Comparative effectiveness of an individualized model of hemodialysis vs conventional hemodialysis: a study protocol for a multicenter randomized controlled trial (the TwoPlus trial).

Background: Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients.

Kinetics of β -2-Microglobulin with Hemodiafiltration and High-Flux Hemodialysis.

Key Points: Addition of hemodiafiltration has a relatively small impact on reducing either predialysis or time-averaged serum -2-microglobulin levels. Residual kidney function has a major impact on the predialysis and time-averaged serum -2-microglobulin levels.

Background: A kinetic model for -2-microglobulin removal and generation was used to explore the impact of adding hemodiafiltration on predialysis and time-averaged serum values.

Ultrafiltration Rate Levels in Hemodialysis Patients Associated with Weight-Specific Mortality Risks.

Background: We hypothesized that the association of ultrafiltration rate with mortality in hemodialysis patients was differentially affected by weight and sex and sought to derive a sex- and weight-indexed ultrafiltration rate measure that captures the differential effects of these parameters on the association of ultrafiltration rate with mortality.

Methods: Data were analyzed from the US Fresenius Kidney Care (FKC) database for 1 year after patient entry into a FKC dialysis unit (baseline) and over 2 years of follow-up for patients receiving thrice-weekly in-center hemodialysis. To investigate the joint effect of baseline-year ultrafiltration rate and postdialysis weight on survival, we fit Cox proportional hazards models using bivariate tensor product spline functions and constructed contour plots of weight-specific mortality hazard ratios over the entire range of ultrafiltration rate values and postdialysis weights (W).

Comparison of measured vs kinetic-model predicted phosphate removal during hemodialysis and hemodiafiltration.

Background: To what extent hemodiafiltration (HDF) improves management of hyperphosphatemia over hemodialysis (HD) is a subject of ongoing investigation.

Methods: We modified a previously described phosphate kinetic model to include incorporation of EUDIAL recommended equations for hemodiafiltration (HDF) clearance. We used the model to predict the recovery of phosphate from spent dialysate/hemofiltrate and compared this with averaged data from five published studies.

Comparison of modeled versus reported phosphate removal and modeled versus postdialysis serum phosphate levels in conventional hemodialysis.

Background: We compared predictions of phosphate removal by a 2-pool kinetic model with measured phosphate removal in spent dialysate as reported by others.

Methods: Twenty-six studies were identified that reported phosphate removal in 35 groups of patients. In almost all studies, patients were dialyzed for close to 4 h (range 3 to 6 h).

Ultrafiltration Rate Thresholds Associated With Increased Mortality Risk in Hemodialysis, Unscaled or Scaled to Body Size.

Introduction: One proposed threshold ultrafiltration rate (UFR) of concern in hemodialysis patients is 13 ml/h per kg. We evaluated associations among UFR, postdialysis weight, and mortality to determine whether exceeding such a threshold would result in similar levels of risk for patients of different body weights.

Methods: Data were analyzed in this retrospective cohort study for 1 year following dialysis initiation (baseline) and over 2 years of follow-up in incident patients receiving thrice-weekly in-center hemodialysis.

Residual Renal Phosphate Clearance in Patients Receiving Hemodialysis or Hemodiafiltration.

Objectives: Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described.

Methods: We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100 mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period.

The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.

Introduction: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity.

Equations to Estimate the Normalized Creatinine Generation Rate (CGRn) in 3/Week Dialysis Patients With or Without Residual Kidney Function.

Objective: Normalized creatinine generation rate (CGRn) can be computed for a variety of dialysis schedules using a recently described kinetic modeling program. However, the availability of estimating equations might facilitate broader study of this metric. We developed equations to estimate CGRn based on modeling and then tested them against modeled CGRn values in the Frequent Hemodialysis Network Nocturnal Trial baseline (3/week) dataset.

Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements.

Rationale & Objectives: Conventional monitoring of hemodialysis dose is implemented using urea kinetic modeling based on single-pool Kt/V, which requires both pre- and postdialysis serum urea nitrogen (SUN) measurements. We compared this conventional approach to one in which Kt/V is calculated using conductivity clearance, thereby reducing the need for regular postdialysis SUN measurements.

Study Design: Comparative study of 2 diagnostic tests.

Quantifying the Effect of Plasma Viscosity on In Vivo Dialyzer Performance.

Dialyzer manufacturers characterize performance of their devices based on measurements of clearance using crystalloid solutions. Typically, in vitro dialyzer mass transfer area coefficients for urea (K0A) are substantially higher than values measured in vivo. The reason for this reduction has not been clearly determined.

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

Background: Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established.

Methods: To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate.

Modeled Daily Ingested, Absorbed and Bound Phosphorus: New Measures of Mineral Balance in Hemodialysis Patients.

Background: Control of predialysis serum phosphorus in hemodialysis patients is challenging. We explored the utility of a novel kinetic phosphorus modeling program.

Methods: As part of a quality assurance program, urea kinetic modeling results were combined with those from phosphorus kinetic modeling to compute modeled daily ingested phosphorus (DIP) and components making up this metric, including absorbed, bound, and nonabsorbed, nonbound phosphorus.

Intradialytic hypotension and splanchnic shifting: Integrating an overlooked mechanism with the detection of ischemia-related signals during hemodialysis.

In the most simple analysis, a patient's hematocrit during hemodialysis will rise when the rate of ultrafiltration exceeds the rate at which the fluid is mobilized from extravascular spaces; the greater the rise in hematocrit, the lower blood volume is and the more likely intradialytic hypotension (IDH) is to occur. A secondary mechanism of IDH may be due to sudden shift of blood volume away from the heart under conditions of borderline cardiac filling. A substantial portion of blood volume resides in the splanchnic venous system.

Eliminating the need for routine monthly postdialysis serum urea nitrogen measurement: A method for monitoring Kt/V and normalized protein catabolic rate using conductivity determined dialyzer clearance.

Many dialysis machines can compute dialyzer sodium clearances at multiple time points during a dialysis treatment using conductivity. For a given treatment, the average dialyzer sodium clearance (K), when combined with treatment time (t), and the estimated urea distribution volume (V, usually based on either anthropometry or bioimpedance), can be used to estimate Kt/V, an important measure of hemodialysis adequacy. While this conductivity-derived value for Kt/V correlates moderately with Kt/V calculated from predialysis and postdialysis serum urea nitrogen (SUN) values (urea reduction ratio, URR), the ultrafiltration volume, and session length it is, unfortunately, not sufficiently accurate to replace URR-based Kt/V.

Changes in Total Protein Concentration Due to Fluid Removal During and Shortly after Hemodialysis.

Background: Changes in plasma volume during hemodialysis are complex and have been shown to depend on the rate of fluid removal and the degree of fluid overload. We examined changes in total protein concentration during and shortly after a dialysis treatment in archived data from the HEMO study.

Methods: During follow-up months 4 and 36 of the HEMO study, additional blood samples were obtained during a typical dialysis session at 30 and 60 min after dialysis.

Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

Background: Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study.

Methods: Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD.

Renal Replacement Therapy and Incremental Hemodialysis for Veterans with Advanced Chronic Kidney Disease.

Each year approximately 13,000 Veterans transition to maintenance dialysis, mostly in the traditional form of thrice-weekly hemodialysis from the start. Among >6000 dialysis units nationwide, there are currently approximately 70 Veterans Affairs (VA) dialysis centers. Given this number of VA dialysis centers and their limited capacity, only 10% of all incident dialysis Veterans initiate treatment in a VA center.