Publications by authors named "Frank M van der Sande"

168 Publications

Amino acid removal during hemodialysis can be compensated for by protein ingestion and is not compromised by intradialytic exercise: a randomized controlled crossover trial.

Am J Clin Nutr 2021 Sep 12. Epub 2021 Sep 12.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.

Background: Patients with end-stage renal disease (ESRD) undergoing hemodialysis experience a rapid decline in skeletal muscle mass and strength. Hemodialysis removes amino acids (AAs) from the circulation, thereby lowering plasma AA concentrations and stimulating proteolysis.

Objectives: In the present study, we evaluate the impact of intradialytic protein ingestion at rest and following exercise on AA removal and plasma AA availability in patients with ESRD.

Methods: Ten patients (age: 65 ± 16 y, male/female: 8/2, BMI: 24.2 ± 4.8 kg/m2, serum albumin: 3.4 ± 0.3 g/dL) with ESRD undergoing hemodialysis participated in this randomized controlled crossover trial. During 4 hemodialysis sessions, patients were assigned to ingest 40 g protein or a placebo 60 min after initiation, both at rest (PRO and PLA, respectively) and following exercise (PRO + EX and PLA + EX, respectively). Spent dialysate and blood samples were collected every 30 min throughout hemodialysis to assess AA removal and plasma AA availability.

Results: Plasma AA concentrations declined by 26.1 ± 4.5% within 30 min after hemodialysis initiation during all interventions (P < 0.001, η2p > 0.79). Protein ingestion, but not intradialytic exercise, increased AA removal throughout hemodialysis (9.8 ± 2.0, 10.2 ± 1.6, 16.7 ± 2.2, and 17.3 ± 2.3 g during PLA, PLA + EX, PRO, and PRO + EX interventions, respectively; protein effect P < 0.001, η2p = 0.97; exercise effect P = 0.32, η2p = 0.11). Protein ingestion increased plasma AA concentrations until the end of hemodialysis, whereas placebo ingestion resulted in decreased plasma AA concentrations (time effect P < 0.001, η2p > 0.84). Plasma AA availability (incremental AUC) was greater during PRO and PRO + EX interventions (49 ± 87 and 70 ± 34 mmol/L/240 min, respectively) compared with PLA and PLA + EX interventions (-227 ± 54 and -208 ± 68 mmol/L/240 min, respectively; protein effect P < 0.001, η2p = 0.98; exercise effect P = 0.21, η2p = 0.16).

Conclusions: Protein ingestion during hemodialysis compensates for AA removal and increases plasma AA availability both at rest and during recovery from intradialytic exercise. Intradialytic exercise does not compromise AA removal or reduce plasma AA availability during hemodialysis in a postabsorptive or postprandial state.
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http://dx.doi.org/10.1093/ajcn/nqab274DOI Listing
September 2021

Estimation of Muscle Mass in the Integrated Assessment of Patients on Hemodialysis.

Front Nutr 2021 16;8:697523. Epub 2021 Aug 16.

Division on Nephrology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, Netherlands.

Assessment of muscle mass (MM) or its proxies, lean tissue mass (LTM) or fat-free mass (FFM), is an integral part of the diagnosis of protein-energy wasting (PEW) and sarcopenia in patients on hemodialysis (HD). Both sarcopenia and PEW are related to a loss of functionality and also increased morbidity and mortality in this patient population. However, loss of MM is a part of a wider spectrum, including inflammation and fluid overload. As both sarcopenia and PEW are amendable to treatment, estimation of MM regularly is therefore of major clinical relevance. Whereas, computer-assisted tomography (CT) or dual-energy X-ray absorptiometry (DXA) is considered a reference method, it is unsuitable as a method for routine clinical monitoring. In this review, different bedside methods to estimate MM or its proxies in patients on HD will be discussed, with emphasis on biochemical methods, simplified creatinine index (SCI), bioimpedance spectroscopy (BIS), and muscle ultrasound (US). Body composition parameters of all methods are related to the outcome and appear relevant in clinical practice. The US is the only parameter by which muscle dimensions are measured. BIS and SCI are also dependent on either theoretical assumptions or the use of population-specific regression equations. Potential caveats of the methods are that SCI can be influenced by residual renal function, BIS can be influenced by fluid overload, although the latter may be circumvented by the use of a three-compartment model, and that muscle US reflects regional and not whole body MM. In conclusion, both SCI and BIS as well as muscle US are all valuable methods that can be applied for bedside nutritional assessment in patients on HD and appear suitable for routine follow-up. The choice for either method depends on local preferences. However, estimation of MM or its proxies should always be part of a multidimensional assessment of the patient followed by a personalized treatment strategy.
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http://dx.doi.org/10.3389/fnut.2021.697523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415223PMC
August 2021

Effect of citric-acid dialysate on the QTC-interval.

Sci Rep 2021 05 10;11(1):9909. Epub 2021 May 10.

Department of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands.

Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p < 0.001), but not with A1.5 (from 439 to 443 ms; p = 0.13). In conclusion, we found that the use of C1.5 or A1.25 is associated with a significant prolongation of QTc which was however relatively limited.
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http://dx.doi.org/10.1038/s41598-021-89083-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110800PMC
May 2021

COVID-19 in ESRD and Acute Kidney Injury.

Blood Purif 2021;50(4-5):610-620. Epub 2020 Dec 15.

Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.

The COVID-19 pandemic has greatly affected nephrology. Firstly, dialysis patients appear to be at increased risk for infection due to viral transmission next to an enhanced risk for mortality as compared to the general population, even in the face of an often apparently mild clinical presentation. Derangements in the innate and adaptive immune systems may be responsible for a reduced antiviral response, whereas chronic activation of the innate immune system and endothelial dysfunction provide a background for a more severe course. The presence of severe comorbidity, older age, and a reduction of organ reserve may lead to a rapid deterioration of the clinical situation of the patients in case of severe infection. Secondly, patients with COVID-19 are at increased risk of acute kidney injury (AKI), which is related to the severity of the clinical disease. The presence of AKI, and especially the need for renal replacement therapy (RRT), is associated with an increased risk of mortality. AKI in COVID-19 has a multifactorial origin, in which direct viral invasion of kidney cells, activation of the renin-angiotensin aldosterone system, a hyperinflammatory response, hypercoagulability, and nonspecific factors such as hypotension and hypoxemia may be involved. Apart from logistic challenges and the need for strict hygiene within units, treatment of patients with ESRD and COVID-19 is not different from that of the general population. Extracorporeal treatment of patients with AKI with RRT can be complicated by frequent filter clotting due to the hypercoagulable state, for which regional citrate coagulation provides a reasonable solution. Also, acute peritoneal dialysis may be a reasonable option in these patients. Whether adjuncts to extracorporeal therapies, such as hemoadsorption, provide additional benefits in the case of severely ill COVID-19 patients needs to be addressed in controlled studies.
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http://dx.doi.org/10.1159/000513214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802200PMC
July 2021

The Effects of Chronic Dialysis on Physical Status, Quality of Life, and Arterial Stiffness: A Longitudinal Study in Prevalent Dialysis Patients.

Nephron 2021 27;145(1):44-54. Epub 2020 Oct 27.

Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center+, Maastricht, The Netherlands.

Introduction: It is widely known that dialysis patients have significantly impaired functional outcomes and arterial stiffness, but still few studies have investigated the effects of dialysis longitudinally by a multidimensional approach. We aimed to assess longitudinal patterns of physical activity (PA), physical functioning (PF), health-related quality of life (HrQoL), body composition (BC), and arterial stiffness in prevalent dialysis patients.

Materials And Methods: Thirty-nine prevalent dialysis patients (23 conventional hemodialysis [CHD] and 16 peritoneal dialysis) with a mean vintage of 25.7 (±22.1) months were included in this observational prospective study with a 2-year follow-up, and at baseline 20 healthy controls were included. Measurements were performed every 6 months. HrQoL was assessed using the Short Form-36 (SF-36) questionnaire. PA was assessed using the SenseWear™ Pro3 accelerometer. PF was assessed by walking speed, the PF subscale of the SF-36, and handgrip strength (HGS). BC was assessed using the Body Composition Monitor® and arterial stiffness by measuring carotid-femoral pulse wave velocity (PWV). The longitudinal trend was assessed using linear mixed models, correcting for sex, age, and dialysis vintage. For PWV, the trend was additionally corrected for diabetes and systolic blood pressure.

Results: After correction, no statistically significant changes over time were observed for the parameters of PA, PF, HrQoL, and BC. In the combined group and in the group of CHD patients only, a significant change was observed for PWV (overall trend: p = 0.007 and p = 0.008, respectively). A statistically significant difference at baseline was observed between dialysis patients and healthy controls in all parameters, except for HGS and PWV.

Discussion/conclusion: We observed no statistically significant changes in functional outcomes during a 2-year follow-up period, but a significant increase was observed for arterial stiffness. These results might suggest that after a certain period in time, a relatively stable course is present in functional outcomes, but an ongoing deterioration in arterial stiffness occurs, which might increase the risk of cardiovascular disease and all-cause mortality in these patients.
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http://dx.doi.org/10.1159/000510624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845435PMC
November 2021

Artificial intelligence enabled applications in kidney disease.

Semin Dial 2021 01 13;34(1):5-16. Epub 2020 Sep 13.

Fresenius Medical Care, Waltham, MA, USA.

Artificial intelligence (AI) is considered as the next natural progression of traditional statistical techniques. Advances in analytical methods and infrastructure enable AI to be applied in health care. While AI applications are relatively common in fields like ophthalmology and cardiology, its use is scarcely reported in nephrology. We present the current status of AI in research toward kidney disease and discuss future pathways for AI. The clinical applications of AI in progression to end-stage kidney disease and dialysis can be broadly subdivided into three main topics: (a) predicting events in the future such as mortality and hospitalization; (b) providing treatment and decision aids such as automating drug prescription; and (c) identifying patterns such as phenotypical clusters and arteriovenous fistula aneurysm. At present, the use of prediction models in treating patients with kidney disease is still in its infancy and further evidence is needed to identify its relative value. Policies and regulations need to be addressed before implementing AI solutions at the point of care in clinics. AI is not anticipated to replace the nephrologists' medical decision-making, but instead assist them in providing optimal personalized care for their patients.
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http://dx.doi.org/10.1111/sdi.12915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891588PMC
January 2021

Changes in pre-dialysis blood pressure variability in the first year of dialysis associate with mortality in European hemodialysis patients: a retrospective cohort study on behalf of the MONDO Initiative.

J Hum Hypertens 2021 05 9;35(5):437-445. Epub 2020 Jun 9.

Renal Research Institute, New York, NY, USA.

Pre-hemodialysis systolic blood pressure variability (pre-HD SBPV) has been associated with outcomes. The association of a change in pre-HD SBPV over time with outcomes, and predictors of this change, has not yet been studied. Therefore, we studied this in a cohort of 8825 incident hemodialysis (HD) patients from the European Monitoring Dialysis Outcomes Initiative database. Patient level pre-HD SBPV was calculated as the standard deviation of the residuals of a linear regression model of systolic blood pressure (SBP) over time divided by individual mean SBP in the respective time periods. The pre-HD SBPV difference between months 1-6 and 7-12 was used as an indicator of pre-HD SBPV change. The association between pre-HD SBPV change and all-cause mortality in year 2 was analyzed by multivariate Cox models. Predictors of pre-HD SBPV change was determined by logistic regression models. We found the highest pre-HD SBPV tertile, in the first 6 months after initiation of HD, had the highest mortality rates (adjusted HR 1.44 (95% confidence intervals (95% CI): 1.15-1.79)). An increase in pre-HD SBPV between months 1-6 and 7-12 was associated with an increased risk of mortality in year 2 (adjusted HR 1.29 (95% CI: 1.05-1.58)) compared with stable pre-HD SPBV. A pre-HD SBPV increase was associated with female gender, higher mean pre-HD SBP and pulse pressure, and lower HD frequency.
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http://dx.doi.org/10.1038/s41371-020-0354-0DOI Listing
May 2021

Wearable health devices and personal area networks: can they improve outcomes in haemodialysis patients?

Nephrol Dial Transplant 2020 03;35(Suppl 2):ii43-ii50

Renal Research Institute, New York, NY, USA.

Digitization of healthcare will be a major innovation driver in the coming decade. Also, enabled by technological advancements and electronics miniaturization, wearable health device (WHD) applications are expected to grow exponentially. This, in turn, may make 4P medicine (predictive, precise, preventive and personalized) a more attainable goal within dialysis patient care. This article discusses different use cases where WHD could be of relevance for dialysis patient care, i.e. measurement of heart rate, arrhythmia detection, blood pressure, hyperkalaemia, fluid overload and physical activity. After adequate validation of the different WHD in this specific population, data obtained from WHD could form part of a body area network (BAN), which could serve different purposes such as feedback on actionable parameters like physical inactivity, fluid overload, danger signalling or event prediction. For a BAN to become clinical reality, not only must technical issues, cybersecurity and data privacy be addressed, but also adequate models based on artificial intelligence and mathematical analysis need to be developed for signal optimization, data representation, data reliability labelling and interpretation. Moreover, the potential of WHD and BAN can only be fulfilled if they are part of a transformative healthcare system with a shared responsibility between patients, healthcare providers and the payors, using a step-up approach that may include digital assistants and dedicated 'digital clinics'. The coming decade will be critical in observing how these developments will impact and transform dialysis patient care and will undoubtedly ask for an increased 'digital literacy' for all those implicated in their care.
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http://dx.doi.org/10.1093/ndt/gfaa015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066542PMC
March 2020

End-Stage Renal Disease Patients Lose a Substantial Amount of Amino Acids during Hemodialysis.

J Nutr 2020 05;150(5):1160-1166

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: Poor nutritional status is frequently observed in end-stage renal disease patients and associated with adverse clinical outcomes and increased mortality. Loss of amino acids (AAs) during hemodialysis (HD) may contribute to protein malnutrition in these patients.

Objective: We aimed to assess the extent of AA loss during HD in end-stage renal disease patients consuming their habitual diet.

Methods: Ten anuric chronic HD patients (mean ± SD age: 67.9 ± 19.3 y, BMI: 23.2 ± 3.5 kg/m2), undergoing HD 3 times per week, were selected to participate in this study. Spent dialysate was collected continuously and plasma samples were obtained directly before and after a single HD session in each participant. AA profiles in spent dialysate and in pre-HD and post-HD plasma were measured through ultra-performance liquid chromatography to determine AA concentrations and, as such, net loss of AAs. In addition, dietary intake before and throughout HD was assessed using a 24-h food recall questionnaire during HD. Paired-sample t tests were conducted to compare pre-HD and post-HD plasma AA concentrations.

Results: During an HD session, 11.95 ± 0.69 g AAs were lost via the dialysate, of which 8.26 ± 0.46 g were nonessential AAs, 3.69 ± 0.31 g were essential AAs, and 1.64 ± 0.17 g were branched-chain AAs. As a consequence, plasma total and essential AA concentrations declined significantly from 2.88 ± 0.15 and 0.80 ± 0.05 mmol/L to 2.27 ± 0.11 and 0.66 ± 0.05 mmol/L, respectively (P < 0.05). AA profiles of pre-HD plasma and spent dialysate were similar. Moreover, AA concentrations in pre-HD plasma and spent dialysate were strongly correlated (Spearman's ρ = 0.92, P < 0.001).

Conclusions: During a single HD session, ∼12 g AAs are lost into the dialysate, causing a significant decline in plasma AA concentrations. AA loss during HD can contribute substantially to protein malnutrition in end-stage renal disease patients. This study was registered at the Netherlands Trial Registry (NTR7101).
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http://dx.doi.org/10.1093/jn/nxaa010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198312PMC
May 2020

Association of all-cause mortality with pre-dialysis systolic blood pressure and its peridialytic change in chronic hemodialysis patients.

Nephrol Dial Transplant 2020 09;35(9):1602-1608

Research Department, Renal Research Institute, New York, NY, USA.

Background: Pre-dialysis systolic blood pressure (pre-HD SBP) and peridialytic SBP change have been associated with morbidity and mortality among hemodialysis (HD) patients in previous studies, but the nature of their interaction is not well understood.

Methods: We analyzed pre-HD SBP and peridialytic SBP change (calculated as post-HD SBP minus pre-HD SBP) between January 2001 and December 2012 in HD patients treated in US Fresenius Medical Care facilities. The baseline period was defined as Months 4-6 after HD initiation, and all-cause mortality was noted during follow-up. Only patients who survived baseline and had no missing covariates were included. Censoring events were renal transplantation, modality change or study end. We fitted a Cox proportional hazard model with a bivariate spline functions for the primary predictors (pre-HD SBP and peridialytic SBP change) with adjustment for age, gender, race, diabetes, access-type, relative interdialytic weight gain, body mass index, albumin, equilibrated normalized protein catabolic rate and ultrafiltration rate.

Results: A total of 172 199 patients were included. Mean age was 62.1 years, 61.6% were white and 55% were male. During a median follow-up of 25.0 months, 73 529 patients (42.7%) died. We found that a peridialytic SBP rise combined with high pre-HD SBP was associated with higher mortality. In contrast, when concurrent with low pre-HD SBP, a peridialytic SBP rise was associated with better survival.

Conclusion: The association of pre-HD and peridialytic SBP change with mortality is complex. Our findings call for a joint, not isolated, interpretation of pre-HD SBP and peridialytic SBP change.
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http://dx.doi.org/10.1093/ndt/gfz289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473807PMC
September 2020

Three compartment bioimpedance spectroscopy in the nutritional assessment and the outcome of patients with advanced or end stage kidney disease: What have we learned so far?

Hemodial Int 2020 04 22;24(2):148-161. Epub 2020 Jan 22.

Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center+, Maastricht, The Netherlands.

Bioimpedance spectroscopy (BIS) is an easily applicable tool to assess body composition. The three compartment model BIS (3C BIS) conventionally expresses body composition as lean tissue index (LTI) (lean tissue mass [LTM]/height in meters squared) and fat tissue index (FTI) (adipose tissue mass/height in meters squared), and a virtual compartment reflecting fluid overload (FO). It has been studied extensively in relation to diagnosis and treatment guidance of fluid status disorders in patients with advanced-stage or end-stage renal disease. It is the aim of this article to provide a narrative review on the relevance of 3C BIS in the nutritional assessment in this population. At a population level, LTI decreases after the start of hemodialysis, whereas FTI increases. LTI below the 10th percentile is a consistent predictor of outcome whereas a low FTI is predominantly associated with outcome when combined with a low LTI. Recent research also showed the connection between low LTI, inflammation, and FO, which are cumulatively associated with an increased mortality risk. However, studies toward nutritional interventions based on BIS data are still lacking in this population. In conclusion, 3C BIS, by disentangling the components of body mass index, has contributed to our understanding of the relevance of abnormalities in different body compartments in chronic kidney disease patients, and appears to be a valuable prognostic tool, at least at a population level. Studies assessing the effect of BIS guided nutritional intervention could further support its use in the daily clinical care for renal patients.
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http://dx.doi.org/10.1111/hdi.12812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216830PMC
April 2020

The impact of volume overload on technique failure in incident peritoneal dialysis patients.

Clin Kidney J 2021 Feb 22;14(2):570-577. Epub 2019 Dec 22.

Department of Medicine, Zealand University Hospital, Roskilde, Denmark.

Background: Technique failure in peritoneal dialysis (PD) can be due to patient- and procedure-related factors. With this analysis, we investigated the association of volume overload at the start and during the early phase of PD and technique failure.

Methods: In this observational, international cohort study with longitudinal follow-up of incident PD patients, technique failure was defined as either transfer to haemodialysis or death, and transplantation was considered as a competing risk. We explored parameters at baseline or within the first 6 months and the association with technique failure between 6 and 18 months, using a competing risk model.

Results: Out of 1092 patients of the complete cohort, 719 met specific inclusion and exclusion criteria for this analysis. Being volume overloaded, either at baseline or Month 6, or at both time points, was associated with an increased risk of technique failure compared with the patient group that was euvolaemic at both time points. Undergoing treatment at a centre with a high proportion of PD patients was associated with a lower risk of technique failure.

Conclusions: Volume overload at start of PD and/or at 6 months was associated with a higher risk of technique failure in the subsequent year. The risk was modified by centre characteristics, which varied among regions.
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http://dx.doi.org/10.1093/ckj/sfz175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886558PMC
February 2021

Using Bioimpedance Spectroscopy to Assess Volume Status in Dialysis Patients.

Blood Purif 2020 18;49(1-2):178-184. Epub 2019 Dec 18.

Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands,

The aim of the paper is to reflect on the current status of bioimpedance spectroscopy (BIS) in fluid management in dialysis patients. BIS identifies fluid overload (FO) as a virtual (overhydration) compartment, which is calculated from the difference between the measured extracellular volume and the predicted values based on a fixed hydration of lean and adipose tissue mass. FO is highly prevalent in both hemodialysis (HD) and peritoneal dialysis (PD) patients, while levels of FO are at a population level comparable between PD patients and HD patients when measured before the dialysis treatment. Even mild levels of FO are independently related to outcome in patients on HD, PD as well as in nondialysis patients with advanced chronic kidney disease. FO is not only related to left ventricular hypertrophy (LVH) but also forms part of a multidimensional spectrum with noncardiovascular risk factors such as malnutrition and inflammation. Even after multiple adjustments, FO remains an independent predictor of mortality. BIS-assisted adjustment of dry weight in HD patients has been shown to improve hypertension control and LVH and has resulted in a decline in intradialytic symptomatology. On the other hand, with increased fluid removal, target weight may not always be reached due to an increase in intradialytic symptomatology, and care should be applied in target weight adjustment in fluid overloaded patients with severe malnutrition and/or inflammation. Although a reduction in hospitalization rate was suggested, the effect of BIS-guided dry weight adjustment on mortality has not yet been shown, however, although available studies are underpowered. In PD patients, results have been more equivocal, which may be partly related to differences in treatment protocols or study populations. Future large-scale studies are needed to assess the full potential of BIS.
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http://dx.doi.org/10.1159/000504079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114899PMC
December 2020

Intradialytic Hypotension: Mechanisms and Outcome.

Blood Purif 2020 18;49(1-2):158-167. Epub 2019 Dec 18.

Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands,

Intradialytic hypotension (IDH) occurs in approximately 10-12% of treatments. Whereas several definitions for IDH are available, a nadir systolic blood pressure carries the strongest relation with outcome. Whereas the relation between IDH may partly be based on patient characteristics, it is likely that also impaired organ perfusion leading to permanent damage, plays a role in this relationship. The pathogenesis of IDH is multifactorial and is based on a combination of a decline in blood volume (BV) and impaired vascular resistance at a background of a reduced cardiovascular reserve. Measurements of absolute BV based on an on-line dilution method appear more promising than relative BV measurements in the prediction of IDH. Also, feedback treatments in which ultrafiltration rate is automatically adjusted based on changes in relative BV have not yet resulted in improvement. Frequent assessment of dry weight, attempting to reduce interdialytic weight gain and prescribing more frequent or longer dialysis treatments may aid in preventing IDH. The impaired vascular response can be improved using isothermic or cool dialysis treatment which has also been associated with a reduction in end organ damage, although their effect on mortality has not yet been assessed. For the future, identification of vulnerable patients based on artificial intelligence and on-line assessment of markers of organ perfusion may aid in individualizing treatment prescription, which will always remain dependent on the clinical context of the patient.
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http://dx.doi.org/10.1159/000503776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114908PMC
December 2020

Dietary Protein and Physical Activity Interventions to Support Muscle Maintenance in End-Stage Renal Disease Patients on Hemodialysis.

Nutrients 2019 Dec 5;11(12). Epub 2019 Dec 5.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

End-stage renal disease patients have insufficient renal clearance capacity left to adequately excrete metabolic waste products. Hemodialysis (HD) is often employed to partially replace renal clearance in these patients. However, skeletal muscle mass and strength start to decline at an accelerated rate after initiation of chronic HD therapy. An essential anabolic stimulus to allow muscle maintenance is dietary protein ingestion. Chronic HD patients generally fail to achieve recommended protein intake levels, in particular on dialysis days. Besides a low protein intake on dialysis days, the protein equivalent of a meal is extracted from the circulation during HD. Apart from protein ingestion, physical activity is essential to allow muscle maintenance. Unfortunately, most chronic HD patients have a sedentary lifestyle. Yet, physical activity and nutritional interventions to support muscle maintenance are generally not implemented in routine patient care. To support muscle maintenance in chronic HD patients, quantity and timing of protein intake should be optimized, in particular throughout dialysis days. Furthermore, implementing physical activity either during or between HD sessions may improve the muscle protein synthetic response to protein ingestion. A well-orchestrated combination of physical activity and nutritional interventions will be instrumental to preserve muscle mass in chronic HD patients.
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http://dx.doi.org/10.3390/nu11122972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950262PMC
December 2019

Citric-acid dialysate improves the calcification propensity of hemodialysis patients: A multicenter prospective randomized cross-over trial.

PLoS One 2019 5;14(12):e0225824. Epub 2019 Dec 5.

Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center+, Maastricht, the Netherlands.

Introduction: The concentration of dialysate calcium (dCa) has been suggested to affect vascular calcification, but evidence is scarce. Calcification propensity reflects the intrinsic capacity of serum to prevent calcium and phosphate to precipitate. The use of citric-acid dialysate may have a beneficial effect on the calcification propensity due to the chelating effect on calcium and magnesium. The aim of this study was to compare the intradialytic and short-term effects of haemodialysis with either standard acetic-acid dialysate with dCa1.50 (A1.5) or dCa1.25 (A1.25), as well as citric-acid dialysate with dCa1.50 (C1.5) in bicarbonate dialysis on the calcification propensity of serum.

Methods: Chronic stable hemodialysis patients were included. This multicenter randomized cross-over study consisted out of a baseline week (A1.5), followed by the randomized sequence of A1.25 or C1.5 for one week after which the alternate treatment was provided after a washout week with A1.5. Calcification propensity of serum was assessed by time-resolved nephelometry where the T50 reflects the transition time between formation of primary and secondary calciprotein particles.

Results: Eighteen patients (median age 70 years) completed the study. Intradialytic change in T50 was increased with C1.5 (121 [90-152]min) compared to A1.25 (83 [43-108]min, p<0.001) and A1.5 (66 [18-102]min, p<0.001). During the treatment week, predialysis T50 increased significantly from the first to the third session with C1.5 (271 [234-291] to 280 [262-339]min, p = 0.002) and with A1.25 (274 [213-308] to 307 [256-337]min, p<0.001), but not with A1.5 (284 [235-346] to 300 [247-335]min, p = 0.33).

Conclusion: Calcification propensity, as measured by the change in T50, improved significantly during treatment in C1.5 compared to A1.25 and A1.5. Long-term studies are needed to investigate the effects of different dialysate compositions concentrations on vascular calcification and bone mineral disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225824PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894765PMC
March 2020

Relationship between serum phosphate levels and survival in chronic hemodialysis patients: interactions with age, malnutrition and inflammation.

Clin Kidney J 2021 Jan 5;14(1):348-357. Epub 2019 Dec 5.

Research Department, Renal Research Institute, New York, NY, USA.

Background: Evidence indicates that the inverse relationships between phosphate levels and mortality maybe modified by age. Furthermore, malnutrition and inflammation could strengthen the risk associated with phosphate abnormalities. This study aimed to assess the associations between phosphate levels and mortality while accounting for the interactions with age and parameters associated with malnutrition and inflammation in hemodialysis (HD) patients.

Methods: Adult HD patients ( = 245 853) treated in Fresenius Medical Care North America clinics from January 2010 to October 2018 were enrolled. Baseline was defined as Months 4-6 on dialysis, with the subsequent 12 months as the follow-up period. Univariate and multivariate Cox proportional hazard models with spline terms were applied to study the nonlinear relationships between serum phosphate levels and mortality. The interactions of phosphate levels with albumin, creatinine, normalized protein catabolic rate (nPCR) and neutrophil-lymphocyte ratio (NLR) were assessed with smoothing spline analysis of variance Cox proportional hazard models.

Results: Older patients tended to have lower levels of serum phosphate, albumin, creatinine and nPCR. Additionally, both low (<4.0 mg/dL) and high (>5.5 mg/dL) phosphate levels were associated with higher risk of mortality across all age strata. The U-shaped relationships between phosphate levels and outcome persisted even for patients with low or high levels of serum albumin, creatinine, nPCR and NLR, respectively.

Conclusion: The consistent U-shaped relationships between serum phosphate and mortality across age strata and levels of inflammatory and nutritional status should prompt the search for underlying causes and potentially nutritional intervention in clinical practice.
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http://dx.doi.org/10.1093/ckj/sfz143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857835PMC
January 2021

Endothelial dysfunction and low-grade inflammation in the transition to renal replacement therapy.

PLoS One 2019 13;14(9):e0222547. Epub 2019 Sep 13.

Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center+, Maastricht, the Netherlands.

Introduction: End-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce.

Methods: We compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology.

Results: In linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter.

Conclusions: Levels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222547PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743867PMC
March 2020

Advanced glycation endproducts and dicarbonyls in end-stage renal disease: associations with uraemia and courses following renal replacement therapy.

Clin Kidney J 2020 Oct 28;13(5):855-866. Epub 2019 Aug 28.

CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.

Background: End-stage renal disease (ESRD) is strongly associated with cardiovascular disease (CVD) risk. Advanced glycation endproducts (AGEs) and dicarbonyls, major precursors of AGEs, may contribute to the pathophysiology of CVD in ESRD. However, detailed data on the courses of AGEs and dicarbonyls during the transition of ESRD patients to renal replacement therapy are lacking.

Methods: We quantified an extensive panel of free and protein-bound serum AGEs [ -(carboxymethyl)lysine (CML), -(carboxyethyl)lysine (CEL), -(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)], serum dicarbonyls [glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG)] and tissue AGE accumulation [estimated by skin autofluorescence (SAF)] in a combined cross-sectional and longitudinal observational study of patients with ESRD transitioning to dialysis or kidney transplantation (KTx), prevalent dialysis patients and healthy controls. Cross-sectional comparisons were performed with linear regression analyses, and courses following renal replacement therapy were analysed with linear mixed models.

Results: Free and protein-bound AGEs, dicarbonyls and SAF were higher in chronic kidney disease (CKD) Stage 5 non-dialysis (CKD 5-ND; = 52) and CKD Stage 5 dialysis (CKD 5-D; = 35) than in controls ( = 42). In addition, free AGEs, protein-bound CML, GO and SAF were even higher in CKD 5-D than in CKD5-ND. Similarly, following dialysis initiation ( = 43) free and protein-bound AGEs, and GO increased, whereas SAF remained similar. In contrast, following KTx ( = 21), free and protein-bound AGEs and dicarbonyls, but not SAF, markedly declined.

Conclusions: AGEs and dicarbonyls accumulate in uraemia, which is even exaggerated by dialysis initiation. In contrast, KTx markedly reduces AGEs and dicarbonyls. Given their associations with CVD risk in high-risk populations, lowering AGE and dicarbonyl levels may be valuable.
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http://dx.doi.org/10.1093/ckj/sfz099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577778PMC
October 2020

Relations of advanced glycation endproducts and dicarbonyls with endothelial dysfunction and low-grade inflammation in individuals with end-stage renal disease in the transition to renal replacement therapy: A cross-sectional observational study.

PLoS One 2019 13;14(8):e0221058. Epub 2019 Aug 13.

CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.

Background: Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited.

Methods: We examined cross-sectional Spearman's rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N∈-(carboxymethyl)lysine (CML), N∈-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α.

Results: After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI.

Conclusions: In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221058PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692010PMC
March 2020

Residual Renal Function and Effect of Low-Sodium Solution on Blood Pressure in Peritoneal Dialysis Patients.

Perit Dial Int 2019 Jul-Aug;39(4):335-343. Epub 2019 May 23.

Clinical and Epidemiological Research, Fresenius Medical Care, Bad Homburg, Germany

Residual renal function (RRF) affects sodium and fluid balance. The aim of this analysis was to examine the impact of RRF on the effect of a sodium-reduced peritoneal dialysis fluid (PDF) on blood pressure (BP).This is a post-hoc analysis of a prospective, randomized, controlled double-blind clinical trial with 82 patients on continuous ambulatory PD (CAPD) treated with a low-sodium (125 mmol/L Na) or a standard-sodium (134 mmol/L Na) PDF. Subgroups according to glomerular filtration rate (GFR) at baseline (≤ / > 6 mL/min/1.73 m) were analyzed for BP and antihypertensive medication.In the low-GFR group on low-sodium PDF ( = 26), systolic BP was reduced from 152 ± 24 mmHg at baseline to 137 ± 21 mmHg at week 12, diastolic BP from 90 ± 16 mmHg to 83 ± 11 mmHg. In the low-GFR group on standard-sodium PDF and in the high-GFR group on both PDF types, only minor changes were observed. For the low-GFR subgroup, the confounder-adjusted mean study group difference in systolic BP at week 12 between low-sodium and standard-sodium PDF was -16.9 (95% confidence interval [CI] -27.2 to -6.6) mmHg, for diastolic BP, it was -7.0 (95% CI -12.6 to -1.4) mmHg. In both GFR subgroups, more patients had a reduced daily dose of antihypertensive medication and fewer patients an increased daily dose in the low-sodium compared with the standard-sodium group at week 12.The reduction of BP with a sodium-reduced PDF seems to be more effective in patients with no or low RRF than in patients with residual capacity of renal sodium and fluid control.
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http://dx.doi.org/10.3747/pdi.2018.00120DOI Listing
April 2020

Longitudinal patterns of health-related quality of life and dialysis modality: a national cohort study.

BMC Nephrol 2019 01 8;20(1). Epub 2019 Jan 8.

Fresenius Medical Care North America, Waltham, MA, USA.

Background: Health-related quality of life (HrQoL) varies among dialysis patients. However, little is known about the association of dialysis modality with HrQoL over time. We describe longitudinal patterns of HrQoL among chronic dialysis patients by treatment modality.

Methods: National retrospective cohort study of adult patients who initiated in-center dialysis or a home modality (peritoneal or home hemodialysis) between 1/2013 and 6/2015. Patients remained on the same modality for the first 120 days of the first two years. HrQoL was assessed by the Kidney Disease and Quality of Life-36 (KDQOL) survey in the first 120 days of the first two years after dialysis initiation. Home modality patients were matched to in-center patients in a 1:5 fashion.

Results: In-center (n=4234) and home modality (n=880) patients had similar demographic and clinical characteristics. In-center dialysis patients had lower mean KDQOL scores across several domains compared to home modality patients. For patients who remained on the same modality, there was no change in HrQoL. However, there were trends towards clinically meaningful changes in several aspects of HrQoL for patients who switched modalities. Specifically, physical functioning decreased for patients who switched from home to in-center dialysis (p< 0.05).

Conclusions: Among a national cohort of chronic dialysis patients, there was a trend towards different patterns of HrQoL life that were only observed among patients who changed modality. Patients who switched from home to in-center modalities had significant lower physical functioning over time. Providers and patients should be mindful of HrQoL changes that may occur with dialysis modality change.
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http://dx.doi.org/10.1186/s12882-018-1198-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325821PMC
January 2019

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative.

Am J Nephrol 2019 13;49(1):1-10. Epub 2018 Dec 13.

Renal Research Institute, New York, New York, USA.

Background: Low serum sodium (SNa) is associated with an increased mortality in chronic hemodialysis (HD) patients. Dialysis patients are thought to have an individual pre-dialysis SNa set-point, yet there is evidence for variability of pre-dialysis SNa in individual patient. In this study, we explored the association of several SNa variability metrics with all-cause mortality in a large patient population from the international MONitoring Dialysis Outcomes (MONDO) Initiative.

Methods: All adult incident patients from the MONDO database with more than 5 SNa measurements during the first year on HD were included. All patients were required to survive the first year on HD (defined as the baseline). During the subsequent 2 years of follow-up, all-cause mortality was recorded. The following variability indicators were calculated during baseline: mean SNa and its SD; average real variability (ARV, average the absolute distance of the 2 consecutive SNa measurements), and average directional range (DR, the difference between minimum and maximum values). We used Cox Proportional hazard model with bivariate spline terms to analyze the joint association of SNa and SD, ARV and DR, respectively, with all-cause mortality. While conducting the multivariate Cox regression analyses, patients were stratified into 3 groups of DR (Negative DR: -20≤ DR ≤ -6, Null DR: -6< DR < 6 and Positive DR: 6≤ DR ≤20) with the Null DR as the reference group.

Results: We included 20,216 patients in the study. A SNa ≤135 mEq/L was observed to be the strongest predictor of evaluated mortality risk. Higher SNa variability (quantified as SD, ARV, and DR) was also associated with an increased mortality irrespective of SNa levels. When compared with higher SD or ARV, greater DR showed a stronger association with an elevated risk of death. Controlling the Cox Proportional hazard models for additional parameters showed consistent results.

Conclusion: Higher SNa variability associated with increased all-cause mortality at all levels of SNa. DR of SNa showed the strongest association with mortality and may constitute a Simple and novel prognostic indicator, easily applicable at the bedside.
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http://dx.doi.org/10.1159/000495354DOI Listing
March 2020

Association of Central Venous Oxygen Saturation Variability and Mortality in Hemodialysis Patients.

Blood Purif 2019 6;47(1-3):246-253. Epub 2018 Dec 6.

Renal Research Institute, New York, New York, USA,

Background: Central venous oxygen saturation (ScvO2) is correlated with cardiac output. In most patients, ScvO2 declines during hemodialysis (HD) due to factors such as reduced preload, myocardial stunning, and intermittent arrhythmias. Previous research has shown that low ScvO2 is associated with higher mortality in chronic HD patients. In this research, we tested the hypothesis that ScvO2 variability is associated with all-cause mortality.

Methods: We conducted a retrospective study in 232 chronic HD patients with central venous catheter as vascular access. ScvO2 was recorded 1× per minute during dialysis using the Crit-Line monitor. A 6-month baseline comprising at least 10 dialysis treatments with ScvO2 recordings preceded a follow-up period of up to 3 years. The coefficient of variation (CV) of ScvO2 (100 times the ratio of the standard deviation and mean of ScvO2) served as a measure of ScvO2 stability during baseline. Patients were stratified by median population CV of ScvO2 during baseline, and survival during follow-up was compared between the 2 groups by Kaplan Meier and multivariate Cox analysis. The association between CV of ScvO2 and all-cause mortality during follow-up was further assessed by Cox analysis with a spline term for CV of ScvO2.

Results: The mean CV ± standard deviation of ScvO2 in our population was 6.1 ± 2.7% and the median was 5.3%. Univariate Kaplan-Meier analysis (p = 0.043) and multivariate Cox analysis (hazard ratio [HR] 1.16; p = 0.0005) indicated that a CV of ScvO2 > 5.3% was significantly associated with increased mortality. In Cox analysis with spline term, a CV of ScvO2 >  11% was associated with a significantly increased HR for all-cause mortality.

Conclusion: High ScvO2 variability during dialysis is associated with increased all-cause mortality.
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http://dx.doi.org/10.1159/000494630DOI Listing
May 2019

Dialysate Calcium Levels: Do They Matter?

Blood Purif 2019 5;47(1-3):230-235. Epub 2018 Dec 5.

Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: Calcium (Ca) is an essential element that plays a critical role in many biological processes. In dialysis patients, the regulation of Ca balance is highly complex, given the absence of kidney function, endocrine disturbances and the use of drugs such as phosphate binders, vitamin D analogues, and calcimimetics. Also, the use of different dialysate Ca (DCa) baths has profound effect on Ca balance, which depends both on the difference between the Ca concentration in the bath and the serum of the patients, as on the ultrafiltration volume.

Summary: The choice of DCa may have important short- and long-term consequences. While lower DCa (especially < 2.5 mEq/L) concentrations have been associated with an increased risk of sudden cardiac death in observational studies, DCa in the higher ranges (3.0 mEq/L and above) may contribute to vascular pathology. Intra-dialytic hemodynamics may also be affected by the choice of DCa. In general, lower DCa concentrations are associated with an increase, and higher DCa concentrations with a decrease in parathyroid hormone (PTH) levels. Preliminary data has suggested that a DCa of 2.75 mEq/L may help in obtaining a net zero intradialytic Ca balance in individual patients, but clinical experience is still limited. Key Message: The optimal Ca balance depends on multiple parameters including blood Ca levels, PTH and the use of phosphate binders and vitamin D analogues, as well as on the risk of hemodynamic stability and cardiac arrhythmias. Therefore, DCa prescription should be individualised. A DCa of 2.75 mEq/L may be useful adjunct for dialysis providers.
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http://dx.doi.org/10.1159/000494584DOI Listing
May 2019

Body Fluids in End-Stage Renal Disease: Statics and Dynamics.

Blood Purif 2019 5;47(1-3):223-229. Epub 2018 Dec 5.

Maastricht University Medical Center, Maastricht, The Netherlands.

Background: Abnormalities in fluid status in hemodialysis (HD) patients are highly prevalent and are related to adverse outcomes.

Summary: The inherent discontinuity of the HD procedure in combination with an often compromised cardiovascular response is a major contributor to this phenomenon. In addition, systemic inflammation and endothelial dysfunction are related to extracellular fluid overload (FO). Underlying this relation may be factors such as hypoalbuminemia and an increased capillary permeability, leading to an altered fluid distribution between the blood volume (BV) and the interstitial fluid compartments, compromising fluid removal during dialysis. Indeed, whereas estimates of extracellular volume by bioimpedance spectroscopy are highly predictive of mortality, absolute BV assessed by the saline dilution technique was predictive of intra-dialytic morbidity. Changes in relative BV during HD are positively related to ultrafiltration rate (UFR) and, at least in some studies, negatively to FO. High UFR is also related to changes in central venous oxygen saturation (ScvO2), a marker for tissue perfusion. On the one hand, high UFR and more pronounced declines in ScvO2, but on the other hand, flat relative BV curves are also predictive of mortality; the relation between outcome which statics and dynamics of fluid status appears to be complex. Key Message: While technological developments enable the clinician to monitor statics and dynamics of fluid status and hemodynamics during HD in an accessible way, the role of technology-based interventions needs further study.
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http://dx.doi.org/10.1159/000494583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492508PMC
May 2019

Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?

Blood Purif 2019 16;47(1-3):171-184. Epub 2018 Nov 16.

Renal Research Institute, New York, New York, USA.

Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1-2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning -approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.
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http://dx.doi.org/10.1159/000494827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492515PMC
May 2019

TRANSITION PERIOD CLINICAL TRAJECTORIES FOR PD VERSUS HD STARTERS.

Perit Dial Int 2019 Jan-Feb;39(1):42-50. Epub 2018 Sep 25.

Medical Office, Fresenius Medical Care North America, Waltham, United States.

Background: Peritoneal dialysis (PD) starters generally have a better outcome compared with hemodialysis (HD) starters, perhaps related to treatment characteristics or case mix. We previously showed that pre- and post-dialysis start clinical parameter trajectories are related to outcomes. The aim of this study was to investigate these trajectories in PD and HD starters.

Methods: This retrospective observational study analyzing data from the Fresenius Medical Care-chronic kidney disease (CKD) Registry from January 2009 to March 2018 examines trends in key clinical parameters through the transition period covering 12 months before to 12 months after dialysis start in 8,088 HD and 1,015 PD starters.

Results: Hemodialysis starters differed from PD starters by a significantly greater decline in estimated glomerular filtration rate (eGFR) slope (-0.64 vs -0.45 mL/min/1.73 m2/month) before and higher eGFR (9.85 vs 7.84 mL/min/1.73 m2) at dialysis start. Relatedly, differences in phosphorus (0.07 vs 0.05 mg/dL/month) and hemoglobin (-0.08 vs -0.01 g/dL/month) slopes before the transition to dialysis therapy were observed. After dialysis start, HD starters experienced a greater increase in albumin (0.01 vs 0 g/dL/month) whereas PD starters experienced a decline in serum sodium and higher white blood cell counts compared with HD starters.

Conclusion: For nephrology practice CKD patients, HD and PD starters appear clinically comparable in the year before dialysis start although HD starters exhibit a more rapid pre-dialytic eGFR decline. Ideally, studies comparing incident HD and PD outcomes should also consider CKD eGFR trajectories. In the first dialysis year, divergence occurs in albumin, white blood cell count, sodium and hemoglobin trends, which may be partly treatment-related.
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http://dx.doi.org/10.3747/pdi.2017.00252DOI Listing
July 2020

All-cause mortality in relation to changes in relative blood volume during hemodialysis.

Nephrol Dial Transplant 2019 08;34(8):1401-1408

Renal Research Institute, New York, NY, USA.

Background: Relative blood volume (RBV) monitoring is widely used in hemodialysis (HD) patients, yet the association between intradialytic RBV and mortality is unknown.

Methods: Intradialytic RBV was recorded once/min during a 6-month baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and 3 h into HD served as a predictor of all-cause mortality during follow-up. We employed Kaplan-Meier analysis, univariate and adjusted Cox proportional hazards models for survival analysis.

Results: We studied 842 patients. During follow-up (median 30.8 months), 249 patients (29.6%) died. The following hourly RBV ranges were associated with improved survival: first hour, 93-96% [hazard ratio (HR) 0.58 (95% confidence interval (CI) 0.42-0.79)]; second hour, 89-94% [HR 0.54 (95% CI 0.39-0.75)]; third hour, 86-92% [HR 0.46 (95% CI 0.33-0.65)]. In about one-third of patients the RBV was within these ranges and in two-thirds it was above. Subgroup analysis by median age (≤/> 61 years), sex, race (white/nonwhite), predialysis systolic blood pressure (SBP; ≤/> 130 mmHg) and median interdialytic weight gain (≤/> 2.3 kg) showed comparable favorable RBV ranges. Patients with a 3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and rates, similar intradialytic average and nadir SBPs and hypotension rates, lower postdialysis SBP and a lower prevalence of congestive heart failure when compared with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges remained independent and significant outcome predictors.

Conclusion: Specific hourly intradialytic RBV ranges are associated with lower all-cause mortality in chronic HD patients.
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http://dx.doi.org/10.1093/ndt/gfy286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680100PMC
August 2019

Interactions Between Malnutrition, Inflammation, and Fluid Overload and Their Associations With Survival in Prevalent Hemodialysis Patients.

J Ren Nutr 2018 11 23;28(6):435-444. Epub 2018 Aug 23.

Maastricht University Medical Center, Maastricht, The Netherlands.

Objective: Predialysis fluid overload (FO) in hemodialysis (HD) patients is associated with an increased risk of death, further increased by the presence of inflammation. Malnutrition is also associated with outcome. Study objectives were, firstly, to investigate if the presence of FO is associated with malnutrition and whether this association is influenced by the presence of inflammation. Second, we assessed the associations of FO, malnutrition, and inflammation with outcome individually and in combination.

Design: International cohort study.

Setting: European patients of the Monitoring Dialysis Outcome Initiative cohort where bioimpedance and C-reactive protein measurements are performed as standard of care.

Subjects: 8883 prevalent HD patients.

Main Outcome Measure: Body composition, nutritional and inflammation status were assessed during a 3-month baseline period, and all-cause mortality was noted during 1 year follow-up. Malnutrition was defined as a lean tissue index <10th percentile (of age and gender matched healthy controls), FO as a predialysis overhydration >+1.1 L and inflammation as a C-reactive protein > 6.0 mg/L. We used Cox models to investigate the association with outcome.

Results: The presence of malnutrition was associated with higher levels of FO, this amount further increased when inflammation was present. Only 11.6% of the patients did not have any of the 3 risk factors and only 6.5% of the patients were only malnourished, which was not associated with an increased risk of death (Hazard Ratio [HR] 1.22 [95% Confidence Interval [CI]: 0.75-1.97]), whereas the combination of severe malnutrition, FO, and inflammation comprised the highest risk of death (HR 5.89 [95% CI: 2.28-8.01]).

Conclusion: In HD patients, predialysis FO associates with both malnutrition and the presence of inflammation, with the highest levels of FO observed when both are present. Malnutrition as singular risk factor was not associated with increased mortality risk. The highest mortality risk was observed in patients where all 3 risk factors were present.
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http://dx.doi.org/10.1053/j.jrn.2018.06.005DOI Listing
November 2018
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