Publications by authors named "Jeroen P Kooman"

209 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634611PMC
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

Trajectories of clinical and laboratory characteristics associated with COVID-19 in hemodialysis patients by survival.

Hemodial Int 2021 Aug 10. Epub 2021 Aug 10.

Global Medical Office, Fresenius Medical Care, Waltham, Massachusetts, USA.

Introduction: The clinical impact of COVID-19 has not been established in the dialysis population. We evaluated the trajectories of clinical and laboratory parameters in hemodialysis (HD) patients.

Methods: We used data from adult HD patients treated at an integrated kidney disease company who received a reverse transcription polymerase chain reaction (RT-PCR) test to investigate suspicion of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection between May 1 and September 1, 2020. Nonparametric smoothing splines were used to fit data for individual trajectories and estimate the mean change over time in patients testing positive or negative for SARS-CoV-2 and those who survived or died within 30 days of first suspicion or positive test date. For each clinical parameter of interest, the difference in average daily changes between COVID-19 positive versus negative group and COVID-19 survivor versus nonsurvivor group was estimated by fitting a linear mixed effects model based on measurements in the 14 days before (i.e., Day -14 to Day 0) Day 0.

Results: There were 12,836 HD patients with a suspicion of COVID-19 who received RT-PCR testing (8895 SARS-CoV-2 positive). We observed significantly different trends (p < 0.05) in pre-HD systolic blood pressure (SBP), pre-HD pulse rate, body temperature, ferritin, neutrophils, lymphocytes, albumin, and interdialytic weight gain (IDWG) between COVID-19 positive and negative patients. For COVID-19 positive group, we observed significantly different clinical trends (p < 0.05) in pre-HD pulse rate, lymphocytes, neutrophils, and albumin between survivors and nonsurvivors. We also observed that, in the group of survivors, most clinical parameters returned to pre-COVID-19 levels within 60-90 days.

Conclusion: We observed unique temporal trends in various clinical and laboratory parameters among HD patients who tested positive versus negative for SARS-CoV-2 infection and those who survived the infection versus those who died. These trends can help to define the physiological disturbances that characterize the onset and course of COVID-19 in HD patients.
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http://dx.doi.org/10.1111/hdi.12977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444916PMC
August 2021

Real-time prediction of intradialytic relative blood volume: a proof-of-concept for integrated cloud computing infrastructure.

BMC Nephrol 2021 08 9;22(1):274. Epub 2021 Aug 9.

Fresenius Medical Care, Global Medical Office, 920 Winter Street, Waltham, MA, 02451, USA.

Background: Inadequate refilling from extravascular compartments during hemodialysis can lead to intradialytic symptoms, such as hypotension, nausea, vomiting, and cramping/myalgia. Relative blood volume (RBV) plays an important role in adapting the ultrafiltration rate which in turn has a positive effect on intradialytic symptoms. It has been clinically challenging to identify changes RBV in real time to proactively intervene and reduce potential negative consequences of volume depletion. Leveraging advanced technologies to process large volumes of dialysis and machine data in real time and developing prediction models using machine learning (ML) is critical in identifying these signals.

Method: We conducted a proof-of-concept analysis to retrospectively assess near real-time dialysis treatment data from in-center patients in six clinics using Optical Sensing Device (OSD), during December 2018 to August 2019. The goal of this analysis was to use real-time OSD data to predict if a patient's relative blood volume (RBV) decreases at a rate of at least - 6.5 % per hour within the next 15 min during a dialysis treatment, based on 10-second windows of data in the previous 15 min. A dashboard application was constructed to demonstrate how reporting structures may be developed to alert clinicians in real time of at-risk cases. Data was derived from three sources: (1) OSDs, (2) hemodialysis machines, and (3) patient electronic health records.

Results: Treatment data from 616 in-center dialysis patients in the six clinics was curated into a big data store and fed into a Machine Learning (ML) model developed and deployed within the cloud. The threshold for classifying observations as positive or negative was set at 0.08. Precision for the model at this threshold was 0.33 and recall was 0.94. The area under the receiver operating curve (AUROC) for the ML model was 0.89 using test data.

Conclusions: The findings from our proof-of concept analysis demonstrate the design of a cloud-based framework that can be used for making real-time predictions of events during dialysis treatments. Making real-time predictions has the potential to assist clinicians at the point of care during hemodialysis.
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http://dx.doi.org/10.1186/s12882-021-02481-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351092PMC
August 2021

Machine learning directed interventions associate with decreased hospitalization rates in hemodialysis patients.

Int J Med Inform 2021 09 24;153:104541. Epub 2021 Jul 24.

Fresenius Medical Care, Global Medical Office, Waltham, United States. Electronic address:

Background: An integrated kidney disease company uses machine learning (ML) models that predict the 12-month risk of an outpatient hemodialysis (HD) patient having multiple hospitalizations to assist with directing personalized interdisciplinary interventions in a Dialysis Hospitalization Reduction Program (DHRP). We investigated the impact of risk directed interventions in the DHRP on clinic-wide hospitalization rates.

Methods: We compared the hospital admission and day rates per-patient-year (ppy) from all hemodialysis patients in 54 DHRP and 54 control clinics identified by propensity score matching at baseline in 2015 and at the end of the pilot in 2018. We also used paired T test to compare the between group difference of annual hospitalization rate and hospitalization days rates at baseline and end of the pilot.

Results: The between group difference in annual hospital admission and day rates was similar at baseline (2015) with a mean difference between DHRP versus control clinics of -0.008 ± 0.09 ppy and -0.05 ± 0.96 ppy respectively. The between group difference in hospital admission and day rates became more distinct at the end of follow up (2018) favoring DHRP clinics with the mean difference being -0.155 ± 0.38 ppy and -0.97 ± 2.78 ppy respectively. A paired t-test showed the change in the between group difference in hospital admission and day rates from baseline to the end of the follow up was statistically significant (t-value = 2.73, p-value < 0.01) and (t-value = 2.29, p-value = 0.02) respectively.

Conclusions: These findings suggest ML model-based risk-directed interdisciplinary team interventions associate with lower hospitalization rates and hospital day rate in HD patients, compared to controls.
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http://dx.doi.org/10.1016/j.ijmedinf.2021.104541DOI Listing
September 2021

Arterial oxygen saturation and hypoxemia in hemodialysis patients with COVID-19.

Clin Kidney J 2021 Apr 1;14(4):1222-1228. Epub 2021 Feb 1.

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

Background: Maintenance hemodialysis (MHD) patients are particularly vulnerable to coronavirus disease 2019 (COVID-19), a viral disease that may cause interstitial pneumonia, impaired alveolar gas exchange and hypoxemia. We ascertained the time course of intradialytic arterial oxygen saturation (SaO) in MHD patients between 4 weeks pre-diagnosis and the week post-diagnosis of COVID-19.

Methods: We conducted a quality improvement project in confirmed COVID-19 in-center MHD patients from 11 dialysis facilities. In patients with an arterio-venous access, SaO was measured 1×/min during dialysis using the Crit-Line monitor (Fresenius Medical Care, Waltham, MA, USA). We extracted demographic, clinical, treatment and laboratory data, and COVID-19-related symptoms from the patients' electronic health records.

Results: Intradialytic SaO was available in 52 patients (29 males; mean ± standard deviation age 66.5 ± 15.7 years) contributing 338 HD treatments. Mean time between onset of symptoms indicative of COVID-19 and diagnosis was 1.1 days (median 0; range 0-9). Prior to COVID-19 diagnosis the rate of HD treatments with hypoxemia, defined as treatment-level average SaO <90%, increased from 2.8% (2-4 weeks pre-diagnosis) to 12.2% (1 week) and 20.7% (3 days pre-diagnosis). Intradialytic O supplementation increased sharply post-diagnosis. Eleven patients died from COVID-19 within 5 weeks. Compared with patients who recovered from COVID-19, demised patients showed a more pronounced decline in SaO prior to COVID-19 diagnosis.

Conclusions: In HD patients, hypoxemia may precede the onset of clinical symptoms and the diagnosis of COVID-19. A steep decline of SaO is associated with poor patient outcomes. Measurements of SaO may aid the pre-symptomatic identification of patients with COVID-19.
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http://dx.doi.org/10.1093/ckj/sfab019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929020PMC
April 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

The oxygen cascade in patients treated with hemodialysis and native high-altitude dwellers: lessons from extreme physiology to benefit patients with end-stage renal disease.

Am J Physiol Renal Physiol 2021 03 28;320(3):F249-F261. Epub 2020 Dec 28.

Renal Research Institute, New York, New York.

Patients treated with hemodialysis (HD) repeatedly undergo intradialytic low arterial oxygen saturation and low central venous oxygen saturation, reflecting an imbalance between upper body systemic oxygen supply and demand, which are associated with increased mortality. Abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, contribute to the reduced tissue oxygen supply. HD treatment impairs pulmonary gas exchange and reduces ventilatory drive, whereas ultrafiltration can reduce tissue perfusion due to a decline in cardiac output. In addition to these factors, capillary rarefaction and reduced mitochondrial efficacy can further affect the balance between cellular oxygen supply and demand. Whereas it has been convincingly demonstrated that a reduced perfusion of heart and brain during HD contributes to organ damage, the significance of systemic hypoxia remains uncertain, although it may contribute to oxidative stress, systemic inflammation, and accelerated senescence. These abnormalities along the oxygen cascade of patients treated with HD appear to be diametrically opposite to the situation in Tibetan highlanders and Sherpa, whose physiology adapted to the inescapable hypobaric hypoxia of their living environment over many generations. Their adaptation includes pulmonary, vascular, and metabolic alterations with enhanced capillary density, nitric oxide production, and mitochondrial efficacy without oxidative stress. Improving the tissue oxygen supply in patients treated with HD depends primarily on preventing hemodynamic instability by increasing dialysis time/frequency or prescribing cool dialysis. Whether dietary or pharmacological interventions, such as the administration of L-arginine, fermented food, nitrate, nuclear factor erythroid 2-related factor 2 agonists, or prolyl hydroxylase 2 inhibitors, improve clinical outcome in patients treated with HD warrants future research.
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http://dx.doi.org/10.1152/ajprenal.00540.2020DOI Listing
March 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

Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO.

TH Open 2020 Oct 19;4(4):e365-e375. Epub 2020 Nov 19.

Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands.

 Severe cases of coronavirus disease 2019 (COVID-19) can require continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Unfractionated heparin (UFH) to prevent circuit clotting is mandatory but monitoring is complicated by (pseudo)-heparin resistance. In this observational study, we compared two different activated partial thromboplastin time (aPTT) assays and a chromogenic anti-Xa assay in COVID-19 patients on CRRT or ECMO in relation to their UFH dosages and acute phase reactants.  The aPTT (optical [aPTT-CS] and/or mechanical [aPTT-STA] clot detection methods were used), anti-Xa, factor VIII (FVIII), antithrombin III (ATIII), and fibrinogen were measured in 342 samples from 7 COVID-19 patients on CRRT or ECMO during their UFH treatment. Dosage of UFH was primarily based on the aPTT-CS with a heparin therapeutic range (HTR) of 50-80s. Associations between different variables were made using linear regression and Bland-Altman analysis.  Dosage of UFH was above 35,000IU/24 hours in all patients. aPTT-CS and aPTT-STA were predominantly within the HTR. Anti-Xa was predominantly above the HTR (0.3-0.7 IU/mL) and ATIII concentration was >70% for all patients; mean FVIII and fibrinogen were 606% and 7.5 g/L, respectively. aPTT-CS correlated with aPTT-STA (  = 0.68) with a bias of 39.3%. Correlation between aPTT and anti-Xa was better for aPTT-CS (0.78 ≤   ≤ 0.94) than for aPTT-STA (0.34 ≤   ≤ 0.81). There was no general correlation between the aPTT-CS and ATIII, FVIII, fibrinogen, thrombocytes, C-reactive protein, or ferritin.  All included COVID-19 patients on CRRT or ECMO conformed to the definition of heparin resistance. A patient-specific association was found between aPTT and anti-Xa. This association could not be explained by FVIII or fibrinogen.
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http://dx.doi.org/10.1055/s-0040-1719083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676995PMC
October 2020

Dialysis-Induced Cardiovascular and Multiorgan Morbidity.

Kidney Int Rep 2020 Nov 9;5(11):1856-1869. Epub 2020 Sep 9.

Renal Research Institute, New York, NY, USA.

Hemodialysis has saved many lives, albeit with significant residual mortality. Although poor outcomes may reflect advanced age and comorbid conditions, hemodialysis may harm patients, contributing to morbidity and perhaps mortality. Systemic circulatory "stress" resulting from hemodialysis treatment schedule may act as a disease modifier, resulting in a multiorgan injury superimposed on preexistent comorbidities. New functional intradialytic imaging (i.e., echocardiography, cardiac magnetic resonance imaging [MRI]) and kinetic of specific cardiac biomarkers (i.e., Troponin I) have clearly documented this additional source of end-organ damage. In this context, several factors resulting from patient-hemodialysis interaction and/or patient management have been identified. Intradialytic hypovolemia, hypotensive episodes, hypoxemia, solutes, and electrolyte fluxes as well as cardiac arrhythmias are among the contributing factors to systemic circulatory stress that are induced by hemodialysis. Additionally, these factors contribute to patients' symptom burden, impair cognitive function, and finally have a negative impact on patients' perception and quality of life. In this review, we summarize the adverse systemic effects of current intermittent hemodialysis therapy, their pathophysiologic consequences, review the evidence for interventions that are cardioprotective, and explore new approaches that may further reduce the systemic burden of hemodialysis. These include improved biocompatible materials, smart dialysis machines that automatically may control the fluxes of solutes and electrolytes, volume and hemodynamic control, health trackers, and potentially disruptive technologies facilitating a more personalized medicine approach.
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http://dx.doi.org/10.1016/j.ekir.2020.08.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609914PMC
November 2020

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

Dietary protein interventions to improve nutritional status in end-stage renal disease patients undergoing hemodialysis.

Curr Opin Clin Nutr Metab Care 2021 01;24(1):79-87

Department of Human Biology.

Purpose Of Review: Poor nutritional status is prevalent among end-stage renal disease patients undergoing hemodialysis. Chronic hemodialysis patients show an accelerated decline in skeletal muscle mass and strength, which is associated with higher mortality rates and a reduced quality of life. The current review aims to summarize recent advances regarding underlying causes of muscle loss and interventions that support muscle mass maintenance in patients with chronic hemodialysis.

Recent Findings: Muscle maintenance in chronic hemodialysis patients is compromised by low dietary protein intake levels, anabolic resistance of skeletal muscle tissue, sedentary behavior, and amino acid removal during hemodialysis. Studies assessing the effect of increased protein intake on nutritional status generally show beneficial results, especially in hypoalbuminemic chronic hemodialysis patients. The muscle protein synthetic response following protein ingestion in chronic hemodialysis patients may be enhanced through incorporation of structured physical activity and/or concurrent ketoacid ingestion.

Summary: A coordinated program that combines nutritional and physical activity interventions is likely required to attenuate the decline in muscle mass and strength of chronic hemodialysis patients. Nephrologists, dieticians, and exercise specialists should collaborate closely to establish guidelines regarding the appropriate quantity and timing of protein ingestion. In addition, they should provide tailored nutritional and physical activity interventions for chronic hemodialysis patients (see video, Supplemental Digital Content 1, Video abstract, http://links.lww.com/COCN/A14).
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http://dx.doi.org/10.1097/MCO.0000000000000703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752218PMC
January 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

Associations of 24-Hour Urinary Sodium and Potassium Excretion with Cardiac Biomarkers: The Maastricht Study.

J Nutr 2020 06;150(6):1413-1424

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

Background: It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood.

Objectives: We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction.

Methods: We included 2961 participants from the population-based Maastricht Study (mean ± SD age 59.8 ± 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors.

Results: Median [IQR] 24-h UNaE and UKE were 3.7 [2.8-4.7] g/24 h and 3.0 [2.4-3.6] g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8-3.2 g/24 h), participants in the first quintile (range: 0.5-2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium.

Conclusions: Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports recommendations to increase potassium intake in the general population. In addition, it suggests that cardiac dysfunction and/or cardiomyocyte injury may underlie previously reported associations of lower potassium intake with CVD mortality.
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http://dx.doi.org/10.1093/jn/nxaa080DOI Listing
June 2020

Smart sensors for real-time monitoring of patients on dialysis.

Nat Rev Nephrol 2020 10 17;16(10):554-555. Epub 2020 Apr 17.

Maastricht University, Faculty of Health, Medicine and Life Sciences, Maastricht, Netherlands.

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http://dx.doi.org/10.1038/s41581-020-0287-4DOI Listing
October 2020

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

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

Fabry Disease: A New Model of Premature Ageing?

Nephron 2020 27;144(1):1-4. Epub 2019 Sep 27.

Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

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http://dx.doi.org/10.1159/000503290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979416PMC
March 2021

Serum Phosphate and Microvascular Function in a Population-Based Cohort.

Clin J Am Soc Nephrol 2019 11 20;14(11):1626-1633. Epub 2019 Sep 20.

Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California.

Background And Objectives: Higher serum phosphate is associated with cardiovascular events and all-cause mortality. Explanations of this association have focused on large vessel calcification and stiffness. Studies suggest that a higher serum phosphate induces microvascular dysfunction, but relationships in humans with direct measures of microvascular function are lacking.

Design, Setting, Participants, & Measurements: We performed a cross-sectional analysis of 3189 community-living participants that underwent skin capillaroscopy, laser-Doppler flowmetry, and flicker light-induced retinal vessel responses. We used linear regression to assess the association between serum phosphate and each microvascular outcome. The primary outcome was skin capillary recruitment during postocclusive peak reactive hyperemia by capillaroscopy. Secondary outcomes included capillary recruitment during venous congestion, heat-induced skin hyperemic response, flicker light-induced retinal arteriolar, and venular dilation.

Results: The mean age of the cohort was 59±8 years, 48% were women, 7% had an eGFR <60 ml/min per 1.73 m, and the mean serum phosphate concentration was 3.2±0.5 mg/dl. A 1 mg/dl higher serum phosphate was independently associated with a 5.0% lower postocclusive capillary recruitment (95% CI, -10.0% to -0.1%). Results were similar for capillary recruitment with venous congestion (-4.5%; 95% CI, -9.8% to 0.7%). A 1 mg/dl higher serum phosphate was also independently associated with a 0.23% lower retinal venular dilation in response to flicker light (95% CI, -0.44% to -0.02%). A higher serum phosphate was not associated with change in flicker light-induced retinal arteriolar dilation or heat-induced skin hyperemic response, however a higher serum phosphate was associated with a lower heat-induced skin hyperemic response among men (-149% [95% CI, -260 to -38] per 1 mg/dl higher serum phosphate) but not women ( interaction, 0.01).

Conclusions: Higher serum phosphate concentrations, even within the normal range, are associated with microvascular dysfunction in community-living individuals.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_20_CJN02610319.mp3.
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http://dx.doi.org/10.2215/CJN.02610319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832044PMC
November 2019

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
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