The effect of frequent hemodialysis on matrix metalloproteinases,their tissue inhibitors,and FGF23: Implications for blood pressure and left ventricular mass modification in the Frequent Hemodialysis Network trials

Background: Frequent hemodialysis modifies serum phosphorus, blood pressure, and left ventricular mass (LVM). We ascertained whether frequent hemodialysis is associated with specific changes in biomarker profile among patients enrolled in the frequent hemodialysis network (FHN) trials. Methods: This was a post hoc analysis of biomarkers among patients enrolled to the FHN trials. In particular, we hypothesized that frequent hemodialysis is associated with changes in a specific set of biomarkers which are linked with changes in blood pressure or LVM. Results: Among 332 randomized patients, 243 had biomarker data available. Of these, 124 patients were assigned to 3‐times‐a‐week hemodialysis (94 [Daily Trial] and 30 [Nocturnal Trial]) and 119 patients were assigned to 6‐times‐a‐week hemodialysis (87 [Daily Trial] and 32 [Nocturnal Trial]). Frequent hemodialysis lowered phosphate, blood pressures, LVM, log fibroblast growth factor (FGF)23, and tissue inhibitors of metalloproteinase (TIMP)—2 levels. The fall in phosphate was associated with changes in FGF23 (r = 0.48, P < 0.001) [Daily Trial] and (r = 0.55, P < 0.001) [Nocturnal Trial]) and tended to be associated with changes in systolic blood pressure (r = 0.18, P = 0.057) [Daily Trial] and (r = 0.31, P = 0.04) [Nocturnal Trial]. Within the Daily Trial, changes in MMP2 (r = 0.20, P = 0.034) were associated with changes in LVM. In the Nocturnal Trial, changes in TIMP‐1 (r = 0.37, P = 0.029) and MMP 9 (r = ?0.38, P = 0.01) were associated with LVM changes. MMP2 changes were associated with changes in systolic blood pressure. Conclusions: Reduction of serum phosphate by frequent hemodialysis may modulate FGF23 levels and systolic blood pressure. Markers of matrix turnover are associated with LVM changes. Frequent hemodialysis may affect pathological mediators of chronic kidney disease‐mineral bone‐metabolism disorder.     

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.     

Longitudinal associations of depressive symptoms and pain with quality of life in patients receiving chronic hemodialysis

Depressive symptoms and pain are common in patients on chronic hemodialysis (HD), yet their associations with quality of life (QOL) are not fully understood. We sought to characterize the longitudinal associations of these symptoms with QOL. As part of a trial comparing two symptom management strategies in patients receiving chronic HD, we assessed depressive symptoms using the Patient Health Questionnaire‐9 (PHQ‐9), and pain using the Short Form McGill Pain Questionnaire (SF‐MPQ) monthly over 24 months. We assessed health‐related QOL (HR‐QOL) quarterly using the Short Form 12 (SF‐12) and global QOL (G‐QOL) using a single‐item survey. We used random effects linear regression to analyze the independent associations of depressive symptoms and pain, scaled based on 5‐point increments in symptom scores, with HR‐QOL and G‐QOL. Overall, 286 patients completed 1417 PHQ‐9 and SF‐MPQ symptom assessments, 1361 SF‐12 assessments, and 1416 G‐QOL assessments. Depressive symptoms were independently and inversely associated with SF‐12 physical HR‐QOL scores (β = ?1.09; 95% confidence interval [CI]: ?1.69, ?0.50, P < 0.001); SF‐12 mental HR‐QOL scores (β = ?4.52; 95% CI: ?5.15, ?3.89, P < 0.001); and G‐QOL scores (β = ?0.64; 95%CI: ?0.79, ?0.49, P < 0.001). Pain was independently and inversely associated with SF‐12 physical HR‐QOL scores (β = ?0.99; 95% CI: ?1.30, ?0.68, P < 0.001) and G‐QOL scores (β = ?0.12; 95%CI: ?0.20, ?0.05, P = 0.002); but not with SF‐12 mental HR‐QOL scores (β = ?0.16; 95%CI: ?0.050, 0.17, P = 0.34). In patients receiving chronic HD, depressive symptoms and to a lesser extent pain, are independently associated with reduced HR‐QOL and G‐QOL. Interventions to alleviate these symptoms could potentially improve patients' HR‐QOL and G‐QOL.     

Echocardiographic epicardial adipose tissue measurements provide information about cardiovascular risk in hemodialysis patients

Epicardial adipose tissue (EAT) is a cardiovascular risk predictor in general population. However, its value has not been well validated in maintainance hemodialysis (MHD) patients. We aimed to assess associations of EAT with cardiovascular risk predictors in nondiabetic MHD patients. In this cross‐sectional study, we measured EAT thickness by transthoracic echocardiography in 50 MHD patients (45.8 ± 14.6 years of age, 37 male). Antropometric measurements, bioimpedance analysis, left ventricular (LV) mass, carotis intima media thickness, blood tests, homeostasis model assessment for insulin resistance (HOMA‐IR) and hemodialysis dose by single‐pool urea clearence index (spKt/V) were determined. The mean EAT thickness was 3.28 ± 1.04 mm. There were significant associations of EAT with body mass index (β = 0.590, P < 0.001), waist circumference (β = 0.572, P < 0.001), body fat mass (β = 0.562, P < 0.001), percentage of body fat mass (β = 0.408, P = 0.003), percentage of lean tissue mass (β = ?0.421, P = 0.002), LV mass (β = 0.426, P = 0.002), carotis intima media thickness (β = 0.289, P = 0.042), triglyceride/high‐density lipoprotein cholesterol ratio (β = 0.529, P < 0.001), 1/HOMA‐IR (β = ?0.386, P = 0.006), and spKt/V (β = ?0.311, P = 0.028). No association was exhibited with visfatin C, high‐sensitivity C‐reactive protein, interleukin‐6, and tumor necrosis factor‐alpha (for all, P > 0.05). Body mass index, waist circumference, body fat mass, percentage of lean tissue mass, LV mass, triglyceride/high‐density lipoprotein cholesterol ratio, HOMA‐IR, and spKt/V appeared as independent predictors of EAT. EAT was significantly associated with body fat measures, cardiovascular risk predictors, and dialysis dose in MHD patients.     

Prevalence and correlates of functional dependence among maintenance dialysis patients

Functional dependence is an important determinant of longevity and quality of life. The purpose of the current study was to determine the prevalence and correlates of functional dependence among patients with end‐stage renal disease (ESRD) receiving maintenance dialysis. We enrolled 148 participants with ESRD from five clinics. Functional status, as measured by basic and instrumental activities of daily living (ADL, IADL), was ascertained by validated questionnaires. Functional dependence was defined as needing assistance in at least one of seven IADLs or at least one of four ADLs. Demographic characteristics, chronic health conditions, anthropometric measurements, and laboratories were assessed by a combination of self‐report and chart review. Cognitive function was assessed with a neurocognitive battery, and depressive symptoms were assessed by questionnaire. Mean age of the sample was 56.2 ± 14.6 years. Eighty‐seven participants (58.8%) demonstrated dependence in ADLs or IADLs, 70 (47.2%) exhibited IADL dependence alone, and 17 (11.5%) exhibited combined IADL and ADL dependence. In a multivariable‐adjusted model, stroke, cognitive impairment, and higher systolic blood pressure were independent correlates of functional dependence. We found no significant association between demographic characteristics, chronic health conditions, depressive symptoms or laboratory measurements, and functional dependence. Impairment in executive function was more strongly associated with functional dependence than memory impairment. Functional dependence is common among ESRD patients and independently associated with stroke, systolic blood pressure, and executive function impairment.     

Changes in circulating biomarkers during a single hemodialysis session

The hemodialysis (HD) procedure induces an inflammatory response potentially contributing to cardiovascular disease. Here we investigated the acute impact of HD on circulating biomarkers. Circulating biomarkers (small solutes, middle molecular‐sized peptides, and proteins) related to inflammation, oxidative stress, and vascular calcification (VC) were measured before and after a single session of HD in 45 clinically stable patients. Concentrations were corrected for ultrafiltration‐induced hemoconcentration. Among vascular calcification‐related biomarkers, osteoprotegerin and fetuin‐A remained unchanged while fibroblast growth factor‐23 (FGF23) decreased by ?19%. Changes of FGF23 and changes of phosphate correlated (ρ = 0.61, P < 0.001). While C‐reactive protein did not change, interleukin‐6 (IL‐6) increased by 14% and pentraxin 3 (PTX3) increased by 45%. IL‐6 and PTX3 appear to be valid biomarkers of the intradialytic inflammatory response. VC‐related markers were in general not affected by the single HD session; however, the observed correlation between acute changes of FGF‐23 and phosphate during HD warrants further studies.     

D‐dimer levels in maintenance hemodialysis patients: High prevalence of positive values also in the group without predisposing diseases

We aimed to estimate the prevalence of elevated D‐dimer levels in all chronic hemodialysis patients and those without additional disease, and to identify factors associated with increased D‐dimer. In 167 chronic hemodialysis patients from our center, D‐dimer was measured before dialysis. The effects of age, C‐reactive protein (CRP), recent acute illness, vascular access, anticoagulation type, dialysis vintage, and chronic diseases, considered to predispose for increased D‐dimer levels, were analyzed. The median D‐dimer in the whole group was 966 (inter‐quartile range [IQR] 524–1947) μg/L and was positive (>500 μg/L) in 75% of cases. D‐dimer was positive in 91% of patients with acute illness, 76% of those with predisposing chronic diseases, but was still positive in 52% of patients without additional disease (i.e., acute illness or predisposing chronic diseases) – median D‐dimer was 538.5 (IQR 359–966) μg/L. D‐dimer was correlated to patients' age, but not dialysis vintage. In univariate analysis, the D‐dimer levels were significantly higher in patients with atrial fibrillation, ischemic heart disease, recent acute illness, increased CRP, dialyzed over a catheter, and on citrate anticoagulation. Multivariate logistic regression showed that only age >65 years (odds ratio [OR] 2.93), catheter (OR 4.86), and positive CRP (OR 4.07) were independently associated with positive D‐dimer at 500 μg/L cut‐off, while the significance of age disappeared at 2000 μg/L cut‐off. To conclude, the high prevalence of positive D‐dimer values even in hemodialysis patients without additional disease limits the use of D‐dimer for exclusion of thromboembolic diseases in hemodialysis patients.     

Clinical and psychosocial factors predicting health‐related quality of life in hemodialysis patients

Many patients with end‐stage renal disease have significant impairment in health‐related quality of life (HRQoL). Most previous studies have focused on clinical factors; however, quality of life can also be affected by psychosocial factors. The aim of this study was to identify the possible predictors of HRQoL among clinical and psychosocial factors in hemodialysis (HD) patients. The study included 101 patients who were undergoing HD. Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also assessed laboratory and clinical factors, including albumin, Kt/V as a marker of dialysis adequacy, normalized protein catabolic rate, and duration of HD. The Euro Quality of Life Questionnaire 5‐Dimensional Classification (EQ‐5D) was used to evaluate HRQoL. The mean EQ‐5D index score was 0.704 ± 0.199. The following variables showed a significant association with the EQ‐5D index: age (P < 0.001), depression (P < 0.001), anxiety (P < 0.001), support from friends (P < 0.001), cognitive function (P < 0.001), duration of HD (P = 0.034), triglyceride (P = 0.031), total iron‐binding capacity (P = 0.036), and phosphorus (P = 0.037). Multiple regression analysis showed that age (95% confidence interval [CI] ?0.008 to ?0.002), anxiety (95% CI ?0.025 to ?0.009), and support from friends (95% CI 0.004 to 0.018) were independent predictors of impaired HRQoL. This study explored determinants of impaired HRQoL in HD patients. We found that impaired HRQoL was independently associated with age, anxiety, and support from friends. We should consider psychosocial as well as clinical factors when evaluating ways to improve HRQoL in HD patients.     

Is hepcidin‐25 a predictor of atherosclerosis in hemodialysis patients?

Atherosclerotic cardiovascular disease is an important cause of mortality and morbidity in hemodialysis patients. Iron accumulation in arterial wall macrophages is increased in atherosclerotic lesions. Hepcidin is a key hepatic hormone regulating iron balance. It inhibits iron release from macrophages and iron absorption from enterocytes by binding and inactivating the cellular iron exporter ferroportin. The aim of this study is to investigate the relation of hepcidin‐25, iron parameters, and atherosclerosis measured by carotid intima media thickness (CIMT) in hemodialysis patients. Eighty‐two hemodialysis patients were enrolled in this cross‐sectional study. Predialysis blood samples were centrifuged at 1500 g and 4°C for 10 minutes and stored at ?80°C for the measurement of hepcidin‐25. DRG hepcidin enzyme‐linked immunosorbent assay kit was used for the measurement of hepcidin‐25. Ultrasonographical B‐mode imaging of bilateral carotid arteries was performed with a high‐resolution real‐time ultrasonography (Mindray DC7). Mean age of the study population was 57.90 ± 16.08 years and 43.9% were men. Total study population was grouped into two according to median value of hepcidin‐25. There was no difference between groups with respect to age, dialysis vintage, and C‐reactive protein. CIMT was found to be statistically significantly higher in low hepcidin‐25 group. In correlation analysis, CIMT was found to be correlated with age (P < 0.01, R = 0.33) and hepcidin‐25 (P < 0.01, R = 0.46). In linear regression analysis, age (β = 0.31) and hepcidin‐25 (β = 0.44) were found to be the determinants of CIMT in hemodialysis patients. Our results implicate that hepcidin may take part in pathophysiology of atherosclerosis and cardiovascular disease in hemodialysis patients.     

Treatment of vitamin D deficiency/insufficiency with ergocalciferol is associated with reduced vascular access dysfunction in chronic hemodialysis patients

Vitamin D deficiency or insufficiency is highly prevalent among patients with chronic kidney disease (CKD). This study aims to determine the relationship between vitamin D and frequency of vascular access dysfunction (VAD) in hemodialysis (HD) patients. We reviewed medical records of all HD patients who had serum 25‐hydroxyvitamin D (25OHD) levels at 4 outpatient dialysis facilities between January 2011 and January 2012. Patients were included if they were ≥18 years of age, had been on maintenance dialysis for ≥3 months, and had native arteriovenous fistula or synthetic polytetrafluoroethylene grafts for dialysis access. Patients with catheters were excluded. 25‐Hydroxyvitamin D levels <30 ng/mL were documented in 183 patients (86%). Median and interquartile range [Q1, Q3] of 25OHD level was 16 [11, 25] ng/mL. Among 213 dialysis patients, 102 had VAD. Median 25OHD level was significantly lower in patients who had VAD than in those without VAD (14.5 [10, 22] vs. 19 [12, 27.5] ng/mL; P = 0.003). There was significant association between VAD and the lowest quartile relative to the highest quartile of 25OHD level. A 25OHD level <12 ng/mL was associated with more than doubling of risk for VAD (OR 2.56; 95% CI [1.05–6.23], P < 0.05). Of 213 patients, 140 were treated with ergocalciferol and 73 were not treated. Treatment was associated with significant reduction in VAD (OR = 0.36; 95% CI [0.19–0.68], P = 0.002). Vitamin D deficiency or insufficiency is an independent risk factor for VAD in HD patients; its treatment with ergocalciferol is associated with decreased VAD.     

Thyroid function in end stage renal disease and effects of frequent hemodialysis

Introduction: End‐stage renal disease (ESRD) is associated with perturbations in thyroid hormone concentrations and an increased prevalence of hypothyroidism. Few studies have examined the effects of hemodialysis dose or frequency on endogenous thyroid function. Methods: Within the Frequent Hemodialysis Network (FHN) trials, we examined the prevalence of hypothyroidism in patients with ESRD. Among those with endogenous thyroid function (without overt hyper/hypothyroidism or thyroid hormone supplementation), we examined the association of thyroid hormone concentration with multiple parameters of self‐reported health status, and physical and cognitive performance, and the effects of hemodialysis frequency on serum thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri‐iodothyronine (FT3) levels. Conventional thrice‐weekly hemodialysis was compared to in‐center (6 d/wk) hemodialysis (Daily Trial) and Nocturnal (6 nights/wk) home hemodialysis (Nocturnal Trial) over 12 months. Findings: Among 226 FHN Trial participants, the prevalence of hypothyroidism was 11% based on thyroid hormone treatment and/or serum TSH ≥8 mIU/mL. Among the remaining 195 participants (147 Daily, 48 Nocturnal) with endogenous thyroid function, TSH concentrations were modestly (directly) correlated with age (r = 0.16, P = 0.03) but not dialysis vintage. Circulating thyroid hormone levels were not associated with parameters of health status or physical and cognitive performance. Furthermore, frequent in‐center and nocturnal hemodialysis did not significantly change (baseline to month 12) TSH, FT4, or FT3 concentrations in patients with endogenous thyroid function. Discussion: Among patients receiving hemodialysis without overt hyper/hypothyroidism or thyroid hormone treatment, thyroid indices were not associated with multiple measures of health status and were not significantly altered with increased dialysis frequency.     

Measures of blood pressure and cognition in dialysis patients

There are few reports on the relationship of blood pressure with cognitive function in maintenance dialysis patients. The Cognition and Dialysis Study is an ongoing investigation of cognitive function and its risk factors in six Boston area hemodialysis units. In this analysis, we evaluated the relationship between different domains of cognitive function with systolic and diastolic blood pressure, pulse pressure, and intradialytic changes in systolic blood pressure, using univariate and multivariable linear regression models adjusted for age, sex, race, education, and primary cause of end‐stage renal disease. Among 314 participants, mean age was 63 years; 47% were female, 22% were African American, and 48% had diabetes. The mean (SD) of systolic blood pressure, diastolic blood pressure, pulse pressure, and intradialytic change in systolic blood pressure were 141 (21), 73 (12), 68 (15), and ?10 (24) mmHg, respectively. In univariate analyses, the performance on cognitive tests primarily assessing executive function and processing speeds was worse among participants with lower diastolic blood pressure and higher pulse pressure. These relationships were not statistically significant, however, in multivariable analyses. There was no association between cognitive function and systolic blood pressure or intradialytic change in systolic blood pressure in either univariate or multivariable analyses. We found no association between different measures of blood pressure and cognitive function in cross‐sectional analysis. Longitudinal studies are needed to confirm these results.     

Reduction of carbamylated albumin by extended hemodialysis

Introduction Among conventional hemodialysis (CHD) patients, carbamylated serum albumin (C‐Alb) correlates with urea and amino acid deficiencies and is associated with mortality. We postulated that reduction of C‐Alb by intensive HD may correlate with improvements in protein metabolism and cardiac function. Methods One‐year observational study of in‐center nocturnal extended hemodialysis (EHD) patients and CHD control subjects. Thirty‐three patients receiving 4‐hour CHD who converted to 8‐hour EHD were enrolled, along with 20 controls on CHD. Serum C‐Alb, biochemistries, and cardiac MRI parameters were measured before and after 12 months of EHD. Findings EHD was associated with reduction of C‐Alb (average EHD change ?3.20 mmol/mol [95% CI ?4.23, ?2.17] compared to +0.21 [95% CI ?1.11, 1.54] change in CHD controls, P < 0.001). EHD was also associated with increases in average essential amino acids (in standardized units) compared to CHD (+0.38 [0.08, 0.68 95%CI]) vs. ?0.12 [?0.50, 0.27, 95% CI], P = 0.047). Subjects who reduced C‐Alb more than 25% were found to have reduced left ventricular mass, increased urea reduction ratio, and increased serum albumin compared to nonresponders, and % change in C‐Alb significantly correlated with % change in left ventricular mass. Discussion EHD was associated with reduction of C‐Alb as compared to CHD, and reduction of C‐Alb by EHD correlates with reduction of urea. Additional studies are needed to test whether reduction of C‐Alb by EHD also correlates with improved clinical outcomes.     

Clearance of FGF‐23 during continuous renal replacement therapy

FGF‐23 is a 32 kDa protein that is a key regulator of phosphorus and vitamin D metabolism. Emerging evidence also demonstrates that FGF‐23 increases within 24 hours of acute kidney injury (AKI) and may be associated with adverse clinical outcomes. We conducted this study to evaluate FGF23 clearance during continuous veno‐venous hemofiltration (CVVH) in critically ill patients with AKI. We demonstrate that plasma clearance of FGF‐23 during CVVH is ～11 mL/min and the mean sieving coefficient is 0.27 ± 0.1. Future studies will need to clarify FGF‐23's role in adverse outcomes among AKI patients, and whether therapies aimed at reducing FGF‐23 levels may be beneficial.     

Severe Cortical and Trabecular Osteopenia in Secondary Hyperparathyroidism

Background: Peripheral quantitative computed tomography (pQCT) provides real volumetric bone density values, not only of the total, but also of trabecular and cortical bone, separately. In addition, it provides data on bone geometry that can be related to the risk of fracture. Methods: Total, cortical, and trabecular volumetric bone mineral densities (BMD), as well as the main geometric parameters (cross‐sectional area, cortical area, trabecular area, and cortical thickness) were assessed by pQCT at the distal radius in 24 hemodialysis patients affected by severe secondary hyperparathyroidism (PTH, mean ± SD: 1444 ± 695 pg/mL). The strength‐strain index (SSI), a biomechanical parameter describing bone fragility, was also determined. Results: Compared with a control group of 64 healthy age‐matched subjects, volumetric BMD (mg/cm³) was significantly reduced in all patients (total BMD: 243 ± 87 vs. 405 ± 138, cortical BMD: 605 ± 218 vs. 856 ± 204, trabecular BMD: 95 ± 51 vs. 182 ± 75). Cortical area and cortical thickness showed significant modifications, while cross‐sectional area did not. SSI was significantly reduced (547 ± 125 vs. 927 ± 306 mm³). PTH levels showed a significant inverse correlation with cortical BMD (r = ?0.56), cortical thickness (r = ?0.46), cortical area (r = ?0.61), and SSI (r = ?0.54). Quantitative analysis of bone demonstrated cortical porosity. Conclusions: In dialysis patients with severe secondary hyperparathyroidism, pQCT showed a significant cortical osteopenia, associated with geometric and mechanical bone impairment. Interestingly, we also found a comparable deficit of trabecular bone, which may be related to the very high PTH levels. Generalized cortical thinning, intracortical porosity and cortical‐endosteal resorption (“trabecularization” of the cortical bone) are major determinants of reduced bone strength, which may be quantitated by pQCT.     

Factors associated with serum magnesium and vascular stiffness in maintenance hemodialysis patients

Introduction : We evaluated the associated factors of serum magnesium in patients on maintenance hemodialysis (MHD). Furthermore, we evaluated the relationship between low serum magnesium and arteriosclerosis in these patients. Methods : In 129 patients on MHD, we evaluated the blood levels of magnesium, brachial‐ankle pulse wave velocity (ba‐PWV), ankle‐brachial index (ABI), and intima‐media thickness of the common carotid artery (IMT). Findings : In MHD patients, the serum level of magnesium was significantly correlated with age, calcium, TNF‐α, albumin, and ba‐PWV but not with ABI or IMT. In the multiple regression analysis, albumin (P = 0.0001, β = 0.31) and calcium (P = 0.029, β = 0.18) were selected as significant predictors of the magnesium level in MHD patients. Furthermore, the serum level of magnesium, as well as systolic blood pressure (P = 0.0001, β = 0.32) and age (P = 0.005, β = 0.25), were selected as significant (P = 0.012, β = ?0.22) predictors of ba‐PWV in MHD patients. Discussion : In MHD patients, the serum magnesium level was associated with the serum levels of calcium and albumin. Furthermore, a low serum magnesium level in MHD patients was associated with the index of vascular stiffness.     

Coronary and aortic calcifications in patients new to dialysis

Background: Vascular calcification has been associated with all cause and cardiovascular mortality in patients with end‐stage kidney disease (ESRD). Whether vascular calcification is present in persons with advanced chronic kidney disease starting dialysis or develops in patients on dialysis is unknown. The purpose of this study was to examine the prevalence of vascular and coronary calcification in patients new to hemodialysis. Methods: A total of 129 subjects new to dialysis were evaluated using electron beam computed tomography. The primary outcome was the presence and extent of coronary artery, aortic, and valvular calcification. Results: Forty‐three percent of subjects had no significant coronary artery calcification (total score ≤ 30) and 27% had no detectable aortic calcification. Thirty‐four percent had coronary artery scores that placed them above the 90th percentile for age and sex. Coronary artery calcification was significantly associated with a history of coronary artery disease and atherosclerotic vascular disease (ASVD) whereas aortic calcification was significantly associated with ASVD. Age (p < 0.0001), pulse pressure (p = 0.004), diabetes mellitus (p = 0.009), and a history of smoking (p = 0.026) were independently associated with the extent of coronary artery calcification. Age (p < 0.0001) and pulse pressure (p = 0.0003) were independently associated with the extent of aortic calcification. Conclusions: A large fraction of patients new to hemodialysis had no evidence of coronary artery or aortic calcification. Coupled with the extensive vascular calcification reported by others in prevalent dialysis patients these findings suggest that dialysis‐specific factors contribute to calcific vascular disease in ESRD.     

Quality of life development during initial hemodialysis therapy and association with loss of residual renal function

Introduction: Health related quality of life (HRQOL) is markedly reduced in hemodialysis patients compared to the general population. We investigated the course of self‐reported HRQOL over time and the association with selected factors, focusing on changes in glomerular filtration rate (GFR). Methods: Eighty‐two newly started hemodialysis patients from the SAFIR cohort filled out the Kidney Disease Quality of Life Short Form Version 1.3 (KDQOL‐SF^TM) questionnaire at baseline, 6 and 12 months. The SAFIR study was a randomized, placebo‐controlled, double‐blind intervention study, examining the effects of the angiotensin II receptor blocker irbesartan. HRQOL was a secondary outcome measure. Main inclusion criteria: Dialysis vintage <1 year, left ventricular ejection fraction >30% and urinary output >300 mL/day. GFR was measured with mean creatinine and urea clearance from 24‐hour urine collections at baseline, 6 and 12 months. Findings: Irbesartan treatment did not affect HRQOL. Patients were pooled into one group for further analyses. Decline in GFR correlated significantly with decreasing HRQOL over time. HRQOL was stable over time, with a slight nonsignificant tendency toward improved HRQOL. The largest HRQOL‐differences (positive values equal improved HRQOL) observed during the 12 month study period were (mean[95% confidence interval]): Burden of kidney disease:6.4[?2.2;15.0], Role limitations‐physical:12.7[?2.1;27.5], and Role limitations‐emotional:9.7[?5.2;24.6]. Comorbidity, especially diabetes, hospital admissions, female gender, and age were strongly associated with lower HRQOL in cross sectional analysis. Discussion: Preservation of residual renal function seems to be important for HRQOL. In newly started HD patients, HRQOL showed little change after 12 months. HRQOL was negatively affected by comorbidity, especially diabetes, hospital admissions, female gender, and age.     

Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients

Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3‐dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we reexamined whether an increased indoleamine 2,3‐dioxygenase activity, as estimated by the Kyn/Trp ratio (μM/mM), is associated with atherosclerotic parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243 HD patients by liquid chromatography/electrospray ionization tandem mass spectrometry. We measured carotid artery intima‐medial thickness, brachial‐ankle pulse wave velocity, ankle‐brachial pressure index, and the cardio‐ankle vascular index. Log‐transformed Kyn/Trp ratio was significantly correlated with log‐transformed time on HD (ρ=0.28, P<0.01), log‐transformed highly sensitive C‐reactive protein (ρ=0.20, P<0.01), and peripheral total lymphocyte count (ρ=?0.13, P<0.05). A significant association was found between log‐transformed Kyn/Trp ratio and mean carotid artery intima‐medial thickness (ρ=0.18, P<0.01). Mean carotid artery intima‐medial thickness was significantly higher in the lowest quartile of Kyn/Trp ratio (<165) (0.62±0.12 mm) when compared with the highest quartile (≥304) (0.68±0.15 mm) (P<0.01). Ankle‐brachial pressure index was lower in the second quartile (1.01±0.20), the third quartile (1.01±0.19), and the fourth quartile (1.03±0.15) compared with that in the first quartile (1.09±0.13) (P<0.05). It follows from these findings that the Kyn/Trp ratio increases with time on HD, and is associated with advanced atherosclerotic changes in chronic HD patients.     

Epicardial fat thickness is associated with impaired coronary flow reserve in hemodialysis patients

Cardiovascular disease (CVD) is the main cause of mortality in hemodialysis (HD) patients. Epicardial fat tissue (EFT) is a new risk factor in CVD. The aim of this study was to evaluate the association between EFT and coronary artery flow reserve (CFR), which is an early indicator of endothelial dysfunction in coronary vessels of HD patients. We performed a cross‐sectional study including 71 chronic HD patients and 65 age‐ and sex‐matched healthy controls. Epicardial fat tissue was significantly higher in HD patients when compared to healthy controls (6.53 ± 1.01 mm vs. 5.79 ± 1.06 mm, respectively, P < 0.001). On transthoracic Doppler echocardiography, CFR values were significantly lower in HD patients when compared to healthy controls (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001). Correlation analysis showed CFR values to be inversely correlated with EFT (r = ?0.287, P < 0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. Artery flow reserve, age, body mass index and total cholesterol levels were independently correlated with EFT thickness. This study demonstrated that EFT was significantly higher among HD patients compared to healthy controls. In addition, this study was the first to demonstrate an inverse correlation between EFT and CFR in this patient population.