Early Versus Late Initiation of Dialysis in CKD Stage 5: Time for a Consensus.

Chronic kidney disease (CKD), a major global public health problem, emerged as one of the leading causes of death, affecting over 800 million individuals worldwide, with significant burden to patients and their caregivers, and may lead to end-stage kidney disease (ESKD). The decision on optimal initiation of chronic dialysis is a common problem faced by nephrologists, patients, and caregivers due to lack of adequate data. Determining the ideal time to initiate maintenance dialysis for individuals struggling with ESKD has remained a puzzle.

Biomarker Panels for Predicting Progression of Kidney Disease in Acute Kidney Injury Survivors.

Background: Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). We aimed to identify combinations of clinical variables and biomarkers that predict long-term kidney disease risk after AKI.

Methods: We analyzed data from a prospective cohort of 723 hospitalized patients with AKI in the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (ASSESS-AKI) Study.

Avoiding arrythmias by personalizing the dialysate concentration: a case for precision medicine in patients on dialysis.

Cardiac arrythmias are common in patients undergoing maintenance hemodialysis. In this issue, Charytan et al. showed that in patients with hyperkalemia (serum potassium concentration 5.

The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.

Objective: The objective of this study was to identify the transcriptional landscape of insulin resistance (IR) in subcutaneous adipose tissue (SAT) in humans across the spectrum of obesity.

Methods: We used SAT RNA sequencing in 220 individuals with metabolic phenotyping.

Results: We identified a 35-gene signature with high predictive accuracy for homeostatic model of IR that was expressed across a variety of non-immune cell populations.

Intermuscular adipose tissue accumulation is associated with higher tissue sodium in healthy individuals.

Background And Aims: High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower-extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association.

Methods: Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (Na-MRI) and proton (1H-MRI) imaging of the calf.

Myeloid Cell Glucocorticoid, Not Mineralocorticoid Receptor Signaling, Contributes to Salt-Sensitive Hypertension in Humans via Cortisol.

Background: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality, yet the etiology is poorly understood. We previously found that serum/glucocorticoid-regulated kinase 1 (SGK1) and epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel (ENaC)-dependent sodium entry into monocyte-derived antigen-presenting cells (APCs) and activation of NADPH oxidase, leading to the formation of isolevuglandins (IsoLGs) in SSBP. Whereas aldosterone via the mineralocorticoid receptor (MR) activates SGK1 leading to hypertension, our past findings indicate that levels of plasma aldosterone do not correlate with SSBP, and there is little to no MR expression in APCs.

Acute Kidney Injury, Systemic Inflammation, and Long-Term Cognitive Function: ASSESS-AKI.

Key Points: This study highlights that AKI is associated with long-term cognitive decline. Soluble TNF receptor 1 concentrations seem to mediate a significant proportion of the risk of long-term cognitive impairment after AKI.

Background: Cognitive dysfunction is a well-known complication of CKD, but it is less known whether cognitive decline occurs in survivors after AKI.

Nutrition Management in Geriatric Patients with CKD.

Sarcopenia, defined as age-related decline in skeletal muscle mass and functional capacity, is a hallmark nutritional abnormality observed in patients with moderate-to-advanced CKD. Uremic state and associated medical conditions also predispose older patients with CKD to protein-energy wasting, a nutritional abnormality that could include sarcopenia. Prevention of protein and energy depletion and replenishing the already low nutritional reserves elderly patients with CKD should focus on conventional and innovative strategies.

Personalizing electrolytes in the dialysis prescription: what, why and how?

Maintenance hemodialysis patients suffer from multiple comorbidities and treatment-related complications. A personalized approach to hemodialysis prescription could reduce some of these burdens by preventing complications such as excessive changes in blood pressure, arrhythmias, post-dialysis fatigue and decreased quality of life. A patient-centered approach to dialysate electrolyte concentrations represents one such opportunity.

A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.

Background: Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD.

Methods: Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12 weeks.

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk.

Importance: Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones.

Objective: To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones.

Design, Setting, And Participants: This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics.

Eicosanoid-Regulated Myeloid ENaC and Isolevuglandin Formation in Human Salt-Sensitive Hypertension.

Background: The mechanisms by which salt increases blood pressure in people with salt sensitivity remain unclear. Our previous studies found that high sodium enters antigen-presenting cells (APCs) via the epithelial sodium channel and leads to the production of isolevuglandins and hypertension. In the current mechanistic clinical study, we hypothesized that epithelial sodium channel-dependent isolevuglandin-adduct formation in APCs is regulated by epoxyeicosatrienoic acids (EETs) and leads to salt-sensitive hypertension in humans.

The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events.

Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure.

Fluid management protocols in hemodialysis patients using bioimpedance validation: time to look elsewhere?

The management of volume status in dialysis patients is an important determinant of the rate of decline of residual kidney function. The implementation of clinical protocols to guide volume management in the in-center hemodialysis unit resulted in comparable rates of development of anuria and decline in residual kidney function when compared with bioimpedance spectroscopy-guided volume management. Clinical judgment and experience are important drivers of patient outcomes.

Genome-wide Association Study for AKI.

Key Points: Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.

Background: Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.

Genome-Wide Association Study of CKD Progression.

Significance Statement: Rapid progression of CKD is associated with poor clinical outcomes. Most previous studies looking for genetic factors associated with low eGFR have used cross-sectional data. The authors conducted a meta-analysis of genome-wide association studies of eGFR decline among 116,870 participants with CKD, focusing on longitudinal data.

Integrated Analysis of Blood and Urine Biomarkers to Identify Acute Kidney Injury Subphenotypes and Associations With Long-term Outcomes.

Rationale & Objective: Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology, and outcomes. We incorporated plasma and urine biomarker measurements to identify AKI subgroups (subphenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes.

Study Design: Multicenter cohort study.

Bradykinin B receptor blockade and intradialytic hypotension.

Introduction: Intradialytic hypotension (IDH) is a common clinical complication and is associated with increased morbidity and mortality in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of IDH has been attributed to the rapid reduction of plasma volume during hemodialysis and the inadequate compensatory mechanisms in response to hypovolemia, such as the lack of vasoconstriction. This may be due to the increased production of vasodilators, such as bradykinin.