the associations of most urinary biomarkers with clinical outcomes.
Pain is a frequent complication of autosomal dominant polycystic kidney disease (ADPKD) and includes back and abdominal pain. We hypothesized that in adults with early- and late-stage ADPKD, overweight and obesity are independently associated with greater self-reported back, abdominal, and radicular pain at baseline and that weight loss would be associated with decreased pain over a follow-up period.

Post hoc analysis of pooled data from 2 randomized trials.

Participants in the HALT-PKD study A or B. 867 individuals were included in a cross-sectional analysis. 4,248 observations from 871 participants were included in a longitudinal analysis.

Overweight and obesity (cross-sectional); annual change in weight as a time-varying predictor (longitudinal).

Pain (Likert-scale responses; cross-sectional); annual change in pain (binary outcome of worsening pain or not worsening; longitudinal).

Multivariable ordinal logistic regression (cross-sectional); generalized estimating equation analysis (longitudinal).
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