James Tattersall

Long-Term Outcomes in Online Hemodiafiltration and High-Flux Hemodialysis : A Comparative Analysis

BACKGROUND AND OBJECTIVES Theoretical advantages exist of online hemodiafiltration (HDF) over high-flux hemodialysis (HD), but outcome data are scarce. Our objective was to compare outcomes between these modalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied 858 incident patients in our incremental high-flux HD and online HDF program during an 18-yr period. We compared outcomes, including survival, in those who were treated predominantly with HDF (>50% sessions) and those with high-flux HD. Survival comparisons used a Cox model taking into account the time-varying proportion of time spent on HDF. All data were prospectively collected. RESULTS A total of 152,043 sessions were delivered as HDF and 291,222 as high-flux HD. A total of 232 (27%) patients were treated predominantly with HDF and 626 (73%) with high-flux HD. Total Kt/V, serum albumin, erythropoietin resistance index, and BP were similar in both groups up to 5 yr after HD initiation. Intradialytic hypotension was less frequent in the predominant HDF group. Predominant HDF treatment was associated with a reduced risk for death after correction for confounding variables. In a second Cox model, proportion of time spent on HDF predicted survival, such that patients who were treated solely by HDF would have a hazard for death of 0.66 compared with those who solely used high-flux HD. CONCLUSIONS We found no benefits of HDF over high-flux HD with respect to anemia management, nutrition, mineral metabolism, and BP control. The mortality benefit associated with HDF requires confirmation in large randomized, controlled trials. These data may contribute to their design.

Online haemodiafiltration: definition, dose quantification and safety revisited

The general objective assigned to the EUropean DIALlysis (EUDIAL) Working Group by the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) was to enhance the quality of dialysis therapies in Europe in the broadest possible sense. Given the increasing interest in convective therapies, the Working Group has started by focusing on haemodiafiltration (HDF) therapies. Several reports suggest that those therapies potentially improve the outcomes for end-stage renal disease patients. Europe is the leader in the field, having introduced the concept of ultra-purity for water and dialysis fluids and with notified bodies of the European Community having certified water treatment systems and online HDF machines. The prevalence of online HDF-treated patients is steadily increasing in Europe, averaging 15%. A EUDIAL consensus conference was held in Paris on 13 October 2011 to revisit terminology, safety and efficacy of online HDF. This is the first report of the expert group arising from that conference.

When to start dialysis: updated guidance following publication of the Initiating Dialysis Early and Late (IDEAL) study

This position statement is intended to be used in conjunction with the original 2002 European guideline on when to start dialysis [1]. The original guideline was based on a formal review of all evidence available at the time. The position statement considers mainly the results of the Initiating Dialysis Early and Late (IDEAL) study [2], but it also considers other relevant studies published since 2002. A formal literature review was not undertaken. The position statement has been prepared by a working group whose members were nominated by the European Renal Best Practice (ERBP) advisory board.

The clinical significance of early proteinuria after renal transplantation.

Background. Late-onset proteinuria after renal transplantation has been universally associated with poor allograft outcomes. However, the significance of early low-grade posttransplant proteinuria remains uncertain. Methods. We analyzed the effect of proteinuria 3 months posttransplantation on death-censored graft loss, death with a functioning graft, vascular events within the grafts life, and estimated glomerular filtration rate at 5 years. Four hundred seventy-seven renal transplants from a single center (1988–2003) with a mean follow-up of 122 months were divided into four groups based on the median protein creatinine ratio (PCR) during the 3rd posttransplant month (PCR<0.15 [group 1, n=85]; PCR 0.15–0.5 [group 2, n=245]; PCR 0.5–1.00 [group 3, n=96]; PCR>1.00 [group 4, n=51]). Cox proportional hazards analysis was performed to study the impact of proteinuria on the various outcomes. Results. Multivariate analysis revealed that even low-level proteinuria at 3 months predicted death-censored graft failure (group 1 [reference]—hazard ratio [HR]=1, group 2—HR=7.1, group 3—HR = 10.5, group 4—HR 16.0; P=0.001). The impact on death and the occurrence of vascular events was only significant for group 4 (HR: 2.6; P=0.01 for death and HR: 2.2; P=0.04 for vascular events). Estimated glomerular filtration rate at 5 years was group 1, 48.5 mL/min; group 2, 41.2 mL/min; group 3, 31.1 mL/min; and group 4, 24.5 mL/min (P<0.001). Continued observation of group 2 to 1 year revealed adverse outcomes with increasing proteinuria. Conclusions. Low-grade proteinuria at 3 months is associated with adverse clinical outcomes and identifies high-risk group of patients who may benefit from further intervention.

High-flux or low-flux dialysis: a position statement following publication of the Membrane Permeability Outcome study

The European Renal Best Practice (ERBP) Advisory Board recently decided to follow up existing guidelines, and to publish position statements when new evidence would necessitate a change in the existing guideline [1]. The purpose of this document is to provide guidance on the interpretation and relevancy of the current European Best Practice Guideline (EBPG) on dialysis strategy [2], in the light of the recently published Membrane Permeability Outcome (MPO) study [3].This position statement is intended to be considered in conjunction with the current guideline. It does not replace the guideline as we do not include a new systematic review of the literature. The MPO study specifically focused on the question whether the use of a high-, compared to a low-flux dialyser membrane, would have a measurable effect on survival.

CLEARANCE OF BETA-2-MICROGLOBULIN AND MIDDLE MOLECULES IN HAEMODIAFILTRATION

Middle molecules, consisting mostly of peptides and small proteins with molecular weight the range of 500-60,000 Da, accumulate in renal failure and contribute to the uraemic toxic state. Beta2-microglobulin (beta2-MG) with a molecular weight of 11,000 is considered representative of these middle molecules. These solutes are not well cleared by low-flux dialysis. High-flux dialysis will clear middle molecules, partly by internal filtration. This convective component of high-flux dialysis can be enhanced in a predictable way by haemodiafiltration (HDF). The convective and diffusive clearance rates of any middle molecule across any haemodiafilter can be predicted from known or measurable factors such as its sieving coefficient, bound fraction and molecular weight. The removal of middle molecules is also influenced by factors within the patient. Beta2-MG is distributed within the extracellular fluid. During HDF, beta2-MG must transfer into the intravascular compartment across the capillary walls. This transcapillary transfer at a rate of approximately 100 ml/min slows beta2-MG removal from the body. Continuing transfer after the end of a treatment session results in a significant rebound of beta2-MG levels. This intercompartment transfer and its effect on beta2-MG clearance and concentration can be predicted by a 2-compartment model. By extrapolation, the behaviour of other middle molecules can be predicted. The 2-compartment model, which takes non-dialytic beta2-MG clearance at a rate of 3 ml/min and beta2-MG generation at a rate of 0.1 mg/min into account, can predict the effect of any HDF schedule on beta2-MG levels. Low-flux dialysis results in a beta2-MG level of around 40 mg/l. Three times weekly, 4-hour HDF can reduce beta2-MG levels to around 20 mg/l. Long (nocturnal) HDF can reduce beta2-MG levels to around 10 mg/l, compared to physiological levels of less than 5 mg/l.

A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury: part 2: renal replacement therapy

This paper provides an endorsement of the KDIGO guideline on acute kidney injury; more specifically, on the part that concerns renal replacement therapy. New evidence that has emerged since the publication of the KDIGO guideline was taken into account, and the guideline is commented on from a European perspective. Advice is given on when to start and stop renal replacement therapy in acute kidney injury; which modalities should be preferentially be applied, and in which conditions; how to gain access to circulation; how to measure adequacy; and which dose can be recommended.

Modeling the postdialysis rebound: the reconciliation of current formulas.

Three approaches are currently used in kinetic models (UKMs) to account for the postdialysis rebound in urea concentration, and thereby accurately measure the hemodialysis dose, KT/V (where K, T, V denote dialyzer clearance, dialysis duration, and urea distribution volume, respectively). The approach developed by Smye uses an intradialytic sample to predict the postdialysis equilibrium concentration, Ce, which is then used in a single pool UKM to give KT/V. A second approach developed by Tattersall introduces a patient clearance time, tp. The true dialysis dose is then given by T/(T + tp) x apparent dose, and tp is estimated to be 36 minutes. The Daugirdas analysis uses an empiric regression equation to give the true dose; KT/V)true from the single pool value, KT/V)sp; KT/V)true = KT/V)sp - (36/T)(KT/V)sp + 0.03. The analysis confirms the equivalence of all three formulas, which arises from the observation that during the later stages of dialysis, the urea concentration decreases as a single exponential. The formulas are independent of whether a flow or diffusion model is used to describe the kinetics of urea removal. The original analysis assumed constant volumes, but the effect of ultrafiltration volume u on C(e) may be accounted for by multiplying by (1 + u/V). The Smye equation is more vulnerable to error in practice, because small errors in the intradialytic sample give larger errors in the equilibrium concentration estimate, whereas dose estimates based on the Tattersall and Daugirdas equations are less affected by sampling errors. However, unlike the Smye approach, these two formulas would need adaptation for use with other solutes. The advent of continuous urea monitoring should permit more accurate, prospective estimates of equilibrium concentrations and dialysis dose.

Automated monitoring of hemodialysis adequacy by dialysis machines: potential benefits to patients and cost savings

Hemodialysis adequacy can be quantified using ultraviolet absorbance of the spent dialysate, or by analysis of dialysate conductivity at the dialyzer inlet and outlet in response to changes in dialysate electrolyte concentration. These measurements can be made at every dialysis, including initial and acute treatments and can help detect access recirculation. No disposables or reagents are required. Cost may be reduced by reducing the need for blood sampling and laboratory analysis.

A predictive algorithm for the management of anaemia in haemodialysis patients based on ESA pharmacodynamics: better results for less work

BACKGROUND Many anaemia management algorithms recommend changes to erythropoiesis-stimulating agent (ESA) doses based on frequent measurement of haemoglobin levels in keeping with the ESA datasheets. We designed a predictive anaemia algorithm based on ESA pharmacodynamics, which we hoped would improve compliance with haemoglobin targets and reduce workload. METHODS A new algorithm was designed which predicted the 3-month steady-state haemoglobin concentration following a change in ESA dose and only recommended a change if it was outside the range 10.5-12.5 g/dL. Data were collected prospectively for 3 months prior and 15 months subsequent to implementing the algorithm. RESULTS A total of 214 prevalent dialysis patients were included in the audit. After 12 months, the haemoglobin concentration was 11.4 g/dL, near the midpoint of the target range, with a narrowing of the distribution (SD 1.46 to 1.25 g/dL, P < 0.0001). The proportion of patients with a haemoglobin level in the target range increased from 56% to 66% (P < 0.001) principally due to a reduction in the number of patients with high haemoglobin levels. There was no significant change in the ESA dose over the audit period. The number of prescription changes fell from 1/2.5 months to 1/6.1 months after 12 months (P < 0.001). CONCLUSIONS Switching prevalent haemodialysis patients to a predictive anaemia management algorithm improved compliance with haemoglobin targets, reduced the number of patients with high haemoglobin levels and reduced the number of ESA dose changes required.