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BACKGROUND AND AIMS: Multimorbidity is becoming the norm rather than the exception, especially among the ageing population and people with lower socio-economic status. In addition to the rising healthcare cost, multimorbidity poses considerable difficulty in the delivery of adequate holistic care for affected patients. METHODS: This review presents a discussion of the current barriers to delivering holistic care to people with multimorbidity and proposes a model of clinical care for people living with cardiovascular-kidney-metabolic (CKM) syndrome as an exemplar of a multimorbidity cluster. RESULTS: Single organ/disease services may not be able to provide optimum care to people with multimorbidity due to the potential complex interactions between multiple disease symptoms and management. In addition, people with multimorbidity may be required to attend multiple appointments in different healthcare centres. This may negatively impact access to services due to time and financial burden. Other barriers include co-ordinating communication between healthcare professionals and reduced continuity of care. Optimising CKM health requires patient-centred care led by an interdisciplinary care team who ideally should possess CKM competencies utilising a shared care protocol to coordinate evidence-based care and use of telehealth to empower patients. Stakeholders and policymakers need to adapt new policy models to establish and enhance CKM care models by allocating funds and implementing frameworks for educational reforms. CONCLUSIONS: A CKM service has the potential to increase the uptake of cardiac and renal protective medications as well as optimising metabolic care, increase capacity in both primary and secondary care, improve quality of life and clinical outcomes, reduce patient inconvenience, and importantly allow rapid translation of advances in cardiorenal metabolic diseases into clinical practice.
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Background: Due to the high correlation of chronic kidney disease (CKD) with other comorbidities, the sole effect of CKD on deprived people is not clear. In addition, there is a paucity of evidence in the literature linking isolated domains of deprivation to outcomes. This study aimed to examine whether deprivation was associated with adverse outcomes in patients with CKD, independent of cardiometabolic morbidities. Individual domains of deprivation were also evaluated. Methods: A retrospective study of patients with non-dialysis-dependent CKD (ND-CKD) in the Salford Kidney Study to investigate the association of deprivation with outcomes. The English Indices of Deprivation was used for the comparative analysis of the five quintiles of deprivation. Two propensity score methods were used to attenuate the confounding effect of cardiometabolic morbidities between the least and the most deprived groups. Results: People living in the least deprived areas (n = 319) had a lower risk of combined outcomes (all-cause mortality and renal replacement therapy) when compared with the most deprived group (n = 813) [hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.71-0.98]. The negative association of deprivation remained after matching but with mixed statistical significance when using different propensity methods (HR 0.85; 95% CI 0.70-1.03 for propensity score matching and HR 0.77; 95% CI 0.61-0.98 for inverse probability weighting). The association of combined outcomes varied across component index of multiple deprivation domains with wide CIs. However, areas with lower scores for education, income and employment were significantly associated with a higher risk. Conclusions: This study has identified that in people with ND-CKD, unemployment, poor educational attainment and lower household income were associated with poor outcomes. The association of deprivation with adverse outcomes persists despite adjustment for cardiometabolic morbidities.
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Background: Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS. Objectives: Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies. Design: A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline (nâ =â 1167) and their ability to detect change over 3 years (nâ =â 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components (nâ =â 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs (nâ =â 875). Setting: Primary, secondary and tertiary care. Participants: Adults (≥ 18 years) with stage 3 chronic kidney disease. Interventions: Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Main outcome measures: Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated. Results: Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior (pâ <â 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 yearsâ =â £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate. Limitations: Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target. Future work: Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken. Conclusions: Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease. Trial registration: This trial is registered as ISRCTN42955626. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.
Chronic kidney disease, which affects approximately 14% of the adult population, often has no symptoms but, in some people, may later develop into kidney failure. Kidney disease is most often detected using a blood test called creatinine. Creatinine does not identify everyone with kidney disease, or those most likely to develop more serious kidney disease. An alternative blood test called cystatin C may be more accurate, but it is more expensive than the creatinine test. We compared the accuracy of these two tests in more than 1000 people with moderate kidney disease. Participants were tested over 3 years to see if the tests differed in their ability to detect worsening kidney function. We also wanted to identify risk factors associated with loss of kidney function, and how much the tests normally vary to better understand what results mean. We compared the accuracy and costs of monitoring people with the two markers. Cystatin C was found slightly more accurate than the creatinine test at estimating kidney function when comparing the baseline single measurements (95% accurate compared to 90%), but not at detecting worsening function over time. This means that the additional cost of monitoring people over time with cystatin C to detect kidney disease progression could not be justified. Kidney test results could vary by up to 20% between tests without necessarily implying changes in underlying kidney function this is the normal level of individual variation. Cystatin C marginally improved accuracy of kidney function testing but not ability to detect worsening kidney function. Cystatin C improves identification of moderate chronic kidney disease, but our results do not support its use for routine monitoring of kidney function in such patients.
Subject(s)
Creatinine , Cystatin C , Disease Progression , Glomerular Filtration Rate , Renal Insufficiency, Chronic , Humans , Cystatin C/blood , Creatinine/blood , Male , Female , Renal Insufficiency, Chronic/physiopathology , Middle Aged , Aged , Prospective Studies , Longitudinal Studies , Biomarkers , Cost-Benefit Analysis , Adult , United Kingdom , AlbuminuriaABSTRACT
INTRODUCTION: The prevalence of heart failure (HF) is more common in people with advanced non-dialysis chronic kidney disease (ND-CKD) compared to the general population. It is well known that HF with reduced ejection fraction (HFrEF) is associated with a higher risk of mortality in people with ND-CKD. However, the impact of HFrEF on progression into end-stage kidney disease (ESKD) is not well studied. Our study aimed to examine the independent association of HFrEF on progression to ESKD after correcting for confounding factors using two methods of propensity scoring. METHODS: This study used data from the Salford Kidney Study, a longitudinal study which has recruited more than 3,000 patients with ND-CKD since 2002. Patients without a history of HF during the recruitment questionnaire were included in the control group. Patients with a reported history of HF and echo showing left ventricular ejection fraction <40% at enrolment were included in the HFrEF group. Two propensity score methods were used to attenuate the effects of confounding factors between the two groups - propensity score matching (PSM) and inverse probability weighting (IPW). Univariate and multivariate Cox-regression analyses were performed. RESULTS: A total of 2,383 patients were included in the analysis. Patients with HFrEF had significantly higher median age and a higher percentage of male gender compared to patients with no HF (72.5 vs. 66.6 years and 71.8 vs. 61.1%, respectively). Univariate and 5 models of multivariate Cox-regression analysis showed that HFrEF in people with CKD was a strong predictor for a higher incidence of ESKD (model 5: hazard ratio 1.38; 95% confidence interval = 1.01-1.90; p = 0.044). The association between HFrEF and the risk of ESKD remained significant after using the PSM and the IPW methods. CONCLUSION: Patients with concomitant advanced ND-CKD and prevalent HFrEF were found to have a higher risk of ESKD when compared to patients with no HF. This risk persists despite the adjustment of confounding factors using PSM and IPW.
Subject(s)
Disease Progression , Heart Failure , Kidney Failure, Chronic , Propensity Score , Renal Insufficiency, Chronic , Stroke Volume , Humans , Male , Female , Heart Failure/physiopathology , Heart Failure/complications , Heart Failure/epidemiology , Stroke Volume/physiology , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/complications , Aged , Middle Aged , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Longitudinal Studies , Prevalence , Glomerular Filtration Rate/physiologyABSTRACT
Introduction: Post-transplant cardiovascular disease (PTCVD) poses a significant challenge in kidney transplantation, potentially impacting graft outcomes and patient survival. This retrospective study aimed to investigate the incidence, risk factors, and consequential impact of PTCVD in kidney transplant recipients (KTRs) devoid of pre-existing cardiovascular disease (CVD). Method: The cohort comprised 1114 KTRs, with 749 individuals included after excluding those with pre-existing CVD and early graft loss. PTCVD encompasses ischemic heart disease, myocardial infarction, arrhythmias, heart failure, stroke, peripheral vascular disease, and valvular heart disease. Competing risk regression analysis was performed to identify predictors of PTCVD, while Cox proportional hazards analysis assessed the impact of PTCVD on graft and recipient survival. Results: The cumulative incidence of PTCVD at 5, 10, and 20 years was 5.4%, 14.3%, and 22.5%, respectively. Competing risk regression identified increased age (sub-hazard ratio [SHR], 1.22; p = 0.036) per decade, duration of dialysis (SHR, 1.07; p = 0.048) per year on dialysis, and the slope of the estimated glomerular filtration rate (SHR, 1.08; p = 0.008) mL/min/year decline as independent predictors of higher-risk PTCVD. A higher baseline estimated glomerular filtration rate (eGFR) was protective (SHR, 0.98; p = 0.032). PTCVD was not significantly associated with death-censored graft loss (adjusted hazard ratio [aHR] 1.31; p = 0.48) but was correlated with higher all-cause graft loss (aHR, 1.71; p = 0.011) and recipient mortality (aHR, 1.97; p = 0.004). Conclusion: This study provides insights into PTCVD predictors. Although not directly associated with graft loss, PTCVD significantly correlates with heightened mortality in kidney transplant recipients, emphasizing the need for enhanced clinical management and surveillance strategies.
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BACKGROUND: The early identification of patients at high-risk for end-stage renal disease (ESRD) is essential for providing optimal care and implementing targeted prevention strategies. While the Kidney Failure Risk Equation (KFRE) offers a more accurate prediction of ESRD risk compared to static eGFR-based thresholds, it does not provide insights into the patient-specific biological mechanisms that drive ESRD. This study focused on evaluating the effectiveness of KFRE in a UK-based advanced chronic kidney disease (CKD) cohort and investigating whether the integration of a proteomic signature could enhance 5-year ESRD prediction. METHODS: Using the Salford Kidney Study biobank, a UK-based prospective cohort of over 3000 non-dialysis CKD patients, 433 patients met our inclusion criteria: a minimum of four eGFR measurements over a two-year period and a linear eGFR trajectory. Plasma samples were obtained and analysed for novel proteomic signals using SWATH-Mass-Spectrometry. The 4-variable UK-calibrated KFRE was calculated for each patient based on their baseline clinical characteristics. Boruta machine learning algorithm was used for the selection of proteins most contributing to differentiation between patient groups. Logistic regression was employed for estimation of ESRD prediction by (1) proteomic features; (2) KFRE; and (3) proteomic features alongside KFRE. RESULTS: SWATH maps with 943 quantified proteins were generated and investigated in tandem with available clinical data to identify potential progression biomarkers. We identified a set of proteins (SPTA1, MYL6 and C6) that, when used alongside the 4-variable UK-KFRE, improved the prediction of 5-year risk of ESRD (AUC = 0.75 vs AUC = 0.70). Functional enrichment analysis revealed Rho GTPases and regulation of the actin cytoskeleton pathways to be statistically significant, inferring their role in kidney function and the pathogenesis of renal disease. CONCLUSIONS: Proteins SPTA1, MYL6 and C6, when used alongside the 4-variable UK-KFRE achieve an improved performance when predicting a 5-year risk of ESRD. Specific pathways implicated in the pathogenesis of podocyte dysfunction were also identified, which could serve as potential therapeutic targets. The findings of our study carry implications for comprehending the involvement of the Rho family GTPases in the pathophysiology of kidney disease, advancing our understanding of the proteomic factors influencing susceptibility to renal damage.
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Introduction: Post-transplant malignancy is a significant cause of morbidity and mortality following kidney transplantation often emerging after medium- to long-term follow-up. To understand the risk factors for the development of de novo post-transplant malignancy (DPTM), this study aimed to assess the incidence, risk factors, and outcomes of DPTM at a single nephrology centre over two decades. Methods: This retrospective cohort study included 963 kidney transplant recipients who underwent kidney transplantation between January 2000 and December 2020 and followed up over a median follow-up of 7.1 years (IQR 3.9-11.4). Cox regression models were used to identify the significant risk factors of DPTM development, the association of DPTM with graft survival, and mortality with a functioning graft. Results: In total, 8.1% of transplant recipients developed DPTM, and the DPTM incidence rate was 14.7 per 100 patient-years. There was a higher mean age observed in the DPTM group (53 vs. 47 years, p < 0.001). The most affected organ systems were genitourinary (32.1%), gastrointestinal (24.4%), and lymphoproliferative (20.5%). Multivariate Cox analysis identified older age at transplant (aHR 9.51, 95%CI: 2.60-34.87, p < 0.001) and pre-existing glomerulonephritis (aHR 3.27, 95%CI: 1.10-9.77, p = 0.03) as significant risk factors for DPTM. Older age was significantly associated with poorer graft survival (aHR 8.71, 95%CI: 3.77-20.20, p < 0.001). When age was excluded from the multivariate Cox model, DPTM emerged as a significant risk factor for poor survival (aHR 1.76, 95%CI: 1.17-2.63, p = 0.006). Conclusion: These findings underscore the need for tailored screening, prevention, and management strategies to address DPTM in an aging and immunosuppressed kidney transplant population.
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BACKGROUND AND OBJECTIVES: Atherosclerotic renal artery stenosis may cause hypertension, chronic kidney disease and heart failure, but large randomized control trials to date have shown no major additional benefit of renal revascularization over optimal medical management. However, these trials did not consider outcomes specifically in relation to clinical presentations. Given that atherosclerotic renal artery stenosis is a heterogenous condition, measures of success likely differ according to the clinical presentation. Our retrospective study objectives were to determine the effects of revascularization when applied to specific clinical presentations and after careful multi-disciplinary team review. METHODS: All patients presenting to our centre and its referring hospitals with radiological findings of at least one renal artery stenosis > 50% between January 2015 and January 2020 were reviewed at the renovascular multi-disciplinary team meeting with revascularization considered in accordance with international guidelines, notably for patients with anatomically significant renal artery stenosis, adequately sized kidney and presentations with any of; deteriorating kidney function, heart failure syndrome, or uncontrollable hypertension. Optimal medical management was recommended for all patients which included lipid lowering agents, anti-platelets and anti-hypertensives targeting blood pressure ≤ 130/80 mmHg. The effect of revascularization was assessed according to the clinical presentation; blood pressure and number of agents in those with renovascular hypertension, delta glomerular filtration rate in those with ischaemic nephropathy and heart failure re-admissions in those with heart failure syndromes. RESULTS: During this 5-year period, 127 patients with stenosis ≥ 50% were considered by the multidisciplinary team, with 57 undergoing revascularization (17 primarily for severe hypertension, 25 deteriorating kidney function, 6 heart failure syndrome and 9 for very severe anatomical stenosis). Seventy-nine percent of all revascularized patients had a positive outcome specific to their clinical presentation, with 82% of those with severe hypertension improving blood pressure control, 72% with progressive ischaemic nephropathy having attenuated GFR decline, and no further heart failure admissions in those with heart failure. Seventy-eight percent of patients revascularized for high grade stenosis alone had better blood pressure control with 55% also manifesting renal functional benefits. CONCLUSIONS: Multi-disciplinary team discussion successfully identified a group of patients more likely to benefit from revascularization based on 3 key factors: clinical presentation, severity of the renal artery lesion and the state of the kidney beyond the stenotic lesion. In this way, a large proportion of patients can clinically improve after revascularization if their outcomes are considered according to the nature of their clinical presentation.
Subject(s)
Hypertension, Renovascular , Renal Artery Obstruction , Humans , Renal Artery Obstruction/therapy , Renal Artery Obstruction/complications , Renal Artery Obstruction/physiopathology , Retrospective Studies , Aged , Female , Male , Hypertension, Renovascular/therapy , Hypertension, Renovascular/etiology , Hypertension, Renovascular/physiopathology , Hypertension, Renovascular/diagnosis , Treatment Outcome , Middle Aged , Atherosclerosis/complications , Glomerular Filtration Rate , Patient Care Team , Antihypertensive Agents/therapeutic useABSTRACT
BACKGROUND AND AIMS: What is the relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure? METHODS: In the IRONMAN trial, 1137 patients with heart failure, ejection fraction ≤ 45%, and either serum ferritin < 100â µg/L or transferrin saturation (TSAT) < 20% were randomized to intravenous ferric derisomaltose (FDI) or usual care. Relationships were investigated between baseline anaemia severity, ferritin and TSAT, to changes in haemoglobin from baseline to 4 months, Minnesota Living with Heart Failure (MLwHF) score and 6-minute walk distance achieved at 4 months, and clinical events, including heart failure hospitalization (recurrent) or cardiovascular death. RESULTS: The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014). MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin. Blood tests did not predict difference in achieved walking distance for those randomized to FDI compared to control. The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI. More severe anaemia or TSAT < 20%, especially when ferritin was ≥100â µg/L, was associated with higher event rates and greater absolute reductions in events with FDI, albeit not statistically significant. CONCLUSIONS: This hypothesis-generating analysis suggests that anaemia or TSAT < 20% with ferritin > 100â µg/L might identify patients with heart failure who obtain greater benefit from intravenous iron. This interpretation requires confirmation.
Subject(s)
Anemia, Iron-Deficiency , Anemia , Heart Failure , Iron Deficiencies , Humans , Iron/therapeutic use , Anemia, Iron-Deficiency/drug therapy , Ferritins/therapeutic use , Ferric Compounds/therapeutic use , Hemoglobins , Heart Failure/drug therapyABSTRACT
BACKGROUND: This study investigated whether nature of primary renal disease affects clinical outcomes after renal transplantation at a single center in the United Kingdom. METHODS: This was a retrospective cohort study of 961 renal transplant recipients followed up at a large renal center from 2000 to 2020. Separation of diseases responsible for end-stage kidney disease included glomerulonephritis, diabetic kidney disease, hypertensive nephropathy, autosomal dominant polycystic kidney disease, unknown cause, other causes and chronic pyelonephritis. Outcome data included graft loss, cardiovascular events, malignancy, post-transplant diabetes mellitus and death, analyzed according to primary disease type. RESULTS: The mean age at transplantation was 47.3 years. During a mean follow-up of 7.6 years, 18% of the overall cohort died corresponding to an annualised mortality rate of 2.3%. Death with a functioning graft occurred at a rate of 2.1% per annum, with the highest incidence observed in in patients with diabetic kidney disease (4.1%/year). Post-transplant cardiovascular events occurred in 21% of recipients (2.8% per year), again highest in recipients with diabetic kidney disease (5.1%/year) and hypertensive nephropathy (4.5%/year). Post-transplant diabetes mellitus manifested in 19% of the cohort at an annualized rate of2.1% while cancer incidence stood at 9% with an annualized rate of 1.1% . Graft loss occurred in 6.8% of recipients at the rate of1.2% per year with chronic allograft injury, acute rejection and recurrent glomerulonephritis being the predominant causative factors. Median + IQR dialysis-free survival of the whole cohort was 16.2 (9.9 - > 20) years, being shortest for diabetic kidney disease (11.0 years) and greatest for autosomal dominant polycystic kidney disease (18.2 years) .The collective mean decline in eGFR over time was -1.14ml/min/year. Recipients with Pre-transplant diabetic kidney disease exhibited the fastest rate of decline(-2.1ml/min/year) a statistically significant difference in comparison to the other native kidney diseases with Autosomal dominant polycystic kidney disease exhibiting the lowest rate of decline(-0.05ml/min/year) CONCLUSION: Primary renal disease can influence the outcome after renal transplantation, with patients with prior diabetic kidney disease having the poorest outcome in terms of dialysis-free survival and loss of transplant function. Autosomal polycystic kidney disease, other cause and unknown cause had the best outcomes compared to other primary renal disease groups.
Subject(s)
Diabetic Nephropathies , Glomerulonephritis , Hypertension, Renal , Kidney Transplantation , Nephritis , Polycystic Kidney, Autosomal Dominant , Humans , Middle Aged , Kidney Transplantation/adverse effects , Retrospective StudiesABSTRACT
Chronic kidney diseases (CKD) have genetic associations with kidney function. Univariate genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with estimated glomerular filtration rate (eGFR) and blood urea nitrogen (BUN), two complementary kidney function markers. However, it is unknown whether additional SNPs for kidney function can be identified by multivariate statistical analysis. To address this, we applied canonical correlation analysis (CCA), a multivariate method, to two individual-level CKD genotype datasets, and metaCCA to two published GWAS summary statistics datasets. We identified SNPs previously associated with kidney function by published univariate GWASs with high replication rates, validating the metaCCA method. We then extended discovery and identified previously unreported lead SNPs for both kidney function markers, jointly. These showed expression quantitative trait loci (eQTL) colocalisation with genes having significant differential expression between CKD and healthy individuals. Several of these identified lead missense SNPs were predicted to have a functional impact, including in SLC14A2. We also identified previously unreported lead SNPs that showed significant correlation with both kidney function markers, jointly, in the European ancestry CKDGen, National Unified Renal Translational Research Enterprise (NURTuRE)-CKD and Salford Kidney Study (SKS) datasets. Of these, rs3094060 colocalised with FLOT1 gene expression and was significantly more common in CKD cases in both NURTURE-CKD and SKS, than in the general population. Overall, by using multivariate analysis by CCA, we identified additional SNPs and genes for both kidney function and CKD, that can be prioritised for further CKD analyses.
Subject(s)
Genome-Wide Association Study , Renal Insufficiency, Chronic , Humans , Genome-Wide Association Study/methods , Canonical Correlation Analysis , Renal Insufficiency, Chronic/genetics , Renal Insufficiency, Chronic/epidemiology , Kidney , Quantitative Trait Loci/geneticsABSTRACT
Background: Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention. Method: The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic). Results: Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0 kg/m2, ß -0.037, 95% CI -0.058 to -0.016, P = .001), HADS depression score ≥8 (ß -0.159, -0.182 to -0.137, P < .001), anxiety score ≥8 (ß -0.090, -0.110 to -0.069, P < .001), taking ≥10 medications (ß -0.065, -0.085 to -0.046, P < .001), sarcopenia (ß -0.062, -0.080 to -0.043, P < .001) haemoglobin <100 g/L (ß -0.047, -0.085 to -0.010, P = .012) and pain (ß -0.134, -0.152 to -0.117, P < .001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin-angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities. Conclusion: Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.
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BACKGROUND: There is a marked increase in the global prevalence of obesity over the last decades with an estimated 1.9 billion adults living with overweight or obesity. This is associated with a sharp rise in prevalence of cardiorenal metabolic diseases such as type 2 diabetes mellitus, chronic kidney disease, and heart failure. With recent evidence of the efficacy of sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal protection and weight reduction, it is reasonable to investigate common causative pathways for cardiorenal metabolic diseases. SUMMARY: Central obesity is a common condition with 41.5% prevalence worldwide. It is associated with adverse outcomes even in people with a normal body mass index. Central obesity develops when the personal fat threshold for expansion in the subcutaneous adipose tissue exceeds a certain level. Multiple factors such as age, gender, genetics, and hormones may play a role in determining personal susceptibility to central obesity. Cardiorenal metabolic diseases usually cluster in certain populations - commonly in people with central obesity - and cause a substantial burden on health services and increase the risk of all-cause mortality. In this review, we investigate the pathophysiological pathways between central obesity and cardiorenal metabolic diseases. These pathways include activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, inflammation and oxidative stress, haemodynamic impairment, insulin resistance, and endothelial dysfunction. KEY MESSAGE: Central obesity has a pivotal role in the development of cardiorenal metabolic diseases and should be targeted with population-based approaches, such as dietary and lifestyle interventions, as well as the development of pharmacotherapy to reduce the burden of cardiorenal metabolic diseases.
Subject(s)
Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Adult , Humans , Obesity, Abdominal/complications , Obesity, Abdominal/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Obesity/complications , Obesity/epidemiology , Obesity/metabolism , Renin-Angiotensin System , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiologyABSTRACT
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
Subject(s)
Ageusia , COVID-19 , Humans , Anosmia/epidemiology , Anosmia/etiology , COVID-19/diagnosis , COVID-19 Testing , COVID-19 Vaccines , Longitudinal Studies , SARS-CoV-2 , Clinical Trials, Phase III as TopicABSTRACT
This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.
Subject(s)
Kidney , Renal Insufficiency, Chronic , Adult , Female , Humans , Male , Blogging , Exercise , Pilot Projects , Renal Insufficiency, Chronic/therapy , Middle Aged , AgedABSTRACT
BACKGROUND: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life. METHODS: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933. FINDINGS: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001). INTERPRETATION: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions. FUNDING: Kidney Research UK.