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.     

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.     

Long‐term effects of angiotensin II blockade with irbesartan on inflammatory markers in hemodialysis patients: A randomized double blind placebo controlled trial (SAFIR study)

Introduction: Low‐grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti‐inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients. Methods: Adult HD patients were randomized for double‐blind treatment with the ARB irbesartan 150–300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C‐reactive protein (hsCRP), interleukin (IL)?1β, IL‐6, IL‐8, IL‐18, and transforming growth factor‐β (TGF‐β) were measured using Luminex and enzyme‐linked immunosorbent assay (ELISA) technology. Findings: Eighty‐two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2–23.4)/2.7(0.2–29.6) μg/mL; IL‐1β 1.1(0.0–45.9)/1.1(0.0‐7.2) pg/mL; IL‐6 10(1–90)/12(1–84) pg/mL; IL‐8 31(9–134)/34(5–192) pg/mL; IL‐18 364(188–1343)/377(213–832) pg/mL; TGF‐β 3.2(0.8–13.9)/3.6(1.3–3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL‐6, IL‐8, and TGF‐β between placebo and ARB‐treated patients during the study period, and hsCRP, IL‐6, IL‐8, and TGF‐β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL‐1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL‐18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB‐treated (P ≥ 0.51 in tests for parallel curves and equal levels). Discussion: Inflammatory biomarkers were neither acutely, nor in the long‐term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti‐inflammatory effects.     

Interventions to improve hemodialysis adherence: A systematic review of randomized‐controlled trials

Over 485,000 people in the United States have chronic kidney disease, a progressive kidney disease that may lead to hemodialysis. Hemodialysis involves a complex regimen of treatment, medication, fluid, and diet management. In 2005, over 312,000 patients were undergoing hemodialysis in the United States. Dialysis nonadherence rates range from 8.5% to 86%. Dialysis therapy treatment nonadherence, including treatment, medication, fluid, and diet nonadherence, significantly increases the risk of morbidity and mortality. The purpose of this paper is to systematically review randomized‐controlled trial intervention studies designed to increase treatment, medication, fluid, and diet adherence in adult hemodialysis patients. A search of Cumulative Index of Nursing and Allied Health Literature (CINAHL) (1982 to May 2008), MEDLINE (1950 to May 2008), PsycINFO (1806 to May 2008), and all Evidence‐Based Medicine (EBM) Reviews (Cochran DSR, ACP Journal Club, DARE, and CCTR) was conducted to identify randomized‐controlled studies that tested the efficacy of interventions to improve adherence in adult hemodialysis patients. Eight randomized‐controlled trials met criteria for inclusion. Six of the 8 studies found statistically significant improvement in adherence with the intervention. Of these 6 intervention studies, all studies had a cognitive component, with 3 studies utilizing cognitive/behavioral intervention strategies. Based on this systematic review, interventions utilizing a cognitive or cognitive/behavioral component appear to show the most promise for future study.     

Weekly high‐dose ergocalciferol to correct vitamin D deficiency/insufficiency in hemodialysis patients: A pilot trial

Controversy exists on which vitamin D (D2 or D3) and which dosage scheme is the best to obtain and maintain adequate 25 OH D levels in dialysis patients safely. We tried to determine whether high‐dose vitamin D2 supplementation could obtain optimal vitamin D status without inducing hypercalcemia. We studied 82 patients on dialysis not taking active vitamin D therapy and supplemented them with oral vitamin D2 72,000 IU/week for 12 weeks followed by 24,000 IU/week as maintenance therapy during 36 weeks. By week 12, serum 25(OH)D increased from 15.2 ± 5.4 to 42.5 ± 13.2 ng/mL (P < 0.01) at week 12 and remained optimal (34.7 ± 12.0); 84.8% of the patients reached values ≥30 ng/mL. iPTH and alkaline phosphatase did not change at 48 weeks compared with baseline, but bone alkaline phosphatase decreased significantly (54.3 ± 46.0 to 44.3 ± 25.0; P = 0.02). Uncorrected serum Ca increased significantly at the end of follow‐up (9.03 ± 0.42 to 9.14 ± 0.62; P = 0.04); hypercalcemia was presented in two patients in the first control visit (week 12), in one patient in the second control (week 30), and in one patient in the third control (week 48). In 222 serum calcium determinations during follow‐up, hypercalcemia was observed in only 1.8% of cases. This vitamin D2 oral regimen with initial high doses was safe and sufficient to obtain and maintain optimal serum 25(OH)D concentrations and prevent vitamin D insufficiency in chronic kidney disease patients on dialysis.     

Effects of thrice-weekly in-center nocturnal vs. conventional hemodialysis on integrated backscatter of myocardial tissue

Ultrasonic tissue characterization with integrated backscatter (IBS) offers a promising method for the noninvasive assessment of myocardial fibrosis and contractile performance. The aim of this study was to investigate the effect of thrice-weekly in-center nocturnal hemodialysis (INHD) and conventional hemodialysis (CHD) on myocardial fibrosis and left ventricular function in end-stage renal disease patients. Thirty-two INHD and 58 matched CHD patients were enrolled; baseline and 12-month measures of blood pressure (BP), serum calcium and phosphorus, echocardiographic left ventricular mass index (LVMI) and left ventricular function, the myocardial calibrated IBS (C-IBS), and systodiastolic cyclical variations in IBS (CV-IBS) were collected. The baseline characteristics were similar between groups, except that serum phosphorus and calcium × phosphorus were higher in the INHD group. At 12-month follow-up, there was a significant decrease in the mean C-IBS (-20.2 ± 3.7 to -28.1 ± 4.0 dB, P<0.01) and a significant increase in CV-IBS (5.0 ± 1.5 to 7.1 ± 1.6 dB, P<0.01) in INHD patients. Multivariate analysis showed that the mean C-IBS was positively related to SBP, DBP, LVMI, serum phosphorus, and left atrial volume index and inversely related to midwall fractional shortening, transmitral E/A ratio, and E(m) . The mean CV-IBS was positively correlated with left ventricular midwall fractional shortening, E/A ratio, E(m) and inversely correlated with SBP, DBP, LVMI, serum phosphorus, E/E(m) , and left atrial volume index. There was no significant change in the mean C-IBS, mean CV-IBS, and LVMI in the CHD group. Compared with CHD, INHD improves myocardial fibrosis and left ventricular function, and control of serum phosphorus is associated with the improvement of myocardial fibrosis. Improvement of myocardial fibrosis contributes to the reduction of left ventricle hypertrophy.     

Treating mineral metabolism disorders in patients undergoing long hemodialysis: A search for an optimal strategy

In hemodialysis (HD) patients, mineral metabolism (MM) disorders have been associated with an increased mortality rate. We report the evolution of MM parameters in a stable HD population undergoing long hemodialysis by performing an annual cross-sectional analysis for every year from 1994 to 2008. The therapeutic strategy has changed: the dialysate calcium concentration has decreased from a mean of 1.7 ± 0.1 to 1.5 ± 0.07 mmol/L and has been adapted to parathyroid hormone serum levels (from 1 to 1.75 mmol/L). The use of calcium-based and aluminum-based phosphate binders has decreased and they have been replaced by sevelamer; alfacalcidol has partly been replaced by native vitamin D. The percentage of patients with a parathyroid hormone serum level between 150 and 300 pg/mL has increased from 9% to 67% (P<0.001); the percentage of patients with phosphataemia between 1.15 and 1.78 mmol/L has increased from 39% to 84% (P<0.001). The percentage of those with albumin-corrected calcemia between 2.1 and 2.37 mmol/L has increased from 29% to 61% (P<0.001), and that of patients with a calcium-phosphorous product (Ca × P) level >4.4 mmol/L decreased from 8.8% to 2% (P=0.02). Although patients undergo long and intensive HD treatment, MM disorders are common. However, an appropriate strategy, mostly consisting of native vitamin D supplementation, progressive replacement of calcium-based phosphate binders with non–calcium-based ones, and individualization of dialysis session duration and dialysate calcium concentration, would result in a drastic improvement.     

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.     

Management of hypophosphatemia in nocturnal hemodialysis with phosphate-containing enema: a technical study

Hypophosphatemia is observed in patients undergoing nocturnal hemodialysis. Phosphate is commonly added to the dialysate acid bath, but systematic evaluation of the safety and reliability of this strategy is lacking. The objectives of this study were 4‐fold. First, we determined whether predictable final dialysate phosphate concentrations could be achieved by adding varying amounts of Fleet^® enema. Second, we assessed the stability of calcium (Ca) and phosphate dialysate levels under simulated nocturnal hemodialysis conditions. Third, we assessed for Ca‐phosphate precipitate. Finally, we evaluated whether dialysate containing Fleet^® enema met the current sterility standards. We added serial aliquots of enema to 4.5 L of dialysate acid concentrate and proportioned the solution on Gambro and Althin/Baxter dialysis machines for up to 8 hours. We measured dialysate phosphate, Ca, pH, and bicarbonate concentrations at baseline, and after simulated dialysis at 4 and 8 hours. We evaluated for precipitation visually and by assessing optical density at 620 nm. We used inoculation of agar to detect bacteria and Pyrotell reaction for endotoxin. For every 30 mL of Fleet^® (1.38 mmol/mL of phosphate) enema added, the dialysate phosphate concentration increased by 0.2 mmol/L. There were no significant changes in dialysate phosphate, Ca, pH, and bicarbonate concentrations over 8 hours. No precipitate was observed in the dialysate by optical density measures at 620 nm for additions of up to 90 mL of enema. Bacterial and endotoxin testing met sterility standards. The addition of Fleet^® enema to dialysate increases phosphate concentration in a predictable manner, and no safety problems were observed in our in vitro studies.     

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.     

Long‐term effects of daily hemodialysis on vascular access outcomes: A prospective controlled study

Daily hemodialysis has been associated with surrogate markers of improved survival among hemodialysis patients. A potential disadvantage of daily hemodialysis is that frequent vascular access cannulations may affect long‐term vascular access patency. The study design was a 4‐year, nonrandomized, contemporary control, prospective study of 77 subjects in either 3‐h daily hemodialysis (six 3‐h dialysis treatments weekly; n = 26) or conventional dialysis (three 4‐h dialysis treatments weekly; n = 51). Outcomes of interest were vascular access procedures (fistulagram, thrombectomy and access revision). Total access procedures (fistulagram, thrombectomy and access revision) were 543.2 (95% confidence interval [CI]: 432.9, 673.0) per 1000 person‐years in the conventional dialysis group vs. 400.8 (95% CI: 270.2, 572.4) per 1000 person‐years in the daily hemodialysis dialysis group (incidence rate ratio = 0.74 with 95% CI: from 0.40 to 1.36, P = 0.33), after adjusting for age, gender, diabetes status, serum phosphorus, hemoglobin level and erythropoietin dose, there was no significant differences in incidence rate of total access procedures (P‐value > 0.05). There was no difference in time to first access revision between the daily dialysis and the conventional dialysis groups after adjustment for covariates (hazard ratio = 0.99 95% CI: 0.42, 2.36, P = 0.96). Daily hemodialysis is not associated with increased vascular access complications, or increased vascular access failure rates.     

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.     

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.     

Assessing the contact‐activation of coagulation during hemodialysis with three different polysulfone filters: A prospective randomized cross‐over trial

Introduction: During hemodialysis (HD) the interaction of the blood with the dialyzer triggers both an inflammatory reaction and an activation of the coagulation cascade. An accepted parameter to quantify the extent of coagulation activation during HD is not available. This study aims to evaluate its amplitude, comparing dialyzers made of different polysulfone polymers, by measuring D‐dimers in the filter‐rinsing fluids (Frf) and to test whether Frf D‐dimers are suitable candidate markers to assess contact coagulation activation during HD. Methods: In a prospective, cross‐over study 41 hemodialysis patients were randomly allocated to nine HD sessions with three types of polysulfone membranes: Filter A: Poliflux®RevaclearMAX; Filter B: Helixone®Fx80, Filter C: Polyflux®H210. Findings: A total of 117 HD sessions were studied. The mean (SD) filter (Frf) D‐dimers were 0.19 µg/L (0.56) for Filter A; 0.66 µg/L (2.81) for Filter B; 0.33 µg/L (1.13) for Filter C. Significant differences were found: A vs. B (P < 0.01), A vs. C (P = 0.01); B vs. C not significant. A large between‐patient variability of D‐dimer filter levels was found. D‐Dimers in blood showed a similar trend but differences were not significant. Discussion: The contact activation of coagulation during HD may also vary among filters made up with similar polysulfones. D‐dimer in the filter rinsing fluid but not in the blood can be considered a candidate marker for the evaluation of thrombogenicity during HD. Further studies are needed to elucidate the mechanism(s) and to confirm the usefulness of filter rinsing fluid D‐Dimers as a clotting activation marker during HD.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

Anti‐inflammatory effects of linagliptin in hemodialysis patients with diabetes

Inflammation and glycemic control are important prognosis‐related factors for hemodialysis (HD) patients; moreover, inflammation affects insulin secretion. Here, we evaluated the anti‐inflammatory effects of monotherapy with linagliptin—a dipeptidase‐4 inhibitor—in HD patients with type 2 diabetes. We examined 21 diabetic HD patients who were not receiving oral diabetes drugs or insulin therapy and with poor glycemic control (glycated albumin [GA] level, >20%). Linagliptin (5 mg) was administered to the patients daily. The levels of prostaglandin E2 (PGE2), interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein, GA, blood glucose, and active glucagon‐like peptide‐1 were determined before and 6 months after treatment. Body weight and serum levels of albumin, hemoglobin, total cholesterol, and low‐density lipoprotein cholesterol were also recorded before and after treatment. The levels of PGE2 and GA were significantly decreased 1 month after starting linagliptin therapy, whereas the IL‐6 levels were significantly decreased 6 months after starting linagliptin therapy. After 6 months of treatment, the PGE2 levels decreased from 188 ± 50 ng/mL to 26 ± 5 ng/mL; IL‐6 levels, from 1.5 ± 0.4 pg/mL to 0.6 ± 0.1 pg/mL; and GA levels, from 21.3% ± 0.6% to 18.0% ± 0.6%. Glucagon‐like peptide‐1 levels increased 2.5‐fold during the treatment. Over the 6‐month treatment period, body weight and levels of high‐sensitivity C‐reactive protein, blood glucose, albumin, hemoglobin, and cholesterol did not change; none of the patients exhibited hypoglycemia. The anti‐inflammatory effects of linagliptin monotherapy indicate that it may serve as a useful glucose control strategy for HD patients with diabetes.     

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.