Calcium phosphate metabolism and bone mineral density with nocturnal hemodialysis

An elevated calcium x phosphate product (Ca x P) is an independent risk factor for vascular calcification and cardiovascular death in dialysis patients. More physiological dialysis in patients undergoing nocturnal hemodialysis (NHD) has been shown to produce biochemical advantages compared with conventional hemodialysis (CHD) including superior phosphate (P) control. Benefits of dialysate with greater calcium (Ca) concentration are also reported in NHD to prevent Ca depletion and subsequent hyperparathyroidism, but there are concerns that a higher dialysate Ca concentration may contribute to raised serum Ca levels and greater Ca x P and vascular disease. The NHD program at our unit has been established for 4 years, and we retrospectively analyzed Ca and P metabolism in patients undergoing NHD (8-9 h/night, 6 nights/week). Our cohort consists of 11 patients, mean age 49.3 years, who had been on NHD for a minimum of 12 months, mean 34.3 months. Commencement was with low-flux (LF) NHD and 1.5 mmol/L Ca dialysate concentration, with conversion to high-flux (HF) dialyzers after a period (mean duration 18.7 months). We compared predialysis serum albumin, intact parathyroid hormone, P, total corrected Ca, and Ca x P at baseline on CHD, after conversion to LF NHD and during HF NHD. We also prospectively measured bone mineral density (BMD) on all patients entering the NHD program. Bone densitometry (DEXA) scans were performed at baseline (on CHD) and yearly after commencement of NHD. With the introduction of HF dialyzers, the Ca dialysate concentration was concurrently raised to 1.75 mmol/L after demonstration on DEXA scans of worsening osteopenia. Analysis of BMD, for all parameters, revealed a decrease over the first 12 to 24 months (N = 11). When the dialysate Ca bath was increased, the median T and Z scores subsequently increased (data at 3 years, N = 6). The mean predialysis P levels were significantly lower on LF NHD vs. CHD (1.51 vs. 1.77 mmol/L, p = 0.014), while on HF NHD P was lower again (1.33 mmol/L, p = 0.001 vs. CHD). Predialysis Ca levels decreased with conversion from CHD to LF NHD (2.58 vs. 2.47 mmol/L, p = 0.018) using a 1.5 mmol/L dialysate Ca concentration. The mean Ca x P on CHD was 4.56 compared with a significant reduction of 3.74 on LF NHD (p = 0.006) and 3.28 on HF NHD (p = 0.001 vs. CHD), despite the higher dialysate Ca in the latter. We conclude that an elevated dialysate Ca concentration is required to prevent osteopenia. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown. Better P control on NHD, however, reduces the overall Ca x P, despite the increased Ca concentration, therefore reducing the risk of vascular calcification.     

Daily (quotidian) nocturnal home hemodialysis: Nine years later

Daily nocturnal home hemodialysis was developed to satisfy the need for a highly effective, smooth, and cost‐effective home dialysis therapy. It combines the benefits of the following dialysis methods: long, frequent, and home hemodialysis. It provides a high dialysis dose for small, as well as large, molecules including β₂‐microglobulin; improves quality if life; and leads to control of hyperphosphatemia without the need for phosphate binders, as well as dissolution for extraosseous calcifications. Furthermore, it controls blood pressure often without medications, is associated with regression of left ventricular hypertrophy, improves cardiac function, improves anemia as well as nutrition, allows an unrestricted diet, and corrects sleep apnea. Finally, it decreases the overall cost of patient care and improves cost utility when compared to conventional hemodialysis. The main obstacle to its wider utilization is the structure of the current reimbursement system. Along with short daily hemodialysis, long intermittent dialysis, and the convective dialysis techniques, daily nocturnal hemodialysis promises to improve dialysis outcomes.     

Remote monitoring in nocturnal home hemodialysis 2003

Over the past several years there has been growth in the number of dialysis units performing remote monitoring in nocturnal home hemodialysis, there has been growth in the technical options available for remote monitoring, and there have been more creative approaches to overcoming previous limitations. This article will review this growth and the diverse factors driving the innovations internationally.     

Patient experiences and preferences on short daily and nocturnal home hemodialysis

Quotidian/intensive hemodialysis (short daily and nocturnal) has variable effects on health‐related quality of life (HRQOL) as measured by standard HRQOL tools. We sought to understand the perceived benefits and limitations of quotidian dialysis by interviewing patients who had switched from conventional to home quotidian dialysis. We used a qualitative, phenomenological approach to explore the perceived benefits of quotidian dialysis from 10 patients using either short daily or nocturnal hemodialysis at a tertiary health care center in London, Canada. The patients varied in gender, age, employment status, home support, physical capacity, primary cause of kidney disease, previous forms of renal replacement therapy, and level of education. Four major themes emerged: (1) improvement in physical and mental well‐being including better blood pressure and concentration, (2) increased control over patient's own life including time availability, choosing when to dialyze, and dialyzing at home, (3) decreased perception of being sick including returning to regular employment and avoiding sicker patients who must have in‐center dialysis, and (4) identification of the competencies and supports required for quotidian dialysis including ability to provide self‐care, supportive family, and medical support. Our findings suggest when patients' willingness and physical ability to use quotidian dialysis are coupled with education and support systems to assist patients' and families' self‐directed care, patients qualitatively perceive benefits of both increased physical and mental health, both measures of health‐related quality of life.     

Changes in hemoglobin and albumin concentration during nocturnal home hemodialysis

The hemoglobin (Hb) and the serum albumin (S.Alb) concentration commonly rise during seated, conventional thrice-weekly 4 to 4.5 hr hemodialysis (CHD) as a result of rapid fluid removal from the intravascular compartment. Conversely, in long, slow, recumbent nocturnal home hemodialysis (NHHD), the intra-dialytic S.Alb concentration has been shown to fall. In normal human physiology, plasma volume expansion rapidly follows recumbency and is sustained until a resumption of an upright position re-induces plasma volume contraction. The plasma protein dilution of recumbency has been suggested as the mechanism behind this finding in NHHD. Our retrospective analysis of 585 consecutive measurements of predialysis and postdialysis S.Alb and Hb taken from 71 NHHD patients confirmed an intra-dialytic fall in S.Alb (0.99% in alternate night NHHD and 1.4% in 6 nights/week NHHD) compared with an 8.4% rise in a control group of 104 CHD patients (p<0.001). Although the NHHD intra-dialytic Hb rose (3.8% in alternate night NHHD and 2.6% in 6 nights/week NHHD), this rise was significantly greater (8%) in CHD patients (p<0.001), and as physiological data confirm that recumbent dilution for albumin is greater than that for Hb, this may provide the explanation. We conclude that NHHD provides a more physiological volume milieu with the normal physiological dilution mechanisms of recumbency still operating despite the slow, steady volume reduction that accompanied longer hour and more frequent dialysis. These mechanisms are subverted, however, in CHD by the more-aggressive plasma contraction needed to attain adequate control of the intravascular volume in the face of shorter hour, less-frequent dialysis.     

Quality of life and alternate nightly nocturnal home hemodialysis

Hemodialysis has been associated with reduced quality of life (QOL). Small cohort studies of quotidian hemodialysis regimens suggest general QOL and dialysis-related symptoms may improve compared with conventional regimens. An observational cohort study was conducted on 63 patients (age 51.7 ± 12.9 years; 79.4% male; 33.3% diabetes; duration of renal replacement therapy 1.9 [0.7–6.4] years) converted from conventional home hemodialysis (3–5 sessions weekly, 3–6 h/session) to home nocturnal home hemodialysis (NHD) (3–5 sessions weekly, 6–10 h/session). Kidney Disease Quality of Life (KDQOL) and Assessment of Quality of Life instruments and 6-minute–walk tests were applied at baseline and 6 months. Baseline and 6 month surveys were returned by 70% of patients. On KDQOL, significant improvements in general health (P=0.02) and overall health ratings (P=0.0008), physical function (P=0.003), physical role (P=0.018), and energy and fatigue (P=0.027) were documented. There was a trend toward improvement in burden of kidney disease (P=0.05) and emotional role (P=0.066). There was a significant improvement in distance covered in the 6-minute–walk test from 513 m (420.5–576.4) to 536.5 m (459–609), P=0.007. On Assessment of Quality of Life, there was a trend toward improvement in overall utility score from 0.65 (0.39–0.81) to 0.73 (0.46–0.86), P=0.096. After 86.2 patient-years of observation, 23 patients have discontinued NHD (12 transplanted, 5 deceased, 4 psychosocial problems, 1 dialysis access problem, 1 medically unsuitable). Nocturnal home hemodialysis is a sustainable therapy. In addition to improving general QOL, alternate nightly NHD can significantly improve physical functioning as measured by KDQOL and 6-minute–walk tests.     

Dialysate calcium and calcium/phosphate balance in hemodialysis

The changing pattern of pharmaceutical use in dialysis patients has resulted in several alterations to dialysate calcium concentration over the past 40 years. Non‐calcium–containing phosphate binders and calcimimetics are the most recent examples of drugs that influence the overall calcium balance in dialysis patients. Renal osteodystrophy, vascular disease, and mortality are believed to be linked in patients with chronic kidney disease (CKD), although to date most of the evidence is based only on statistical associations. The precise pathophysiology of vascular calcification in end‐stage renal disease is unknown, but risk factors include age, hypertension, time on dialysis, and, most significantly, abnormalities in calcium and phosphate balance. Prospective studies are required before “cause and effect” can be established with certainty, but it is an active metabolic process with inhibitors and promoters. Serum calcium levels are clearly influenced by dialysate calcium and may therefore play an important role in influencing vascular calcification. Clinical management of hyperphosphatemia is being made easier by the introduction of potent non‐calcium–based oral phosphate binders such as lanthanum carbonate. Short‐term and long‐term studies have demonstrated its efficacy and safety. Vitamin D analogs have been a disappointment in the control of serum parathyroid hormone (PTH) levels, but evidence is emerging that vitamin D has other important metabolic effects apart from this, and may confer survival advantages to patients with CKD. Calcimimetics such as cinacalcet enable much more effective and precise control of PTH levels, but at the cost of a major financial burden. While it is unreasonable to expect that any one of these recent pharmacological developments will be a panacea, they provide researchers with the tools to begin to examine the complex interplay between calcium, phosphate, vitamin D, and PTH, such that further progress is fortunately inevitable.     

Adrenal insufficiency presenting as unexplained hypotension in nocturnal home hemodialysis

Adrenal insufficiency is a complication of chronic corticosteroid therapy. Unexplained hypotension may be a manifestation of an adrenal insufficient state in patients with a history of corticosteroid therapy on hemodialysis. We present a series of five cases of patients on nocturnal home hemodialysis with hypotension as the main manifestation of adrenal insufficiency. Unexplained hypotension in patients with a history of corticosteroid therapy should prompt the managing clinician to consider adrenal insufficiency as a possible cause.     

Vascular access‐related infection in nocturnal home hemodialysis

Frequent hemodialysis is associated with increased vascular access adverse events. We hypothesized that bacteremia would be more frequent in patients with central venous catheter (CVC) than arteriovenous fistula or arteriovenous graft (AVF/AVG) in nocturnal home hemodialysis (NHHD). We reviewed blood culture reports and concurrent clinical data for a cohort of one hundred eighty‐seven NHHD patients between January 1, 2006 and June 30, 2012. The primary outcome was time to first bacteremia, technique failure, or death after commencing NHHD. Types of bacteremia and clinical consequences were analyzed. Analyses were adjusted for a priori defined confounders. One hundred eighty‐seven patients were included with a total follow up of six hundred five patient years. Initial vascular access was AVF in seventy‐eight (42%) patients, AVG in eleven (6%) patients, and CVC in ninety‐eight (52%) patients. A total of 79.3% of patients with a CVC reached the composite endpoint of bacteremia, technique failure, or death in the study period; 44.5% of patients with an AVF or AVG reached this composite endpoint. Adjusted time to first bacteremia, technique failure, or death was significantly shorter in patients with initial CVC access (hazard ratio 2.42, 95% confidence interval 1.50–3.90, p < 0.001). Risk factors for bacteremia were comorbid status quantified by the Charlson Comorbidity Index (p < 0.001) and diabetes (p < 0.001). Coagulase negative staphylococcus was the commonest organism cultured accounting for 51.4% bacteremias. The second commonest organism was staphylococcus aureus (20.3% bacteremias). Patients undergoing NHHD with a CVC have a shorter duration to first infection, technique failure, or death than those with permanent vascular access.     

Quantifying home medication regimen changes and quality of life in patients receiving nocturnal home hemodialysis

Medication regimen simplification may improve adherence in end-stage kidney disease. The effect of nocturnal home hemodialysis (NHHD) on medication burden is unknown. A retrospective pilot study of NHHD patients was conducted. Medication information was collected at baseline, NHHD start, and at 3, 6, 12, 18, and 24 months. SF-36 scores were collected at baseline, 6, 12, and 24 months. The number of medications, pill burden, and number of administrations per day were determined. Medication Regimen Complexity Index was used at each time point as a comparator. Medications for anemia, mineral and bone disorders (MBD), cardiovascular (CV) disease, infection, and vitamins were analyzed for number of medications and pill burden. Thirty-five patients were included. Patients used 10.5 ± 4.4 medications at baseline and 11.8 ± 4.7 at the end of the study (P=NS). Regarding the number of medications, anemia medications, anti-infectives, and vitamins increased; MBD and CV medications decreased by the end of the study. Total pill burden did not change over 24 months, nor did anemia pill burden. Mineral bone disorder and CV pill burden decreased, and vitamins and anti-infective pill burden increased. Daily medication administration times decreased significantly from 5.0 ± 1.5 to 3.6 ± 1.5 by 24 months. Switching to NHHD was associated with a significant increase in Medication Regimen Complexity Index at 24 months (P<0.05). SF-36 scores increased significantly once patients began on NHHD. No measure of medication regimen complexity was correlated with the SF-36 score. Medication burden changes over time after starting NHHD. It is unknown what effect NHHD has on adherence or medication costs, and warrants further study in a prospective comparative investigation.     

Catheter‐related bacteremia and mortality in frequent nocturnal home hemodialysis

Frequent nightly home hemodialysis (NHHD) has emerged as an attractive alternative to thrice weekly in‐center hemodialysis, albeit with preponderant long‐term hemodialysis catheter used. Sixty‐three NHHD patients from University of Virginia Lynchburg Dialysis Facility were matched 1:2 with 121 conventional hemodialysis patients admitted to Fresenius Medical Care North America facilities from January 1, 2007 to December 31, 2010. Matching considered age (± 5 years), gender, race, dialysis vintage, and diabetes. The primary end‐point was the combined incidence of bacteremia/sepsis, for up to 20 months or upon changing to a fistula/graft (with catheter removal), transferring to peritoneal dialysis (PD), or at the time of kidney transplant or death. No significant differences were observed in rate of fistula/graft conversion, transfer to PD, transplant, or death between NHHD and in‐center hemodialysis (IHD) groups. For the first catheter used, the rate of catheter‐related sepsis was not significantly different between the NHHD (1.77 per 100 patient months) and IHD (2.03 per 100 patient months; P = 0.21). Combining all catheters, the rate of bacteremia/sepsis per 100 patient months in the NHHD group was 1.51 and in the IHD group was 2.01 (P = 0.35). Median catheter lifespan for the first catheter was 5.6 (1.7～19.0) for NHHD and 4.6 (2.7～7.8) for the IHD group (P = 0.64), and for all catheters used was 5.2 (Q1～Q3 = 1.5～15.2) months in NHHD group, and 4.1 (2.0～6.8) months in IHD group (P = 0.20). The rate of bacteremia and death is not different for up to 20 months in catheter users who dialyze via frequent NHHD vs. thrice weekly IHD.     

Quality of life of end-stage renal disease patients and study on the implementation of nocturnal home hemodialysis in Greece

The aim of this study was to measure the overall health-related quality of life of patients receiving hemodialysis in Greece and to assess willingness, motivation, and concerns about participating in a nocturnal home hemodialysis program. This review measured successfully the quality of life of 146 end-stage renal disease (ESRD) patients undergoing hemodialysis in 10 hemodialysis centers all over Greece and studied the factors that affect their choice to adopt a specific treatment. Physical and mental health status and health-related quality of life, measured by the Kidney Disease Quality of Life Short Form accompanied by the demographic data gathered, provide information that can help to improve ESRD patient care in Greece. A comparison with the Greek general population identifies lower physical functioning scores for the ESRD patients, while the mental functioning scores are comparable with those of the Greek general population. Moreover, it is important to notice the willingness expressed by half of the patients to participate in a potential program of nocturnal home hemodialysis.     

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

Calcium phosphate formation induced on silica in bamboo

The effect of in vitro induction of calcium phosphate on bamboo surfaces is reported for the first time. Bamboo is studied for biomaterial application due to its elasticity modulus being closer to human bone than other biomaterials. Following an earlier study of cytotoxicity and precipitation of apatite on ground tissue and vascular bundles of bamboo, the composition and function of the minerals in bamboo, especially silica, are considered in the present work. It is found that in both outer and inner surfaces of bamboo culm, there exists some silica. Bamboo elicits an inert response when soaked directly in calcification solution. After the rind of bamboo is treated with sodium hydroxide solution, the silica underneath can induce precipitation of calcium phosphate in an ambient environment. Furthermore, by subsequent grafting with polyethylene glycol (PEG 1000), calcium phosphate induction of bamboo rind can be improved, depending on the concentration of NaOH solution and treatment time. Heat treatment of bamboo can remove the organic materials around the minerals in bamboo, allowing the calcification behaviour of the silica-containing inorganic phase of bamboo in aqueous solution to be studied.     

Calcium phosphate crystallization on polyglycine, polytyrosine and polymethionine

The kinetics of hydroxyapatite (HAP) crystallization on the polyaminoacids polyglycine, polytyrosine, polymethionine, was investigated by the constant composition technique. The apparent order for the crystallization process was found to be 2, indicative of a surface diffusion control mechanism. There are three possible mechanisms for critical nucleus formation with size n* = 3 ± 1 as defined by computational chemistry calculations at 310 K. The calculated surface energy from kinetic data for the growing HAP phase was 109 ± 15 mJ m^− 2.     

Determinants of training and technique failure in home hemodialysis

Home hemodialysis (HHD) has clinical and economic advantages compared with in‐center conventional hemodialysis. Many health systems wish to broaden the population to which this modality can be successfully offered. However, determinants of successful HHD training and technique survival are unknown. We hypothesize that both medical and social factors play a role when patients fail to successfully adopt HHD. We examined characteristics of consecutive patients who initiated training for HHD between 2003 and 2011. Patients were classified as “failure” if they failed to complete HHD training or experienced technique failure (TF) within the first year of treatment. Remaining patients were classified as “success.” One hundred seventy‐seven patients initiated HHD training. In the “failure” group (n = 32), 24 did not finish training and 8 had TF. In the “success” group (n = 145), 65 (45%) patients remained on NHD, 49 (34%) discontinued HHD because of renal transplantation and 21 (14%) because of death, while only 10 (7%) eventually transferred to another dialysis modality. In a multivariable logistic regression analysis, the strongest predictors of “failure” were end‐stage renal disease because of diabetes (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.4–10.3, P = 0.008) and use of rental housing (OR 3.1, 95% CI 1.3–6.0, P = 0.01). Both medical and social factors are associated with failure to adopt HHD. Enhanced supports or a customized education strategy for these vulnerable patients should be considered.     

Personal Support Worker (PSW)‐supported home hemodialysis: A paradigm shift

Introduction: Despite improving clinical outcomes associated with the use of home hemodialysis (HD), its utilization is low in most countries. The inability or unwillingness of patients and their families to participate in their own treatment is one of the most important barriers to the adoption of home HD. Methods: We hypothesized that paid helper‐delivered home HD supported by public funds would be successful and welcomed by patients and be delivered at an affordable cost. We conducted a pilot project to dialyze six patients at home using Personal Support Workers (PSW) and resolve regulatory, organizational and financial constraints. Findings: cWe provided publically‐funded PSW‐supported home HD to six patients. We describe the administrative structure of the pilot project allowing scalability and turnkey operation in the province of Ontario. Regulatory and insurance concerns were resolved and patients and staff were enthusiastic. The projected total dialysis cost, when economies of scale are met, are expected to be lower than the cost of in‐center HD. Discussion: A second phase of the project is currently under way including 8 hospitals and 67 patients. If equally successful, it may have significant implications for the delivery of care for End Stage Renal Disease in Ontario and similar jurisdictions. It promises to increase the utilization of home dialysis possibly at a lower cost than in‐center HD. This would be particularly important in providing dialysis in underserviced and geographically hard to access areas.