Creatinine generation from kinetic modeling with or without postdialysis serum creatinine measurement: results from the HEMO study.

Background: A convenient method to estimate the creatinine generation rate and measures of creatinine clearance in hemodialysis patients using formal kinetic modeling and standard pre- and postdialysis blood samples has not been described.

Methods: We used data from 366 dialysis sessions characterized during follow-up month 4 of the HEMO study, during which cross-dialyzer clearances for both urea and creatinine were available. Blood samples taken at 1 h into dialysis and 30 min and 60 min after dialysis were used to determine how well a two-pool kinetic model could predict creatinine concentrations and other kinetic parameters, including the creatinine generation rate.

Assessing the Adequacy of Small Solute Clearance for Various Dialysis Modalities, with Inclusion of Residual Native Kidney Function.

Measurement of small molecule clearance remains important in the clinical care of patients requiring long-term dialysis. Many patients maintain a significant degree of residual native kidney function and may have nontraditional schedules with or without combined dialysis modalities. In this review, we examine and outline methods for comparing small molecule clearances among various dialysis prescriptions and modalities, with inclusion of residual kidney urea clearance.

Dose Targeting Metrics in Conventional and Intensive Maintenance Dialysis.

Hemodialysis has come a long way since its early days and is a life sustaining therapy for millions of people with end-stage kidney disease throughout the world. Although thrice weekly hemodialysis remains the most common form of renal replacement therapy, other therapies such as more frequent, prolonged dialysis modalities have seen a rise recently. In this review, we compare and contrast methods for measuring the dialysis dose, with a focus on small molecule clearance (Kt/V ) among various dialysis modalities.

Metabolic Profiling of Impaired Cognitive Function in Patients Receiving Dialysis.

Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis.

The Saga of Two Centuries of Urea: Nontoxic Toxin or Vice Versa?

In the early 1700s, a substance ultimately identified as urea was reported for the first time in urine. About a century later, in 1828, synthesis of this organic compound was achieved, thus giving rise to modern organic chemistry. In parallel, physicians showed that urine comes from the kidneys and contains large amounts of urea, which is produced outside of the kidneys, establishing the humoral approach of renal physiology.

Effect of frequent hemodialysis on residual kidney function.

Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD.

Improved equation for estimating single-pool Kt/V at higher dialysis frequencies.

Rationale: To measure adequacy in patients dialyzed other than three times per week, guidelines recommend the use of 'standard' Kt/V, which commonly is estimated from treatment Kt/V, time and frequency; however, the accuracy of equations that predict treatment Kt/V in patients being dialyzed other than three times per week has not been evaluated.

Methods: In patients enrolled in the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials who were being dialyzed three, four or six times per week, we tested the accuracy of the following Kt/V prediction equation: Kt/V = -ln(R - GFAC × T_hours) + (4-3.5 × R) × 0.

Dialysate flow rate and delivered Kt/Vurea for dialyzers with enhanced dialysate flow distribution.

Background And Objectives: Previous in vitro and clinical studies showed that the urea mass transfer-area coefficient (K(o)A) increased with increasing dialysate flow rate. This observation led to increased dialysate flow rates in an attempt to maximize the delivered dose of dialysis (Kt/V(urea)). Recently, we showed that urea K(o)A was independent of dialysate flow rate in the range 500 to 800 ml/min for dialyzers incorporating features to enhance dialysate flow distribution, suggesting that increasing the dialysate flow rate with such dialyzers would not significantly increase delivered Kt/V(urea).

Modeled urea distribution volume and mortality in the HEMO Study.

Background And Objectives: In the Hemodialysis (HEMO) Study, observed small decreases in achieved equilibrated Kt/V(urea) were noncausally associated with markedly increased mortality. Here we examine the association of mortality with modeled volume (V(m)), the denominator of equilibrated Kt/V(urea).

Design, Setting, Participants, & Measurements: Parameters derived from modeled urea kinetics (including V(m)) and blood pressure (BP) were obtained monthly in 1846 patients.

In-center hemodialysis six times per week versus three times per week.

Background: In this randomized clinical trial, we aimed to determine whether increasing the frequency of in-center hemodialysis would result in beneficial changes in left ventricular mass, self-reported physical health, and other intermediate outcomes among patients undergoing maintenance hemodialysis.

Methods: Patients were randomly assigned to undergo hemodialysis six times per week (frequent hemodialysis, 125 patients) or three times per week (conventional hemodialysis, 120 patients) for 12 months. The two coprimary composite outcomes were death or change (from baseline to 12 months) in left ventricular mass, as assessed by cardiac magnetic resonance imaging, and death or change in the physical-health composite score of the RAND 36-item health survey.

Can rescaling dose of dialysis to body surface area in the HEMO study explain the different responses to dose in women versus men?

Background And Objectives: In the Hemodialysis (HEMO) Study, the lower death rate in women but not in men assigned to the higher dose (Kt/V) could have resulted from use of "V" as the normalizing factor, since women have a lower anthropometric V per unit of surface area (V/SA) than men.

Design, Setting, Participants, & Measurements: The effect of Kt/V on mortality was re-examined after normalizing for surface area and expressing dose as surface area normalized standard Kt/V (SAn-stdKt/V).

Results: Both men and women in the high-dose group received approximately 16% more dialysis (when expressed as SAn-stdKt/V) than the controls.

Effects of reduced intradialytic urea generation rate and residual renal clearance on modeled urea distribution volume and Kt/V in conventional, daily, and nocturnal dialysis.

Classic urea modeling assumes that both urea generation rate (G) and residual renal urea clearance (Kru) are constant throughout the week, but this may not be true. Reductions in intradialysis G could be caused by lower plasma amino acid levels due to predialysis/intradialysis fasting and also to losses of amino acids into the dialysate. Intradialytic reductions in Kru could be due to lower intravascular volume, blood pressure, or osmotic load.

Standard Kt/Vurea: a method of calculation that includes effects of fluid removal and residual kidney clearance.

Standard Kt/V(urea) (stdKt/V) is a hypothetical continuous clearance in patients treated with intermittent hemodialysis based on the generation rate of urea nitrogen and the average predialysis urea nitrogen. Previous equations to estimate stdKt/V were derived using a fixed-volume model. To determine the impact of fluid removal as well as residual urea clearance on stdKt/V, we modeled 245 hemodialysis sessions (including conventional 3/week, in-center 6/week, and at-home nocturnal 6/week) in 210 patients enrolled in the Frequent Hemodialysis Network Daily and Nocturnal clinical trials.

Solute-solver: a web-based tool for modeling urea kinetics for a broad range of hemodialysis schedules in multiple patients.

Practical application of urea kinetic modeling to measure the delivered dose of hemodialysis is hampered by lack of a reference or gold-standard program that would be widely available and freely distributed. We developed and here describe an open-source JavaScript tool, "Solute-Solver," capable of batch processing of urea kinetics calculations. The Solute-Solver online interface is available at (www.

Solute clearances and fluid removal in the frequent hemodialysis network trials.

Background: The Frequent Hemodialysis Network (FHN) is conducting 2 randomized clinical trials, a daytime in-center trial ("daily") comparing 6 versus 3 treatments/wk, and a home nocturnal trial comparing 6 nocturnal treatments versus 3 conventional treatments/wk. The goal of this study was to project separation between the treatment and control arms of these studies for measures of dialysis dose by using simulations based on 2-compartment variable-volume models.

Setting & Participants: Data from the most recent hemodialysis treatment in 100 patients dialyzed 3 times/wk at facilities of the Renal Research Institute in New York and from 2 data sets (n = 154 and 115 patients) from the Hemodialysis (HEMO) trial.

Surface-area-normalized Kt/V: a method of rescaling dialysis dose to body surface area-implications for different-size patients by gender.

Dialysis is measured as Kt/V, which scales the dose (Kt) to body water content (V). Scaling dialysis dose to body surface area (S(dub)) has been advocated, but the implications of such rescaling have not been examined. We developed a method of rescaling measured Kt/V to S(dub) and studied the effect of such alternative scaling on the minimum adequacy values that might then be applied in male and female patients of varying body size.

Comparison of proposed alternative methods for rescaling dialysis dose: resting energy expenditure, high metabolic rate organ mass, liver size, and body surface area.

A number of denominators for scaling the dose of dialysis have been proposed as alternatives to the urea distribution volume (V). These include resting energy expenditure (REE), mass of high metabolic rate organs (HMRO), visceral mass, and body surface area. Metabolic rate is an unlikely denominator as it varies enormously among humans with different levels of activity and correlates poorly with the glomerular filtration rate.

Dosing intermittent haemodialysis in the intensive care unit patient with acute renal failure--estimation of urea removal and evidence for the regional blood flow model.

Background: Blood-side dosing methods may overestimate urea removal in comparison to dialysate-side measurements during intermittent HD (IHD) for acute renal failure (ARF). The present study sought to quantify this mass balance error (MBE) and explore potential explanatory factors.

Methods: Prospective, formal, blood-side urea kinetic modelling was performed in serial sessions (n = 42) in 18 intensive care unit ARF patients.

Effect of change in vascular access on patient mortality in hemodialysis patients.

Background: Hemodialysis patients using a catheter have a greater mortality risk than those using an arteriovenous (AV) access (fistula or graft). However, catheter-dependent patients also differ from those with an AV access in several clinical features, and these differences may themselves contribute to their excess mortality.

Methods: The current study evaluates whether a change in vascular access affects risk for mortality in patients enrolled in the Hemodialysis Study.

Design of the Dialysis Access Consortium (DAC) Aggrenox Prevention Of Access Stenosis Trial.

Background: Surgically created arteriovenous (AV) grafts are the most common type of hemodialysis vascular access in the United States, but fail frequently due to the development of venous stenosis. The Dialysis Access Consortium (DAC) Aggrenox Prevention of Access Stenosis Trial tests the hypothesis that Aggrenox (containing dipyridamole and aspirin) can prevent stenosis and prolong survival of arteriovenous grafts.

Methods: This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1056 subjects over four years with one-half year follow-up.