Publications by authors named "Maarten W Taal"

121 Publications

Randomized Trial-PrEscription of intraDialytic exercise to improve quAlity of Life in Patients Receiving Hemodialysis.

Kidney Int Rep 2021 Aug 30;6(8):2159-2170. Epub 2021 May 30.

School of Health Sciences, Queen Margaret University, Edinburgh, UK.

Introduction: Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program.

Methods: In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]). Primary outcome was change in Kidney Disease Quality of Life Short-Form Physical Component Summary (KDQOL-SF 1.3 PCS) from baseline to 6 months. Cost-effectiveness was determined using health economic analysis; physiological impairment was evaluated by peak oxygen uptake; and harms were recorded.

Results: We randomized 379 participants; 335 and 243 patients (EX  = 127; CON  = 116) completed baseline and 6-month assessments, respectively. Mean difference in change PCS from baseline to 6 months between EX and CON was 2.4 (95% confidence interval [CI]: -0.1 to 4.8) arbitrary units ( = 0.055); no improvements were observed in peak oxygen uptake or secondary outcome measures. Participants in the intervention group had poor compliance (47%) and poor adherence (18%) to the exercise prescription. Cost of delivering intervention ranged from US$598 to US$1092 per participant per year. The number of participants with harms was similar between EX ( = 69) and CON ( = 56). A primary limitation was the lack of an attention CON. Many patients also withdrew from the study or were too unwell to complete all physiological outcome assessments.

Conclusions: A 6-month intradialytic aerobic exercise program was not clinically beneficial in improving HRQoL as delivered to this cohort of deconditioned patients on HD.
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http://dx.doi.org/10.1016/j.ekir.2021.05.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343798PMC
August 2021

Multiparametric MRI assessment of renal structure and function in acute kidney injury and renal recovery.

Clin Kidney J 2021 Aug 10;14(8):1969-1976. Epub 2021 Feb 10.

Centre for Kidney Research and Innovation, University of Nottingham, Royal Derby Hospital Campus, Nottingham, UK.

Background: Acute kidney injury (AKI) is associated with a marked increase in mortality as well as subsequent chronic kidney disease (CKD) and end-stage kidney disease. We performed multiparametric magnetic resonance imaging (MRI) with the aim of identifying potential non-invasive MRI markers of renal pathophysiology in AKI and during recovery.

Methods: Nine participants underwent inpatient MRI scans at time of AKI; seven had follow-up scans at 3 months and 1 year following AKI. Multiparametric renal MRI assessed total kidney volume (TKV), renal perfusion using arterial spin labelling, T mapping and blood oxygen level-dependent (BOLD) R* mapping.

Results: Serum creatinine concentration had recovered to baseline levels at 1-year post-AKI in all participants. At the time of AKI, participants had increased TKV, increased cortex/medulla T and reduced cortical perfusion compared with the expected ranges in healthy volunteers and people with CKD. TKV and T values decreased over time after AKI and returned to expected values in most but not all patients by 1 year. Cortical perfusion improved to a lesser extent and remained below the expected range in the majority of patients by 1-year post-AKI. BOLD R* data showed a non-significant trend to increase over time post-AKI.

Conclusions: We observed a substantial increase in TKV and T during AKI and a marked decrease in cortical perfusion. Despite biochemical recovery at 1-year post-AKI, MRI measures indicated persisting abnormalities in some patients. We propose that such patients may be more likely to have further AKI episodes or progress to CKD and further longitudinal studies are required to investigate this. .
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http://dx.doi.org/10.1093/ckj/sfaa221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323137PMC
August 2021

An Analysis of Frequency of Continuous Blood Pressure Variation and Haemodynamic Responses during Haemodialysis.

Blood Purif 2021 Jul 22:1-15. Epub 2021 Jul 22.

Centre for Kidney Research and Innovation, Academic unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, United Kingdom.

Background: Higher beat-to-beat blood pressure (BP) variation during haemodialysis (HD) has been shown to be associated with elevated cardiac damage markers and white matter ischaemic changes in the brain suggesting relevance to end-organ perfusion. We aimed to characterize individual patterns of BP variation and associated haemodynamic responses to HD.

Methods: Fifty participants underwent continuous non-invasive haemodynamic monitoring during HD and BP variation were assessed using extrema point (EP) frequency analysis. Participants were divided into those with a greater proportion of low frequency (LF, n = 21) and high frequency (HF, n = 22) of BP variation. Clinical and haemodynamic data were compared between groups.

Results: Median EP frequencies for mean arterial pressure (MAP) of mid-week HD sessions were 0.54 Hz (interquartile range 0.18) and correlated with dialysis vintage (r = 0.32, p = 0.039), NT pro-BNP levels (r = 0.32, p = 0.038), and average real variability (ARV) of systolic BP (r = 0.33, p = 0.029), ARV of diastolic BP (r = 0.46, p = 0.002), and ARV of MAP (r = 0.57, p < 0.001). In the LF group, MAP positively correlated with cardiac power index (CPI) in each hour of dialysis, but not with total peripheral resistance index (TPRI). In contrast, in the HF group, MAP correlated with TPRI in each hour of dialysis but only with CPI in the first hour.

Conclusions: EP frequency analysis of continuous BP monitoring during dialysis allows assessment of BP variation and categorization of individuals into low- or high-frequency groups, which were characterized by different haemodynamic responses to dialysis. This may assist in improved individualization of dialysis therapy.
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http://dx.doi.org/10.1159/000516935DOI Listing
July 2021

Impact of malnutrition on health-related quality of life in persons receiving dialysis: a prospective study.

Br J Nutr 2021 Jul 5:1-24. Epub 2021 Jul 5.

Centre for Kidney Research and Innovation, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Royal Derby Hospital, Uttoxeter Rd, Derby, DE22 3NE, United Kingdom.

Health-related quality of life (HRQoL) is severely impaired in persons receiving dialysis. Malnutrition has been associated with some measures of poor HRQoL in cross-sectional analyses in dialysis populations, but no studies have assessed the impact of malnutrition and dietary intake on change in multiple measures of HRQoL over time. We investigated the most important determinants of poor HRQoL and the predictors of change in HRQoL over time using several measures of HRQoL. We enrolled 119 haemodialysis and 31 peritoneal dialysis patients in this prospective study. Nutritional assessments (Subjective Global Assessment [SGA], anthropometry and 24-hour dietary recalls) and HRQoL questionnaires (Short Form-36 [SF-36] mental [MCS] and physical component scores [PCS] and European QoL-5 Dimensions [EQ5D] health state [HSS] and visual analogue scores [VAS]) were performed at baseline, 6 and 12 months. Mean age was 64(14) years. Malnutrition was present in 37% of the population. At baseline, malnutrition assessed by SGA was the only factor independently (and negatively) associated with all four measures of HRQoL. No single factor was independently associated with decrease in all measures of HRQoL over 1 year. However, prevalence/development of malnutrition over one year was an independent predictor of 1-year decrease in EQ5D HSS and 1-year decrease in fat intake independently predicted the 1-year decline in SF-36 MCS and PCS, and EQ5D VAS. These findings strengthen the importance of monitoring for malnutrition and providing nutritional advice to all persons on dialysis. Future studies are needed to evaluate the impact of nutritional interventions on HRQoL and other long-term outcomes.
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http://dx.doi.org/10.1017/S000711452100249XDOI Listing
July 2021

Exercise programme to improve quality of life for patients with end-stage kidney disease receiving haemodialysis: the PEDAL RCT.

Health Technol Assess 2021 Jun;25(40):1-52

School of Health Sciences, Queen Margaret University, Edinburgh, UK.

Background: Whether or not clinically implementable exercise interventions in haemodialysis patients improve quality of life remains unknown.

Objectives: The PEDAL (PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease) trial evaluated the clinical effectiveness and cost-effectiveness of a 6-month intradialytic exercise programme on quality of life compared with usual care for haemodialysis patients.

Design: We conducted a prospective, multicentre randomised controlled trial of haemodialysis patients from five haemodialysis centres in the UK and randomly assigned them (1 : 1) using a web-based system to (1) intradialytic exercise training plus usual-care maintenance haemodialysis or (2) usual-care maintenance haemodialysis.

Setting: The setting was five dialysis units across the UK from 2015 to 2019.

Participants: The participants were adult patients with end-stage kidney disease who had been receiving haemodialysis therapy for > 1 year.

Interventions: Participants were randomised to receive usual-care maintenance haemodialysis or usual-care maintenance haemodialysis plus intradialytic exercise training.

Main Outcome Measures: The primary outcome of the study was change in Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score (from baseline to 6 months). Cost-effectiveness was determined using health economic analysis and the EuroQol-5 Dimensions, five-level version. Additional secondary outcomes included quality of life (Kidney Disease Quality of Life Short Form, version 1.3, generic multi-item and burden of kidney disease scales), functional capacity (sit-to-stand 60 and 10-metre Timed Up and Go tests), physiological measures (peak oxygen uptake and arterial stiffness), habitual physical activity levels (measured by the International Physical Activity Questionnaire and Duke Activity Status Index), fear of falling (measured by the Tinetti Falls Efficacy Scale), anthropometric measures (body mass index and waist circumference), clinical measures (including medication use, resting blood pressure, routine biochemistry, hospitalisations) and harms associated with intervention. A nested qualitative study was conducted.

Results: We randomised 379 participants; 335 patients completed baseline assessments and 243 patients (intervention,  = 127; control,  = 116) completed 6-month assessments. The mean difference in change in physical component summary score from baseline to 6 months between the intervention group and control group was 2.4 arbitrary units (95% confidence interval -0.1 to 4.8 arbitrary units;  = 0.055). Participants in the intervention group had poor compliance (49%) and very poor adherence (18%) to the exercise prescription. The cost of delivering the intervention ranged from £463 to £848 per participant per year. The number of participants with harms was similar in the intervention ( = 69) and control ( = 56) groups.

Limitations: Participants could not be blinded to the intervention; however, outcome assessors were blinded to group allocation.

Conclusions: On trial completion the primary outcome (Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score) was not statistically improved compared with usual care. The findings suggest that implementation of an intradialytic cycling programme is not an effective intervention to enhance health-related quality of life, as delivered to this cohort of deconditioned patients receiving haemodialysis.

Future Work: The benefits of longer interventions, including progressive resistance training, should be confirmed even if extradialytic delivery is required. Future studies also need to evaluate whether or not there are subgroups of patients who may benefit from this type of intervention, and whether or not there is scope to optimise the exercise intervention to improve compliance and clinical effectiveness.

Trial Registration: Current Controlled Trials ISRCTN83508514.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 40. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta25400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256322PMC
June 2021

The PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease trial: study design and baseline data for a multicentre randomized controlled trial.

Clin Kidney J 2021 May 10;14(5):1345-1355. Epub 2020 Sep 10.

School of Health Sciences, Centre for Health, Activity and Rehabilitation Research, Queen Margaret University, Edinburgh, UK.

Background: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK.

Methods: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke's Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team.

Results: At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry.

Conclusion: The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally.

Trial Registration: ISRCTN N83508514; registered on 17 December 2014.
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http://dx.doi.org/10.1093/ckj/sfaa107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087141PMC
May 2021

What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline?

Rheumatology (Oxford) 2021 Mar 16. Epub 2021 Mar 16.

Academic Rheumatology, School of Medicine, University of Nottingham, Nottingham, UK.

Objectives: To examine incidence of treatment changes due to abnormal blood-test results and, to explore rates of treatment changes due to liver, kidney and haematological blood-test abnormalities in autoimmune rheumatic diseases (AIRD) treated with low-dose methotrexate or leflunomide.

Methods: Data for people with AIRDs prescribed methotrexate or leflunomide were extracted from the Clinical Practice Research Datalink. Participants were followed-up from first prescription of methotrexate or leflunomide in primary-care. Primary outcome of interest was drug discontinuation, defined as a prescription gap of ≥ 90 days following an abnormal (or severely abnormal) blood-test result. Dose reduction was examined between consecutive prescriptions. Incidence rates per 1,000 person-years were calculated.

Results: 15,670 and 2,689 participants contributing 46,571 and 4,558 person-years follow-up were included in methotrexate and leflunomide cohorts respectively. The incidence of methotrexate and leflunomide discontinuation with abnormal (severely abnormal) blood-test was 42.24(6.16) and 106.53(9.42)/1,000 person-years in year-1, and 22.44(2.84) and 31.69(4.40)/1,000 person-years respectively thereafter. The cumulative incidence of methotrexate and leflunomide discontinuation with abnormal (severely abnormal) blood-tests was 1 in 24(1 in 169), 1 in 9(1 in 106) at 1-year; and 1 in 45(1 in 352), 1 in 32(1 in 227) per-year respectively thereafter. Raised liver enzymes were the commonest abnormality associated with drug discontinuation. Methotrexate and leflunomide dose reduction incidence were comparable in year-1, however, thereafter methotrexate dose was reduced more often than leflunomide (16.60(95% CI; 13.05-21.13) vs. 8.10(95% CI; 4.97-13.20)/1,000 person-years).

Conclusion: Methotrexate and leflunomide were discontinued for blood-test abnormalities after year-1 of treatment, however, discontinuations for severely abnormal results were uncommon.
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http://dx.doi.org/10.1093/rheumatology/keab254DOI Listing
March 2021

Application of the Lomb-Scargle Periodogram to InvestigateHeart Rate Variability during Haemodialysis.

J Healthc Eng 2020 8;2020:8862074. Epub 2020 Dec 8.

Centre for Kidney Research and Innovation, University of Nottingham, Derby, UK.

Short-term cardiovascular compensatory responses to perturbations in the circulatory system caused by haemodialysis can be investigated by the spectral analysis of heart rate variability, thus providing an important variable for categorising individual patients' response, leading to a more personalised treatment. This is typically accomplished by resampling the irregular heart rate to generate an equidistant time series prior to spectral analysis, but resampling can further distort the data series whose interpretation can already be compromised by the presence of artefacts. The Lomb-Scargle periodogram provides a more direct method of spectral analysis as this method is specifically designed for large, irregularly sampled, and noisy datasets such as those obtained in clinical settings. However, guidelines for preprocessing patient data have been established in combination with equidistant time-series methods and their validity when used in combination with the Lomb-Scargle approach is missing from literature. This paper examines the effect of common preprocessing methods on the Lomb-Scargle power spectral density estimate using both real and synthetic heart rate data and will show that many common techniques for identifying and editing suspect data points, particularly interpolation and replacement, will distort the resulting power spectrum potentially misleading clinical interpretations of the results. Other methods are proposed and evaluated for use with the Lomb-Scargle approach leading to the main finding that suspicious data points should be excluded rather than edited, and where required, denoising of the heart rate signal can be reliably accomplished by empirical mode decomposition. Some additional methods were found to be particularly helpful when used in conjunction with the Lomb-Scargle periodogram, such as the use of a false alarm probability metric to establish whether spectral estimates are valid and help automate the assessment of valid heart rate records, potentially leading to greater use of this powerful technique in a clinical setting.
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http://dx.doi.org/10.1155/2020/8862074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738214PMC
December 2020

Patients' and kidney care team's perspectives of treatment burden and capacity in older people with chronic kidney disease: a qualitative study.

BMJ Open 2020 12 12;10(12):e042548. Epub 2020 Dec 12.

Primary Care, Population Sciences and Medical Education, University of Southampton Faculty of Medicine, Southampton, Southampton, UK.

Objective: Chronic kidney disease (CKD) is often a multimorbid condition and progression to more severe disease is commonly associated with increased management requirements, including lifestyle change, more medication and greater clinician involvement. This study explored patients' and kidney care team's perspectives of the nature and extent of this workload (treatment burden) and factors that support capacity (the ability to manage health) for older individuals with CKD.

Design: Qualitative semistructured interview and focus group study.

Setting And Participants: Adults (aged 60+) with predialysis CKD stages G3-5 (identified in two general practitioner surgeries and two renal clinics) and a multiprofessional secondary kidney care team in the UK.

Results: 29 individuals and 10 kidney team members were recruited. Treatment burden themes were: (1) understanding CKD, its treatment and consequences, (2) adhering to treatments and management and (3) interacting with others (eg, clinicians) in the management of CKD. Capacity themes were: (1) personal attributes (eg, optimism, pragmatism), (2) support network (family/friends, service providers), (3) financial capacity, environment (eg, geographical distance to unit) and life responsibilities (eg, caring for others). Patients reported poor provision of CKD information and lack of choice in treatment, whereas kidney care team members discussed health literacy issues. Patients reported having to withdraw from social activities and loss of employment due to CKD, which further impacted their capacity.

Conclusion: Improved understanding of and measures to reduce the treatment burden (eg, clear information, simplified medication, joined up care, free parking) associated with CKD in individuals as well as assessment of their capacity and interventions to improve capacity (social care, psychological support) will likely improve patient experience and their engagement with kidney care services.
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http://dx.doi.org/10.1136/bmjopen-2020-042548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735091PMC
December 2020

A Feasibility Study of Non-Invasive Continuous Estimation of Brachial Pressure Derived From Arterial and Venous Lines During Dialysis.

IEEE J Transl Eng Health Med 2021;9:2700209. Epub 2020 Nov 4.

Centre for Kidney Research and InnovationUniversity of NottinghamNottinghamNG7 2RDU.K.

Intradialytic haemodynamic instability is a significant clinical problem, leading to end-organ ischaemia and contributing to morbidity and mortality in haemodialysis patients. Non-invasive continuous blood pressure monitoring is not currently part of routine practice but may aid detection and prevention of significant falls in blood pressure during dialysis. Brachial blood pressure is currently recorded intermittently during haemodialysis via a sphygmomanometer. Current methods of continuous non-invasive blood pressure monitoring tend to restrict movement, can be sensitive to external disturbances and patient movement, and can be uncomfortable for the wearer. Additionally, poor patient blood circulation can lead to unreliable measurements. In this feasibility study we performed an initial validation of a novel method and associated technology to continuously estimate blood pressure using pressure sensors in the extra-corporeal dialysis circuit, which does not require any direct contact with the person receiving dialysis treatment. The paper describes the development of the measurement system and subsequent patient feasibility study with concurrent measurement validation by physiological measurement device. Real-time physiological data is collected over the entire period of (typically 4-hour) dialysis treatment. We identify a quasi-linear mathematical function to describe the relationship between arterial line pressure and brachial artery BP, which is confirmed in a patient study. The results from this observational study suggest that it is feasible to derive a continuous measurement of brachial pressure from continuous measurements of arterial and venous line pressures via an empirically based and updated mathematical model. The methodology presented requires no interfacing to proprietary dialysis machine systems, no sensors to be attached to the patient directly, and is robust to patient movement during treatment and also to the effects of the cyclical pressure waveforms induced by the hemodialysis peristaltic blood pump. This represents a key enabling factor to the development of a practical continuous blood pressure monitoring device for dialysis patients.
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http://dx.doi.org/10.1109/JTEHM.2020.3035988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665243PMC
November 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

Acute kidney injury associated with COVID-19: A retrospective cohort study.

PLoS Med 2020 10 30;17(10):e1003406. Epub 2020 Oct 30.

Department of Nephrology, University Hospitals of Derby and Burton, Royal Derby Hospital, Derby, United Kingdom.

Background: Initial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19-associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom.

Methods And Findings: We extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19-negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p < 0.001), had a greater proportion of men (56.6% versus 44.9%, p < 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p < 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19-positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19-negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p < 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p < 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p < 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ≥85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region.

Conclusions: We observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this.

Trial Registration: ClinicalTrials.gov NCT04407156.
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http://dx.doi.org/10.1371/journal.pmed.1003406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598516PMC
October 2020

Nutritional status assessment: a neglected biomarker in persons with end-stage kidney disease.

Curr Opin Nephrol Hypertens 2020 11;29(6):547-554

Centre for Kidney Research and Innovation, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham.

Purpose Of Review: Malnutrition is a frequent complication and risk factor for adverse outcomes in the dialysis population that is often underrecognized and neglected. This article reviews published literature on the associations between malnutrition, mortality, quality of life and hospitalizations in persons on dialysis in order to raise awareness of the importance of preventing and treating it.

Recent Findings: All methods of nutritional assessment namely serum biochemistry, body composition, dietary intake, handgrip strength and nutritional scoring tools are independently associated with increased mortality in dialysis populations. Malnutrition severely affects physical and mental measures of quality of life and increases the number and length of hospitalizations in persons receiving dialysis, resulting in increased healthcare costs. Worsening of nutritional status is also associated with poor survival and higher rates of hospitalizations in this patient population.

Summary: Malnutrition is an unacceptably common complication in dialysis patients that is substantially associated with adverse outcomes and higher hospital costs. Further interventional studies assessing the impact of preventing and treating malnutrition on clinical outcomes are warranted and should be considered a priority.
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http://dx.doi.org/10.1097/MNH.0000000000000651DOI Listing
November 2020

Prevalence of chronic kidney disease in adults in England: comparison of nationally representative cross-sectional surveys from 2003 to 2016.

BMJ Open 2020 08 13;10(8):e038423. Epub 2020 Aug 13.

School of Primary Care, Population Sciences, and Medical Education, University of Southampton Faculty of Medicine, Southampton, UK.

Objectives: To identify recent trends in chronic kidney disease (CKD) prevalence in England and explore their association with changes in sociodemographic, behavioural and clinical factors.

Design: Pooled cross-sectional analysis.

Setting: Health Survey for England 2003, 2009/2010 combined and 2016.

Participants: 17 663 individuals (aged 16+) living in private households.

Primary And Secondary Outcome Measures: Prevalence of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m and albuminuria (measured by albumin-creatinine ratio) during 2009/2010 and 2016 and trends in eGFR between 2003 and 2016. eGFR was estimated using serum creatinine Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations.

Results: GFR <60 mL/min/1.73 m prevalence was 7.7% (95% CI 7.1% to 8.4%), 7.0% (6.4% to 7.7%) and 7.3%(6.5% to 8.2%) in 2003, 2009/2010 and 2016, respectively. Albuminuria prevalence was 8.7% (8.1% to 9.5%) in 2009/2010 and 9.8% (8.7% to 10.9%) in 2016. Prevalence of CKD G1-5 (eGFR <60 mL/min/1.73 m or albuminuria) was 12.6% (11.8% to 13.4%) in 2009/2010 and 13.9% (12.8% to 15.2%) in 2016. Prevalence of diabetes and obesity increased during 2003-2016 while prevalence of hypertension and smoking fell. The age-adjusted and gender-adjusted OR of eGFR <60 mL/min/1.73 m for 2016 versus 2009/2010 was 0.99 (0.82 to 1.18) and fully adjusted OR was 1.13 (0.93 to 1.37). There was no significant period effect on the prevalence of albuminuria or CKD G1-5 from 2009/2010 to 2016 in age and gender or fully adjusted models.

Conclusion: The fall in eGFR <60 mL/min/1.73 m seen from 2003 to 2009/2010 did not continue to 2016. However, absolute CKD burden is likely to rise with population growth and ageing, particularly if diabetes prevalence continues to increase. This highlights the need for greater CKD prevention efforts and continued surveillance.
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http://dx.doi.org/10.1136/bmjopen-2020-038423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430464PMC
August 2020

Health-related quality of life, functional impairment and comorbidity in people with mild-to-moderate chronic kidney disease: a cross-sectional study.

BMJ Open 2020 08 6;10(8):e040286. Epub 2020 Aug 6.

The Department of Renal Medicine, Royal Derby Hospital NHS Foundation Trust, Derby, UK.

Objectives: To determine the associations between comorbidities, health-related quality of life (HRQoL) and functional impairment in people with mild-to-moderate chronic kidney disease (CKD) in primary care.

Design: Cross-sectional analysis at 5-year follow-up in a prospective cohort study.

Setting: Thirty-two general practitioner surgeries in England.

Participants: 1008 participants with CKD stage 3 (of 1741 people recruited at baseline in the Renal Risk in Derby study) who survived to 5 years and had complete follow-up data for HRQoL and functional status (FS).

Primary And Secondary Outcome Measures: HRQoL assessed using the 5-level EQ-5D version (EQ-5D-5L, with domains of mobility, self-care, usual activities, pain/discomfort and anxiety/depression and index value using utility scores calculated from the English general population), and FS using the Karnofsky Performance Status scale (functional impairment defined as Karnofksy score ≤70). Comorbidity was defined by self-reported or doctor-diagnosed condition, disease-specific medication or blood result.

Results: Mean age was 75.8 years. The numbers reporting some problems in EQ-5D-5L domains were: 582 (57.7%) for mobility, 166 (16.5%) for self-care, 466 (46.2%) for usual activities, 712 (70.6%) for pain/discomfort and 319 (31.6%) for anxiety/depression. Only 191 (18.9%) reported no problems in any domain. HRQoL index values showed greater variation among those with lower FS (eg, for those with Karnofsky score of 60, the median (IQR) EQ-5D index value was 0.45 (0.24 to 0.68) compared with 0.94 (0.86 to 1) for those with Karnofsky score of 90). Overall, 234 (23.2%) had functional impairment.In multivariable logistic regression models, functional impairment was independently associated with experiencing problems for all EQ-5D-5L domains (mobility: OR 16.87 (95% CI 8.70 to 32.79, p<0.001, self-care: OR 13.08 (95% CI 8.46 to 20.22), p<0.001, usual activities: OR 8.27 (95% CI 5.43 to 12.58), p<0.001, pain/discomfort: OR 2.94 (95% CI 1.86 to 4.67), p<0.001, anxiety/depression: 3.08 (95% CI 2.23 to 4.27), p<0.001). Higher comorbidity count and obesity were independently associated with problems in mobility, self-care, usual activities and pain/discomfort: for three or more comorbidities versus none: (mobility: OR 2.10 (95% CI 1.08 to 4.10, p for trend 0.002), self-care: OR 2.64 (95% CI 0.72 to 9.67, p for trend 0.05), usual activities: OR 4.20 (95% CI 2.02 to 8.74, p for trend <0.001), pain/discomfort: OR 3.06 (95% CI 1.63 to 5.73, p for trend <0.001)), and for obese (body mass index (BMI) ≥30 kg/m) versus BMI <25 kg/m: (mobility: OR 2.44 (95% CI 1.61 to 3.69, p for trend <0.001), self-care: OR 1.98 (95% CI 1.06 to 3.71, p for trend 0.003), usual activities: OR 1.82 (95% CI 1.19 to 2.76, p for trend 0.019), pain/discomfort: OR 2.37 (95% CI 1.58 to 3.55, p for trend <0.001)). Female sex, lower FS and lower educational attainment were independently associated with anxiety/depression (ORs 1.60 (95% CI 1.18 to 2.16, p 0.002), 3.08 (95% CI 2.23 to 4.27, p<0.001) and 1.67 (95% CI 1.10 to 2.52, p 0.009), respectively). Older age, higher comorbidity count, albuminuria (≥30 mg/mmol vs <3 mg/mmol), lower educational attainment (no formal qualifications vs degree level) and obesity were independently associated with functional impairment (ORs 1.07 (95% CI 1.04 to 1.09, p<0.001), 2.18 (95% CI 0.80 to 5.96, p for trend <0.001), 1.74 (95% CI 0.82 to 3.68, p for trend 0.005), 2.08 (95% CI 1.26 to 3.41, p for trend <0.001) and 4.23 (95% CI 2.48 to 7.20), respectively).

Conclusions: The majority of persons with mild-to-moderate CKD reported reductions in at least one HRQoL domain, which were independently associated with comorbidities, obesity and functional impairment.

Trial Registration Number: National Institute for Health Research Clinical Research Portfolio Study Number 6632.
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http://dx.doi.org/10.1136/bmjopen-2020-040286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412591PMC
August 2020

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study.

PLoS Med 2020 07 13;17(7):e1003163. Epub 2020 Jul 13.

Centre for Kidney Research and Innovation, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Derby, United Kingdom.

Background: Tissue advanced glycation end product (AGE) accumulation has been proposed as a marker of cumulative metabolic stress that can be assessed noninvasively by measurement of skin autofluorescence (SAF). In persons on haemodialysis, SAF is an independent risk factor for cardiovascular events (CVEs) and all-cause mortality (ACM), but data at earlier stages of chronic kidney disease (CKD) are inconclusive. We investigated SAF as a risk factor for CVEs and ACM in a prospective study of persons with CKD stage 3.

Methods And Findings: Participants with estimated glomerular filtration rate (eGFR) 59 to 30 mL/min/1.73 m2 on two consecutive previous blood tests were recruited from 32 primary care practices across Derbyshire, United Kingdom between 2008 and 2010. SAF was measured in participants with CKD stage 3 at baseline, 1, and 5 years using an AGE reader (DiagnOptics). Data on hospital admissions with CVEs (based on international classification of diseases [ICD]-10 coding) and deaths were obtained from NHS Digital. Cox proportional hazards models were used to investigate baseline variables associated with CVEs and ACM. A total of 1,707 of 1,741 participants with SAF readings at baseline were included in this analysis: The mean (± SD) age was 72.9 ± 9.0 years; 1,036 (60.7%) were female, 1,681 (98.5%) were of white ethnicity, and mean (±SD) eGFR was 53.5 ± 11.9 mL/min/1.73 m2. We observed 319 deaths and 590 CVEs during a mean of 6.0 ± 1.5 and 5.1 ± 2.2 years of observation, respectively. Higher baseline SAF was an independent risk factor for CVEs (hazard ratio [HR] 1.12 per SD, 95% CI 1.03-1.22, p = 0.01) and ACM (HR 1.16, 95% CI 1.03-1.30, p = 0.01). Additionally, increase in SAF over 1 year was independently associated with subsequent CVEs (HR 1.11 per SD, 95% CI 1.00-1.22; p = 0.04) and ACM (HR 1.24, 95% CI 1.09-1.41, p = 0.001). We relied on ICD-10 codes to identify hospital admissions with CVEs, and there may therefore have been some misclassification.

Conclusions: We have identified SAF as an independent risk factor for CVE and ACM in persons with early CKD. These findings suggest that interventions to reduce AGE accumulation, such as dietary AGE restriction, may reduce cardiovascular risk in CKD, but this requires testing in prospective randomised trials. Our findings may not be applicable to more ethnically diverse or younger populations.
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http://dx.doi.org/10.1371/journal.pmed.1003163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357739PMC
July 2020

Factors Associated With Change in Skin Autofluorescence, a Measure of Advanced Glycation End Products, in Persons Receiving Dialysis.

Kidney Int Rep 2020 May 15;5(5):654-662. Epub 2020 Feb 15.

Centre for Kidney Research and Innovation, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, UK.

Introduction: An increase over time in skin autofluorescence (SAF), a measure of accumulation of advanced glycation end products (AGE), predicts higher mortality on hemodialysis (HD). However, evidence is lacking regarding factors that contribute to changes in SAF over time in populations on dialysis. We investigated the rate of change in SAF over 1 year and the factors associated with these changes.

Methods: We enrolled 109 patients on HD and 28 on peritoneal dialysis in a prospective study. SAF was measured at baseline, 3, 6, 9, and 12 months. Rate of change in SAF was calculated using the SLOPE function in Microsoft Excel (Microsoft, Redmond, WA). Participants were then grouped into those with stable SAF or increasing SAF. Dietary AGE intake and nutritional assessments were performed at baseline, 6, and 12 months.

Results: The mean SAF trend observed was an increase of 0.30 ± 0.63 arbitrary units (AU) per year, but this varied from a decrease of 0.15 ± 0.44 to an increase of 0.76 ± 0.42 AU per year in stable and increasing SAF groups, respectively. Increasing SAF was more common in participants who developed malnutrition during the observation period, whereas those who became well-nourished were more likely to have stable SAF (8 [80%] vs. 14 [42%]; 0.02). Development/prevalence of malnutrition over 1 year, HD as first dialysis modality, and current smoking were independent predictors of increasing SAF.

Conclusion: SAF increases over time in most persons on dialysis. Independent determinants of increasing SAF were development/prevalence of malnutrition, HD as first dialysis modality, and current smoking. Strategies to reduce/prevent the rise in SAF, including prevention/correction of malnutrition, should be investigated in prospective studies.
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http://dx.doi.org/10.1016/j.ekir.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210606PMC
May 2020

Skin autofluorescence and malnutrition as predictors of mortality in persons receiving dialysis: a prospective cohort study.

J Hum Nutr Diet 2020 12 8;33(6):852-861. Epub 2020 May 8.

Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, Centre for Kidney Research and Innovation, University of Nottingham, Royal Derby Hospital, Derby, UK.

Background: Skin autofluorescence (SAF), which is a measure of accumulation of advanced glycation end-products (AGE), and malnutrition are each associated with higher mortality in dialysis populations, although no studies have investigated these potentially related associations together. We simultaneously assessed SAF and malnutrition as risk factors for mortality in persons receiving dialysis.

Methods: SAF was measured in 120 haemodialysis and 31 peritoneal dialysis patients using an AGE Reader (DiagnOptics, Groningen, The Netherlands). Dietary AGE, energy, protein and fat intake, handgrip strength, anthropometry, biochemistry and Subjective Global Assessment were also evaluated. Time to event was days from baseline to death, kidney transplantation or 30 September 2018.

Results: Median observation time was 576 days, during which 33 (21.9%) patients died. Those who died had higher baseline SAF levels [3.8 ± 1.0 versus 3.3 ± 0.8 arbitrary units (AU); P = 0.001] and were more likely to be malnourished (58% versus 31%; P = 0.006). Malnourished persons who died had higher SAF values than those who died but were well-nourished (4.2 ± 1.1 versus 3.3 ± 0.7 AU; P = 0.007). Survival was significantly better in participants with baseline SAF below the median and in those well-nourished than those with baseline SAF above the median and in those malnourished, respectively. Multivariable analysis identified SAF [hazards ratio (HR) = 1.44; 95% confidence interval (CI) = 1.05-1.97; P = 0.02], malnutrition (HR = 2.35; 95% CI = 1.16-4.78; P = 0.02) and chronological age (HR = 1.60; 95% CI = 1.10-2.33; P = 0.01) as independent predictors of mortality.

Conclusions: Although higher SAF and malnutrition are potentially inter-related, they were both independently associated with increased mortality in this population. Interventions to improve outcomes by reducing SAF through correction of malnutrition or dietary AGE restriction require testing in prospective studies.
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http://dx.doi.org/10.1111/jhn.12764DOI Listing
December 2020

An updated overview of diabetic nephropathy: Diagnosis, prognosis, treatment goals and latest guidelines.

Diabetes Obes Metab 2020 04;22 Suppl 1:3-15

Centre for Kidney Research and Innovation, University of Nottingham, Nottingham, UK.

Diabetic nephropathy (DN) is a major healthcare challenge. It occurs in up to 50% of those living with diabetes, is a major cause of end-stage kidney disease (ESKD) that requires treatment with dialysis or renal transplantation, and is associated with significantly increased cardiovascular morbidity and mortality. DN is a clinical syndrome characterized by persistent albuminuria and a progressive decline in renal function, but it is increasingly recognized that the presentation and clinical course of kidney disease in diabetes is heterogeneous. The term diabetic kidney disease (DKD) is now commonly used to encompass the spectrum of people with diabetes who have either albuminuria or reductions in renal function. In this article, the clinical presentation and approach to diagnosis of DKD will be discussed, as will its prognosis. The general principles of management of DKD will also be reviewed with reference to current international guidelines.
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http://dx.doi.org/10.1111/dom.14007DOI Listing
April 2020

Association between non-malignant monoclonal gammopathy and adverse outcomes in chronic kidney disease: A cohort study.

PLoS Med 2020 02 28;17(2):e1003050. Epub 2020 Feb 28.

University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

Background: In studies including the general population, the presence of non-malignant monoclonal gammopathy (MG) can be causally associated with kidney damage and shorter survival. We assessed whether the presence of an MG is associated with a higher risk of kidney failure or death in individuals with chronic kidney disease (CKD).

Methods And Findings: Data were used from 3 prospective cohorts of individuals with CKD (not on dialysis or with a kidney transplant): (1) Renal Impairment in Secondary Care (RIISC, Queen Elizabeth Hospital and Heartlands Hospital, Birmingham, UK, N = 878), (2) Salford Kidney Study (SKS, Salford Royal Hospital, Salford, UK, N = 861), and (3) Renal Risk in Derby (RRID, Derby, UK, N = 1,739). Participants were excluded if they had multiple myeloma or any other B cell lymphoproliferative disorder with end-organ damage. Median age was 71.0 years, 50.6% were male, median estimated glomerular filtration rate was 42.3 ml/min/1.73 m2, and median urine albumin-to-creatinine ratio was 3.4 mg/mmol. All non-malignant MG was identified in the baseline serum of participants of RIISC. Further, light chain MG (LC-MG) was identified and studied in participants of RIISC, SKS, and RRID. Participants were followed up for kidney failure (defined as the initiation of dialysis or kidney transplantation) and death. Associations with the risk of kidney failure were estimated by competing-risks regression (handling death as a competing risk), and associations with death were estimated by Cox proportional hazards regression. In total, 102 (11.6%) of the 878 RIISC participants had an MG. During a median follow-up time of 74.0 months, there were 327 kidney failure events and 202 deaths. The presence of MG was not associated with risk of kidney failure (univariable subhazard ratio [SHR] 0.97 [95% CI 0.68 to 1.38], P = 0.85; multivariable SHR 1.16 [95% CI 0.80 to 1.69], P = 0.43), and although there was a higher risk of death in univariable analysis (hazard ratio [HR] 2.13 [95% CI 1.49 to 3.02], P < 0.001), this was not significant in multivariable analysis (HR 1.37 [95% CI 0.93 to 2.00], P = 0.11). Fifty-five (1.6%) of the 3,478 participants from all 3 studies had LC-MG. During a median follow-up time of 62.5 months, 564 of the 3,478 participants progressed to kidney failure, and 803 died. LC-MG was not associated with risk of kidney failure (univariable SHR 1.07 [95% CI 0.58 to 1.96], P = 0.82; multivariable SHR 1.42 [95% CI 0.78 to 2.57], P = 0.26). There was a higher risk of death in those with LC-MG in the univariable model (HR 2.51 [95% CI 1.59 to 3.96], P < 0.001), but not in the multivariable model (HR 1.49 [95% CI 0.93 to 2.39], P = 0.10). An important limitation of this work was that only LC-MG, rather than any MG, could be identified in participants from SKS and RRID.

Conclusions: The prevalence of MG was higher in this CKD cohort than that reported in the general population. However, the presence of an MG was not independently associated with a significantly higher risk of kidney failure or, unlike in the general population, risk of death.
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http://dx.doi.org/10.1371/journal.pmed.1003050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048272PMC
February 2020

The authors reply.

Kidney Int 2020 03;97(3):616

Royal Derby Hospital, Derby, UK.

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http://dx.doi.org/10.1016/j.kint.2019.12.009DOI Listing
March 2020

Impact of Dietetic Intervention on Skin Autofluorescence and Nutritional Status in Persons Receiving Dialysis: A Proof of Principle Study.

J Ren Nutr 2020 11 7;30(6):540-547. Epub 2020 Feb 7.

Division of Medical Sciences and Graduate Entry Medicine, Centre for Kidney Research and Innovation, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Renal Medicine, University Hospitals of Derby and Burton NHS Foundation Trust, Royal Derby Hospital, Derby, United Kingdom.

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from oxidative stress and food consumption. It has been reported that markers of malnutrition are more important determinants of increased skin autofluorescence (SAF), a measure of AGE accumulation and risk factor for mortality, than high dietary AGE intake in a hemodialysis (HD) population, suggesting that correcting malnutrition may decrease SAF.

Design And Methods: We investigated this hypothesis in a single-center, nonrandomized proof-of-principle study. We enrolled 27 patients on HD and one on peritoneal dialysis with malnutrition who received individualized nutritional advice and support over 6 months. SAF was measured at baseline, 3 months, and 6 months. Dietary intake and nutritional status were assessed at baseline and 6 months. Results were compared with a control group of malnourished patients on dialysis (n = 41 HD and 8 peritoneal dialysis) from a previous observational study.

Results: The intervention group showed a significant increase in dietary intake, including AGEs, Subjective Global Assessment score, and serum albumin, while SAF levels remained stable for over 6 months (3.8 ± 0.7 arbitrary units [AU] vs. 3.7 ± 0.7 AU; P = .3). Conversely, in the control group, SAF increased significantly during the observation period (3.5 ± 0.9 AU vs. 3.8 ± 1.2 AU; P = .03) during which there was no improvement in nutritional intake and other markers of nutrition, although dietary AGE intake and Subjective Global Assessment score did increase.

Conclusion: Dietetic support was associated with stable SAF levels in this proof-of-principal study despite an increase in dietary AGE intake, suggesting that interventions to improve nutrition may be important in preventing the rise in SAF observed in malnourished dialysis populations. Further long-term studies are needed to test this hypothesis and evaluate the impact on survival.
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http://dx.doi.org/10.1053/j.jrn.2019.12.006DOI Listing
November 2020

Sodium-glucose linked transporter-2 inhibitor renal outcome modification in type 2 diabetes: Evidence from studies in patients with high or low renal risk.

Diabetes Obes Metab 2020 07 2;22(7):1024-1034. Epub 2020 Mar 2.

Division of Medical Sciences and Graduate Entry Medicine, University of Nottingham, Nottingham, UK.

Data from three completed cardiovascular outcome trials (CVOTs), EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58, add to the evidence supporting the potential renoprotective effects of sodium-glucose linked transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes. Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient-relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4401 patients vs. 69 events/34 322 patients, respectively), which shows the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal-specific elements of this primary endpoint (P <0.001). Canagliflozin has therefore become the first US-approved SGLT2 inhibitor to include an indication for RRR, in addition to type 2 diabetes glycaemic control and cardiovascular risk reduction. While confirmatory of the exploratory data from CVOTs, CREDENCE provides the first robust data on the effects of canagliflozin on patient-relevant renal endpoints. Extrapolation to a conclusion of a SGLT2 inhibitor class effect cannot be made until additional renal trials with other SGLT2 inhibitors are reported.
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http://dx.doi.org/10.1111/dom.13994DOI Listing
July 2020

Coffee Consumption and Kidney Function: A Mendelian Randomization Study.

Am J Kidney Dis 2020 05 11;75(5):753-761. Epub 2019 Dec 11.

Primary Care & Population Sciences Faculty of Medicine, University of Southampton, Southampton, United Kingdom.

Rationale & Objective: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide, with limited strategies for prevention and treatment. Coffee is a complex mixture of chemicals, and consumption has been associated with mostly beneficial health outcomes. This work aimed to determine the impact of coffee consumption on kidney function.

Study Design: Genome-wide association study (GWAS) and Mendelian randomization.

Setting & Participants: UK Biobank baseline data were used for a coffee consumption GWAS and included 227,666 participants. CKDGen Consortium data were used for kidney outcomes and included 133,814 participants (12,385 cases of CKD) of mostly European ancestry across various countries.

Exposure: Coffee consumption.

Outcomes: Estimated glomerular filtration rate (eGFR), CKD GFR categories 3 to 5 (G3-G5; eGFR<60mL/min/1.73m), and albuminuria.

Analytical Approach: GWAS to identify single-nucleotide polymorphisms (SNPs) associated with coffee consumption in UK Biobank and use of those SNPs in Mendelian randomization analyses of coffee consumption and kidney outcomes in CKDGen.

Results: 2,126 SNPs were associated with coffee consumption (P<5×10), 25 of which were independent and available in CKDGen. Drinking an extra cup of coffee per day conferred a protective effect against CKD G3-G5 (OR, 0.84; 95% CI, 0.72-0.98; P=0.03) and albuminuria (OR, 0.81; 95% CI, 0.67-0.97; P=0.02). An extra cup was also associated with higher eGFR (β=0.022; P=1.6×10) after removal of 3 SNPs responsible for significant heterogeneity (Cochran Q P = 3.5×10).

Limitations: Assays used to measure creatinine and albumin varied between studies that contributed data and a sex-specific definition was used for albuminuria rather than KDIGO guideline recommendations.

Conclusions: This study provides evidence of a beneficial effect of coffee on kidney function. Given widespread coffee consumption and limited interventions to prevent CKD incidence and progression, this could have significant implications for global public health in view of the increasing burden of CKD worldwide.
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http://dx.doi.org/10.1053/j.ajkd.2019.08.025DOI Listing
May 2020

Skin autofluorescence: an emerging biomarker in persons with kidney disease.

Curr Opin Nephrol Hypertens 2019 11;28(6):507-512

Centre for Kidney Research and Innovation, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham.

Purpose Of Review: Skin autofluorescence (SAF) is a measure of the accumulation of advanced glycation end-products (AGEs) proposed to act as a marker of 'cumulative metabolic stress'. This article discusses mechanisms of AGE formation and reviews published literature on SAF as a biomarker and risk factor across the spectrum of kidney disease.

Recent Findings: SAF is elevated in adults and children on dialysis. Higher SAF is an independent risk factor for cardiovascular and all-cause mortality in persons receiving haemodialysis and for all-cause mortality in persons performing peritoneal dialysis, though the increase in discrimination when SAF was added to traditional risk factors was modest. In less advanced chronic kidney disease, higher SAF predicts all-cause mortality and progression. SAF is elevated in renal transplant recipients, but to a lesser extent than in dialysis patients. In one study, higher SAF predicted graft loss and mortality. SAF has been reported to be increased in patients with acute kidney injury.

Summary: A growing body of evidence attests that SAF, a marker of AGE accumulation, is a risk factor for mortality and kidney function decline in multiple types of kidney disease. Further studies are warranted to evaluate interventions to reduce SAF and the impact on clinical outcomes.
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http://dx.doi.org/10.1097/MNH.0000000000000549DOI Listing
November 2019

Determinants of change in arterial stiffness over 5 years in early chronic kidney disease.

Nephrol Dial Transplant 2021 01;36(2):281-288

Centre for Kidney Research and Innovation, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital, Derby, UK.

Background: Arterial stiffness (AS) is an established and potentially modifiable risk factor for cardiovascular disease associated with chronic kidney disease (CKD). There have been few studies to evaluate the progression of AS over time or factors that contribute to this, particularly in early CKD. We therefore investigated AS over 5 years in an elderly population with CKD Stage 3 cared for in primary care.

Methods: A total of 1741 persons with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m2 underwent detailed clinical and biochemical assessment at baseline and Years 1 and 5. Carotid to femoral pulse wave velocity (PWV) was measured to assess AS using a Vicorder device.

Results: 970 participants had PWV assessments at baseline and 5 years. PWV increased significantly by a mean of 1.1 m/s (from 9.7 ± 1.9 to 10.8 ± 2.1 m/s). Multivariable linear regression analysis identified the following independent determinants of ΔPWV at Year 5: baseline age, diabetes status, baseline systolic blood pressure (SBP) and diastolic blood pressure, baseline PWV, ΔPWV at 1 year, ΔSBP over 5 years and Δserum bicarbonate over 5 years (R2 = 0.38 for the equation).

Conclusions: We observed a clinically significant increase in PWV over 5 years in a cohort with early CKD despite reasonably well-controlled hypertension. Measures of BP were identified as the most important modifiable determinant of ΔPWV, suggesting that interventions to prevent arterial disease should focus on improved control of BP, particularly in those who evidence an early increase in PWV. These hypotheses should now be tested in prospective trials.
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http://dx.doi.org/10.1093/ndt/gfz170DOI Listing
January 2021

CKD: A Call for an Age-Adapted Definition.

J Am Soc Nephrol 2019 10 10;30(10):1785-1805. Epub 2019 Sep 10.

Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m, whereas in elderly people it is increased at levels <45 ml/min per 1.73 m Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.
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http://dx.doi.org/10.1681/ASN.2019030238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779354PMC
October 2019

Peritoneal Ultrafiltration for Heart Failure: Lessons from a Randomized Controlled Trial.

Perit Dial Int 2019 Sep-Oct;39(5):486-489

University Hospitals of Derby and Burton, Derby, UK.

Peritoneal ultrafiltration (PuF) has been employed for severe heart failure (HF), but evidence for its benefit is lacking. The Peritoneal Dialysis for Heart Failure (PDHF) study was a multicenter prospective randomized controlled trial which aimed to investigate this issue. The trial stopped early due to inadequate recruitment. We describe methods, trial activity, and lessons learned.The trial aimed to recruit 130 participants with severe diuretic-resistant HF (New York Heart Association [NYHA] 3/4) and chronic kidney disease (CKD) stage 3/4 on optimal medical treatment for ≥ 4 weeks from 6 UK centers. Participants were randomized to either continuation of conventional HF treatment or to additionally receiving PuF (1 overnight exchange using Icodextrin dialysate). Primary outcome was change in 6-minute walk test (6MWT) between baseline and 28 weeks (end of trial). Secondary outcomes were changes in patient reported quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire, short form 36 (SF 36) health survey results, hospitalization, and mortality.Over a 2-year period, 290 patients were screened from which only 20 met inclusion criteria and 10 were recruited. Reasons for ineligibility were fluctuating estimated glomerular filtration rate (eGFR), suboptimal HF treatment, frailty, and patients being too unwell for randomization. Barriers to recruitment included patient frailty, with some participants considered only when they were at end of life, unwillingness to engage in an invasive therapy, and suboptimal coordination between cardiology and renal services. This is a challenging patient group in which to perform research, and lessons learned from the peritoneal dialysis (PD)-HF trial will be helpful in the planning of future studies in this area.
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http://dx.doi.org/10.3747/pdi.2018.00272DOI Listing
August 2020
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