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.     

Perihospitalization patterns of hemoglobin levels and erythropoiesis‐stimulating agent doses in US hemodialysis patients, 1998–2009

Anemia management in hemodialysis patients is of primary importance for clinicians and dialysis providers. Through a retrospective claims analysis, we studied prevalent US hemodialysis patients 1998–2009, and examined patterns of hemoglobin levels and erythropoiesis‐stimulating agent (ESA, epoetin [EPO], and darbepoetin [DPO] ) doses surrounding hospitalization events. Medicare outpatient claims were used to determine monthly ESA doses and associated hemoglobin levels. ESA dose trajectories were defined with repeated measures models incorporating an autoregressive covariance matrix that compared subsequent measurements with the index month of hospitalization, with variance component covariance matrices chosen for pair‐wise comparisons. Regarding prehospitalization hemoglobin levels, a biphasic pattern occurred in both the EPO (1998–2009, n = 161,242) and DPO (2004–2009, n = 4391) populations; levels rose from 1998 to 2004, fell thereafter in the EPO population, and fell after 2006 or 2007 in the DPO population. In the EPO population, the proportions of patients with hemoglobin less than 10 g/dL were 30.1% in 1998, 14.5% in 2004, and 28.3% in 2009; corresponding values for the DPO population were 21.0% in 2004 and 31.6% in 2009. While some degree of year‐to‐year variability occurred, EPO dose trends were less pronounced, with an apparent peak in 2004 followed by a modest decline; trends were similar for DPO. Trends in EPO dose trajectories did not completely parallel those for hemoglobin level; while EPO doses increased yearly up to 2004, doses stabilized, but did not materially decrease after 2004. No definite annual trends for DPO dose trajectories were apparent.     

Erythrocyte folate status and serum iron levels in patients undergoing hemodialysis

The present study was aimed to evaluate erythrocyte folate and the iron levels in diabetes and hypertension patients treated with/without hemodialysis. The effects of erythropoietin and iron treatment as well as vitamin supplementation on measured parameters were considered. The 67 controls consisted of healthy subjects (n = 22), hypertensive subjects (n = 22), and diabetic subjects (n = 23) without any renal disorder. According to primary renal disorders, the patients undergoing hemodialysis (n = 68) were classified into four groups as diabetic nephropathy, hypertensive nephropathy, reflux nephropathy or interstitial nephritis, and renal insufficiency depending on other causative factors. The mean value of erythrocyte folate levels of all patients undergoing hemodialysis was higher than the healthy control group (P < 0.05). Erythrocyte folate levels in hypertensive and diabetic nephropathy patients were higher than their own hypertensive or diabetic controls and also healthy controls (both, P < 0.05). Serum iron levels of all subgroups in hemodialysis patients were found to be similar with healthy controls (all, P > 0.05). The only significance observed within the subgroups was between diabetic controls and diabetic nephropathy patients (P < 0.05). None of the treatment or supplementation of erythropoietin, iron and vitamin affected erythrocyte folate levels (all, P > 0.05). The increase in erythrocyte folate status of patients with end stage renal diseases might be the result of sum or individual effects of causative factors such as renal pathology, compensation mechanism against renal anemia, or routine folate supplementation.     

The level of C‐reactive protein in chronic hemodialysis patients: A comparative study between patients with noninfected catheters and arteriovenous fistula in two large Gulf hemodialysis centers

Hemodialysis (HD) patients have greater morbidity and mortality when they have a central venous catheter (CVC) rather than an arteriovenous fistula (AVF) access. Inflammation associated with dialysis catheter use and resultant higher C‐reactive protein (CRP) levels could have an independent adverse effect on patient outcomes. In this prospective study, we investigated whether HD catheters induce inflammation independent of infection. We compared the mean levels of the inflammatory marker (CRP) in 67 patients on maintenance HD using noninfected catheters with 86 HD patients using AVFs at Prince Salman Center for Kidney Diseases, Saudi Arabia (KSA), and Jahra Hospital, Kuwait, who met our inclusion criteria. C‐reactive protein levels were measured every 2 months over a period of 6 months using immunoturbidimetric assay. One hundred fifty‐three patients on maintenance HD for more than 6 months were included in the study, with mean age of 52.19 ± 16.06 years; 66% were males and 34% were females. Serial levels of mean CRP were statistically and significantly higher in group with noninfected catheters (1.33, 1.24, and 1.10 mg/dL) compared to those with AVFs (0.65, 0.59, and 0.68 mg/dL) with P value of 0.000. In our study, we found no relation between CRP level and age, sex, hemoglobin, albumin, calcium, phosphorus, and iPTH level in both groups. Hemodialysis patients with a catheter have a heightened state of inflammation independent of infection, and thus our study supports the avoidance of catheters and a timely conversion to AVFs with catheter removal.     

Effect of incident nocturnal home hemodialysis versus incident continuous ambulatory peritoneal dialysis on employment rate,clinical, and laboratory outcomes: A 1‐year retrospective observation study

Introduction: While studies demonstrated favorable outcomes of nocturnal home hemodialysis (NHHD), direct comparison on employment rate, clinical and laboratory outcomes between the NHHD and continuous ambulatory peritoneal dialysis (CAPD) had not been previously performed. Methods: A 1‐year retrospective observation study was performed in 20 incidents alternate night NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic status, and Charlson comorbidity index matched, but not age due to our center's age limit for NHHD enrollment. The primary outcome was the difference in employment rate at 1 year. Secondary outcomes included differences in clinical parameters (weight, blood pressure, number of antihypertensive medication, dosage of phosphate binders, and erythropoietin stimulating agent) and laboratory parameters (residual renal function, mineral metabolic markers, hemoglobin). Findings: NHHD subjects were 5 years younger than CAPD patients, and they had higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age‐adjusted odds ratio for employment was 6.10 (95% confidence interval 1.77–20.99, P = 0.04). They consumed less aluminum‐based phosphate binder (0 vs. 1800 mg, P < 0.01), but showed no significant disparities in other clinical parameters. Residual renal function in both groups declined comparably, nonetheless NHHD group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium phosphate product (3.13 vs. 4.12 mmol²/L², P < 0.01), with similar hemoglobin levels. Discussion: NHHD appeared to offer higher employment rate, lower dosage of aluminum‐based phosphate binder and mineral metabolic markers at 1 year compared with CAPD in Hong Kong.     

FGF‐23 and cognitive performance in hemodialysis patients

Although cognitive impairment is common in hemodialysis patients, the etiology of and risk factors for its development remain unclear. Fibroblast growth factor 23 (FGF‐23) levels are elevated in hemodialysis patients and are associated with increased mortality and left ventricular hypertrophy. Despite FGF‐23 being found within the brain, there are no prior studies assessing whether FGF‐23 levels are associated with cognitive performance. We measured FGF‐23 in 263 prevalent hemodialysis patients in whom comprehensive neurocognitive testing was also performed. The cross‐sectional association between patient characteristics and FGF‐23 levels was assessed. Principal factor analysis was used to derive two factors from cognitive test scores, representing memory and executive function, which carried a mean of 0 and a standard deviation of 1. Multivariable linear regression adjusting for age, sex, education status, and other relevant covariates was used to explore the relationship between FGF‐23 and each factor. Mean age was 63 years, 46% were women and 22% were African American. The median FGF‐23 level was 3098 RU/mL. Younger age, lower prevalence of diabetes, longer dialysis vintage, and higher calcium and phosphorus were independently associated with higher FGF‐23 levels. Higher FGF‐23 was independently associated with a lower memory score (per doubling of FGF‐23, β = ?0.08 SD [95% confidence interval, CI: ?0.16, ?0.01]) and highest quartile vs. lowest quartile (β = ?0.42 SD [?0.82, ?0.02]). There was no definite association of FGF 23 with executive function when examined as a continuous variable (β = ?0.03 SD [?0.10, 0.04]); however, there was a trend in the quartile analysis (β = ?0.28 SD [?0.63, 0.07], P = 0.13, for 4th quartile vs. 1st quartile). FGF‐23 was associated with worse performance on a composite memory score, including after adjustment for measures of mineral metabolism. High FGF‐23 levels in hemodialysis patients may contribute to cognitive impairment.     

Infective spondylodiscitis in patients on high‐flux hemodialysis and on‐line hemodiafiltration

Infective spondylodiscitis (ISD) is a rare but potentially devastating condition in hemodialysis (HD) patients. Reports are limited especially in patients receiving high‐flux HD and hemodiafiltration (HDF). In a retrospective analysis, 13 patients on our maintenance high‐flux HD/HDF program were identified as having has infective spondylodiscitis over a 10‐year period (1997–2006), an incidence of approximately 1 episode every 215 patient‐years. The incidence was around 3 times higher in patients dialyzing with tunnelled central venous catheters (TCVC) than in those with arteriovenous fistulae. Affected patients were elderly (mean age 70 years) and had multiple comorbidities. Access problems, particularly TCVC infection, were common in the months preceding it's onset. Tunnelled central venous catheter removal during these episodes did not necessarily prevent it. Diagnosis was based on a history of back pain, raised C‐reactive protein, positive blood cultures, and characteristic magnetic resonance findings. Many patients were apyrexial and had normal white cell counts. In our patients on high‐flux HD/hemodiafiltration, its incidence appears comparable to that in conventional HD settings. No patients had infection with waterborne organisms. Blood cultures were positive in 77%. Gram‐positive organisms predominated, particularly Staphylococcus aureus. The major route of infection was hematogenous, with the most likely source the venous access. All received antibiotics for 6 to 12 weeks or until death. Only 2 patients underwent surgical drainage. Mortality was high (46%) and predicted by the development of complications, and by pre‐existing cardiovascular comorbidity. Prevention, using strategies to reduce the prevalence of bacteremia, including limiting the use of TCVC, should be an overriding aim.     

Use of 3‐hour daily hemodialysis and paricalcitol in patients with severe secondary hyperparathyroidism: A case series

Patients with poor metabolic control receiving conventional hemodialysis are at risk for developing severe secondary hyperparathyroidism. We postulated that daily hemodialysis may be effective at controlling parathyroid hormone (PTH) in the setting of severe secondary hyperparathyroidism by improving the control of hyperphosphatemia and allowing increased use of vitamin D analogs. We present 5 patients with severe secondary hyperparathyroidism (median iPTH=1783 pg/mL) who were treated with 3‐hour daily hemodialysis (3 hours × 6 times a week). Daily hemodialysis, at 1 year, was associated with a 70.4% reduction in median PTH (1783 pg/mL [interquartile range: 1321–1983]–472 pg/mL [334, 704], P<0.001). Additionally, there was an increase in paricalcitol dose from 0 mcg/d to 10.8 (2.00, 11.7) mcg/d, a 39% reduction in calcium × phosphorus product (80.3 ± 26.8–48.9 ± 14.0, P<0.01), a 52% reduction in serum phosphorus (9.90 ± 2.34–4.75 ± 0.79 mg/dL, P<0.0001), and a 17.6% increase in serum calcium (8.18 ± 2.04–9.62 ± 0.93 mg/dL, P<0.01). Three‐hour daily hemodialysis with the use of high‐dose paricalcitol is associated with improved control of severe secondary hyperparathyroidism.     

Hemodialysis decreases carotid‐brachial and carotid‐femoral pulse wave velocities: A 5‐year follow‐up study

Aortic stiffness is a prognostic parameter associated with patient mortality. Vascular access creation has been shown to have effects on arterial stiffness both in the aorta and in the upper limb arteries in chronically hemodialyzed patients (CHPs). However, no longitudinal studies have been conducted in order to characterize the evolution of arterial stiffness in CHPs. The aims of this work were (a) to measure baseline pulse wave velocity (PWV) in the carotid‐femoral and in right and left carotid‐brachial pathways in a cohort of CHP and (b) to conduct a 5‐year prospective study on the same cohort to determine possible time‐related differences. Pulse wave velocity was measured both in the carotid‐femoral and in the carotid‐brachial pathways, and clinical and biochemical parameters were collected in 25 CHPs, which were followed up after a 5‐year lapse. Right and left carotid‐brachial pathway PWV values showed significant decreases after the 5‐year follow‐up, independently of the presence of the vascular access (P < 0.001). Additionally, baseline carotid‐brachial PWV was significantly higher (P < 0.001) than values measured 5 years later for upper limbs with vascular access (11.97 ± 2.97 m/sec vs. 6.76 ± 1.48 m/sec, respectively) and without vascular access (12.25 ± 2.38 m/sec vs. 7.18 ± 1.88 m/sec, respectively). Similarly, PWV values in the carotid‐femoral pathway decreased significantly (P < 0.001) over the same period (13.27 ± 2.96 m/sec vs. 9.75 ± 2.99 m/sec, respectively). The 5‐year follow‐up of PWV showed significant decreases in both carotid‐brachial and carotid‐femoral pathways. The general changes in arterial stiffness could be related to the vascular access creation, hemodialysis therapy, and to the improvement of arterial pressure management.     

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.     

Survival and other clinical outcomes of maintenance hemodialysis patients in Taiwan: A 5‐year multicenter follow‐up study

The increasing aging and diabetes mellitus (DM) patients in dialysis population make the quality maintenance of dialysis an imperative issue. Recently, an increasing number of dialysis centers were run by private dialysis providers, many of which apply quality assurance programs and performance management systems to dialysis care. We studied patients in dialysis facilities in Taiwan run by a private chain to see clinical outcomes of centers operating under these systemic strategies. Hemodialysis patients from January 1, 2008 to December 31, 2012 in 25 dialysis facilities in Taiwan, which received the management and consultation from a dialysis service provider, NephroCare (NC), were included. Data pivotal to quality of dialysis were analyzed. During a 5‐year interval, 5161 hemodialysis patients were included. For volume control, the proportion of patients with weight gain ≥4.5% decreases from 41.7% to 30.2%. Mean Kt/V is 1.74 ± 0.28. Mean albumin level is 3.92 ± 0.38 g/dL. Patients with phosphate <5.5 mg/dL is up to 71.8%. The mean hemoglobin level is 10.70 ± 1.40 g/dL. More than 80% of patients have adequate iron status. Further, 73% of patients use native arteriovenous fistula. Hospitalization‐free survival rate was 56% at the fifth year. Patient survival rate at the fifth year was 66.4%. Overall clinical performances were maintained very stable in NC facilities from this temporal data analysis. The hospitalization and survival rate also compare favorably with those reported internationally. These results warrant further studies to justify the application of this kind of quality assurance programs and performance management systems in dialysis care.     

Post‐hemodialysis dosing of 1 vs. 2 g of ceftazidime in anuric end‐stage renal disease patients on low‐flux dialysis and its pharmacodynamic implications on clinical use

Ceftazidime is a cost‐effective antimicrobial against Gram‐negative pathogens associated with sepsis in end‐stage renal disease (ESRD) hemodialysis patients with potential for wider use with the advent of ceftazidime‐avibactam. Dosing ceftazidime post‐hemodialysis appears attractive and convenient, but limited in vivo data on pharmacodynamic efficacy (PE) attainment, defined as >70% of the interdialytic period drug concentrations exceed susceptible pathogens minimal inhibitory concentrations (MICs) (%TMIC), warrants further assessment. We therefore evaluated PE and tolerability of 1 against 2 g regime in anuric ESRD patients on low‐flux hemodialysis. Two doses of 1 or 2 g ceftazidime were administered post‐hemodialysis prior to 48‐ and 72‐hour interdialytic intervals in ESRD inpatients without active infections. Peak and trough concentrations (mg/L) were assayed using a validated liquid chromatography–tandem mass spectrometry method. Proportion of patients achieving PE for known pathogens with MICs ≤ 8 mg/L and adverse effects were assessed. Six (43%) and eight (57%) adult patients received 1 and 2 g dose, respectively. Median (25th–75th percentile), peak, 48‐ and 72‐hour trough ceftazidime concentrations were 78 (60–98) vs. 158 (128–196), 37 (23–37) vs. 49 (39–71), and 13 (12–20) vs. 26 (21–41) mg/L, respectively, resulting in 100% TMIC for both doses. One patient on the 1‐g dose experienced mild pruritus. Reliable and safe PE attainment over both 48‐ and 72‐hour interdialytic interval was achievable with 1 g of ceftazidime dosed post‐hemodialysis. The 2 g dose was equally effective and well tolerated but may not be necessary. These findings need validation in non‐anuric patients, high‐flux hemodialysis, and during avibactam co‐administration.