Explore the vast range of titles available.

Patients with chronic kidney failure—defined as a glomerular filtration rate persistently below 15 mL/min per 1·73 m2—have an unacceptably high mortality rate. In developing countries, mortality results primarily from an absence of access to renal replacement therapy. Additionally, cardiovascular and non-cardiovascular mortality are several times higher in patients on dialysis or post-renal transplantation than in the general population. Mortality of patients on renal replacement therapy is affected by a combination of socioeconomic factors, pre-existing medical disorders, renal replacement treatment modalities, and kidney failure itself. Characterisation of the key pathophysiological contributors to increased mortality and cardiorenal risk staging systems are needed for the rational design of clinical trials aimed at decreasing mortality. Policy changes to improve access to renal replacement therapy should be combined with research into low-cost renal replacement therapy and optimum clinical care, which should include multifaceted approaches simultaneously targeting several of the putative contributors to increased mortality.

The choice of the most appropriate unsupervised machine-learning method for “heterogeneous” or “mixed” data, i.e. with both continuous and categorical variables, can be challenging. Our aim was to examine the performance of various clustering strategies for mixed data using both simulated and real-life data. We conducted a benchmark analysis of “ready-to-use” tools in R comparing 4 model-based (Kamila algorithm, Latent Class Analysis, Latent Class Model [LCM] and Clustering by Mixture Modeling) and 5 distance/dissimilarity-based (Gower distance or Unsupervised Extra Trees dissimilarity followed by hierarchical clustering or Partitioning Around Medoids, K-prototypes) clustering methods. Clustering performances were assessed by Adjusted Rand Index (ARI) on 1000 generated virtual populations consisting of mixed variables using 7 scenarios with varying population sizes, number of clusters, number of continuous and categorical variables, proportions of relevant (non-noisy) variables and degree of variable relevance (low, mild, high). Clustering methods were then applied on the EPHESUS randomized clinical trial data (a heart failure trial evaluating the effect of eplerenone) allowing to illustrate the differences between different clustering techniques. The simulations revealed the dominance of K-prototypes, Kamila and LCM models over all other methods. Overall, methods using dissimilarity matrices in classical algorithms such as Partitioning Around Medoids and Hierarchical Clustering had a lower ARI compared to model-based methods in all scenarios. When applying clustering methods to a real-life clinical dataset, LCM showed promising results with regard to differences in (1) clinical profiles across clusters, (2) prognostic performance (highest C-index) and (3) identification of patient subgroups with substantial treatment benefit. The present findings suggest key differences in clustering performance between the tested algorithms (limited to tools readily available in R). In most of the tested scenarios, model-based methods (in particular the Kamila and LCM packages) and K-prototypes typically performed best in the setting of heterogeneous data.

Acute kidney injury is associated with many short- and long-term adverse events. This review considers the cardiovascular consequences and strategies that can be used during acute kidney injury and recovery, with the aim of reducing subsequent cardiovascular risks.

Mineralocorticoid receptor antagonists can prevent cardiovascular events in patients with heart failure and non-severe chronic kidney disease, but their effects in patients with kidney failure requiring dialysis are uncertain. We aimed to assess the efficacy and safety of mineralocorticoid receptor antagonists in this patient population. In this systematic review and meta-analysis, we updated our previous systematic review by searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature for randomised controlled trials published between database inception and March 18, 2025. Trials comparing a mineralocorticoid receptor antagonist with placebo or standard of care in adults (aged ≥18 years) receiving maintenance dialysis were eligible. Studies that did not report an outcome of interest (cardiovascular mortality, heart failure hospitalisation, all-cause mortality, all-cause hospitalisation, hyperkalaemia, gynaecomastia or breast pain, or hypotension) were excluded. Two reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane risk-of-bias tool. The main outcome was cardiovascular mortality assessed using the empirical Bayes random-effects models, stratified by risk-of-bias. The protocol is registered with PROSPERO (CRD420251008119). 19 trials of steroidal mineralocorticoid receptor antagonists including 4675 participants met eligibility criteria. Effect estimates differed trials with low and high risk of bias. In four trials with a low risk of bias (n=3562), 264 cardiovascular deaths occurred in 1785 patients in the mineralocorticoid receptor antagonist group compared with 276 of 1777 patients in the control group (odds ratio 0·98 [95% CI 0·80–1·20]; I2=0·0%; τ2=0·0; moderate certainty) resulting in an absolute risk reduction of 1 fewer event per 1000 patients per year (95% CI 14 fewer to 11 more). Our findings suggest that steroidal mineralocorticoid receptor antagonists have little to no effect on cardiovascular mortality in patients requiring dialysis. There is insufficient information on the effects of steroidal mineralocorticoid receptor antagonists in subgroups of patients requiring dialysis and no information on non-steroidal mineralocorticoid receptor antagonists. Future trials would need to consider the likelihood of only smaller effects or effects limited to patients or events with pathophysiology that is more clearly driven by aldosterone in their design. None.

Galectin-3 (Gal-3), a β-galactoside-binding lectin, is increased in kidney injury and its pharmacological blockade reduces renal damage in acute kidney injury, hyperaldosteronism or hypertensive nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in early renal damage associated with obesity and aortic stenosis (AS). Gal-3 was upregulated in kidneys from high fat diet (HFD) rats and in animals with partial occlusion of ascending aorta (AS). Urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary albumin were enhanced in HFD and AS rats. In kidney from obese rats, fibrotic markers (collagen, TFG-β), epithelial-mesenchymal transition molecules (α-smooth muscle actin, E-cadherin), inflammatory mediator (osteopontin) and kidney injury marker (kidney injury molecule-1) were modified. In kidney from AS rats, fibrotic markers (collagen, CTGF), epithelial-mesenchymal transition molecules (fibronectin, α-smooth muscle actin, β-catenin, E-cadherin) and kidney injury markers (NGAL, kidney injury molecule-1) were altered. Histologic observations of obese and AS rat kidneys revealed tubulointerstitial fibrosis. The pharmacological inhibition of Gal-3 with MCP normalized renal Gal-3 levels as well as functional, histological and molecular alterations in obese and AS rats. In experimental models of mild kidney damage, the increase in renal Gal-3 expression paralleled with renal fibrosis, inflammation and damage, while these alterations were prevented by Gal-3 blockade. These data suggest that Gal-3 could be a new player in renal molecular, histological and functional alterations at early stages of kidney damage.

Congestion score index (CSI), a semiquantitative evaluation of congestion on chest radiography (CXR), is associated with outcome in patients with heart failure (HF). However, its diagnostic value in patients admitted for acute dyspnea has yet to be evaluated. The diagnostic value of CSI for acute HF (AHF; adjudicated from patients' discharge files) was studied in the Pathway of dyspneic patients in Emergency (PARADISE) cohort, including patients aged 18 years or older admitted for acute dyspnea in the emergency department (ED) of the Nancy University Hospital (France) between January 1, 2015 and December 31, 2015. CSI (ranging from 0 to 3) was evaluated using a semiquantitative method on CXR in consecutive patients admitted for acute dyspnea in the ED. Results were validated in independent cohorts (N = 224). Of 1,333 patients, mean (standard deviation [SD]) age was 72.0 (18.5) years, 686 (51.5%) were men, and mean (SD) CSI was 1.42 (0.79). Patients with higher CSI had more cardiovascular comorbidities, more severe congestion, higher b-type natriuretic peptide (BNP), poorer renal function, and more respiratory acidosis. AHF was diagnosed in 289 (21.7%) patients. CSI was significantly associated with AHF diagnosis (adjusted odds ratio [OR] for 0.1 unit CSI increase 1.19, 95% CI 1.16-1.22, p < 0.001) after adjustment for clinical-based diagnostic score including age, comorbidity burden, dyspnea, and clinical congestion. The diagnostic accuracy of CSI for AHF was >0.80, whether alone (area under the receiver operating characteristic curve [AUROC] 0.84, 95% CI 0.82-0.86) or in addition to the clinical model (AUROC 0.87, 95% CI 0.85-0.90). CSI improved diagnostic accuracy on top of clinical variables (net reclassification improvement [NRI] = 94.9%) and clinical variables plus BNP (NRI = 55.0%). Similar diagnostic accuracy was observed in the validation cohorts (AUROC 0.75, 95% CI 0.68-0.82). The key limitation of our derivation cohort was its single-center and retrospective nature, which was counterbalanced by the validation in the independent cohorts. In this study, we observed that a systematic semiquantified assessment of radiographic pulmonary congestion showed high diagnostic value for AHF in dyspneic patients. Better use of CXR may provide an inexpensive, widely, and readily available method for AHF triage in the ED.

Resistant hypertension is defined as blood pressure above goal despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease is the most frequent of several patient factors or comorbidities associated with resistant hypertension. The prevalence of resistant hypertension is increased in patients with chronic kidney disease, while chronic kidney disease is associated with an impaired prognosis in patients with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation, are under investigation especially in patients with advanced chronic kidney disease. We discuss resistant hypertension in chronic kidney disease stages 3–5 (ie, patients with an estimated glomerular filtration rate below 60 mL/min per 1·73 m2 and not on dialysis), in terms of worldwide epidemiology, outcomes, causes and pathophysiology, evidence-based treatment, and a call for action.

Background Arterial stiffness is a major prognostic factor of cardiovascular (CV) morbi-mortality in kidney transplant (KT) patients. Preclinical studies have demonstrated that the vascular toxicity of calcineurin inhibitors (CNI) is mediated through the activation of the mineralocorticoid receptor (MR) in vascular smooth muscle cells. Additionally, the role of MR in contributing to arterial stiffness is well documented in non-transplanted individuals. This study aims to investigate the impact of MR antagonist treatment on the progression of arterial stiffness in KT patients on cyclosporine. Methods This is a randomized, open-label, single-center, cross-over trial involving 36 stable KT patients who have been transplanted for at least 1 year and are maintained on cyclosporine therapy. After a 4-week run-in period, participants will be randomly assigned to one of two groups. Group A will receive eplerenone at a dose of 50 mg daily for 6 months, followed by a 6-month period without treatment. There will be an 8-week washout phase between the treatment and non-treatment periods. Group B will start with 6 months without treatment, followed by the same 8-week washout phase, and then receive eplerenone for 6 months. The primary outcome is to assess the effect of 6 months of eplerenone on arterial stiffness, measured through pulse wave velocity (PWV) using the Sphygmocor® method at the start and end of each treatment period. Secondary outcomes will include changes in (1) central and peripheral blood pressure profiles, (2) intima-media thickness, (3) left ventricular mass, (4) biomarkers of oxidative stress and endothelial dysfunction, and (5) renal graft function markers, such as proteinuria and creatinine levels. Additionally, the incidence of hyperkalemia and episodes of acute renal failure will be monitored. Discussion CNI are a key component of immunosuppressive therapy in KT patients. By limiting vascular toxicity through MR blockade, CV risk in these patients may be reduced. Trial registration ClinicalTrials.gov identifier: NCT04450953. EudraCT number 2019-004243-74.

Background The EXAMINE trial tested the efficacy and safety of alogliptin, an inhibitor of dipeptidyl peptidase 4, compared with placebo in 5380 patients with type 2 diabetes and a recent acute coronary syndrome. Because alogliptin is cleared by the kidney, patients were stratified according to screening renal function within two independently randomized strata: (1) estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73m 2 and (2) eGFR < 60 ml/min/1.73m 2 . We aim to assess the efficacy and safety of alogliptin vs. placebo according to the renal function strata. Methods Cox-proportional hazard models with an interaction term by renal function strata were used. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. Results Patient characteristics were balanced within each renal function strata. In total, 3946 patients were randomized within the eGFR ≥ 60 stratum, and 1434 patients within the eGFR < 60 stratum. The effect of alogliptin was modified by the renal function strata. Primary outcome: eGFR ≥ 60 HR = 0.81, 95%CI, 0.65–0.99, and eGFR < 60 HR = 1.20, 95%CI, 0.95–1.53; interaction p  = 0.014. Cardiovascular death: eGFR ≥ 60 HR = 0.61, 95%CI, 0.42–0.88, and eGFR < 60 HR = 1.16, 95%CI, 0.82–1.65; interaction p  = 0.013. Non-fatal MI: eGFR ≥ 60 HR = 0.86, 95%CI, 0.66–1.13, and eGFR < 60 HR = 1.48, 95%CI, 1.07–2.06; interaction p  = 0.013. Conclusions Alogliptin may benefit patients with eGFR ≥ 60, but may be detrimental to patients with eGFR < 60 ml/min/1.73m 2 . These hypothesis-generating findings require further validation to assess the potential benefit and risk of alogliptin across the renal function spectrum among patients with type 2 diabetes and a recent acute coronary syndrome. Trial registration ClinicalTrials.gov, NCT00968708

Potassium disturbances are associated with adverse prognosis in patients with chronic conditions. Its prognostic implications in stable patients attending the emergency department (ED) is poorly described. This study aimed to assess the prevalence of dyskalemia, describe its predisposing factors and prognostic associations in a population presenting the ED without unstable medical illness. Post-hoc analysis of a prospective, cross-sectional, multicenter study in the ED of 11 French academic hospitals over a period of 8 weeks. All adults presenting to the ED during this period were included, except instances of self-drug poisoning, inability to complete self-medication questionnaire, presence of an unstable medical illness and decline to participate in the study. All-cause hospitalization or deaths were assessed. A total of 1242 patients were included. The mean age was 57.2±22.3 years, 51% were female. The distribution according to potassium concentrations was: hypokalemia5mmol/L(n = 73, 0,6%). The proportion of patients with a kalemia<3.5mmol/L was 8% (n = 101). Renal insufficiency (OR [95% CI] = 3.56[1.94-6.52], p-value <0.001) and hemoglobin <12g/dl (OR [95% CI] = 2.62[1.50-4.60], p-value = 0.001) were associated with hyperkalemia. Female sex (OR [95% CI] = 1.31[1.03-1.66], p-value = 0.029), age <45years (OR [95% CI] = 1.69 [1.20-2.37], p-value = 0.002) and the use of thiazide diuretics (OR [95% CI] = 2.04 [1.28-3.32], p-value = 0.003), were associated with hypokalemia<4mmol/l. Two patients died in the ED and 629 (52.7%) were hospitalized. Hypokalemia <3.5mmol/L was independently associated with increased odds of hospitalization or death (OR [95% CI] = 1.47 [1.00-2.15], p-value = 0.048). Hypokalemia is frequently found in the ED and was associated with worse outcomes in a low-risk ED population.