Dietary protein intake, kidney function, and survival in a nationally representative cohort.

Background: High-protein diets (e.g., Paleo, Atkins, South Beach, ketogenic) have gained popularity as a means to promote weight loss and avoid excess carbohydrate consumption.

Study Design of the Phase 3 Sparsentan Versus Irbesartan (DUPLEX) Study in Patients With Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS), a histologic lesion in the kidney caused by varied pathophysiological processes, leads to end-stage kidney disease in a large proportion of patients. Sparsentan is a first-in-class orally active compound combining endothelin type A (ET) receptor blockade with angiotensin II type 1 (AT) receptor antagonism in a single molecule. A Randomized, Multicenter, Double-Blind, Parallel, Active-Control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS (DUPLEX) study evaluates the long-term antiproteinuric efficacy, nephroprotective potential, and safety profile of sparsentan compared with an AT receptor blocker alone in patients with FSGS.

Special situations: Intradialytic hypertension/chronic hypertension and intradialytic hypotension.

Hypertension is a comorbidity that is present in the majority of end-stage renal disease patients on maintenance hemodialysis. This population is particularly unique because of the dynamic nature of blood pressure (BP) during dialysis. Modest BP decreases are expected in most hemodialysis patients, but intradialytic hypotension and intradialytic hypertension are two special situations that deviate from this as either an exaggerated or paradoxical response to the dialysis procedure.

Intradialytic hypotension, blood pressure changes and mortality risk in incident hemodialysis patients.

Background: Intradialytic hypotension (IDH) occurs frequently in maintenance hemodialysis (HD) patients and may be associated with higher mortality. We hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely related to death risk while iSBP change (Δ) and IDH frequency are incrementally associated with all-cause mortality.

Methods: In a US-based cohort of 112 013 incident HD patients over a 5-year period (2007-11), using niSBP, ΔiSBP (pre-HD SBP minus niSBP) and IDH frequency (proportion of HD treatments with niSBP <90 mmHg) within the first 91 days of HD, we examined mortality-predictability at 1, 2 and 5 years using Cox models and restricted cubic splines adjusted for case-mix, comorbidities and laboratory covariates.

Overcoming Barriers in Kidney Health-Forging a Platform for Innovation.

Innovation in kidney diseases is not commensurate with the effect of these diseases on human health and mortality or innovation in other key therapeutic areas. A primary cause of the dearth in innovation is that kidney diseases disproportionately affect a demographic that is largely disenfranchised, lacking sufficient advocacy, public attention, and funding. A secondary and likely consequent cause is that the existing infrastructure supporting nephrology research pales in comparison with those for other internal medicine specialties, especially cardiology and oncology.

Mechanisms and Treatment of Intradialytic Hypertension.

Background: Intradialytic hypertension is a condition where there is an increase in blood pressure (BP) from pre- to post-hemodialysis; this condition has been recently identified as an independent mortality risk factor in hypertensive hemodialysis patients. The mechanisms and management of intradialytic hypertension have been explored in numerous research studies over the past few years.

Summary: Patients with intradialytic hypertension have been found to be more chronically volume overloaded compared to other hemodialysis patients, although no causal role has been established.

Effect of low versus high dialysate sodium concentration on blood pressure and endothelial-derived vasoregulators during hemodialysis: a randomized crossover study.

Background: Intradialytic hypertension affects ∼15% of hemodialysis patients and is associated with increased morbidity and mortality. While intradialytic hypertension is associated with increases in endothelin 1 relative to nitric oxide (NO), the cause of these imbalances is unknown. In vitro evidence suggests that altering plasma sodium levels could affect endothelial-derived vasoregulators and blood pressure (BP).

The landscape of clinical trials in nephrology: a systematic review of Clinicaltrials.gov.

Background: Well-designed trials are of paramount importance in improving the delivery of care to patients with kidney disease. However, it remains unknown whether contemporary clinical trials within nephrology are of sufficient quality and quantity to meet this need.

Study Design: Systematic review.

Peri-dialytic hypertension and hypotension: another U-shaped BP-outcome association.

Park et al. performed a retrospective analysis of a large hemodialysis cohort to describe the relationship between pre- to postdialysis changes in BP and mortality. Their study demonstrated adverse outcomes associated both with large decreases and with any increase in blood pressure pre- to postdialysis.

Cardiovascular toxicity of epoetin-alfa in patients with chronic kidney disease.

Background: Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events. We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin (Hb) irrespective of treatment target and randomized allocation.

Methods: We performed a post hoc analysis from the CHOIR trial.

Association of intradialytic blood pressure variability with increased all-cause and cardiovascular mortality in patients treated with long-term hemodialysis.

Background: Blood pressure is known to fluctuate widely during hemodialysis; however, little is known about the association between intradialytic blood pressure variability and outcomes.

Study Design: Retrospective observational cohort.

Setting & Participants: A random sample of 6,393 adult, thrice-weekly, in-center, maintenance hemodialysis patients dialyzing at 1,026 dialysis units within a single large dialysis organization.

The prevalence of persistent intradialytic hypertension in a hemodialysis population with extended follow-up.

Background: Intradialytic hypertension, a phenomenon where blood pressure increases during hemodialysis, is associated with increased mortality in hemodialysis patients. The proportion of patients in which intradialytic hypertension persists over time is unknown.

Methods: In a retrospective cohort study, we studied all patients from our outpatient hemodialysis units that received =1 month of treatments during the period from January to August 2010.

Probing the mechanisms of intradialytic hypertension: a pilot study targeting endothelial cell dysfunction.

Background And Objectives: Intradialytic hypertension may be caused by an impaired endothelial cell response to hemodialysis. Carvedilol has been shown to improve endothelial cell function in vivo and to block endothelin-1 release in vitro. This study hypothesized that carvedilol would improve endothelial cell function and reduce the occurrence of intradialytic hypertension.

Impact of higher hemoglobin targets on blood pressure and clinical outcomes: a secondary analysis of CHOIR.

Background: Targeting a higher hemoglobin in patients with chronic kidney disease leads to adverse cardiovascular outcomes, yet the reasons remain unclear. Herein, we sought to determine whether changes in erythropoiesis-stimulating agent (ESA) dose and in hemoglobin were predictive of changes in blood pressure (BP) and whether these changes were associated with cardiovascular outcomes.

Methods: In this secondary analysis of 1421 Correction of Hemoglobin and Outcomes in Renal Disease (CHOIR) participants, mixed model analyses were used to describe monthly changes in ESA dose and hemoglobin with changes in diastolic BP (DBP) and systolic BP (SBP).

Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.

Background: Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.

Study Design: Secondary analysis of a randomized controlled trial.

Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors.

Background: High-dose erythropoiesis-stimulating agents (ESA) for anemia of chronic kidney disease (CKD) have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR).

Methods: A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α (< 1 μg/kg/week) and high-dose (≥ 1 μg/kg/week)).

Interdialytic ambulatory blood pressure in patients with intradialytic hypertension.

Purpose Of Review: Hypertension is common in hemodialysis patients and contributes to this population's high risk for cardiovascular morbidity and mortality. Patients with intradialytic hypertension, or increases in blood pressure during hemodialysis, have been shown to have the highest risk for these outcomes. The purpose of this review is to describe new findings that shed light on the epidemiology and pathophysiology of intradialytic hypertension and discuss how a better understanding of these mechanisms may lead to improved blood pressure management and outcomes in hemodialysis patients.

Veterans more likely to start hemodialysis with an arteriovenous fistula.

Hemodialysis via arteriovenous fistulas (AVFs) is associated with reduced morbidity and mortality when compared to alternative vascular accesses, yet few patients in the United States start dialysis with AVFs. Recent studies have demonstrated higher quality of care for many conditions in Veterans Affairs' Medical Centers (VAMC); however, differences in quality of vascular access care are unknown. We used patient-level data (6/05-5/06) from Medicare claims (n = 25,912) to compare the proportions of AVF among incident patients at VAMC-affiliated (n = 20) and unaffiliated dialysis (n = 1631) facilities.

Intradialytic hypertension and its association with endothelial cell dysfunction.

Background And Objectives: Intradialytic hypertension is associated with adverse outcomes, yet the mechanism is uncertain. Patients with intradialytic hypertension exhibit imbalances in endothelial-derived vasoregulators nitric oxide and endothelin-1, indirectly suggesting endothelial cell dysfunction. We hypothesized that intradialytic hypertension is associated in vivo with endothelial cell dysfunction, a novel predictor of adverse cardiovascular outcomes.