Sex disparities in mortality and cardiovascular outcomes in chronic kidney disease.

Sex (biologically determined) and gender (socially constructed) modulate manifestations and prognosis of a vast number of diseases, including cardiovascular disease (CVD) and chronic kidney disease (CKD). CVD remains the leading cause of death in CKD patients. Population-based studies indicate that women present a higher prevalence of CKD and experience less CVD than men in all CKD stages, although this is not as clear in patients on dialysis or transplantation. When compared to the general population of the same sex, CKD has a more negative impact on women on kidney replacement therapy. European women on dialysis or recipients of kidney transplants have life expectancy up to 44.8 and 19.8 years lower, respectively, than their counterparts of similar age in the general population. For men, these figures stand at 37.1 and 16.5 years, representing a 21% to 20% difference, respectively. Hormonal, genetic, societal, and cultural influences may contribute to these sex-based disparities. To gain a more comprehensive understanding of these differences and their implications for patient care, well-designed clinical trials that involve a larger representation of women and focus on sex-related variables are urgently needed. This narrative review emphasizes the importance of acknowledging the epidemiology and prognosis of sex disparities in CVD among CKD patients. Such insights can guide research into the underlying pathophysiological mechanisms, leading to optimized treatment strategies and ultimately, improved clinical outcomes.

An update review of post-transplant diabetes mellitus: Concept, risk factors, clinical implications and management.

OBJECTIVE: Kidney transplantation is the gold standard therapeutic alternative for patients with end-stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post-transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. METHODS: Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. RESULTS: PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post-transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large-scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose-lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. DISCUSSION: The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients.

Heart disease and stroke statistics 2023 update from the American Heart Association-implications for nephrology.

The annual American Heart Association (AHA) and National Institutes of Health statistical report details the most up to date statistics related to heart disease, stroke and cardiovascular risk factors, primarily within the USA. Although not a formal systematic review or meta-analysis, this 600 page report provides the most comprehensive and best summary of cardiovascular statistics for the year in question. Although data are collated from USA data registries, it serves as a critical resource for clinicians, policymakers, administrators and researchers in the northern and southern hemispheres. In this special report, we have chosen to highlight aspects of the document that are relevant to nephrologists, given the overlap of cardiovascular and renal disease. These include (i) key and emerging cardiovascular data signals in the general and chronic kidney disease (CKD) populations, (ii) ethnic and socio-economic disparity, (iii) environmental and behavioural factors that drive high levels of cardiovascular disease and which are key components of the AHA's eight components of the Life Essential cardiovascular health score, and (iv) the impact of COVID-19 both directly and indirectly on heart health. We provide some commentary and critical analysis of both the data and of the production of such data sets suggesting that similar data on CKD could also be published and linked to the AHA and other datasets.

COVID-19 and cardiovascular disease in patients with chronic kidney disease.

Millions of people worldwide have chronic kidney disease (CKD). Affected patients are at high risk for cardiovascular (CV) disease for several reasons. Among various comorbidities, CKD is associated with the more severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is particularly true for patients receiving dialysis or for kidney recipients. From the start of the SARS-CoV-2 pandemic, several CV complications have been observed in affected subjects, spanning acute inflammatory manifestations, CV events, thrombotic episodes and arrythmias. Several pathogenetic mechanisms have been hypothesized, including direct cytopathic viral effects on the myocardium, endothelial damage and hypercoagulability. This spectrum of disease can occur during the acute phase of the infection, but also months after recovery. This review is focussed on the CV complications of coronavirus disease 2019 (COVID-19) with particular interest in their implications for the CKD population.

Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA).

Chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D) represents a major public health issue; it develops in about 30%-40% of patients with diabetes mellitus and is the most common cause of CKD worldwide. Patients with CKD and T2D are at high risk of both developing kidney failure and of cardiovascular events. Renin-angiotensin system (RAS) blockers were considered the cornerstone of treatment of albuminuric CKD in T2D for more than 20 years. However, the residual risk of progression to more advanced CKD stages under RAS blockade remains high, while in major studies with these agents in patients with CKD and T2D no significant reductions in cardiovascular events and mortality were evident. Steroidal mineralocorticoid receptor antagonists (MRAs) are known to reduce albuminuria in individuals on RAS monotherapy, but their wide clinical use has been curtailed by the significant risk of hyperkalemia and absence of trials with hard renal outcomes. In recent years, non-steroidal MRAs have received increasing interest due to their better pharmacologic profile. Finerenone, the first compound of this class, was shown to effectively reduce the progression of kidney disease and of cardiovascular outcomes in participants with T2D in phase 3 trials. This clinical practice document prepared from a task force of the European Renal Best Practice board summarizes current knowledge on the role of MRAs in the treatment of CKD in T2D aiming to support clinicians in decision-making and everyday management of patients with this condition.

Diagnosis of cardiovascular disease in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at high risk of cardiovascular disease (CVD) and cardiovascular death. Identifying and monitoring cardiovascular complications and hypertension is important for managing patients with CKD or kidney failure and transplant recipients. Biomarkers of myocardial ischaemia, such as troponins and electrocardiography (ECG), have limited utility for diagnosing cardiac ischaemia in patients with advanced CKD. Dobutamine stress echocardiography, myocardial perfusion scintigraphy and dipyridamole stress testing can be used to detect coronary disease in these patients. Left ventricular hypertrophy and left ventricular dysfunction can be detected and monitored using various techniques with differing complexity and cost, including ECG, echocardiography, nuclear magnetic resonance, CT and myocardial scintigraphy. Atrial fibrillation and other major arrhythmias are common in all stages of CKD, and ambulatory heart rhythm monitoring enables precise time profiling of these disorders. Screening for cerebrovascular disease is only indicated in asymptomatic patients with autosomal dominant polycystic kidney disease. Standardized blood pressure is recommended for hypertension diagnosis and treatment monitoring and can be complemented by ambulatory blood pressure monitoring. Judicious use of these diagnostic techniques may assist clinicians in detecting the whole range of cardiovascular alterations in patients with CKD and enable timely treatment of CVD in this high-risk population.

Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype.

Activation of cardiac fibroblasts and differentiation to myofibroblasts underlies development of pathological cardiac fibrosis, leading to arrhythmias and heart failure. Myofibroblasts are characterised by increased α-smooth muscle actin (α-SMA) fibre expression, secretion of collagens and changes in proliferation. Transforming growth factor-beta (TGF-ß) and increased mechanical stress can initiate myofibroblast activation. Reversibility of the myofibroblast phenotype has been observed in murine cells but has not been explored in human cardiac fibroblasts. In this study, chronically activated adult primary human ventricular cardiac fibroblasts and human induced pluripotent stem cell derived cFbs (hiPSC-cFbs) were used to investigate the potential for reversal of the myofibroblast phenotype using either subculture on soft substrates or TGF-ß receptor inhibition. Culture on softer plates (25 or 2 kPa Young's modulus) did not alter proliferation or reduce expression of α-SMA and collagen 1. Similarly, culture of myofibroblasts in the presence of TGF-ß inhibitor did not reverse myofibroblasts back to a quiescent phenotype. Chronically activated hiPSC-cFbs also showed attenuated response to TGF-ß receptor inhibition and inability to reverse to quiescent fibroblast phenotype. Our data demonstrate substantial loss of TGF-ß signalling plasticity as well as a loss of feedback from the surrounding mechanical environment in chronically activated human myofibroblasts.

Gender Disparity in Expression of Sarcopenia in Haemodialysis Recipients: Analysis from the FITNESS Cohort.

Background: There has been little exploration of the interplay between sarcopenia and frailty in haemodialysis, particularly regarding gender difference. We aimed to (1) assess whether ultrasound-derived low muscle mass (LMM) and sarcopenia are more common in male or female haemodialysis recipients; (2) assess whether age influences any observed gender difference, and (3) explore the interplay between sarcopenia, frailty, and gender in haemodialysis recipients. Methods: This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis with frailty phenotype (FP) scores. Bilateral anterior thigh thickness (BATT) was obtained according to an established ultrasound protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, LMM, and sarcopenia with a priori covariables, stratified by gender. Results: In total of 223 studies, participants had ultrasound measurements. Males showed greater prevalence of LMM. On adjusted analyses, LMM was associated with lower hand grip strength in males (ß = -4.17; 95% C.I. -7.57 to -0.77; P=0.02), but not females (ß = -1.88; 95% C.I. -5.41 to 1.64; P=0.29). LMM was also associated with slower walking speed in both males (ß = -0.115; 95% C.I. -0.258 to -0.013; P=0.03) and females (ß = -0.152; 95% C.I. -0.300 to -0.005; P=0.04). Sarcopenia was associated with greater odds of frailty on adjusted models in males (OR = 9.86; 95% C.I. 1.8 to 54.0; P=0.01), but not females (OR = 5.16; 95% C.I. 0.22 to 124; P=0.31). Conclusions: The clinical expression and significance of sarcopenia differ substantially between males and females on haemodialysis. Further work is required to elucidate underlying mechanisms and guide tailored treatment.

Somatic Symptoms of Depression Lose Association with Mortality upon Adjustment for Frailty: Analysis from the Fitness Haemodialysis Cohort.

Introduction: The somatic symptom component of depression is associated with increased hospitalisation and mortality and poorer health-related quality of life (HRQOL). However, the relationship of subsets of depression symptoms with frailty and outcomes is not known. This study aimed to (1) explore the relationship between the Clinical Frailty Scale (CFS) and components of depression and (2) their association with mortality, hospitalisation, and HRQOL in haemodialysis recipients. Methods: We conducted a prospective cohort study of prevalent haemodialysis recipients, with deep bio-clinical phenotyping including CFS and PHQ-9 somatic (fatigue, poor appetite, and poor sleep) and cognitive component scores. EuroQol EQ-5D summary index assessed HRQOL at the baseline. Electronic linkage to English national administration datasets ensured robust follow-up data for hospitalisation and mortality events. Findings. Somatic (ß = 0.067; 95% C.I. 0.029 to 0.104; P < 0.001) and cognitive (ß = 0.062; 95% C.I. 0.034 to 0.089; P<0.001) components were associated with increased CFS scores. Both somatic (ß = -0.062; 95% C.I. -0.104 to -0.021; P<0.001) and cognitive (ß = 0.052; 95% C.I. -0.081 to -0.024; P < 0.001) scores were associated with lower HRQOL. Somatic scores lost mortality association on addition of CFS to the multivariable model (HR1.06; 95% C.I. 0.977 to 1.14; P=0.173). Cognitive symptoms were not associated with mortality. Neither the component score was associated with hospitalisation on multivariable analyses. Conclusions: Both somatic and cognitive depression symptoms are associated with frailty and poorer HRQOL in haemodialysis recipients but were not associated with mortality or hospitalisation when adjusted for frailty. The risk profile of depression somatic scores may be related to overlap with symptoms of frailty.

Cardiovascular complications in chronic kidney disease: a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association.

Chronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called 'uremic toxins', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.

SGLT2i for evidence-based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA.

Chronic kidney disease (CKD) is a major public health issue affecting an estimated 850 million people globally. The leading causes of CKD is diabetes and hypertension, which together account for >50% of patients with end-stage kidney disease. Progressive CKD leads to the requirement for kidney replacement therapy with transplantation or dialysis. In addition, CKD, is a risk factor for premature cardiovascular disease, particularly from structural heart disease and heart failure (HF). Until 2015, the mainstay of treatment to slow progression of both diabetic and many non-diabetic kidney diseases was blood pressure control and renin-angiotensin system inhibition; however, neither angiotensin-converting enzyme inhibitors (ACEIs) nor angiotensin receptor blockers (ARBs) reduced cardiovascular events and mortality in major trials in CKD. The emergence of cardiovascular and renal benefits observed with sodium-glucose cotransporter-2 inhibitors (SGLT2i) from clinical trials of their use as anti-hyperglycaemic agents has led to a revolution in cardiorenal protection for patients with diabetes. Subsequent clinical trials, notably DAPA-HF, EMPEROR, CREDENCE, DAPA-CKD and EMPA-KIDNEY have demonstrated their benefits in reducing risk of HF and progression to kidney failure in patients with HF and/or CKD. The cardiorenal benefits-on a relative scale-appear similar in patients with or without diabetes. Specialty societies' guidelines are continually adapting as trial data emerges to support increasingly wide use of SGLT2i. This consensus paper from EURECA-m and ERBP highlights the latest evidence and summarizes the guidelines for use of SGLT2i for cardiorenal protection focusing on benefits observed relevant to people with CKD.

A clinical frailty scale obtained from MDT discussion performs poorly in assessing frailty in haemodialysis recipients.

BACKGROUND: The Clinical Frailty Scale (CFS) is a commonly utilised frailty screening tool that has been associated with hospitalisation and mortality in haemodialysis recipients, but is subject to heterogenous methodologies including subjective clinician opinion. The aims of this study were to (i) examine the accuracy of a subjective, multidisciplinary assessment of CFS at haemodialysis Quality Assurance (QA) meetings (CFS-MDT), compared with a standard CFS score via clinical interview, and (ii) ascertain the associations of these scores with hospitalisation and mortality. METHODS: We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalisation. Frailty was assessed using the CFS after structured clinical interview. The CFS-MDT was derived from consensus at haemodialysis QA meetings, involving dialysis nurses, dietitians, and nephrologists. RESULTS: 453 participants were followed-up for a median of 685 days (IQR 544-812), during which there were 96 (21.2%) deaths and 1136 hospitalisations shared between 327 (72.1%) participants. Frailty was identified in 246 (54.3%) participants via CFS, but only 120 (26.5%) via CFS-MDT. There was weak correlation (Spearman Rho 0.485, P < 0.001) on raw frailty scores and minimal agreement (Cohen's κ = 0.274, P < 0.001) on categorisation of frail, vulnerable and robust between the CFS and CFS-MDT. Increasing frailty was associated with higher rates of hospitalisation for the CFS (IRR 1.26, 95% C.I. 1.17-1.36, P = 0.016) and CFS-MDT (IRR 1.10, 1.02-1.19, P = 0.02), but only the CFS-MDT was associated with nights spent in hospital (IRR 1.22, 95% C.I. 1.08-1.38, P = 0.001). Both scores were associated with mortality (CFS HR 1.31, 95% C.I. 1.09-1.57, P = 0.004; CFS-MDT HR 1.36, 95% C.I. 1.16-1.59, P < 0.001). CONCLUSIONS: Assessment of CFS is deeply affected by the underlying methodology, with the potential to profoundly affect decision-making. The CFS-MDT appears to be a weak alternative to conventional CFS. Standardisation of CFS use is of paramount importance in clinical and research practice in haemodialysis. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03071107 registered 06/03/2017.

Impact of public restrictive measures on hypertension during the COVID-19 pandemic: existing evidence and long-term implications.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first identified in December 2019 and emerged into an ongoing global pandemic. Both the pandemic itself and the associated public restrictive measures of social mobility established with different intensity over different periods in various countries have significantly affected the everyday activities and lifestyles of people all over the world. The impact of lockdown and quarantine measures on hypertension incidence and blood pressure (BP) control is an important topic that requires further investigation. The aim of this review is: a) to present the current evidence regarding the actual effects of public restrictive measures on BP levels and control, originating primarily from studies investigating the impact of public restrictive measures on BP control with the use of various BP phenotypes; b) to summarize the possible pandemic-related effects of factors known to affect BP levels, including both traditional (e.g. dietary habits including alcohol and sodium intake, body weight, smoking and physical activity) and non-traditional (e.g. sleep patterns, air pollution, environmental noise, delayed diagnosis and medication adherence) ones.

Cognitive Impairment, Frailty, and Adverse Outcomes Among Prevalent Hemodialysis Recipients: Results From a Large Prospective Cohort Study in the United Kingdom.

Rationale & Objective: Frailty and cognitive impairment are common in hemodialysis recipients and have been associated with high mortality. There is considerable heterogeneity in frailty reporting, with little comparison between commonly used frailty tools and little exploration of the interplay between cognition and frailty. The aims were to explore the relationship between frailty scores and cognition and their associations with hospitalization and mortality. Study Design: Prospective cohort study. Setting & Population: Prevalent hemodialysis recipients linked to national datasets for hospitalization and mortality. Predictors: Montreal Cognitive Assessment (MoCA), Frailty Phenotype, Frailty Index (FI), Edmonton Frailty Scale, and Clinical Frailty Scale (CFS) were performed at baseline. Cognitive impairment was defined as MoCA scores of <26, or <21 in dexterity impairment, <18 in visual impairment. Outcomes: Mortality, hospitalization. Analytical Approach: Cox proportional hazards model for mortality, censored for end of follow-up. Negative binomial regression for admission rates, censored for death/end of follow-up. Results: In total, 448 participants were recruited with valid MoCAs and followed up for a median of 685 days. There were 103 (23%) deaths and 1,120 admissions of at least one night. Cognitive impairment was identified in 346 (77.2%) participants. Increasing frailty by all definitions was associated with poorer cognition. Cognition was not associated with mortality (HR, 0.99; 95% CI, 0.95-1.03; P = 0.41) or hospitalization (IRR, 1.01; 95% CI, 0.99-1.04; P = 0.39) on multivariable analyses. There were interactions between MoCA scores and increasing frailty by FI (P = 0.002) and Clinical Frailty Scale (P = 0.005); admissions were highest when both MoCA and frailty scores were high, and when both scores were low. Limitations: As frailty is a dynamic state, a single cross-sectional assessment may not accurately reflect its year-to-year variability. In addition, these findings are in maintenance dialysis and may not be transferable to incident hemodialysis. There were small variations in application of frailty tool criteria from other studies, which may have influenced the results. Conclusions: Cognitive impairment is highly prevalent in this hemodialysis cohort. The interaction between cognition and frailty on rates of admission suggests the MoCA offers value in identifying higher risk hemodialysis populations with both high and low degrees of frailty.

Renal artery stenting in the correct patients with atherosclerotic renovascular disease: time for a proper renal and cardiovascular outcome study?

Atherosclerotic renovascular disease (ARVD) represents the most common type of renal artery stenosis. In the last decade, a few large trials failed to demonstrate the superiority of standard medical therapy plus percutaneous transluminal renal angioplasty (PTRA) compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD. However, this issue remains controversial and an ongoing debate focusses on the benefits that selected patients could experience from renal revascularization procedures. In this regard, several pieces of observational data show that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes. Such evidence resulted in a progressive shift in relevant recommendations, with most recent not-graded suggestions supporting that revascularization should be offered in these high-risk subjects. Existing evidence clearly calls for a properly designed randomized controlled trial with selected patients presenting high-risk ARVD phenotypes, in order to confirm the superiority of PTRA versus non-invasive management in this patient group and objectively guide everyday clinical practice.

Depression is associated with frailty and lower quality of life in haemodialysis recipients, but not with mortality or hospitalization.

Background: Frailty and depression are highly prevalent in haemodialysis recipients, exhibit a reciprocal relationship, and are associated with increased mortality and hospitalization, and lower quality of life. Despite this, there has been little exploration of the relationship between depression and frailty upon patient outcomes. We aimed to explore the relationship between depression and frailty, and their associations with mortality, hospitalization and quality of life. Methods: We performed a prospective cohort study of prevalent haemodialysis recipients linked to national datasets for outcomes including mortality and hospitalization. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), frailty using the Clinical Frailty Scale (CFS) and quality of life using the EuroQol 5-Dimension (EQ-5D) Summary Index. Results: A total of 485 prevalent haemodialysis recipients were recruited, with 111 deaths and 1241 hospitalizations during follow-up. CFS was independently associated with mortality [hazard ratio (HR) 1.31; 95% confidence interval (CI) 1.08, 1.59; P = .006], hospitalization [incidence rate ratio (IRR) 1.13; 95% CI 1.03, 1.25; P = .010] and lower quality of life (Coef. -0.401; 95% CI -0.511, -0.292; P < .001). PHQ-9 score was independently associated with lower quality of life (Coef. -0.042; 95% CI -0.063, -0.021; P < .001), but not mortality (HR 1.00; 95% CI 0.96, 1.04; P = .901) or hospitalization (IRR 0.99; 95% CI 0.97, 1.01; P = .351). In an adjusted model including CFS, moderate depression was associated with reduced hospitalization (IRR 0.72; 95% CI 0.56, 0.93; P = .013). Conclusions: With the addition of frailty, depression was associated with lower hospital admissions, but poorer quality of life. The relationship between frailty and depression, and their influence on outcomes is complex, requiring further study.

Bone Mineral Density and Vascular Calcification in Children and Young Adults With CKD 4 to 5 or on Dialysis.

Introduction: Older adults with chronic kidney disease (CKD) can have low bone mineral density (BMD) with concurrent vascular calcification. Mineral accrual by the growing skeleton may protect young people with CKD from extraosseous calcification. Our hypothesis was that children and young adults with increasing BMD do not develop vascular calcification. Methods: This was a multicenter longitudinal study in children and young people (5-30 years) with CKD stages 4 to 5 or on dialysis. BMD was assessed by tibial peripheral quantitative computed tomography (pQCT) and lumbar spine dual-energy X-ray absorptiometry (DXA). The following cardiovascular imaging tests were undertaken: cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima media thickness z-score (cIMTz), pulse wave velocity z-score (PWVz), and carotid distensibility for arterial stiffness. All measures are presented as age-adjusted and sex-adjusted z-scores. Results: One hundred participants (median age 13.82 years) were assessed at baseline and 57 followed up after a median of 1.45 years. Trabecular BMD z-score (TrabBMDz) decreased (P = 0.01), and there was a nonsignificant decrease in cortical BMD z-score (CortBMDz) (P = 0.09). Median cIMTz and PWVz showed nonsignificant increase (P = 0.23 and P = 0.19, respectively). The annualized increase in TrabBMDz (ΔTrabBMDz) was an independent predictor of cIMTz increase (R 2 = 0.48, ß = 0.40, P = 0.03). Young people who demonstrated statural growth (n = 33) had lower ΔTrabBMDz and also attenuated vascular changes compared with those with static growth (n = 24). Conclusion: This hypothesis-generating study suggests that children and young adults with CKD or on dialysis may develop vascular calcification even as their BMD increases. A presumed buffering capacity of the growing skeleton may offer some protection against extraosseous calcification.

Ultrasound quadriceps muscle thickness is variably associated with frailty in haemodialysis recipients.

BACKGROUND: Ultrasonographic quantitation of quadriceps muscle mass is increasingly used for assessment of sarcopenia, but its relationship with frailty in haemodialysis recipients is not known. This study explores the relationship between ultrasound-derived bilateral anterior thigh thickness (BATT), sarcopenia, and frailty by common frailty tools (Frailty Phenotype [FP], Frailty Index [FI], Edmonton Frailty [EFS], and Clinical Frailty Scale [CFS]). METHODS: This was an exploratory analysis of a subgroup of adult prevalent (≥3 months) haemodialysis recipients deeply phenotyped for frailty. Ultrasound assessment of BATT was obtained with participants at an angle of ≤45°, with legs outstretched and knees resting at 10°-20°, according to an established protocol. Associations with frailty were explored via both linear and logistic regressions for BATT, Low Muscle Mass (LMM), and sarcopenia with stepwise adjustment for a priori covariables. RESULTS: In total 223 study participants had ultrasound measurements. Frailty ranged from 34% for FP to 58% for FI. BATT was associated with increasing frailty on simple linear regression by all frailty tools, but lost significance on addition of covariables. Upon dichotomising frailty tools into Frail/Not Frail, BATT was associated with frailty by all tools on univariable analyses, but only retained association for EFS on the fully adjusted model (OR 0.97, 95% C.I. 0.94-1.00, P = 0.05). CONCLUSIONS: Ultrasound measures of quadriceps thickness is variably associated with frailty in prevalent haemodialysis recipients, dependent upon the frailty tool used, but not independent of other variables. Further work is required to establish the added value of sarcopenia measurement in frail haemodialysis patients. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03071107 registered 06/03/2017.

Management of heart failure in patients with kidney disease-updates from the 2021 ESC guidelines.

The wide overlap between the syndromes of chronic kidney disease (CKD) and chronic heart failure (HF) means that familiarity with the 2021 European Society of Cardiology guidelines is of importance to nephrologists. The common risk factors for the two syndromes together with the adverse cardiac structural remodelling associated with CKD means that many kidney disease patients experience breathlessness and fall within the HF phenotypes categorized in the guidelines. The management of HF is evolving rapidly leading to significant changes in the latest guideline iteration. The 2021 guidelines have changed from the 2016 version firstly by an increased focus on identifying the three phenotypes of HF to guide appropriate evidence-based management. Secondly, a new and simplified treatment algorithm for HF with reduced ejection fraction involving the rapid sequential initiation and up-titration of four 'pillars' of drug treatment-angiotensin-converting enzyme inhibitors or angiotensin-neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists and now, thanks to convincing trial data, sodium-glucose co-transporter 2 inhibitors. Thirdly, guidelines for device therapy have been changed with down-graded advice on indications for primary prevention implantable cardioverter defibrillator therapy for patients with non-ischaemic HF and for cardiac resynchronization therapy with left bundle branch block (LBBB) and a QRS duration <150 ms. There are updated treatment plans for HF associated with non-cardiovascular comorbidities including CKD.