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BACKGROUND: Hyperphosphatemia is an independent risk factor for all-cause and cardiovascular mortality in hemodialysis (HD) patients. Phosphate control often is unsuccessful using conventional dialysis therapies. STUDY DESIGN: Short-term analysis of a secondary outcome of an ongoing randomized controlled trial. SETTING & PARTICIPANTS: 493 (84%) consecutive patients from 589 patients included in the Convective Transport Study (CONTRAST) by January 2009 from 26 centers in 3 countries. INTERVENTION: Online hemodiafiltration (HDF) versus continuation of low-flux HD. OUTCOMES: Differences in change from baseline to 6 months in phosphate levels and proportion of patients reaching phosphate treatment targets (phosphate < or = 5.5 mg/dL). MEASUREMENTS: Phosphate, use of phosphate-binding agents, and proportion of patients achieving treatment targets at baseline, 3 months, and 6 months. RESULTS: Phosphate levels decreased from 5.18 +/- 0.10 (SE) mg/dL at baseline to 4.87 +/- 0.10 mg/dL at 6 months in HDF patients (P < 0.001) and were stable in HD patients (5.10 +/- 0.10 mg/dL at baseline and 5.03 +/- 0.10 mg/dL after 6 months; P = 0.5). The difference in change in phosphate levels between HD and HDF patients (B = -0.24; 95% CI, -0.52 to 0.03; P = 0.08) increased after adjustment for phosphate-binder use (B = -0.36; 95% CI, -0.65 to -0.06; P = 0.02). The proportion of patients reaching phosphate treatment targets increased from 64% to 74% in HDF patients and was stable in HD patients (66% and 66%); the difference between groups reached statistical significance (P = 0.04). Nutritional parameters and residual renal function were similar in both treatment groups. LIMITATIONS: Only predialysis serum phosphate levels were measured; phosphate clearance could therefore not be calculated. CONCLUSION: HDF may help improve phosphate control. Whether this contributes to improved clinical outcome remains to be established. [ABSTRACT FROM AUTHOR]

BACKGROUND: End-stage renal disease and its treatment are associated with sleep disturbances such as deterioration of the circadian sleep-wake pattern. Melatonin rhythm, which has an important role in this pattern, is disturbed. The nocturnal melatonin surge is absent in this population. Whether nocturnal in-center hemodialysis changes melatonin and sleep-wake rhythms is unknown. STUDY DESIGN: A nonrandomized uncontrolled trial. Patients served as their own controls. SETTING & PARTICIPANTS: Thirteen daytime hemodialysis patients (median age, 58 years; 5 women) from our hospital receiving conventional daytime hemodialysis 3 times weekly for 3 to 4 hours each session. INTERVENTIONS: Six months of treatment with nocturnal in-center dialysis 4 nights/wk with 8-hour sessions. OUTCOMES & MEASUREMENTS: At baseline, while still on conventional hemodialysis therapy, polysomnography was performed, sleep questionnaires were filled out, and melatonin concentration in saliva was obtained. After 6 months of in-center nocturnal hemodialysis, all measurements were repeated. RESULTS: After 6 months of in-center nocturnal hemodialysis, polysomnography showed significant improvements in sleep efficiency (P = 0.05) and stage 3/4 sleep (P = 0.03) in comparison to t = 0. Trends in improvement of rapid-eye-movement sleep, awake time, and oxygen saturation were seen after 6 months of in-center nocturnal hemodialysis therapy. Sleep questionnaires showed a trend in improved sleep quality and daytime function. Patients were less exhausted during the daytime. The nocturnal melatonin surge was partially restored. LIMITATIONS: Small sample size and a nonrandomized uncontrolled study design. CONCLUSIONS: Patients after 6 months of in-center nocturnal hemodialysis had significant improvements in subjective and objective sleep parameters and partially restored nocturnal melatonin rhythm. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). The Anti-oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study showed that a multistep treatment strategy improved carotid intima-media thickness, endothelial function, and microalbuminuria in patients with stages 2 to 4 CKD. Increased plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been linked to greater CVD risk in patients with CKD. The aim of this study is to assess effects of the multistep intervention on plasma ADMA concentrations in the ATIC Study.Study Design: Secondary analysis of a randomized double-blind placebo-controlled trial.Setting& Participants: 93 patients with creatinine clearance of 15 to 70 mL/min/1.73 m(2) (according to the Cockcroft-Gault equation) from 7 outpatient clinics in Amsterdam, The Netherlands.Intervention: The treatment group received sequential treatment consisting of pravastatin, 40 mg/d. After 6 months, vitamin E, 300 mg/d, was added, and after another 6 months, homocysteine-lowering therapy (folic acid, 5 mg/d; pyridoxine, 100 mg/d; and vitamin B(12), 1 mg/d, all in 1 tablet) were added and continued for another year. The control group received matching placebos.Outcome& Measures: Plasma ADMA levels.Results: 36 participants (77%) in the treatment group and 38 (83%) in the placebo group completed the study. Mean ADMA and symmetric dimethylarginine concentrations in the total study population were 0.53 +/- 0.07 (SD) and 1.14 +/- 0.46 mumol/L, respectively. After 24 months, there was no overall effect of the treatment strategy on ADMA concentrations (beta = -0.006; P = 0.27). Analysis of separate treatment effects suggested that vitamin E significantly decreased ADMA levels by 4% in the treatment group compared with the placebo group (multiple adjusted P = 0.02).Limitations: The study was a secondary analysis, power calculation was based on the primary end point of carotid intima-media thickness, mean plasma ADMA levels were relatively low.Conclusion: Overall, a multistep treatment strategy consisting of pravastatin, vitamin E, and B vitamins had no effect on plasma ADMA levels in a stage 2 to 4 CKD population. This suggests that the beneficial effects of the intervention were not mediated by changes in ADMA levels. Possible ADMA-lowering effects of vitamin E deserve further attention. [ABSTRACT FROM AUTHOR]

Many patients on haemodialysis (HD) therapy suffer from a dry mouth and xerostomia. This can be relieved by mechanical and gustatory stimulation or palliative care. The aim of this crossover study was to investigate the effect and preferences of a sugar-free chewing gum (Freedent White) and a xanthan gum-based artificial saliva (Xialine) in the management of xerostomia in chronic HD patients. Sixty-five HD patients participated in a 6-week crossover trial. The artificial saliva was rated significantly lower than the chewing gum for effectiveness, taste and a global assessment. No preference differences were found for gender and age, although older subjects rated the artificial saliva with a higher mark. Thirty-nine subjects (60%) preferred chewing gum, 15% (n=10) preferred the artificial saliva. Therefore, both chewing gum and artificial saliva could play an important role in the palliative care of xerostomia in HD patients. [ABSTRACT FROM AUTHOR]

Background: The caloric load from glucose-based peritoneal dialysis (PD) fluids contributes to hypertriglyceridaemia, adiposity and, as result of anorexia, protein malnutrition in PD patients. It has been suggested that replacement of a glucose-based by an amino acids-based PD fluid (AA-PDF) for one exchange per day might improve the nutritional status and lipid profile. Due to the uptake of methionine for the dialysate, however, exposure to AA-PDF might aggravate hyperhomocysteinaemia, a frequently occurring risk factor for atherosclerosis in uraemic patients. [ABSTRACT FROM PUBLISHER]

Catheter-related infections result in high patient morbidity, the need for temporary haemodialysis, and high costs. These infections are the main cause of limited technique survival in peritoneal dialysis. We introduced a protocol for the simultaneous peritoneoscopic insertion and removal of peritoneal catheters in patients with catheter-related infections. Peritoneal dialysis was continued the day after surgery using low-volume dwells and a dry abdomen during the daytime. The dialysate leukocyte count had to be below 100/mm3 before exchanging catheters, which was performed under antibiotic therapy based on culture sensitivity. The old catheter was removed after the new catheter had been inserted in the opposite abdominal region. CAPD patients were switched to APD for 1 week, which made prolonged hospitalization necessary. [ABSTRACT FROM PUBLISHER]

Background.Acetate-free biofiltration (AFB) is a haemodiafiltration technique based on continuous post-dilution infusion of a sterile isotonic bicarbonate solution. We performed a long-term randomized prospective trial to compare dialysis efficacy and metabolic control of AFB versus bicarbonate haemodialysis (HD). [ABSTRACT FROM PUBLISHER]

Background: Hyperhomocysteinaemia is frequent in chronic haemodialysis patients. Because of its potential role in athero-and thrombogenesis, the effects of long-term homocysteine-lowering treatment on endothelial function are of interest. [ABSTRACT FROM PUBLISHER]

Background: The emphasis on implementation of value-based healthcare (VBHC) has increased in the Dutch healthcare system. Yet, the translation of the theoretical principles of VBHC towards actual implementation in daily practice has been rarely described. Our aim is to present a pragmatic step-by-step approach for VBHC implementation, developed and applied in Amsterdam UMC, to share our key elements. The approach may inspire others and can be used as a template for implementing VBHC principles in other hospitals., Methods: The local approach is developed in a major academic hospital in the Netherlands, based at two locations with 15,000 employees in total. Experience-based co-design is used, building on our learning experiences from implementing VBHC for 14 specific patient groups. The described steps and activities devolved from iterative and participative co-design sessions with various experienced stakeholders involved in the implementation of one or more VBHC pathways., Results: The approach includes five phases; preparation, design (team introduction, outcome selection, action agenda), building (outcome set integration in daily practice), implementation (training, outcome registration and implementation) and the continuous improvement cycle. We described two cases for illustration of the approach; the Cleft Lip and Palate and the Chronic Kidney Disease patient groups. For a good start, involvement of a clinical leader as driving force, ensuring participation of patient representatives and sufficient resources are needed., Conclusion: We have experienced that several defining features of the development and implementation of this approach may have contributed to its completeness and applicability. Key elements for success have been organisational readiness and clinical leadership. In conclusion, the approach has provided a first step towards VBHC in our hospital. Further research is needed for evaluation of its effectiveness including impact on value for patients., (© 2022. The Author(s).)

Background: C-type natriuretic peptide (CNP) and its co-product N-terminal proCNP (NTproCNP) have been associated with beneficial effects on the cardiovascular system. In prevalent dialysis patients, however, a relation between NTproCNP and mortality has not yet been investigated. Furthermore, as a middle molecular weight substance, its concentration might be influenced by dialysis modality., Methods: In a cohort of patients treated with haemodialysis (HD) or haemodiafiltration (HDF), levels of NTproCNP were measured at baseline and 6, 12, 24 and 36 months. The relation between serum NTproCNP and mortality and the relation between the 6-month rate of change of NTproCNP and mortality were analysed using Cox regression models. For the longitudinal analyses, linear mixed models were used., Results: In total, 406 subjects were studied. The median baseline serum NTproCNP was 93 pmol/L and the median follow-up was 2.97 years. No relation between baseline NTproCNP or its rate of change over 6 months and mortality was found. NTproCNP levels remained stable in HD patients, whereas NTproCNP decreased significantly in HDF patients. The relative decline depended on the magnitude of the convection volume., Conclusions: In our study, levels of NTproCNP appear strongly elevated in prevalent dialysis patients. Second, while NTproCNP remains unaltered in HD patients, its levels decline in individuals treated with HDF, with the decline dependent on the magnitude of the convection volume. Third, NTproCNP is not related to mortality in this population. Thus NTproCNP does not seem to be a useful marker for mortality risk in dialysis patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: High concentrations of both phosphate and fibroblast growth factor 23 (FGF23) observed in chronic kidney disease (CKD) are associated with an increased risk of cardiovascular morbidity and mortality. Pulse wave velocity (PWV) is a surrogate marker for cardiovascular events and all-cause mortality. It is not known whether a reduction of FGF23 or phosphate alters cardiovascular risk. Sevelamer has shown to have the ability to reduce both phosphate and FGF23 concentrations. Furthermore, reduction of PWV is reported with sevelamer use as well, but it is unclear if this is mediated by decline of phosphate or FGF23. We investigated if sevelamer induced a decline in PWV and if this was associated with a reduction in FGF23., Methods: In all, 24 normophosphataemic CKD Stage 3 patients started treatment with a fixed dose of sevelamer-carbonate (Renvela ® ) 2.4 g twice daily, with their usual diet for 8 weeks in a single-arm study. PWV was measured and blood samples were obtained before, during and after washout of treatment with sevelamer. Vascular calcification was quantified using the Kauppila Index (KI). The primary outcome was the change of PWV from baseline to 8 weeks of treatment and the secondary endpoint was the difference of FGF23 following treatment with sevelamer. One of the linear mixed models was used to analyse the association between treatment and outcome. Mediation analysis was performed as a sensitivity analysis. The study was registered in the Dutch trial register (http://www.trialregister.nl: NTR2383)., Results: A total of 18 patients completed 8 weeks of treatment with sevelamer and were analysed. Overall, treatment with sevelamer did not induce a significant reduction of PWV (β = -0.36, P = 0.12). However, in patients with less vascular calcification (lower KI score), there was a statistically significant reduction of PWV, adjusted for mean arterial pressure, after treatment (β = 0.63, P = 0.02). Addition of FGF23 to the model did not alter this association. Mediation analysis yielded similar results. FGF23 did not decrease during treatment with sevelamer., Conclusion: In this short-term pilot study in normophosphataemic CKD patients, treatment with sevelamer did not improve PWV. In subgroup analysis, however, PWV improved in patients with no or limited abdominal aorta calcifications. This was not associated with a decline of FGF23., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Due to continuing migration there is more interest in the mental health status of immigrants. The aim of this study is to determine the prevalence of depressive/anxiety symptoms in immigrant and native dialysis patients, and to explore if patient characteristics can explain differences. The Beck depression inventory and the beck anxiety inventory were used. Differences between native and immigrant patients were explored using logistic regression models adjusted for patient characteristics. The prevalence of depressive symptoms was 35% for 245 native patients and 50% for 249 immigrant patients. The prevalence of anxiety symptoms was 35% for native patients and 50% for immigrant patients. In addition, the prevalence for co-morbid depressive and anxiety symptoms was 20% for native patients and 32% for immigrant patients. Crude ORs for depressive/anxiety symptoms for immigrant patients versus native patients were 1.8 (1.2-2.5) and 1.7 (1.2-2.5), respectively. After adjustment for patient characteristics ORs remained the same. Clinicians should be aware that immigrant dialysis patients are more prone to develop depressive and anxiety symptoms. Cultural factors might play a role and should therefore be assessed in future research.

Background: The CKD-associated decline in soluble α-Klotho (α-Klotho) levels is considered detrimental. Some studies suggest a direct induction of α-Klotho concentrations by growth hormone (GH). In the present study, the effect of exogenous GH administration on α-Klotho concentrations in a clinical cohort with mild chronic kidney disease (CKD) and healthy subjects was studied., Methods: A prospective, single-center open case-control pilot study was performed involving 8 patients with mild CKD and 8 healthy controls matched for age and sex. All participants received subcutaneous GH injections (Genotropin®, 20 mcg/kg/day) for 7 consecutive days. α-Klotho concentrations were measured at baseline, after 7 days of therapy and 1 week after the intervention was stopped., Results: α-Klotho concentrations were not different between CKD-patients and healthy controls at baseline (554 (388-659) vs. 547 (421-711) pg/mL, P = 0.38). Overall, GH therapy increased α-Klotho concentrations from 554 (405-659) to 645 (516-754) pg/mL, P < 0.05). This was accompanied by an increase of IGF-1 concentrations from 26.8 ± 5.0 nmol/L to 61.7 ± 17.7 nmol/L (P < 0.05). GH therapy induced a trend toward increased α-Klotho concentrations both in the CKD group (554 (388-659) to 591 (358-742) pg/mL (P = 0.19)) and the healthy controls (547 (421-711) pg/mL to 654 (538-754) pg/mL (P = 0.13)). The change in α-Klotho concentration was not different for both groups (P for interaction = 0.71). α-Klotho concentrations returned to baseline levels within one week after the treatment (P < 0.05)., Conclusions: GH therapy increases α-Klotho concentrations in subjects with normal renal function or stage 3 CKD. A larger follow-up study is needed to determine whether the effect size is different between both groups or in patients with more severe CKD., Trial Registration: This trial is registered in EudraCT ( 2013-003354-24 ).

Cardiovascular diseases account for ~50% of mortality in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) is independently associated with endothelial dysfunction and cardiovascular mortality. We hypothesized that CKD impairs microvascular endothelial function and that this can be attributed to FGF23. Mice were subjected to partial nephrectomy (5/6Nx) or sham surgery. To evaluate the functional role of FGF23, non-CKD mice received FGF23 injections and CKD mice received FGF23-blocking antibodies after 5/6Nx surgery. To examine microvascular function, myocardial perfusion in vivo and vascular function of gracilis resistance arteries ex vivo were assessed in mice. 5/6Nx surgery blunted ex vivo vasodilator responses to acetylcholine, whereas responses to sodium nitroprusside or endothelin were normal. In vivo FGF23 injections in non-CKD mice mimicked this endothelial defect, and FGF23 antibodies in 5/6Nx mice prevented endothelial dysfunction. Stimulation of microvascular endothelial cells with FGF23 in vitro did not induce ERK phosphorylation. Increased plasma asymmetric dimethylarginine concentrations were increased by FGF23 and strongly correlated with endothelial dysfunction. Increased FGF23 concentration did not mimic impaired endothelial function in the myocardium of 5/6Nx mice. In conclusion, impaired peripheral endothelium-dependent vasodilatation in 5/6Nx mice is mediated by FGF23 and can be prevented by blocking FGF23. These data corroborate FGF23 as an important target to combat cardiovascular disease in CKD. NEW & NOTEWORTHY In the present study, we provide the first evidence that fibroblast growth factor 23 (FGF23) is a cause of peripheral endothelial dysfunction in a model of early chronic kidney disease (CKD) and that endothelial dysfunction in CKD can be prevented by blockade of FGF23. This pathological effect on endothelial cells was induced by long-term exposure of physiological levels of FGF23. Mechanistically, increased plasma asymmetric dimethylarginine concentrations were strongly associated with this endothelial dysfunction in CKD and were increased by FGF23.

Objective: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined., Methods: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability., Results: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified., Conclusion: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Introduction: While concentric left ventricular hypertrophy (cLVH) predominates in non-dialysis-dependent chronic kidney disease (CKD), eccentric left ventricular hypertrophy (eLVH) is most prevalent in dialysis-dependent CKD stage 5 (CKD5D). In these patients, the risk of sudden death is 5× higher than in individuals with cLVH. Currently, it is unknown which factors determine left ventricular (LV) geometry and how it changes over time in CKD5D., Methods: Data from participants of the CONvective TRAnsport Study who underwent serial transthoracic echocardiography were used. Based on left ventricular mass (LVM) and relative wall thickness (RWT), 4 types of left ventricular geometry were distinguished: normal, concentric remodeling, eLVH, and cLVH. Determinants of eLVH were assessed with logistic regression. Left ventricular geometry of patients who died and survived were compared. Long-term changes in RWT and LVM were evaluated with a linear mixed model., Findings: Three hundred twenty-two patients (63.1 ± 13.3 years) were included. At baseline, LVH was present in 71% (cLVH: 27%; eLVH: 44%). Prior cardiovascular disease (CVD) was positively associated with eLVH and ß-blocker use inversely. None of the putative volume parameters showed any relationship with eLVH. Although eLVH was most prevalent in non-survivors, the distribution of left ventricular geometry did not vary over time., Discussion: The finding that previous CVD was positively associated with eLVH may result from the permanent high cardiac output and the strong tendency for aortic valve calcification in this group of long-term hemodialysis patients, who suffer generally also from chronic anemia and various other metabolic derangements. No association was found between eLVH and parameters of fluid balance. The distribution of left ventricular geometry did not alter over time. The assumption that LV geometry worsens over time in susceptible individuals, who then suffer from a high risk of dying, may explain these findings., (© 2018 The Authors Hemodialysis International published by Wiley Periodicals, Inc. on behalf of International Society for Hemodialysis.)

Introduction: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high mortality. The creatinine-based stage of AKI is considered when deciding to start or delay RRT. However, creatinine is not only determined by renal function (excretion), but also by dilution (fluid balance) and creatinine generation (muscle mass). The aim of this study was to explore whether fluid balance-adjusted creatinine at initiation of RRT is related to 28-day mortality independent of other markers of AKI, surrogates of muscle mass and severity of disease., Methods: We performed a post-hoc analysis on data from the multicentre CASH trial comparing citrate to heparin anticoagulation during continuous venovenous hemofiltration (CVVH). To determine whether fluid balance-adjusted creatinine was associated with 28-day mortality, we performed a logistic regression analysis adjusting for confounders of creatinine generation (age, gender, body weight), other markers of AKI (creatinine, urine output) and severity of disease., Results: Of the 139 patients, 32 patients were excluded. Of the 107 included patients, 36 died at 28 days (34%). Non-survivors were older, had higher APACHE II and inclusion SOFA scores, lower pH and bicarbonate, lower creatinine and fluid balance-adjusted creatinine at CVVH initiation. In multivariate analysis lower fluid balance-adjusted creatinine (OR 0.996, 95% CI 0.993-0.999, p = 0.019), but not unadjusted creatinine, remained associated with 28-day mortality together with bicarbonate (OR 0.869, 95% CI 0.769-0.982, P = 0.024), while the APACHE II score non-significantly contributed to the model., Conclusion: In this post-hoc analysis of a multicentre trial, low fluid balance-adjusted creatinine at CVVH initiation was associated with 28-day mortality, independent of other markers of AKI, organ failure, and surrogates of muscle mass, while unadjusted creatinine was not. More tools are needed for better understanding of the complex determinants of "AKI classification", "CVVH initiation" and their relation with mortality, fluid balance is only one., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HOvS has received research support from Dirinco, and honoraria and speaker's fees from Gambro/Baxter and Fresenius in the past. SN received honoraria/grants from Astellas, Chiesi and Novartis. MV received honoraria from Astellas, Amgen and Baxter in the past and is currently receiving research grants from Shire, Sanofi and Fresenius. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The remaining authors declare that they have no competing interests.

Background: Long-term exposure of conventional peritoneal dialysis (PD) fluid is associated with structural membrane alterations and technique failure. Previously, it has been shown that infiltrating IL-17-secreting CD4+T cells and pro-fibrotic M2 macrophages play a critical role in the PD-induced pathogenesis. Although more biocompatible PD solutions are recognized to better preserve the peritoneal membrane integrity, the impact of these fluids on the composition of the peritoneal cell infiltrate is unknown., Materials and Methods: In a uremic PD mouse model, we compared the effects of daily instillation of standard lactate (LS) or bicarbonate/lactate-buffered solutions (BLS) and respective controls on peritoneal fibrosis, vascularisation, and inflammation., Results: Daily exposure of LS fluid during a period of 8 weeks resulted in a peritoneal increase of αSMA and collagen accompanied with new vessel formation compared to the BLS group. Effluent from LS-treated mouse showed a higher percentage of CD4 + IL-17 + cell population while BLS exposure resulted in an increased macrophage population. Significantly enhanced inflammatory cytokines such as TGFβ1, TNFα, INFγ, and MIP-1β were detected in the effluent of BLS-exposed mice when compared to other groups. Further, immunohistochemistry of macrophage subset infiltrates in the BLS group confirmed a higher ratio of pro-inflammatory M1 macrophages over the pro-fibrotic M2 subset compared to LS., Conclusion: Development of the peritoneal fibrosis and angiogenesis was prevented in the BLS-exposed mice, which may underlie its improved biocompatibility. Peritoneal recruitment of M1 macrophages and lower number of CD4 + IL-17 + cells might explain the peritoneal integrity preservation observed in BLS-exposed mouse.

Background: Long-term peritoneal dialysis (PD) is frequently complicated by technique failure preceded by peritoneal remodeling. Vitamin D has potent immunomodulatory characteristics: anti-inflammatory, anti-angiogenic, anti-fibrotic properties, and influences on the macrophage phenotype. Little is known about the relation between pleiotropic effects attributed to vitamin D 3 and the peritoneal membrane and what is the most appropriate vitamin D sterol in prevention of peritoneal remodeling in PD patients. Animal studies have suggested that paricalcitol has advantageous effects: decrease in plasma markers of inflammation, less peritoneal fibrosis, less pronounced PD-induced omental angiogenesis, and prevention of loss of ultrafiltration. We investigated whether paricalcitol is advantageous over calcitriol in PD patients., Method: A multicenter open-label 1:1 randomized non-blinded clinical pilot study enrolled prevalent continous ambulatory PD (CAPD) patients for a period of 6 months comparing paricalcitol with calcitriol. All patients were treated with biocompatible PD fluids. The primary endpoint was peritoneal transport parameters, exploratory endpoints were biomarkers of peritoneal damage and cell analysis (including M1/M2 macrophages), and safety endpoints were metabolic parameters., Results: Twenty-seven patients were included. Fourteen were randomized to treatment with paricalcitol. There was no difference in peritoneal transport parameters between the groups. We found similar Kt/V, D/P creatinine, D/D0 glucose, ultrafiltration, residual renal function and 24-h urine volume during the study. There was no difference in biomarker concentrations in peritoneal effluents, and no difference in leucocyte differentiation or mesothelial cells between the groups at any time point. Parathyroid hormone (PTH) levels decreased after administration of calcitriol after 12 and 24 weeks compared with baseline ( p = 0.001; p = 0.025). Parathyroid hormone levels in the paricalcitol group did not change significantly., Conclusion: In this pilot study we investigated the effect of active vitamin D in PD patients. We found no specific benefit of active vitamin D 3 in vitamin D 3 -sufficient PD patients. Additional studies in preferably incident patients, with an adequate PTH suppression in the intervention groups and during a longer period, are required to test the beneficial effects of active vitamin D 3 over no treatment and to investigate whether in 25(OH)D 3 -deficient PD patients the type of active vitamin D 3 matters., (Copyright © 2018 International Society for Peritoneal Dialysis.)

The overwhelming majority of patients with chronic kidney disease (CKD) die prematurely before reaching end-stage renal disease, mainly due to cardiovascular causes, of which heart failure is the predominant clinical presentation. We hypothesized that CKD-induced increases of plasma FGF23 impair cardiac diastolic and systolic function. To test this, mice were subjected to 5/6 nephrectomy (5/6Nx) or were injected with FGF23 for seven consecutive days. Six weeks after surgery, plasma FGF23 was higher in 5/6Nx mice compared to sham mice (720 ± 31 vs. 256 ± 3 pg/mL, respectively, P = 0.034). In cardiomyocytes isolated from both 5/6Nx and FGF23 injected animals the rise of cytosolic calcium during systole was slowed (-13% and -19%, respectively) as was the decay of cytosolic calcium during diastole (-15% and -21%, respectively) compared to controls. Furthermore, both groups had similarly decreased peak cytosolic calcium content during systole. Despite lower cytosolic calcium contents in CKD or FGF23 pretreated animals, no changes were observed in contractile parameters of cardiomyocytes between the groups. Expression of calcium handling proteins and cardiac troponin I phosphorylation were similar between groups. Blood pressure, the heart weight:tibia length ratio, α-MHC/β-MHC ratio and ANF mRNA expression, and systolic and diastolic function as measured by MRI did not differ between groups. In conclusion, the rapid, CKD-induced rise in plasma FGF23 and the similar decrease in cardiomyocyte calcium transients in modeled kidney disease and following 1-week treatment with FGF23 indicate that FGF23 partly mediates cardiomyocyte dysfunction in CKD., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Myocardial contrast echocardiography (MCE) offers the opportunity to study myocardial perfusion defects in mice in detail. The value of MCE compared with single-photon emission computed tomography, positron emission tomography, and computed tomography consists of high spatial resolution, the possibility of quantification of blood volume, and relatively low costs. Nevertheless, a number of technical and physiological aspects should be considered to ensure reproducibility among research groups. The aim of this overview is to describe technical aspects of MCE and the physiological parameters that influence myocardial perfusion data obtained with this technique. First, technical aspects of MCE discussed in this technical review are logarithmic compression of ultrasound data by ultrasound systems, saturation of the contrast signal, and acquisition of images during different phases of the cardiac cycle. Second, physiological aspects of myocardial perfusion that are affected by the experimental design are discussed, including the anesthesia regimen, systemic cardiovascular effects of vasoactive agents used, and fluctuations in body temperature that alter myocardial perfusion. When these technical and physiological aspects of MCE are taken into account and adequately standardized, MCE is an easily accessible technique for mice that can be used to study the control of myocardial perfusion by a wide range of factors.

Background: Chronic exposure to peritoneal dialysis (PD) fluid is associated with development of functional and structural alterations of the peritoneal membrane. The exact time point at which these changes actually occur is not known. Whether changes to the peritoneum occur immediately after installation of PD fluids and whether there is a difference between neutral-pH, low glucose degradation product (low-GDP) PD fluids and conventional PD fluids is not known either., Materials and Methods: We performed an observational study. Markers related to inflammation, fibrosis, mesothelial activation, and cytokines/growth factors were measured in effluents immediately after PD-catheter insertion and during the first days and weeks of PD treatment in patients using either dianeal ® or physioneal ® ., Results: Peritoneal response was observed instantly upon insertion of the PD catheter and instillation of PD fluids and persisted during daily PD therapy. Particularly during the first contacts of the peritoneum with PD fluids, high levels of cytokines and biomarkers were observed. In general, CA125 is slightly higher with dianeal. There is no difference between the fluids in hyaluronic acid (HA), IL-6, IL-8, MCP-1, VEGF, and TGFβ-1 levels., Conclusion: Implantation of the Tenckhoff catheter and installation of PD fluids induce inflammation, which in the first days resembles an acute inflammatory response. More continuous infusion of PD fluids further enhances peritoneal inflammation. The use of the bicarbonate/lactate-buffered, neutral-pH, low-GDP PD fluid physioneal exerts lower CA125 levels, lower D/P4 creatinine, but similar inflammatory response compared to conventional dianeal PD fluids in this early stage of PD therapy.
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Background/aims: In hemodialysis (HD) patients, the bromcresol green (BCG) assay overestimates, whereas the bromcresol purple (BCP) assay underestimates albumin concentration. Since corrected calcium concentrations depend on albumin, the albumin assay may have implications for the management of bone mineral disorders., Methods: A subset of patients from CONTRAST, a cohort of prevalent HD patients, was analyzed. Bone mineral parameters and prescription of medication were compared between patients in whom albumin was assessed by BCP versus BCG., Results: Albumin was assessed by BCP in 331 patients (9 of 25 centers) and by BCG in 175 patients (16 of 25 centers). Albumin was the lowest in the BCP group (34.5 ± 4.2 vs. 40.3 ± 3.1 g/L; p < 0.0005). Measured calcium levels and the prescription of calcium-based phosphate binders were similar in both groups. Corrected calcium levels, however, were markedly higher in the BCP group (2.45 ± 0.18 vs. 2.33 ± 0.18 mmol/L; p < 0.0005)., Conclusion: These findings suggest that calcium levels are not corrected for albumin in clinical practice when considering the prescription of calcium-free or calcium-based phosphate-binders in dialysis patients., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: Physical, cognitive and psychosocial functioning are frequently impaired in dialysis patients and impairment in these domains relates to poor outcome. The aim of this analysis was to compare the prevalence of impairment as measured by the Kidney Disease Quality of Life- Short Form (KDQOL-SF) subscales between the different age categories and to assess whether the association of these subscales with mortality differs between younger and older dialysis patients., Methods: This study included data from 714 prevalent hemodialysis patients, from 26 centres, who were enrolled in the CONvective TRAnsport STudy (CONTRAST NCT00205556, 09-12-2005). Baseline HRQOL domains were evaluated for patients <65 years, 65-74 years and over 75 years. Multivariable Cox proportional hazards analyses were performed to assess the relation between the separate domains and 2-year mortality., Results: Emotional health was higher in patients over the age of 75 compared to younger patients (mean level 71, 73 and 77 for increasing age categories respectively, p = 0.02), whilst physical functioning was significantly lower in older patients (mean level 60, 48 and 40, p < 0.01). A low level of physical functioning (Hazard Ratio (HR) 1.72 [95%Confidence Interval (CI) 1.02-2.73]), emotional health (HR 1.85 [95% 1.30-2.63]), and social functioning (HR 1.59 [95% CI 1.12-2.26]), was individually associated with an increased 2-year mortality within the whole population. The absence of effect modification suggests no evidence for different relations within the older age groups., Conclusions: In dialysis patients, older age is associated with lower levels of physical functioning, whilst the level of emotional health is not associated with age. KDQOL-SF domains physical functioning, emotional health and social functioning are independently associated with mortality in prevalent younger and older hemodialysis patients.

Background: in chronic hemodialysis, physical functioning (PF) is known to be poor. We set out to assess to what extent chronic dialysis patients are able to maintain a good physical condition over time and what the influence of age is on the trajectory of PF., Methods: we used data form 714 prevalent hemodialysis patients, enrolled in the CONvective TRAnsport STudy (CONTRAST). The PF subscale of the KDQOL SF-36 was assessed at baseline (n = 679) and during 2 years of follow-up (n = 298). Baseline PF score (0-100) was categorized into tertiles (good, intermediate and low). Change of PF of ≥ 5 points was considered clinically relevant. A regression model was applied to assess factors related to 'decline of PF (≥5 points)/low PF (0-33) at follow-up'., Results: during follow-up, only 15.3 % (1 out of 6) of patients succeeded in maintaining a good physical condition, the remainder deteriorated or died. Of the older patients (≥75) only 3.6% remained in a good physical condition. Factors related to decline/low PF were increasing age (odds ratio [OR] = 1.96 [95% CI: 1.03-3.72] for 65-74 years and OR = 2.38 [95%CI: 1.17-4.84] for ≥75 years compared to <65 years) and albumin (OR = 1.10 [95%CI: 1.01-1.18] per g/L decrease)., Conclusion: very few hemodialysis patients maintain a good physical condition over a 2-year time span. Especially in older patients, physical performance is poor and decline is faster than in the healthy population. These findings should be taken into account when considering dialysis in older patients and more emphasis should be placed to attempts for improving physical condition., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated., Methods: In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl., Results: The mean (±standard deviation) age of 396 test subjects was 63.6 (±13.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P = 0.01)]. Stratified models showed a stable sScl in patients treated with HD (Δ +2.9 pmol/L/year, 95% CI -0.5 to +6.3, P = 0.09) and a decreasing concentration in those treated with HDF (Δ -4.5 pmol/L/year, 95% CI -8.0 to -0.9, P = 0.02). The relative change in the latter group was related to the magnitude of the convection volume., Conclusions: (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The number of older people on dialysis is increasing, along with a need to develop specialized health care to manage their needs. Aging-related changes occur in physiological, psychosocial and medical aspects, all of which present nutritional risk factors ranging from a decline in metabolic rate to assistance with feeding-related activities. In dialysis, these are compounded by the metabolic derangements of chronic kidney disease (CKD) and of dialysis treatment per se, leading to possible aggravation of protein-energy wasting syndrome. This review discusses the nutritional derangements of the older patient on dialysis, debates the need for specific renal nutrition guidelines and summarizes potential interventions to meet their nutritional needs. Interdisciplinary collaborations between renal and geriatric clinicians should be encouraged to ensure better quality of life and outcomes for this growing segment of the dialysis population., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)