Comparison between different dialysate calcium concentrations in nocturnal hemodialysis

Benefits of dialysate with greater calcium (Ca) concentration are reported in nocturnal hemodialysis (NHD) to prevent Ca depletion and subsequent hyperparathyroidism. Studies with patients dialyzing against 1.25 mmol/L Ca baths demonstrate increases in alkaline phosphatase (ALP) and parathyroid hormone (PTH) and increasing dialysate Ca subsequently corrects this problem. However, whether 1.5 or 1.75 mmol/L dialysate Ca is most appropriate for NHD is yet to be determined, and differences in the effect on mineral metabolism of daily vs. alternate daily NHD have also not been well defined. We retrospectively analyzed mineral metabolism in 48 patients, from 2 institutions (30 at Monash and 18 at Geelong), undergoing home NHD (8 hr/night, 3.5-6 nights/week) for a minimum of 6 months. Thirty-seven patients were dialyzed against 1.5 mmol/L Ca bath and 11 patients against 1.75 mmol/L. We divided patients into 4 groups, based on dialysate Ca and also on the hours per week of dialysis, <40 (1.5 mmol/L, n=29 and 1.75 mmol/L, n=8) or > or =40 (n=4 and 7). We compared predialysis and postdialysis serum markers, time-averaged over a 6-month period, and the administration of calcitriol and Ca-based phosphate binders between 1.5 and 1.75 mmol/L Ca dialysate groups. Baseline characteristics between all groups were similar, with a slightly longer, but nonsignificant, duration of NHD in both 1.75 mmol/L dialysate groups compared with 1.5 mmol/L. The mean predialysis Ca, phosphate, and Ca x P were similar between the 1.5 and 1.75 mmol/L groups, regardless of NHD hr/week. Postdialysis Ca was significantly greater, with 1.75 vs. 1.5 mmol/L in those dialyzing <40 hr/week (2.64+/-0.19 vs. 2.50+/-0.12 mmol/L, p=0.046), but postdialysis Ca x P were similar (2.25+/-0.44 vs. 2.16+/-0.29 mmol(2)/L(2), p=0.60). Parathyroid hormone was also lower with 1.75 vs. 1.5 mmol/L baths in the <40 hr/week groups (31.99+/-26.99 vs. 14.47+/-16.36 pmol/L, p=0.03), although this difference was not seen in those undertaking NHD > or =40 hr/week. Hemoglobin, ALP, and albumin were all similar between groups. There was also no difference in vitamin D requirement when using 1.75 mmol/L compared with the 1.5 mmol/L dialysate. Multivariate analysis to determine independent predictors of postdialysis serum Ca showed a statistically significant positive association with predialysis Ca, dialysate Ca, and total NHD hr/week. An elevated dialysate Ca concentration is required in NHD to prevent osteopenia but differences in serum markers of mineral metabolism between 1.5 and 1.75 mmol/L Ca dialysate in NHD in our study were few. This was similar for patients undertaking NHD <40 or > or =40 hr/week, although differences in the frequency of NHD may also be as important as dialysate Ca with regard to serum Ca levels. With concerns that prolonged higher Ca levels contribute to increased cardiovascular mortality, the optimal Ca dialysate bath is still unknown and further studies addressing bone metabolism with larger NHD numbers are required.     

Marked improvement in bone metabolism parameters after increasing the dialysate calcium concentration from 2.5 to 3 mEq/L in nonhypercalcemic hemodialysis patients

The optimal dialysate calcium (Ca) concentration for hemodialysis (HD) patients is set at 2.5 mEq/L according to Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines. This recommendation is opinion-based and could negatively affect secondary hyperparathyroidism. Studies have suggested that a dialysate Ca of 3.0 mEq/L is a compromise between bone protection and cardiovascular risk. The aim of our study was to investigate the effect on bone metabolism parameters after increasing the dialysate Ca concentration from 2.5 to 3.0 mEq/L. The dialysate Ca concentration in our patients was increased from 2.5 to 3.0 mEq/L. Patients with hypercalcemia, normal-high Ca levels with a high Ca-Phosphorus product (Ca x P), excessively suppressed parathyroid hormone (PTH), or a past medical history of calciphylaxis were excluded. Twenty-two patients were studied over 20 weeks. Parathyroid hormone levels decreased significantly (442 +/- 254 vs. 255 +/- 226 pg/mL; p=0.000), without significant changes in serum Ca, P, and Ca x P levels at any sampling point. Better control of secondary hyperparathyroidism allowed us to decrease the paracalcitol dosage in 6 of the 12 patients who had been treated with this drug at the beginning of the study. Other potential factors involved in PTH secretion were not modified. A significant improvement in the rate of patients with 3 or more K-DOQI parameters within the target ranges (8 [36%] vs. 12 [55%]; p=0.026) was observed. In the absence of hypercalcemia or excessively suppressed PTH, an increase from 2.5 mEq to 3.0 mEq/L in dialysate Ca concentration resulted in better control of secondary hyperparathyroidism without affecting Ca, P, and Ca x P levels, thus enabling us to reduce the dosage of vitamin D metabolites.     

The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized‐controlled trial

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized‐controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24–0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty‐one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium‐phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long‐term cardiovascular and bone‐related outcomes requires further investigation.     

Long-term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: A pilot study

Observational data suggest that elevated magnesium levels in dialysis patients may prevent vascular calcification and in vitro magnesium can prevent hydroxyapatite crystal growth. However, the effects of magnesium on vascular calcification and bone mineral density have not been studied prospectively. Seven chronic hemodialysis patients participated in this open label, prospective pilot study to evaluate the effects of a magnesium-based phosphate binder on coronary artery calcification (CAC) scores and vertebral bone mineral density (V-BMD) in patients with baseline CAC scores >30. Magnesium carbonate/calcium carbonate (elemental Mg: 86 mg/elemental Ca 100 mg) was administered as the principal phosphate binder for a period of 18 months and changes in CAC and V-BMD were measured at baseline, 6, 12, and 18 months. Serum magnesium levels averaged 2.2±0.4 mEq/L (range: 1.3–3.9 mEq/L). Phosphorus levels (4.5±0.6 mg/dL) were well controlled throughout the 18 months study. Electron beam computed tomography results demonstrated a small not statically significant increase in absolute CAC scores, no significant change in median percent change, and a small none significant change in V-BMD. Magnesium may have a favorable effect on CAC. The long-term effect on bone mineral density remains unclear. Larger studies are needed to confirm these findings.     

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.     

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 and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low‐flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start‐to‐end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca‐phosphate (P)‐parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. “Severe” secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8–2.1 m²), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca‐P‐PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start‐to‐end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in “severe” secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on “low‐flow” daily home dialysis, in “severe” secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques.     

Effect of needle orientation during arteriovenous access puncture on needed compression time after hemodialysis: A randomized controlled trial

Background

There are two techniques for puncturing an arteriovenous fistula: one where the needle is inserted bevel up and then rotated to a bevel down position, and another where the needle is inserted bevel down. The aim of this study was to compare these two methods of needle insertion on minimum compression time required for hemostasis after needle removal.

Methods

This was a prospective, randomized, cross-over, blinded, single-center, routine care study. Each patient's average post-dialysis puncture site compression time was determined during a 2-week baseline period while using bevel-up access puncture. Subsequently, minimum post-dialysis puncture-site compression time was determined during each of two sequential follow-up periods, during which fistula puncture was done with needles inserted bevel up or down, respectively. The order of treatments (bevel up or bevel down insertion) was randomized. During each follow-up period, the minimum compression time necessary to avoid bleeding on needle removal was determined by progressively shortening the compression time. Puncture-associated pain was also assessed as prepump and venous pressures and ability to achieve desired blood flow rate during the dialysis session.

Results

Forty-two patients were recruited. The baseline compression time after needle removal averaged 9.99 ± 2.7 min During the intervention periods, the minimum compression time was on average 10.8 min (9.23–12.4) when the access needles had been inserted bevel down versus 11.1 min (9.61–12.5) when the access needles had been inserted bevel up (p = 0.72). There was no difference in puncture-associated pain between the two insertion techniques, and no difference in prepump or venous pressures or ability to achieve the desired blood flow rate during the dialysis session.

Conclusion

Bevel-up and bevel-down needle orientation during arteriovenous fistula puncture are equivalent techniques in terms of achieving hemostasis on needle removal, and puncture-associated pain.     

Febuxostat improves endothelial function in hemodialysis patients with hyperuricemia: A randomized controlled study

Endothelial dysfunction is often found in both hyperuricemia and hemodialysis patients. Recent studies have shown that treating hyperuricemia with allopurinol improves endothelial dysfunction. This study is performed to assess the effect of febuxostat on endothelial dysfunction in hemodialysis patients with hyperuricemia. We randomly assigned 53 hemodialysis patients with hyperuricemia to a febuxostat (10 mg daily) group and a control group and measured flow‐mediated dilation, serum uric acid (UA) levels, systolic and diastolic blood pressure, malondialdehyde‐modified low‐density lipoprotein (MDA‐LDL), and highly sensitive C‐reactive protein (hsCRP) at baseline and at the end of a 4‐week study period. Flow‐mediated dilation increased from 5.3% ± 2.4% to 8.9% ± 3.6% in the febuxostat group but did not change significantly in the control group. Treatment with febuxostat resulted in a significant decrease in serum UA level and a significant decrease in MDA‐LDL compared with baseline, but no significant difference was observed in hsCRP level or blood pressure. No significant differences were observed in the control group. Febuxostat improved endothelial dysfunction and reduced serum UA levels and oxidative stress in hemodialysis patients with hyperuricemia.     

Coenzyme Q10 supplementation and diastolic heart functions in hemodialysis patients: A randomized double‐blind placebo‐controlled trial

Coenzyme Q10 (CoQ10) supplementation has been shown to improve diastolic heart function in various patient cohorts. Systolic and diastolic dysfunctions are common in patients with end‐stage renal disease. Favorable effects of CoQ10 on cardiac functions are yet to be seen in hemodialysis patients. We aimed to evaluate effect of CoQ10 supplementation on diastolic function in a cohort of maintenance hemodialysis patients. This was a prospective, double‐blind, placebo‐controlled, crossover study in which all patients received placebo and oral CoQ10 200 mg/d during the 8 weeks in each phase, with a 4‐week washout period. Participants underwent conventional and tissue Doppler echocardiography before and after each study phase. Parameters characterizing left ventricle diastolic function and other standard echocardiographic measurements were recorded. Twenty‐eight patients were randomized, but 22 patients completed study protocol. Intraventricular septum (IVS) thickness and left ventricle mass were significantly decreased in CoQ10 group (P = 0.03 and P = 0.01, respectively). Myocardial peak systolic and early diastolic velocities derived from IVS were significantly increased (P = 0.048 and P = 0.04, respectively). Isovolumetric relaxation time and E/Em ratio calculated for IVS also significantly reduced in CoQ10 group (p = 0.02 and p = 0.04, respectively). There was no significant difference in any of the studied echocardiographic parameters in placebo group. The results of this study showed that CoQ10 supplementation did not significantly improved diastolic heart functions compared with placebo in maintenance hemodialysis patients.     

Low dose heparin lock (1000 U/mL) maintains tunnelled hemodialysis catheter patency when compared with high dose heparin (5000 U/mL): A randomised controlled trial

Introduction Heparin is commonly used after hemodialysis treatments as a locking solution to prevent catheter thrombosis. The comparative efficacy and safety of different heparin concentrations to maintain catheter patency has been previously reported in retrospective studies. We conducted a prospective, randomised, controlled study of 1000 U/mL heparin (low dose) versus 5000 U/mL heparin (high dose) locking solution to maintain patency of tunnelled catheters. Methods One hundred patients receiving chronic, unit‐based hemodialysis with newly placed tunnelled hemodialysis catheters (less than 1 week) were randomly assigned to either a low dose (n = 48) or high dose heparin (n=52). The primary intention‐to‐treat analysis examined time to malfunction in both groups over a 90 day period. A secondary analysis compared baseline patient characteristics in relation to catheter malfunction. Findings Overall rate of catheter patency loss was 32% of catheters by 90 days. There was no significant difference in time to malfunction of catheters locked with low dose or high dose heparin (P = 0.5770). Time to catheter malfunction was not associated with diabetic, hypertensive or smoking status. There was no difference in mean delivered blood flow rate, venous and arterial pressure, and dialysis adequacy between low dose and high dose groups. No patient suffered a hemorrhagic complication requiring hospitalisation during the study period. Discussion Low dose heparin is adequate to maintain tunnelled hemodialysis catheter patency when compared with high dose heparin. The study also suggests that there is no relationship between catheter malfunction and diabetic, hypertensive or smoking status.     

Effect of serum FGF‐23, MGP and fetuin‐A on calcium‐phosphate metabolism in maintenance hemodialysis patients

This study was aimed to explore the role of serum fibroblast growth factor (FGF)‐23, matrix Gla protein (MGP) and fetuin‐A in the calcium‐phosphate metabolism and their predicting value in coronary artery calcification in maintenance hemodialysis (MHD) patients. This study included 64 patients who receive hemodialysis in our hospital. The serum FGF‐23, MGP and fetuin‐A were analyzed by enzyme‐linked immunosorbent assay (ELlSA). Coronary artery calcification score (CACS) was evaluated by coronary artery computed tomography scan. The 64 patients (30 males, 34 females, 60.6 ± 11.3 years of age) received an average dialysis vintage of 6.88 ± 2.94 years. We divided the CACS into three levels, and 13 (20.31%), 16 (25%), and 35 (54.69%) exhibited a CACS of 0–100, 100–400, and >400, respectively. Dialysis vintage, serum FGF‐23, fetuin‐A, phosphorus and high‐density lipoprotein‐C levels were identified as independent variables of CACS by stepwise multiple regression analysis. The area under receiver operating characteristic curve indicated that serum FGF‐23 and fetuin‐A were useful for identifying CAC in MHD patients. The cut‐off value corresponding to the highest Youden's index was serum FGF‐23 ≥ 256 pg/mL and fetuin‐A ≤ 85 μg/mL, which was defined as the optimal predictors of CAC. Different combinations of serum FGF‐23 and fetuin‐A in parallel or in series effectively boosted the identification of CAC. The incidence of CAC is high in MHD patients. Serum FGF‐23 and fetuin‐A levels are closely correlated with CAC.