The Evolution of Home HD - Meeting Modern Patient Needs.

Patients with end-stage renal disease undergoing conventional renal replacement therapy face high morbidities and inappropriately high mortality rates globally. Intensive home hemodialysis has emerged as an alternate form of renal replacement therapy with superior clinical outcomes. In order to describe the international trends in conducting home hemodialysis, we performed a cross-sectional survey of 25 centers reporting the global trends and practices of intensive home hemodialysis. While the practice of home hemodialysis has continued to evolve, similar logistical barriers exist around the world. The Global Forum for Home Hemodialysis was created to provide a user-centric manual to facilitate the delivery of this important mode of renal replacement therapy.

A systematic review of the impact of center volume in dialysis.

BACKGROUND: A significant relationship exists between the volume of surgical procedures that a given center performs and subsequent outcomes. It seems plausible that such a volume-outcome relationship is also present in dialysis. METHODS: MEDLINE and EMBASE were searched in November 2014 for non-experimental studies evaluating the association between center volume and patient outcomes [mortality, morbidity, peritonitis, switch to hemodialysis (HD) or any other treatment], without language restrictions or other limits. Selection of relevant studies, data extraction and critical appraisal were performed by two independent reviewers. We did not perform meta-analysis due to clinical and methodological heterogeneity (e.g. different volume categories). RESULTS: 16 studies met out inclusion criteria. Most studies were performed in the US. The study quality ranged from fair to good. Only few items were judged to have a high risk of bias, while many items were judged to have an unclear risk of bias due to insufficient reporting. All 10 studies that analyzed peritoneal dialysis (PD) technique survival by modeling switch to HD or any other treatment as an outcome showed a statistical significant effect. The relative effect measures ranged from 0.25 to 0.94 (median 0.73) in favor of high volume centers. All nine studies indicated a lower mortality for PD in high volume centers, but only study was statistical significant. CONCLUSIONS: This systematic review supports a volume-outcome relationship in peritoneal dialysis with respect to switch to HD or any other treatment. An effect on mortality is probably present in HD. Further research is needed to identify and understand the associations of center volume that are causally related to patient benefit.

Update: Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass.

After the publication of our paper Dunlop et al. "Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass", we became aware of further data correlating left ventricular (LV) mass index at baseline and their corresponding mass at 12 months, using cardiac magnetic resonance imaging (MRI) in patients on hemodialysis. The original published sample size for the SoLID trial of 118 was a conservative estimate, calculated using analysis of covariance and a within person Pearson's correlation for LV mass index of 0.75. New data communicated to the SoLID trial group has resulted in re-calcuation of the sample size, based upon a within person Pearson's correlation of 0.8 but otherwise unchanged assumptions. As a result, the SoLID trial will now recruit 96 participants.

Rationale and design of the Myocardial Microinjury and Cardiac Remodeling Extension Study in the Sodium Lowering in Dialysate trial (Mac-SoLID study).

BACKGROUND: The Sodium Lowering in Dialysate (SoLID) trial is an ongoing a multi-center, prospective, randomised, single-blind (assessor), controlled, parallel assignment clinical trial, enrolling 96 home and self-care hemodialysis (HD) patients from 7 centers in New Zealand. The trial will evaluate the hypothesis that lower dialysate [Na+] during HD results in lower left ventricular (LV) mass. Since it's inception, observational evidence has suggested increased mortality risk with lower dialysate [Na+], possibly due to exacerbation of intra-dialytic hypotension and subsequent myocardial micro-injury. The Myocardial Micro-injury and Cardiac Remodeling Extension Study in the Sodium Lowering In Dialysate Trial (Mac-SoLID study) aims to determine whether lower dialysate [Na+] results in (i) increased levels of high-sensitivity Troponin T (hsTnT), a well-established marker of intra-dialytic myocardial micro-injury in HD populations, and (ii) increased fixed LV segmental wall motion abnormalities, a marker of recurrent myocardial stunning and micro-injury, and (iii) detrimental changes in LV geometry due to maladaptive homeostatic mechanisms. METHODS/DESIGN: The SoLID trial and the Mac-SoLID study are funded by the Health Research Council of New Zealand. Key exclusion criteria: patients who dialyse > 3.5 times per week, pre-dialysis serum sodium <135 mM, and maintenance haemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials that contraindicate the study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will receive dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure for the Mac-SOLID study is repeated measures of [hsTnT] at 0, 3, 6, 9, and 12 months. The secondary outcomes will be assessed using cardiac magnetic resonance imaging (MRI), and comprise LV segmental wall motion abnormality scores, LV mass to volume ratio and patterns of LV remodeling at 0 and 12 months. DISCUSSION: The Mac-SoLID study enhances and complements the SoLID trial. It tests whether potential gains in cardiovascular health (reduced LV mass) which low dialysate [Na+] is expected to deliver, are counteracted by deterioration in cardiovascular health through alternative mechanisms, namely repeated LV stunning and micro-injury. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.

Increasing the uptake of peritoneal dialysis in New Zealand: a national survey.

BACKGROUND: Peritoneal dialysis (PD) has been shown to offer a high quality of life and independence to patients. New Zealand (NZ) is a world leader in home dialysis, yet over the last decade, rates of PD have been steadily decreasing for unknown reasons. OBJECTIVES: This paper reports on the findings of a national survey which explored the clinicians' perspectives on key factors that influence the rate of PD. DESIGN: Ten multi-answer questions were asked of several groups of dialysis health professionals to assess factors that are barriers and enablers to PD, including patient choice of dialysis modality, information about PD and pre-dialysis education delivery. All NZ nephrologists, pre-dialysis and PD nurses were invited to complete an anonymous online survey. Responses were analysed to identify perceived barriers and enablers influencing the rate of PD uptake amongst incident dialysis patients. RESULTS: Completed surveys were received from 52% of nephrologists, 100% of pre-dialysis nurses and 50% of PD nurses in NZ. In NZ, patients are offered a choice of dialysis modality with pre-dialysis nurses delivering the majority of education. The most frequently identified barriers to uptake of PD were lack of information about PD, established misconceptions about PD and late referrals to dialysis. Important enablers were early and frequent pre-dialysis education. The only two factors which were reported as very important contraindications to PD were dexterity and decreased cognitive function. CONCLUSION: Early and frequent pre-dialysis education encourages patients to choose PD and enables early identification and resolution of barriers to the uptake of PD.

Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass.

BACKGROUND: The current literature recognises that left ventricular hypertrophy makes a key contribution to the high rate of premature cardiovascular mortality in dialysis patients. Determining how we might intervene to ameliorate left ventricular hypertrophy in dialysis populations has become a research priority. Reducing sodium exposure through lower dialysate sodium may be a promising intervention in this regard. However there is clinical equipoise around this intervention because the benefit has not yet been demonstrated in a robust prospective clinical trial, and several observational studies have suggested sodium lowering interventions may be deleterious in some dialysis patients. METHODS/DESIGN: The Sodium Lowering in Dialysate (SoLID) study is funded by the Health Research Council of New Zealand. It is a multi-centre, prospective, randomised, single-blind (outcomes assessor), controlled parallel assignment 3-year clinical trial. The SoLID study is designed to study what impact low dialysate sodium has upon cardiovascular risk in dialysis patients. The study intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over 24 months and follow up each participant over 12 months. Key exclusion criteria are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis serum sodium of <135 mM, and maintenance hemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials, which contraindicate the SoLID study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will be dialysed using dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure is left ventricular mass index, as measured by cardiac magnetic resonance imaging, after 12 months of intervention. Eleven or more secondary outcomes will be studied in an attempt to better understand the physiologic and clinical mechanisms by which lower dialysate sodium alters the primary end point. DISCUSSION: The SoLID study is designed to clarify the effect of low dialysate sodium upon the cardiovascular outcomes of dialysis patients. The study results will provide much needed information about the efficacy of a cost effective, economically sustainable solution to a condition which is curtailing the lives of so many dialysis patients. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.

The organization and financing of dialysis and kidney transplantation services in New Zealand.

In New Zealand, patients receive treatment for end-stage renal disease (ESRD) within the tax-funded health system. All hospital and specialist outpatient services are free, while general practitioner consultations and pharmaceuticals prescribed outside of hospitals incur copayments. Total ESRD prevalence is 0.07%, half the U.S. rate, and the prevalence of home-based and self-care dialysis is the highest in the world. Medical staff are not subject to direct financial incentives that could affect treatment choice. Estimated total expenditure per ESRD patient is relatively low. Funding constraints encourage physicians and patients to consider the probable benefit of dialysis for a patient before treatment is prescribed.

Integrating regression formulas and kernel functions into locally adaptive knowledge-based neural networks: a case study on renal function evaluation.

OBJECTIVE: In many medical areas, there exist different regression formulas to predict/evaluate a medical outcome on the same problem, each of them being efficient only in a particular sub-space of the problem space. The paper aims at the development of a generic, incremental learning model that includes all available regression formulas for a particular prediction problem to define local areas of the problem space with their best performing formula along with useful explanation rules. Another objective of the paper is to develop a specific model for renal function evaluation using nine existing formulas. METHODS AND MATERIALS: We have used a connectionist neuro-fuzzy approach and have developed a knowledge-based neural network model (KBNN) which incorporates and adapts incrementally several existing regression formulas and kernel functions. The model incorporates different non-linear regression functions as neurons in its hidden layer and adapts these functions through incremental learning from data in particular local areas of the space. More specifically, each hidden neural node has a pair of functions associated with it--one regression formula, that represents existing knowledge and one Gaussian kernel function, that defines the sub-space of the whole problem space, in which the formula is locally adapted to new data. All these functions are aggregated and changed through incremental learning. The proposed KBNN model is illustrated using a medical dataset of observed patient glomerular filtration rate (GFR) measurements for renal function evaluation. In this case study, the regression function for each cluster is selected by the model from nine formulas commonly used by medical practitioners to predict GFR. 441 GFR data vectors from 141 patients taken from 12 sites in Australia and New Zealand have been used as a case study experimental data set. RESULTS: The proposed GFR prediction model, based on the proposed generic KBNN model, outperforms at least by 10% accuracy any of the individual regression formulas or a standard neural network model. Furthermore, we have derived locally adapted regression formulas to perform best on local clusters of data along with useful explanatory rules. CONCLUSION: The proposed KBNN model manifests better accuracy then existing regression formulas or neural network models for renal function evaluation and extracts modified formulas that perform well in local areas of the problem space.

Evolving connectionist system versus algebraic formulas for prediction of renal function from serum creatinine.

BACKGROUND: In clinical trials, equation 7 from the Modification of Diet in Renal Disease (MDRD) Study is the most accurate formula for the prediction of glomerular filtration rate (GFR) from serum creatinine. An alternative approach has been developed using evolving connectionist systems (ECOS), which are novel computing structures that can be trained to generate accurate output from a given set of input variables. This study aims to compare the prediction errors associated with each method, using data that reproduce routine clinical practice as opposed to the artificial setting of clinical trials. METHODS: The methods were compared using 441 radioisotope measurements of GFR in 178 chronic kidney disease patients from 12 centers in Australia and New Zealand. All clinical and laboratory measurements were obtained from the patients' center rather than central laboratories, as would be the case in routine clinical practice. Both the MDRD formula and ECOS used the same predictive variables, and both were optimized to the study cohort by stepwise regression and training, respectively. RESULTS: Mean measured GFR in the cohort was 22.6 mL/min/1.73 m(2). The bias and precision of the MDRD formula were -3.5 mL/min/1.73 m(2) and 34.5%, respectively, improving to -1.2 mL/min/1.73 m(2) and 31.1% after maximal optimization of the formula to study data. The bias and precision of the ECOS were 0.7 mL/min/1.73 m(2) and 32.6%, respectively, improving to -0.1 mL/min/1.73 m(2) and 16.6% after maximal optimization of the system to study data. The prediction of GFR using ECOS was improved by accounting for the center from where clinical and laboratory measurements originated within the connectionist model. CONCLUSION: Algebraic formulas will be associated with greater prediction error in routine clinical practice than in the original trials, and machine intelligence is more likely to predict GFR accurately in this setting.