The Effect of Diffusive and Convective Sodium Balance During Hemodialysis on Interdialytic Weight Gain

Patients with end stage renal disease (ESRD) often require hemodialysis treatments in which blood’s water and dissolved solutes undergo diffusion and convection by exposure to an extracorporeal membrane. The leading cause of death in this population is cardiovascular, and how hemodialysis is prescribed alters total sodium balance, a critical determinant of cardiovascular health. We performed retrospective and prospective analysis of data from patients in the Southwestern Ontario Regional Hemodialysis Program. An increased Dialysate sodium (Dial-Na+) to Pre-dialysis plasma sodium (Pre- Na+) concentration difference (DPNa+) leads to adverse clinical outcomes in hemodialysis patients. The post- to pre-dialysis plasma sodium difference (PPNa+) predicts clinical outcomes equally well as DPNa+ so long as Dial-Na+ is within 3 mmol/L of Pre-Na+. Calculation of DPNa+ requires determination of the Pre-Na+, historically thought to be stable in hemodialysis patients and thus termed “setpoint” (SP). However, we determined that SP is modifiable by hemodialysis prescription. Finally, an equation to predict interdialytic weight gain was created, confirming Dial-Na+, dialysis frequency and duration to be modifiable factors affecting IDWG. Further research is required to validate this equation prospectively, and to determine the impact of changes of SP on cardiovascular morbidity and mortality

Renal Association Clinical Practice Guideline on Haemodialysis

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: "what does good quality haemodialysis look like?"The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to - most of this is freely available online, at least in summary form.A few notes on the individual sections: 1. This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines "enough" dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term "eKt/V" is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient. 2. This section deals with "non-standard" dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week - this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here. 3. This section deals with membranes (the type of "filter" used in the dialysis machine) and "HDF" (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it's as good as but not better than regular dialysis. 4. This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this. 5. This section deals with dialysate, which is the fluid used to "pull" toxins out of the blood (it is sometimes called the "bath"). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate. 6. This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects. 7. This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful. 8. This section draws together a few aspects of dialysis which don't easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered. There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.Peer reviewe

The Kinetics of Cystatin C: A Marker for Dialysis Adequacy

When 90% or more of native kidney function is lost, renal replacement therapy must be initiated to sustain life. Renal transplantation is the preferred method, but availability is limited. The ideal dialysis prescription remains elusive. Small molecular weight molecules (such as urea and creatinine) have been used as markers of both kidney (native and transplant) and dialysis toxin clearance (function), but there are pitfalls in using these markers to assess total ‘renal’ dose (kidney plus dialysis). Body weight, gender and other factors also affect the concentrations of these small molecules, but not cystatin C. Furthermore, cystatin C has been shown to be a better marker for estimating kidney function than creatinine, and is associated with cardiovascular morbidity and mortality. Studies have shown that it is removed by dialysis. Therefore, we investigated the use of cystatin C, a naturally occurring endogenous protein, as a marker for estimating dialysis adequacy and renal clearance. This investigation was comprised of four studies to understand the kinetics of cystatin C in patients with advanced kidney disease with or without dialysis. We found that the amount of cystatin C reduction was influenced positively by hemodialysis blood flow rate and treatment time, and negatively by ultrafiltration rate. We further demonstrated that renal hyperfiltration significantly influenced the error of creatinine-based glomerular filtrate rate equation, but not for the cystatin C equation. Therefore, cystatin C appears to be a useful marker for the assessment of kidney function in patients with advanced kidney disease but not yet on dialysis. This was taken further in our third study where we developed an equation, which gave a better estimate of residual renal function than previously published equations in patients on dialysis but who have some remaining kidney function. Finally, we confirmed our hypothesis that cystatin C is cleared during dialysis by both diffusion and convection. It is distributed mainly in the extracellular space but equilibrates slowly between the extravascular and intravascular spaces. Furthermore, we have shown that cystatin C while cleared by dialysis is stable between dialysis treatments rather than being influenced by a single dialysis treatment. It is a marker for both dialysis and renal clearances and, thus, gives a stable index of total renal clearance. The long term goal will be to define the cystatin C threshold level that influences patient morbidity and mortality and to allow better dialysis prescriptions for patients with varying (and changing) residual renal function

An assessment of solute kinetics and the application of mathematical modelling in the haemodialysis process

AIM: The aim of this thesis is to enhance knowledge about solute clearance during haemodialysis and to provide insight into factors that may influence dialysis efficiency. By improving the understanding of the kinetics of solute removal the limitations of current dialysis therapy will be better understood, and suggestions can be made for future improvements in the delivery of dialysis.METHODS: The history of dialysis technique and adequacy measurement is detailed. The origin and potential problems with urea kinetic modelling, including the effect of high haematocrit on adequacy, are explored.Mathematical modelling is utilised to provide potential explanations for the clearance characteristics of phosphate and beta2-microglobulin during chronic dialysis. The phosphate model is explored further with studies in acute renal failure and the effect of dialysis on intra-erythrocytic phosphate concentrations is assessed. Diurnal variation in phosphate concentration is explored.The effect of different dialysis modalities on beta2-microgloblin levels and symptoms of dialysis related amyloid is studied. Dialysis related amyloid deposition is investigated by a scintigraphic imaging technique.RESULTS: Haematocrit. High haematocrit is not found to have a significant effect on the clearance of solutes across a wide range of molecular size.Phosphate. A four-pool model that can be applied in both acute and chronic renal failure is proposed to explain the observed kinetic behaviour of phosphate. Studies of intracellular phosphate concentrations fail to demonstrate release of phosphate from erythrocytic stores during dialysis. Diurnal variation in phosphate concentration is demonstrated in subjects with normal renal function and also in advanced chronic kidney disease.Beta2-microglobulin. A multi-pool model explains the kinetic behaviour of beta2- microglobulin during dialysis. Beta-2-microglobulin deposition is assumed to be a staged process with some deposits easily accessible during dialysis and some more resistant to depuration. Patients receiving high-flux dialysis or haemodiafiltration are shown to have lower circulating beta2-microglobulin levels and less symptomatic dialysis related amyloid, but evidence of amyloid deposition is still found when assessed by a scintigraphic imaging technique. Age and duration of dialysis are shown to be the best predictors of symptomatic amyloid deposition.CONCLUSIONS: The results of the studies in this thesis indicate that, for solutes such as phosphate and beta2-microglobulin which have complex intra-dialytic kinetics, current dialysis techniques are insufficient to achieve adequate solute removal. It will be necessary to deliver longer or perhaps more frequent dialysis therapy in order to achieve this goal. Mathematical modelling facilitates understanding of the pathophysiology of the dialysis process and provides a platform for the development and monitoring of improved dialysis strategies

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome

Progress in Hemodialysis

Hemodialysis (HD) represents the first successful long-term substitutive therapy with an artificial organ for severe failure of a vital organ. Because HD was started many decades ago, a book on HD may not appear to be up-to-date. Indeed, HD covers many basic and clinical aspects and this book reflects the rapid expansion of new and controversial aspects either in the biotechnological or in the clinical field. This book revises new technologies and therapeutic options to improve dialysis treatment of uremic patients. This book consists of three parts: modeling, methods and technique, prognosis and complications

From Benchtop to Beside: Patient-specific Outcomes Explained by Invitro Experiment

Study: Recent analyses show that females have higher early postoperative (PO) mortality and right ventricular failure (RVF) than males after left ventricular assist device (LVAD) implantation; and that this association is partially mediated by smaller LV size in females. Benchtop experiments allow us to investigate patient-specific (PS) characteristics in a reproducible way given the fact that the PS anatomy and physiology is mimicked accurately. With multiple heart models of varying LV size, we can directly study the individual effects of titrating the LVAD speed and the resulting bi-ventricular volumes, shedding light on the interplay between LV and RV as well as resulting inter-ventricular septum (IVS) positions, which may cause the different outcomes pertaining to sex. Methods: In vitro, we studied the impact of the heart size to IVS position using two smaller and two larger sized PS silicone heart phantoms derived from clinical CT images (Fig. 1A). With ultrasound crystals that were integrated on a placeholder inflow cannula, the IVS position was measured during LV and RV volume changes (dV) mimicking varying ventricular loading states (Fig. 1B). Figure 1 A Two small (blue) and two large PS heart phantoms (orange) on B benchtop. C Median septum curvature results. LVEDD/LVV/RVV: LV enddiastolic diameter/LV and RV volume. Results: Going from small to large dV, at zero curvature, the septum starts to shift towards the left; for smaller hearts at dV = -40 mL and for larger hearts at dV = -50 mL (Fig. 1C). This result indicates that smaller hearts are more prone to an IVS shift to the left than larger hearts. We conclude that smaller LV size may therefore mediate increased early PO LVAD mortality and RVF observed in females compared to males. Novel 3D silicone printing technology enables us to study accurate, PS heart models across a heterogeneous patient population. PS relationships can be studied simultaneously to clinical assessments and support the decision-making prior to LVAD implantation