The evaluation of a successful home hemodialysis program: establishing a prospective framework for quality.

A mounting body of clinical data and purported quality of life benefits has been primarily responsible for a renewed interest in programs providing longer more frequent home hemodialysis. As novel forms of home hemodialysis (HHD) like nocturnal (nightly) home hemodialysis (NHD) move from strictly the academic "experimental" arenas to potentially the preferred renal replacement modality for patients, it will be necessary for programs to plan and evaluate standardized metrics for program quality. This will be essential for smaller, less experienced centers to gauge their outcomes against larger, more established programs. Driven by market forces primarily in the United States, conventional hemodialysis programs have begun to explore optimal strategies for reporting quality of care in their respective dialysis centers. Extrapolating this to home hemodialysis modalities the question remains which criteria do we use as measures of quality? The evidence is limited to small, observational studies and one small randomized controlled trial. Extrapolating existing quality indices from conventional hemodialysis seems reasonable however may miss many of the true clinically significant advantages of HHD as a modality. Although definitive evidence does not yet exist for intensive home hemodialysis strategies, clearly clinicians, payers and patients are convinced enough of this approach for programs to justify the expansion of these modalities. We have laid the groundwork for the CANadian Slow Long nightly ExtEnded dialysis Programs (CAN-SLEEP), a multicenter cohort aimed to investigate the clinical and programmatic outcomes of NHD. This will allow for the assessment of numerous outcomes on a global scale for this state-of-the art dialysis modality in the form of a multidimensional programmatic evaluation.

Daily hemodialysis 2006. State of the art.

The need to improve the dialysis outcomes, the negative results from the HEMO and ADEMEX studies as well reports of clinical benefits have rekindled the interest in daily hemodialysis. Although no randomized controlled studies have been published, a large number of manuscripts have described significant benefits from both the short or nocturnal forms of daily (quotidian) dialysis or hemo(dia)filtration. They include improved quality of life, hemodynamic stability, blood pressure control with minimal number of medications, anemia control, regression of cardiac hypertrophy and improved nutrition. Furthermore, quotidian nocturnal hemodialysis provides higher dialysis dose, and has been described to improve endothelial as well as endothelial progenitor cell function, heart rate variability, sleep and phosphate control while it offers unrestricted diet. Several studies have pointed to a lower overall cost and improved cost utility when treating patients using quotidian hemodialysis at home. The obstacles to widespread use are the reimbursement structure in most countries, the willingness and ability of the patients to do home hemodialysis and the availability of user-friendly machines. A prospective randomized controlled study sponsored by the National Institutes of Health (NIH) and US Centers for Medicare and Medicaid services (CMS) currently underway will be pivotal in confirming these benefits and convincing the stakeholders to promote the use of daily hemodialysis.

Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease.

AIM: Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. METHODS: In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. RESULTS: There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up. CONCLUSIONS: Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.

Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2.

In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. To test the presumption of equivalence in humans, we compared the ability of equal molar quantities of vitamin D2 or D3 to increase serum 25-hydroxyvitamin D [25(OH)D], the measure of vitamin D nutrition. Subjects took 260 nmol (approximately 4000 IU) vitamin D2 (n=17) or vitamin D3 (n=55) daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin D2 and D3 forms. With vitamin D3, mean (+/-SD) serum 25(OH)D increased from 41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment. With vitamin D2, the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0 nmol/L after. The increase in 25(OH)D with vitamin D3 was 23.3+/-15.7 nmol/L, or 1.7 times the increase obtained with vitamin D2 (13.7+/-11.4 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. The lowest 2 tertiles for basal 25(OH)D showed larger increases in 25(OH)D: 30.6 and 25.5 nmol/L, respectively, for the first and second tertiles. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

Hypertension aggregates in families of kidney stone patients with high urinary excretion of uric acid.

OBJECTIVE: To determine whether kidney stone disease (KSD) and hypertension (HTN) share a common familial component that is determined by a specific urinary biochemical abnormality. DESIGN: Familial aggregation study. PATIENTS: Two hundred and twelve KSD patients, aged 18-50 years, collected a 24-h urine sample to measure the urinary excretion of uric acid, calcium, oxalate, magnesium and citrate, and were interviewed about the occurrence of HTN among first-degree relatives. OUTCOME: Positive family history (FHx) of HTN defined as two or more relatives with HTN, and HTN occurring in the fathers, mothers and siblings. RESULTS: Positive FHx of HTN was significantly associated with increasing urinary excretion of uric acid (P = 0.03) but not with the excretion of the other substances. When the patients were divided into those with and without hyperuricosuria, the adjusted odds ratio (OR) for positive FHx of HTN in a hyperuricosuric KSD patient was 3.8 (95% CI, 1.22-11.66). Separate analysis on the occurrence of HTN in the fathers, mothers and siblings of the probands indicated that hyperuricosuria is positively related to HTN occurring in the siblings of the patients (P < 0.001) but not in the fathers or in the mothers. The adjusted OR for HTN occurring in siblings of hyperuricosuric patients compared with siblings of non-hyperuricosuric patients was 3.8 (2.12-6.67). CONCLUSION: Siblings of KSD patients with hyperuricosuria had a significantly increased prevalence of HTN that could not be accounted for by age, family size, body-mass index and personal history of HTN of the probands. Additional studies need to be undertaken to determine whether this familial clustering has a genetic or environmental origin.

In search of ideal hemodialysis: is prolonged frequent dialysis the answer?

Advances in technology have made it possible to deliver a high Kt/V in a shorter time. The realization that duration of dialysis may be an important predictor of survival independent of dialysis dose has resulted in the popularity of prolonged slow dialysis (PHD). The longer duration and increased frequency of dialysis achieve excellent small- and middle-molecular weight solute clearance and also attenuate the peak concentration of uremic toxins. The slow dialysis process enables the equilibration of tissue and vascular compartments, resulting in better clearance and decreased postdialysis rebound increase in solutes. Gentle, persistent ultrafiltration allows the control of hypertension with minimal antihypertensive use. The intense and more frequent dialysis improves appetite and permits liberalization of diet. This greater dietary protein intake results in a progressive increase in serum albumin level and dry weight. Nocturnal hemodialysis achieves control of hyperphosphatemia without phosphate binders and a significant reduction in serum beta(2)-microglobulin levels. Normalization of extracellular volume, better clearance of uremic toxins, and improved nutrition result in a significant improvement in survival. The flexible time schedule with home hemodialysis and improvement of sleep and neurocognitive function allow better rehabilitation. The available evidence indicates PHD may be closer to the concept of an ideal dialysis, but there is lingering uncertainty about the consequence of prolonged immune stimulation, catabolism, and loss of essential solutes with these therapies.

Highly elevated levels of prostaglandin D synthase in the serum of patients with renal failure.

OBJECTIVES: To investigate whether prostaglandin D (PGD) synthase levels differ in the serum of patients with or without renal dysfunction. PGD synthase or beta-trace protein is a major constituent (approximately 3% of total protein) of human cerebrospinal fluid (CSF). We previously reported that PGD synthase levels in serum are approximately 40- to 60-fold lower than those in CSF. METHODS: We measured the PGD synthase concentration in various sera with a highly sensitive and specific immunofluorometric assay along with the serum creatinine level. Analysis for PGD synthase and creatinine was performed in 30 sera from non-renal failure subjects, in 7 sera from patients treated with continuous ambulatory peritoneal dialysis, and in 34 sera that were before and after hemodialysis samples from 17 patients with renal failure. RESULTS: Elevated creatinine concentration was observed in patients with renal insufficiency, as expected (Mann-Whitney P < 0.0001; chi-square P < 0.0001 ). We found that serum PGD synthase concentration from patients with renal failure is significantly elevated compared with the serum PGD synthase concentration from non-renal failure subjects (Mann-Whitney P < 0.0001; chi-square P < 0.0001). Approximately a 35-fold increase of serum PGD synthase is observed for patients with renal failure compared with non-renal failure subjects. Serum PGD synthase concentration is not affected by hemodialysis in acute renal failure patients (Mann-Whitney P = 0.918), unlike serum creatinine levels, which were decreased significantly after hemodialysis (Mann-Whitney P = 0.0001). CONCLUSIONS: We conclude that renal impairment is highly associated with elevated serum PGD synthase levels. Measurement of PGD synthase in serum is a new biochemical marker of renal insufficiency.

Venous stenosis and thrombosis associated with the use of internal jugular vein catheters for hemodialysis.

Previous studies have demonstrated venous stenosis and thrombosis in hemodialysis patients who had repeated or prolonged cannulation of the subclavian vein. Early reports, however suggested that patients with catheters placed in the internal jugular vein were not at risk of such complications. We conducted a retrospective case series to determine if this was correct. We report a series of seven patients who were found to have stenosis of the upper neck veins despite having never had subclavian vein cannulation. We suggest that previous reports suggesting a superior safety profile with internal jugular catheters may have been misleading and propose that all measures be taken to encourage wider use of arteriovenous grafts and fistulae.

Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea.

Sleep apnoea is common in patients with end-stage renal disease (ESRD). It was hypothesised that this is related to a narrower upper airway. Upper airway dimensions in patients with and without ESRD and sleep apnoea were compared, in order to determine whether upper airway changes associated with ESRD could contribute to the development of sleep apnoea. An acoustic reflection technique was used to estimate pharyngeal cross-sectional area. Sleep apnoea was assessed by overnight polysomnography. A total of 44 patients with ESRD receiving conventional haemodialysis and 41 subjects with normal renal function were studied. ESRD and control groups were further categorised by the presence or absence of sleep apnoea (apnoea/hypopnoea index > or =10 events.h(-1)). The pharyngeal area was smaller in patients with ESRD compared with subjects with normal renal function: 3.04 +/- 0.84 versus 3.46 +/- 0.80 cm(2) for the functional residual capacity and 1.99 +/- 0.51 versus 2.14 +/- 0.58 cm(2) for the residual volume. The pharynx is narrower in patients with ESRD than in subjects with normal renal function. In conclusion, since a narrower upper airway predisposes to upper airway occlusion during sleep, it is suggested that this factor contributes to the pathogenesis of sleep apnoea in dialysis-dependent patients.

The impact of home nocturnal hemodialysis on end-stage renal disease therapies: a decision analysis.

Home nocturnal hemodialysis (HNHD) is cost-effective relative to in-center hemodialysis (IHD) in short-run analyses. The effect in long-run analyses, when technique failures, declining benefits, delayed training, transplantation and death are considered, is unknown. We used decision analysis techniques to examine the relative cost-effectiveness of HNHD and IHD, projecting future costs and health effects over a lifetime with end-stage renal disease. We developed a Markov state-transition model comparing two strategies: only IHD or starting on IHD and subsequently transferring to HNHD. The model incorporates transplantation. In the base case, half the population was eligible for transplantation, with (1/3) of grafts from live donors. The time to transplant was 0.75 years for live and 5 years for deceased donor transplants. The delay before initiation of HNHD was 5 years. Costs and outcomes were discounted at 3% per annum. Model parameters were derived from a literature review. We also conducted one-way sensitivity analyses and Monte Carlo simulations. The HNHD strategy was associated with a quality-adjusted survival estimate of 5.79 quality-adjusted life years (QALYs), with lifetime costs of $538 094. The values for IHD were 5.31 QALYs and $543 602, respectively. Thus, HNHD is cost saving while improving quality of life. The incremental cost-utility ratio was consistently less than $50 000 per QALY in sensitivity and Monte Carlo analyses. Important determinants of cost-effectiveness were transplantation time and whether benefits declined over time. Our model suggests that HNHD improves quality-adjusted survival over IHD at an economically attractive cost-effectiveness ratio.

Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease.

Although sleep apnoea is very common in patients with end-stage renal disease, the physiological mechanisms for this association have not yet been determined. The current authors hypothesised that altered respiratory chemo-responsiveness may play an important role. In total, 58 patients receiving treatment with chronic dialysis were recruited for overnight polysomnography. A modified Read rebreathing technique, which is used to assess basal ventilation, ventilatory sensitivity and threshold, was completed before and after overnight polysomnography. Patients were divided into apnoeic (n = 38; apnoea/hypopnoea index (AHI) 35+/-22 events.h(-1)) and nonapnoeic (n = 20; AHI 3+/-3 events.h(-1)) groups, with the presence of sleep apnoea defined as an AHI >10 events.h(-1). While basal ventilation and the ventilatory recruitment threshold were similar between groups, ventilatory sensitivity during isoxic hypoxia (partial pressure of oxygen (PO2) 6.65 kPa) and hyperoxia (PO2) 19.95 kPa) was significantly greater in apnoeic patients. Overnight changes in chemoreflex responsiveness were similar between groups. In conclusion, these data indicate that the responsiveness of both the central and peripheral chemoreflexes is augmented in patients with sleep apnoea and end-stage renal disease. Since increased ventilatory sensitivity to hypercapnia destabilises respiratory control, the current authors suggest this contributes to the pathogenesis of sleep apnoea in this patient population.

Effect of therapy time and frequency on effective solute removal.

Increasing dialysis frequency or time increases the removal of the molecules diffusing slowly across the intercompartmental barriers. By offering frequent dialysis the time on dialysis can be decreased, possibly without worsening the outcome. Increasing dialysis time increases large molecule removal. Increasing in both frequency and time on dialysis increases the removal of solutes of all molecular sizes. Increasing frequency and/or time of dialysis may have many other beneficial effects that are not traditionally quantitated and which can affect outcomes.

Daily hemodialysis: why the renewed interest?

There has been an increasing interest in new hemodialysis regimens aiming to address issues of inadequate dialysis, poor quality of life, and poor outcomes. This article reviews the current state of short daily and nocturnal hemodialysis and outlines the advantages of daily over conventional hemodialysis reviews. Furthermore, it attempts to compare these two dialysis regimens.

Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis.

BACKGROUND: Sleep apnea is common in patients with chronic renal failure and is not improved by either conventional hemodialysis or peritoneal dialysis. With nocturnal hemodialysis, patients undergo hemodialysis seven nights per week at home while sleeping. We hypothesized that nocturnal hemodialysis would correct sleep apnea in patients with chronic renal failure because of its greater effectiveness. METHODS: Fourteen patients who were undergoing conventional hemodialysis for four hours on each of three days per week underwent overnight polysomnography. The patients were then switched to nocturnal hemodialysis for eight hours during each of six or seven nights a week. They underwent polysomnography again 6 to 15 months later on one night when they were undergoing nocturnal hemodialysis and on another night when they were not. RESULTS: The mean (+/-SD) serum creatinine concentration was significantly lower during the period when the patients were undergoing nocturnal hemodialysis than during the period when they were undergoing conventional hemodialysis (3.9+/-1.1 vs. 12.8+/-3.2 mg per deciliter [342+/-101 vs. 1131+/-287 micromol per liter], P<0.001). The conversion from conventional hemodialysis to nocturnal hemodialysis was associated with a reduction in the frequency of apnea and hypopnea from 25+/-25 to 8+/-8 episodes per hour of sleep (P=0.03). This reduction occurred predominantly in seven patients with sleep apnea, in whom the frequency of episodes fell from 46+/-19 to 9+/-9 per hour (P= 0.006), accompanied by increases in the minimal oxygen saturation (from 89.2+/-1.8 to 94.1+/-1.6 percent, P=0.005), transcutaneous partial pressure of carbon dioxide (from 38.5+/-4.3 to 48.3+/-4.9 mm Hg, P=0.006), and serum bicarbonate concentration (from 23.2+/-1.8 to 27.8+/-0.8 mmol per liter, P<0.001). During the period when these seven patients were undergoing nocturnal hemodialysis, the apnea-hypopnea index measured on nights when they were not undergoing nocturnal hemodialysis was greater than that on nights when they were undergoing nocturnal hemodialysis, but it still remained lower than it had been during the period when they were undergoing conventional hemodialysis (P=0.05). CONCLUSIONS: Nocturnal hemodialysis corrects sleep apnea associated with chronic renal failure.

beta(2)-microglobulin kinetics in nocturnal haemodialysis.

BACKGROUND: beta(2)-Microglobulin (beta(2)m) is a major component of dialysis-related amyloidosis. The available therapeutic options do not permit normalization of the serum beta(2)m level. In a cross-over trial, we studied the kinetics of beta(2)m during two different dialytic techniques. METHODS: Ten stable, anuric end-stage renal disease patients were studied during two consecutive weeks of three conventional (CHD) and six nocturnal haemodialysis (NHD) sessions. CHD was performed for 4 h three times weekly using a polysulfone dialyser (F80, surface area of 1.8 m(2)) with a mean blood and dialysate flow rate of 401+/-91.6 and 514+/-10.9 ml/min, respectively. The NHD was done with a smaller dialyser (F40, surface area of 0.7 m(2)) and lower blood (281+/-17 ml/min) and dialysate flow rates (99+/-1.2 ml/min) for 8 h, six nights a week. RESULTS: Weekly removal of urea (51.6+/-24.6 vs 43.1+/-20.5 g) and creatinine (8501+/-5204 vs 6319+/-4134 mg) were comparable with the two modalities of dialysis but the mass of beta(2)m removed was significantly higher with NHD (127+/-48 vs 585+/-309 mg, P<0.001), with a percentage reduction in serum level of 20.5+/-5.8 vs 38.8+/-7. 1% (P<0.0001) and a Kt/V(beta2m) of 0.21+/-0.09 vs 0.56+/-0.17 (P<0. 0006). The mean post-dialysis beta(2)m (20.8+/-6.3 vs 14.0+/-3.8 mg/dl, P=0.02), Tac(beta2m) (26.2+/-5.2 vs 19.8+/-3.8 mg/dl, P=0.02) and pre-dialysis beta(2)m (beta(2)m(pre)) at the end of 1 week of therapy (24.4+/-7.6 vs 19.0+/-3.4 mg/dl, P=0.02) were lower with NHD. Long-term follow-up data were available in 13 and seven patients at the end of 1 and 2 years, respectively. Serum beta(2)m(pre) levels progressively declined from 27.2+/-11.7 mg/dl at initiation of NHD to 13.7+/-4.4 mg/dl by 9 months, and they remained stable thereafter. CONCLUSIONS: NHD provides a much higher clearance of beta(2)m than CHD, leading to a long-term decrease in the pre-dialysis concentration of beta(2)m.