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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 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.

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.

Background Frailty among haemodialysis patients is associated with hospitalization and mortality, but high frailty prevalence suggests further discrimination of risk is required. We hypothesized that incorporation of self-reported health with frailty measurement may aid risk stratification. Methods Prospective cohort study of 485 prevalent haemodialysis recipients linked to English national datasets. Frailty Phenotype (FP), Frailty Index (FI), Edmonton Frail Scale (EFS), Clinical Frailty Scale (CFS) and self-reported health change were assessed. Mortality was explored using Fine and Gray regression, and admissions by negative binomial regression. Results Over a median 678 (interquartile range 531–812) days, there were 111 deaths, and 1241 hospitalizations. Increasing frailty was associated with mortality on adjusted analyses for FP [subdistribution hazard ratio (SHR) 1.26, 95% confidence interval (CI) 1.05–1.53, P = .01], FI (SHR 1.21, 95% CI 1.09–1.35, P = .001) and CFS (SHR 1.32, 95% CI 1.11–1.58, P = .002), but not EFS (HR 1.08, 95% CI 0.99–1.18, P = .1). Health change interacted with frailty tools to modify association with mortality; only those who rated their health as the same or worse experienced increased mortality hazard associated with frailty by FP (Pinteraction = .001 and 0.035, respectively), FI (Pinteraction = .002 and .007, respectively) and CFS (Pinteraction = .009 and 0.02, respectively). CFS was the only frailty tool associated with hospitalization (incidence rate ratio 1.12, 95% CI 1.02–1.23, P = .02). Conclusions We confirm the high burden of hospitalization and mortality associated with haemodialysis patients regardless of frailty tool utilized and introduce the discriminatory ability of self-reported health to identify the most at-risk frail individuals.

Chronic kidney disease (CKD) is a complex condition with a prevalence of 10–15% worldwide. An inverse-graded relationship exists between cardiovascular events and mortality with kidney function which is independent of age, sex, and other risk factors. The proportion of deaths due to heart failure and sudden cardiac death increase with progression of chronic kidney disease with relatively fewer deaths from atheromatous, vasculo-occlusive processes. This phenomenon can largely be explained by the increased prevalence of CKD-associated cardiomyopathy with worsening kidney function. The key features of CKD-associated cardiomyopathy are increased left ventricular mass and left ventricular hypertrophy, diastolic and systolic left ventricular dysfunction, and profound cardiac fibrosis on histology. While these features have predominantly been described in patients with advanced kidney disease on dialysis treatment, patients with only mild to moderate renal impairment already exhibit structural and functional changes consistent with CKD-associated cardiomyopathy. In this review we discuss the key drivers of CKD-associated cardiomyopathy and the key role of hypertension in its pathogenesis. We also evaluate existing, as well as developing therapies in the treatment of CKD-associated cardiomyopathy.

Kidney transplantation is considered the treatment of choice for end-stage kidney disease patients. However, the residual cardiovascular risk remains significantly higher in kidney transplant recipients (KTRs) than in the general population. Hypertension is highly prevalent in KTRs and represents a major modifiable risk factor associated with adverse cardiovascular outcomes and reduced patient and graft survival. Proper definition of hypertension and recognition of special phenotypes and abnormal diurnal blood pressure (BP) patterns is crucial for adequate BP control. Misclassification by office BP is commonly encountered in these patients, and a high proportion of masked and uncontrolled hypertension, as well as of white-coat hypertension, has been revealed in these patients with the use of ambulatory BP monitoring. The pathophysiology of hypertension in KTRs is multifactorial, involving traditional risk factors, factors related to chronic kidney disease and factors related to the transplantation procedure. In the absence of evidence from large-scale randomized controlled trials in this population, BP targets for hypertension management in KTR have been extrapolated from chronic kidney disease populations. The most recent Kidney Disease Improving Global Outcomes 2021 guidelines recommend lowering BP to less than 130/80 mmHg using standardized BP office measurements. Dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers have been established as the preferred first-line agents, on the basis of emphasis placed on their favorable outcomes on graft survival. The aim of this review is to provide previous and recent evidence on prevalence, accurate diagnosis, pathophysiology and treatment of hypertension in KTRs.

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 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.

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.

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

Hypertension and chronic kidney disease (CKD) are among the most common comorbidities associated with coronavirus disease 2019 (COVID-19) severity and mortality risk. Renin–angiotensin system (RAS) blockers are cornerstones in the treatment of both hypertension and proteinuric CKD. In the early months of the COVID-19 pandemic, a hypothesis emerged suggesting that the use of RAS blockers may increase susceptibility for COVID-19 infection and disease severity in these populations. This hypothesis was based on the fact that angiotensin-converting enzyme 2 (ACE2), a counter regulatory component of the RAS, acts as the receptor for severe acute respiratory syndrome coronavirus 2 cell entry. Extrapolations from preliminary animal studies led to speculation that upregulation of ACE2 by RAS blockers may increase the risk of COVID-19-related adverse outcomes. However, these hypotheses were not supported by emerging evidence from observational and randomized clinical trials in humans, suggesting no such association. Herein we describe the physiological role of ACE2 as part of the RAS, discuss its central role in COVID-19 infection and present original and updated evidence from human studies on the association between RAS blockade and COVID-19 infection or related outcomes, with a particular focus on hypertension and CKD.

The first successful live donor kidney transplant was performed in 1954. Receiving a kidney transplant from a live kidney donor remains the best option for increasing both life expectancy and quality of life in patients with end-stage kidney disease. However, ever since 1954, there have been multiple questions raised on the ethics of live kidney donation in terms of negative impacts on donor life expectancy. Given the close relationship between reduced kidney function in patients with chronic kidney disease (CKD) and hypertension, cardiovascular disease and cardiovascular mortality, information on the impact of kidney donation on these is particularly relevant. In this article, we review the existing evidence, focusing on the more recent studies on the impact of kidney donation on all-cause mortality, cardiovascular mortality, cardiovascular disease and hypertension, as well as markers of cardiovascular damage including arterial stiffness and uraemic cardiomyopathy. We also discuss the similarities and differences between the pathological reduction in renal function that occurs in CKD, and the reduction in renal function that occurs because of a donor nephrectomy. Kidney donors perform an altruistic act that benefits individual patients as well as the wider society. They deserve to have high-quality evidence on which to make informed decisions.

Background and objectives In a randomized double-blind, placebo-controlled trial, treatment with spironolactone in early-stage CKD reduced left ventricular mass and arterial stiffness compared with placebo. It is not known if these effects were due to BP reduction or specific vascular and myocardial effects of spironolactone. Design, setting, participants, & measurements A prospective, randomized, open-label, blinded end point study conducted in four UK centers (Birmingham, Cambridge, Edinburgh, and London) comparing spironolactone 25 mg to chlorthalidone 25 mg once daily for 40 weeks in 154 participants with nondiabetic stage 2 and 3 CKD (eGFR 30–89 ml/min per 1.73 m2). The primary end point was change in left ventricular mass on cardiac magnetic resonance imaging. Participants were on treatment with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and had controlled BP (target ≤130/80 mm Hg). Results There was no significant difference in left ventricular mass regression; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was −3.8 g (95% confidence interval, −8.1 to 0.5 g, P=0.08). Office and 24-hour ambulatory BPs fell in response to both drugs with no significant differences between treatment. Pulse wave velocity was not significantly different between groups; at week 40, the adjusted mean difference for spironolactone compared with chlorthalidone was 0.04 m/s (−0.4 m/s, 0.5 m/s, P=0.90). Hyperkalemia (defined ≥5.4 mEq/L) occurred more frequently with spironolactone (12 versus two participants, adjusted relative risk was 5.5, 95% confidence interval, 1.4 to 22.1, P=0.02), but there were no patients with severe hyperkalemia (defined ≥6.5 mEq/L). A decline in eGFR >30% occurred in eight participants treated with chlorthalidone compared with two participants with spironolactone (adjusted relative risk was 0.2, 95% confidence interval, 0.05 to 1.1, P=0.07). Conclusions Spironolactone was not superior to chlorthalidone in reducing left ventricular mass, BP, or arterial stiffness in nondiabetic CKD.

Objectives Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). Methods This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. Results Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). Conclusion BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.

Introduction Coronavirus disease 2019 (COVID‐19) adversely affects patients who are older, multimorbid, and from Black, Asian or minority ethnicities (BAME). We assessed whether being from BAME is independently associated with mortality in end‐stage kidney disease (ESKD) patients with COVID‐19. Methods Prospective observational study in a single UK renal center. A study was conducted between March 10, 2020 and April 30, 2020. Demographics, socioeconomic deprivation (index of multiple deprivation), co‐morbidities (Charlson comorbidity index [CCI]), and frailty data (clinical frailty score) were collected. The primary outcome was all‐cause mortality. Data were censored on the 1st June 2020. Findings Overall, 191 of our 3379 ESKD patients contracted COVID‐19 in the 8‐week observation period; 84% hemodialysis, 5% peritoneal dialysis, and 11% kidney transplant recipients (KTR). Of these, 57% were male and 67% were from BAME groups (43% Asian, 17% Black, 2% mixed race, and 5% other). Mean CCI was 7.45 (SD 2.11) and 3.90 (SD 2.10) for dialysis patients and KTR, respectively. In our cohort, 60% of patients lived in areas classified as being in the most deprived 20% in the United Kingdom, and of these, 77% of patients were from BAME groups. The case fatality rate was 29%. Multivariable cox regression demonstrated that BAME (hazard ratio [HR]: 2.37, 95% CI: 1.22–4.61) was associated with all‐cause mortality after adjustment for age, deprivation, co‐morbidities, and frailty. Associations with all‐cause mortality persisted in sensitivity analyses in patients from South Asian (HR: 2.52, 95% CI: 1.24–5.12) and Black (HR: 2.43, 95% CI: 1.04–5.67) ethnic backgrounds. Discussion BAME ESKD patients with COVID‐19 are just over twice as likely to die compared to White patients, despite adjustment for age, deprivation, comorbidity, and frailty. This study highlights the need to develop strategies to improve BAME patient outcomes in future outbreaks of COVID‐19.

International audience; Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.

OBJECTIVES Hypertension is highly prevalent and independently associated with adverse outcomes in patients undergoing hemodialysis. Volume overload is the main mechanism of increased blood pressure (BP) in these individuals. This study examines the long-term effects of dry-weight reduction with a standardized lung-ultrasound (US)-guided strategy on ambulatory BP in hypertensive hemodialysis patients. METHODS This is the report of the 12-month follow-up of a randomized controlled trial in 71 clinically euvolemic, hemodialysis patients with hypertension. Patients were randomized to dry-weight reduction guided by prehemodialysis lung ultrasound and to standard care. A 48-h ambulatory BP monitoring (ABPM) was performed in all study participants at baseline and after 12 months. RESULTS During follow-up, a greater proportion of patients in the active group underwent dry-weight reduction compared with the control group (71.4% vs. 22.2%; P

Screening for occult coronary artery disease in potential kidney transplant recipients has become entrenched in current medical practice as the standard of care and is supported by national and international clinical guidelines. However, there is increasing and robust evidence that such an approach is out-dated, scientifically and conceptually flawed, ineffective, potentially directly harmful, discriminates against ethnic minorities and patients from more deprived socioeconomic backgrounds, and unfairly denies many patients access to potentially lifesaving and life-enhancing transplantation. Herein we review the available evidence in the light of recently published randomized controlled trials and major observational studies. We propose ways of moving the field forward to the overall benefit of patients with advanced kidney disease.

Background Coronary microvascular dysfunction (CMD) is common in end-stage renal disease (ESRD) and is an adverse prognostic marker. Coronary flow velocity reserve (CFVR) is a measure of coronary microvascular function and can be assessed using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as diabetes, hypertension and left ventricular hypertrophy. The contributory role of other mediators important in the development of cardiovascular disease in ESRD has not been studied. The aim of this study was to examine the prevalence of CMD in a cohort of kidney transplant candidates and to look for associations of CMD with markers of anaemia, bone mineral metabolism and chronic inflammation. Methods Twenty-two kidney transplant candidates with ESRD were studied with myocardial contrast echocardiography, Doppler CFVR assessment and serum multiplex immunoassay analysis. Individuals with diabetes, uncontrolled hypertension or ischaemic heart disease were excluded. Results 7/22 subjects had CMD (defined as CFVR Conclusions Among kidney transplant candidates with ESRD, there is a high prevalence of CMD, despite the absence of traditional risk factors. Anaemia may be a potential driver of microvascular dysfunction in this population and requires further investigation.

Supplemental Digital Content is available in the text., Kidney donation reduces renal function by ≈30% allowing study of the cardiovascular effects of a reduced estimated glomerular filtration rate without comorbidities. We report 5-year results of a longitudinal, parallel-group, blinded end-point study of living kidney donors (n=50) and healthy controls (n=45). The primary end point, left ventricular mass, was measured using cardiac magnetic resonance. Secondary end points, 24-hour ambulatory blood pressure, and pulse wave velocity were measured using validated blood pressure monitors and the SphygmoCor device. Effect sizes were calculated as differences between change from baseline in the donor and control groups. In donors, estimated glomerular filtration rate was 95±15 mL/min per 1.73 m2 at baseline (predonation) and 67±14 mL/min per 1.73 m2 at 5 years. In controls, there was a −1±2 mL/min per 1.73 m2 decline per annum. Change in left ventricular mass at 5 years was not significantly different between donors and controls (mean difference, +0.40 g [95% CI, −4.68 to 5.49] P=0.876), despite an initial increase in mass in donors compared with controls at 12 months. Pulse wave velocity, which increased in donors at 12 months, returned to levels not different from controls at 5 years (mean difference, −0.24 m/s [95% CI, −0.69 to 0.21]). Change in ambulatory systolic blood pressure was not different in donors compared with controls (mean difference, +1.91 mm Hg [95% CI, −2.72 to 6.54]). We found no evidence that the reduction in estimated glomerular filtration rate after kidney donation was associated with a change in left ventricular mass detectable by magnetic resonance imaging at 5 years.

Background Few studies show that ambulatory blood pressure (BP) monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population. Methods Major medical databases were searched for studies enrolling adult KTRs undergoing 24-h ABPM compared with office or home BP measurements. The main outcomes were associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed. Results Twenty-two studies (2078 participants) were reviewed. Among 12 studies collecting data on renal endpoints, 10 studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine and/or creatinine clearance or estimated glomerular filtration rate, than traditional office measurements. Twelve studies analysed the relation between different BP recordings and CV target organ damage and reported robust correlations between echocardiographic abnormalities (i.e. left ventricular mass index) and 24-h ABPM, but not with office BPs. Furthermore, 24-h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness, diffuse thickening and endothelial dysfunction. Additionally, an abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities. Conclusions In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, an altered circadian BP profile associated with renal and CV target organ damage.

Aims This study aimed to examine if the cardiac changes associated with uraemic cardiomyopathy are reversed by renal transplantation. Methods and results MEDLINE, Embase, OpenGrey, and the Cochrane Library databases were searched from 1950 to March 2020. The primary outcome measure was left ventricular mass index. Secondary outcome measures included left ventricular dimensions and measures of diastolic and systolic function. Studies were included if they used any imaging modality both before and after successful renal transplantation. Data were analysed through meta‐analysis approaches. Weight of evidence was assessed through the Grading of Recommendations Assessment, Development and Evaluation system. Twenty‐three studies used echocardiography, and three used cardiac magnetic resonance imaging as their imaging modality. The methodological quality of the evidence was generally poor. Four studies followed up control groups, two using cardiac magnetic resonance imaging and two using echocardiography. Meta‐analysis of these studies indicated that there was no difference in left ventricular mass index between groups following transplantation {standardized mean difference −0.07 [95% confidence interval (CI) −0.41 to 0.26]; P = 0.67}. There was also no difference observed in left ventricular ejection fraction [mean difference 0.39% (95% CI −4.09% to 4.87%); P = 0.86] or left ventricular end‐diastolic volume [standardized mean difference −0.24 (95% CI −0.94 to 0.45); P = 0.49]. Inconsistent reporting of changes in diastolic dysfunction did not allow for any meaningful analysis or interpretation. Conclusions The evidence does not support the notion that uraemic cardiomyopathy is reversible by renal transplantation. However, the evidence is limited by methodological weaknesses, which should be considered when interpreting these findings.

Management of hypertension and albuminuria are considered among the primary goals of treatment to slow the progression of chronic kidney disease (CKD). Renin-angiotensin system (RAS) blockers, i.e., angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the main drugs to achieve these goals. Seminal studies have showed that RAS blockers present significant renoprotective effects in CKD patients with very high albuminuria. In post hoc analyses of such trials, these renoprotective effects appeared more robust in patients with more advanced CKD. However, randomized trials specifically addressing whether RAS blockers should be initiated or maintained in patients with advanced CKD are scarce and do not include subjects with normoalbuminuria, thus, many clinicians are unconvinced for the beneficial effects of RAS blockade in these patients. Further, the fear of hyperkalemia or acute renal decline is another factor due to which RAS blockers are usually underprescribed and are easily discontinued in patients with more advanced CKD; i.e., those in Stages 4 and 5. This review summarizes evidence from the literature regarding the use of RAS blockers in patients with advanced CKD.

Background Acute kidney injury (AKI) in hospital-admitted patients is a common complication associated with increased mortality. The diagnosis of AKI relies on the ascertainment of peak increase in serum creatinine (SCr). This study evaluated the incidence of AKI using the increase from mean 7–365 days pre-admission (AKIpre) and admission (AKIadm) SCr levels, and examined the associations of AKI and changes in SCr levels with all-cause mortality. Methods A total of 2436 patients admitted to a tertiary hospital were recruited and followed-up for a median of 47.70 (interquartile range 18.20) months. AKI incidence and severity were defined according to the Kidney Disease: Improving Global Outcomes-AKI Guidelines. Follow-up data were collected from the Hospital Episode Statistics and Office of National Statistics. Mortality was evaluated during a short- (30 days), mid- (1 year) and long-term (4 years) period. Results No difference in the AKI rates using AKIpre and AKIadm (12.5% versus 12.2%; P = 0.695) or in the AKI severity (P = 0.261) was evident. Agreement between the two definitions was modest (Kappa-statistic = 0.596, P 4.00 μmol/L and >6.06% from pre-admission or >6.00 μmol/L and >17.24% from admission SCr levels presented increased mortality risk during follow-up. Conclusions Use of admission or pre-admission SCr provides similar incidence rates, but they diagnose different sets of patients. Even minor increases in SCr, below those required for the classification of AKI, were associated with increased mortality. These findings can help the clinicians to identify patients at higher risk for adverse outcomes.

Chronic kidney disease (CKD) is a major issue of public health. Hypertension control and use of renin--angiotensin system (RAS) blockers are the cornerstones of treatment for CKD of any cause. However, even under optimal RAS blockade, many individuals will progress towards more advanced CKD. Within the past few years, evidence from cardiovascular outcome trials with sodium--glucose co-transporter-2 (SGLT-2) inhibitors clearly suggested that these agents substantially delay CKD progression in patients with diabetes mellitus on top of standard-of-care treatment. The Canagliflozin-and-Renal-Events-in-Diabetes-with-Established-Nephropathy-Clinical-Evaluation (CREDENCE) study, showed that canagliflozin substantially reduced the risk of doubling of SCr, end-stage kidney disease (ESKD), or death from renal or cardiovascular causes in 4401 patients with diabetic CKD compared with placebo (hazard ratio 0.70; 95% CI 0.59-0.82). Recently, the Study-to-Evaluate-the-Effect-of-Dapagliflozin-on-Renal-Outcomes-and-Cardiovascular-Mortality-in-Patients-With-Chronic-Kidney-Disease (DAPA-CKD), including 2510 patients with diabetic and 1803 with nondiabetic CKD, also showed an impressive reduction in the risk of ≥50% decline in eGFR, ESKD, or death from renal or cardiovascular causes (HR 0.61; 95% CI 0.51-0.72). The benefit was similar for patients with diabetic and nondiabetic CKD, including patients with glomerulonephritides. Following this conclusive evidence, relevant guidelines should accommodate their recommendations to implement treatment with SGLT-2 inhibitors for patients with diabetic and nondiabetic CKD.

Aims Patients with chronic kidney disease (CKD) are also susceptible to periodontitis. The causal link between periodontitis and CKD may be mediated via systemic inflammation/oxidative stress. Using structural equation modelling (SEM), this cross‐sectional study aimed to explore the causal relationship between periodontal inflammation (PI) and renal function. Materials and methods Baseline data on 770 patients with stage 3–5 (pre‐dialysis) CKD from an ongoing cohort study were used. Detailed, bioclinical data on PI and renal function, as well as potential confounders and mediators of the relationship between the two, were collected. SEMs of increasing complexity were created to test the causal assumption that PI affects renal function and vice versa. Results Structural equation modelling confirmed the assumption that PI and renal function are causally linked, mediated by systemic oxidative stress. The magnitude of this effect was such that a 10% increase in PI resulted in a 3.0% decrease in renal function and a 10% decrease in renal function resulted in a 25% increase in PI. Conclusions Periodontal inflammation represents an occult source of oxidative stress in patients with CKD. Further clinical studies are needed to confirm whether periodontal therapy, as a non‐pharmacological approach to reducing systemic inflammatory/oxidative stress burden, can improve outcomes in CKD.

Volume overload in haemodialysis (HD) patients associates with hypertension and cardiac dysfunction and is a major risk factor for all-cause and cardiovascular mortality in this population. The diagnosis of volume excess and estimation of dry weight is based largely on clinical criteria and has a notoriously poor diagnostic accuracy. The search for accurate and objective methods to evaluate dry weight and to diagnose subclinical volume overload has been intensively pursued over the last 3 decades. Most methods have not been tested in appropriate clinical trials and their usefulness in clinical practice remains uncertain, except for bioimpedance spectroscopy and lung ultrasound (US). Bioimpedance spectroscopy is possibly the most widely used method to subjectively quantify fluid distributions over body compartments and produces reliable and reproducible results. Lung US provides reliable estimates of extravascular water in the lung, a critical parameter of the central circulation that in large part reflects the left ventricular end-diastolic pressure. To maximize cardiovascular tolerance, fluid removal in volume-expanded HD patients should be gradual and distributed over a sufficiently long time window. This review summarizes current knowledge about the diagnosis, prognosis and treatment of volume overload in HD patients.

Objectives A proof of concept cross-sectional study investigating changes in myocardial abnormalities across stages of chronic kidney disease (CKD). Characterizing noninvasive markers of myocardial fibrosis on cardiac magnetic resonance, echocardiography, and correlating with biomarkers of fibrosis, myocardial injury, and functional correlates including exercise tolerance. Background CKD is associated with an increased risk of cardiovascular death. Much of the excess mortality is attributed to uremic cardiomyopathy, defined by increased left ventricular hypertrophy, myocardial dysfunction, and fibrosis. The prevalence of these abnormalities across stages of CKD and their impact on cardiovascular performance is unknown. Methods A total of 134 nondiabetic, pre-dialysis subjects with CKD stages 2 to 5 without myocardial ischemia underwent cardiac magnetic resonance (1.5-T) including; T1 mapping (biomarker of diffuse fibrosis), T2 mapping (edema), late gadolinium enhancement, and assessment of aortic distensibility. Serum biomarkers including collagen turnover (P1NP, P3NP), troponin T, and N-terminal pro–B-type natriuretic peptide were measured. Cardiovascular performance was quantified by bicycle cardiopulmonary exercise testing and echocardiography. Results Native myocardial T1 times increased incrementally from stage 2 to 5 (966 ± 21 ms vs. 994 ± 33 ms; p Conclusions Imaging and serum biomarkers of myocardial fibrosis increase with advancing CKD independent of effects of left ventricular afterload and might be a key intermediary in the development of uremic cardiomyopathy. Further studies are needed to determine whether these changes lead to the increased rates of heart failure and death in CKD. (Left Ventricular Fibrosis in Chronic Kidney Disease [FibroCKD]; NCT03176862 )

Background. Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk. Methods. This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis. Results. Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = −0.44, P Conclusions. Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4–5D.

Background and objectives The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics. Design, setting, participants, & measurements Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months. Results A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m2 lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, −1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, −0.7 to 2.0) in controls. The between-group difference was −0.5 mm Hg (95% confidence interval, −2.8 to 1.7; P=0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, −0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, −0.2 to 0.3; P=0.49). Conclusions Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls. Clinical Trial registry name and registration number NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924).

Chronic kidney disease (CKD) is a global health problem affecting up to 14% of the adult population in developed countries. On the basis of current guidelines, patients with CKD will often fulfil criteria for both short-term and long-term anticoagulation. Paradoxically, patients with CKD are not only at a higher risk of thrombosis, they are also at increased risk of bleeding. Furthermore, the pharmacokinetics and pharmacodynamics of many anticoagulant therapies are significantly affected by renal dysfunction. In addition, patients with advanced CKD are often systematically excluded from major clinical trials. As such, the decision on whether to anticoagulate or not, and if so with what agent, poses significant challenges. A solid understanding of the condition in question and the available treatments is required to make an informed judgement call. An in-depth appreciation of the advantages and disadvantages of the currently available anticoagulants is a key element in the decision-making process.

Background: The pathophysiology of renal disease progression in autosomal-dominant polycystic kidney disease (ADPKD) involves not only cystogenesis but also endothelial dysfunction, leading to the activation of inflammatory and fibrotic pathways. This study evaluated the levels of biomarkers related to osmoregulation, immune system activation, and tubular injury in ADPKD patients with impaired or preserved renal function. Methods: This study included 26 ADPKD patients with modestly impaired renal function (estimated glomerular filtration rate [eGFR] 45–70 mL/min/1.73 m2; Group A), 26 age- and sex-matched ADPKD patients with relatively preserved renal function (eGFR >70 mL/min/1.73 m2; Group B), and 26 age- and sex-matched controls (Group C). Serum levels of copeptin, the inflammasome nucleotide-binding and oligomerization domain-like receptors pyrin domain-containing protein 3 (NLRP3), and soluble urokinase-type plasminogen activator receptor (suPAR) were measured with ELISA techniques. Results: Patients in Group A had higher levels of copeptin (median [interquartile range]: 50.44 [334.85] pg/mL), NLRP3 (5.86 [3.89] ng/mL), and suPAR (390.05 [476.53] pg/mL) compared to patients in Group B (32.38 [58.33], p = 0.042; 2.42 [1.96], p < 0.001; and 313.78 [178.85], p = 0.035, respectively) and Group C (6.75 [6.43]; 1.09 [0.56]; and 198.30 [28.53], respectively; p < 0.001 for all comparisons). Levels of all studied markers were also significantly higher in Group B patients compared to controls (p < 0.001), despite having similar eGFR. In patients with ADPKD, all studied biomarkers were correlated positively with asymmetric-dimethylarginine (ADMA) and endocan levels, and negatively with eGFR. ADMA and endocan levels were the only parameters independently associated with increased copeptin levels. Conclusions: This study showed that ADPKD patients with impaired and preserved renal function had higher copeptin, NLRP3, and suPAR levels than controls. Such findings support that cystogenesis and inflammation are associated with endothelial dysfunction, even in the early stages of ADKPD.

Background Coronary microvascular dysfunction is prevalent in chronic kidney disease (CKD), and may contribute to the development of myocardial dysfunction in CKD. Coronary flow velocity reserve (CFVR) is a marker of coronary microvascular function and falls with increasing CKD stage. Living kidney donors have renal function consistent with early stage CKD and concern has been raised about their cardiovascular risk. No studies to date have investigated the presence of coronary microvascular dysfunction in living kidney donors. Methods 25 healthy controls and 23 living kidney donors were recruited and underwent assessment with transthoracic echocardiography, Doppler CFVR, myocardial contrast echocardiography and serum multiplex immunoassay panels. Results Doppler CFVR was significantly reduced in living kidney donors compared to controls (mean CFVR 3.4 ± 0.7 vs 3.8 ± 0.6, mean difference 0.4 95% confidence interval 0.03–0.8, p =.036). Quantitative myocardial contrast echocardiography showed a trend towards reduced coronary flow reserve in living kidney donors. Compared to controls, living kidney donors had higher serum high sensitivity C reactive peptide (hsCRP) and lower levels of uromodulin. Conclusions This is the first study of CFVR in living kidney donors. We have shown that the modest drop in estimated glomerular filtration rate in living kidney donors is associated with lower values of Doppler CFVR compared to controls, suggesting that isolated reductions in renal function may lead to altered microvascular function. The increase in hsCRP and reduction in uromodulin suggests that chronic subclinical inflammation may contribute to altered microvascular function in this population., Highlights • Coronary flow velocity reserve is reduced in living kidney donors compared to controls. • Markers of inflammation are elevated in living kidney donors. • Inflammation may cause coronary microvascular dysfunction in living kidney donors. • Living kidney donors need aggressive cardiovascular risk factor management.

Increased serum uric acid (SUA) levels have been associated with various pathologic processes such as increased oxidative stress, inflammation, and endothelial dysfunction. Thus, it is not surprising that increased SUA is associated with various adverse outcomes including cardiovascular (CV) diseases. Recent epidemiological evidence suggests that increased SUA may be related to acute myocardial infarction (AMI). Accumulating data also showed that elevated UA has pathophysiological role in the development of AMI. However, there are also studies showing that SUA is not related to the risk of AMI. In this narrative review, we summarized the recent literature data regarding SUA and AMI after providing some background information for the association between UA and coronary artery disease. Future studies will show whether decreasing SUA levels is beneficial for outcomes related to AMI and the optimum SUA levels for best outcomes in CV diseases.