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Coronary artery disease in older patients is more frequently diffuse and complex, and is often treated by percutaneous coronary intervention on top of medical therapy. There are currently no specific recommendations for antiplatelet therapy in patients aged≥75 years. Aspirin remains pivotal, and is still indicated as a long-term treatment after percutaneous coronary intervention. In addition, a P2Y 12 inhibitor is administered for 6-12 months according to clinical presentation. Age is a minor bleeding risk factor, but because older patients often have several co-morbidities, they are considered as having a high bleeding risk according to different scoring systems. This increased bleeding risk has resulted in different therapeutic strategies for antithrombotic treatment after percutaneous coronary intervention; these include short dual antiplatelet therapy, a switch from potent to less potent antiplatelet therapy or single antiplatelet therapy with a P2Y 12 inhibitor instead of aspirin, among others. A patient-centred approach, taking into account health status, functional ability, frailty, cognitive skills, bleeding and ischaemic risks and patient preference, is essential when caring for older adults with coronary artery disease. The present review focuses on the knowledge base, specificities of antiplatelet therapies, a balance between haemorrhagic and ischaemic risk, strategies for antiplatelet therapy and directions for future investigation pertaining to coronary artery disease in older patients., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 μmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease, including ischemic heart disease, is the leading cause of death worldwide, and percutaneous coronary interventions (PCIs) have been demonstrated to improve the prognosis of these patients on top of optimal medical therapy. PCIs have evolved from plain old balloon angioplasty to coronary stent implantation at the end of the last century. There has been a constant technical and scientific improvement in stent technology from bare metal stents to the era of drug-eluting stents (DESs) to overcome clinical challenges such as target lesion failure related to in-stent restenosis or stent thrombosis. A better understanding of the underlying mechanisms of these adverse events has led DESs to evolve from first-generation DESs to thinner and ultrathin third-generation DESs with improved polymer biocompatibility that seems to have reached a peak in efficiency. This review aims to provide a brief historical overview of the evolution of coronary DES platforms and an update on clinical studies and major characteristics of the most currently used DESs.

About 70% of out-of-hospital cardiac arrests are related to an ischaemic heart disease in Western countries. Percutaneous coronary intervention has been shown to improve the prognosis of survivors when an unstable coronary lesion is identified as the potential cause of the cardiac arrest. Acute complete coronary occlusion is often demonstrated among patients with ST-segment elevation on electrocardiogram after the return of spontaneous circulation. In patients without ST-segment elevation, routine coronary angiography has been shown to be not superior to conservative management. However, an electrocardiogram-based decision to perform immediate coronary angiography could be insufficient to identify unstable coronary lesions, which are frequently associated with intermediate coronary stenosis. Intracoronary imaging can be helpful to detect plaque rupture or erosion and intracoronary thrombus, but could also lead to better stent implantation, and help to reduce the risk of stent thrombosis. In patients with coronary lesions without the instability characteristic, conservative management should be the default strategy, and a search for another cause of the cardiac arrest should be systematic. In the present review, we sought to describe the potential benefit of intracoronary imaging in patients with out-of-hospital cardiac arrest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Percutaneous left atrial appendage closure may be considered in selected patients with atrial fibrillation at significant risk of both thromboembolism and haemorrhage., Aims: To report the experience of a tertiary French centre in percutaneous left atrial appendage closure and to discuss the outcomes compared with previously published series., Methods: This was a retrospective observational cohort study of all patients referred for percutaneous left atrial appendage closure between 2014 and 2020. Patient characteristics, procedural management and outcomes were reported, and the incidence of thromboembolic and bleeding events during follow-up were compared with historical incidence rates., Results: Overall, 207 patients had left atrial appendage closure (mean age 75.3±8.6 years; 68% men; CHA 2 DS 2 -VASc score 4.8±1.5 ; HAS-BLED score 3.3±1.1), with a 97.6% (n=202) success rate. Twenty (9.7%) patients had at least one significant periprocedural complication, including six (2.9%) tamponades and three (1.4%) thromboembolisms. Periprocedural complication rates decreased from earlier to more recent periods (from 13% before 2018 to 5.9% after; P=0.07). During a mean follow-up of 23.1±20.2 months, 11 thromboembolic events were observed (2.8% per patient-year), a 72% risk reduction compared with the estimated theoretical annual risk. Conversely, 21 (10%) patients experienced bleeding during follow-up, with almost half of the events occurring during the first 3 months. After the first 3 months, the risk of major bleeding was 4.0% per patient-year, a 31% risk reduction compared with the expected estimated risk., Conclusion: This real-world evaluation emphasizes the feasibility and benefit of left atrial appendage closure, but also illustrates the need for multidisciplinary expertise to initiate and develop this activity., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Patients with out-of-hospital cardiac arrest (OHCA) due to acute coronary syndromes (ACS) who undergo percutaneous coronary intervention (PCI) are at high risk of bleeding and thrombosis. While predictive bleeding and stent thrombosis risk scores have been established, their performance in patients with OHCA has not been evaluated., Methods: All consecutive patients admitted for OHCA due to ACS who underwent PCI between January 2007 and December 2019 were included. The ACTION and CRUSADE bleeding risk scores and the Dangas score for early stent thrombosis risk were calculated for each patient. A C-statistic analysis was performed to assess the performance of these scores., Results: Among 386 included patients, 82 patients (21.2%) experienced severe bleeding and 30 patients (7.8%) experienced stent thrombosis. The predictive performance of the ACTION and CRUSADE bleeding risk scores for major bleeding was poor, with areas under the curve (AUCs) of 0.596 and 0.548, respectively. Likewise, the predictive performance of the Dangas stent thrombosis risk score was poor (AUC 0.513). Using multivariable analysis, prolonged low-flow (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05; P=0.025), reduced haematocrit or fibrinogen at admission (OR 0.93, 95% CI 0.88-0.98; P=0.010 and OR 0.61; 95% CI 0.41-0.89; P=0.012, respectively) and the use of glycoprotein IIb/IIIa inhibitors (OR 2.10, 95% CI 1.18-3.73; P=0.011) were independent risk factors for major bleeding., Conclusion: The classic bleeding and stent thrombosis risk scores have poor performance in a population of patients with ACS complicated by OHCA. Other predictive factors might be more pertinent to determine major bleeding and stent thrombosis risks in this specific population., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyse the risk factors associated with the occurrence of IAs in ADPKD patients., Methods: A cross-sectional study was performed in 26 nephrology centres from the western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes., Results: Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9%, 6.2% and 8.1% at 50, 60 and 70 years, respectively. While this risk appeared to be similar in male and female individuals <50 years, after that age, the risk continued to increase more markedly in female patients, reaching 10.8% versus 5.4% at 70 years. The diagnosis rate of IAs was >2-fold higher in PKD1 compared with PKD2, with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension <35 years, smoking and PKD1 genotype were associated with an increased risk for diagnosis of IAs., Conclusions: This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of oestrogen., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. Genetic testing remains inconclusive in ∼7% of the families. We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703_704delCA) in ALG5. ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. Four additional families with pathogenic variants in ALG5 were identified. Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Introduction: Incremental hemodialysis (iHD) may attenuate "dialysis shock" and reduce costs, preserving quality of life. It is considered difficult to reconcile with HD wards' routine; fear of underdialysis and increasing mortality are additional concerns. The aim of this study was to evaluate mortality, morbidity, and costs in a large HD ward where iHD is the standard of HD start., Methods: This observational study included all incident HD patients in 2017 to 2021, stratified according to HD start: iHD (1-2 sessions/wk), decremental HD (dHD, 3 sessions/wk at start, later reduced), or standard (3 sessions/wk). Results were compared with data recorded in the same unit before the incremental program (2015-2017) and with a propensity score-matched cohort from the French Renal Epidemiology and Information Network (REIN) registry., Results: A total of 158 patients started HD in 2017 to 2021, 57.6% on iHD, 8.9% dHD, and 33.5% standard HD schedule. Patients on the standard schedule had lower initial estimated glomerular filtration rate (eGFR) (5 vs. 7 ml/min per 1.72 m 2 , P  = 0.003). We found no survival differences according to period of start (same center) and propensity score matching (REIN). Patients intensively followed in the pre-HD period were more likely to start on iHD-dHD. Persistence on iHD-dHD was about 50% at 1 year and 35% at 2 years. Hospitalization rates and time to first hospitalization or death did not differ between the schedules. The iHD-dHD policy allowed a 16% cost saving, even accounting for supplemental biochemical tests., Conclusion: Our study reveals that iHD can be a new standard of care, as it is safe and feasible in up to two-thirds of patients on incident HD., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Oral alkalization with sodium bicarbonate (NaHCO 3 ) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. Although most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO 3 . Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO 3 -containing or no-NaHCO 3 -containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From February 2017 to February 2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 (125, 141) vs. 141 (130, 150), P = 0.02) and diastolic (77 (67, 85) vs. 85 (73, 90), P = 0.03) BP values, a higher plasma chloride (106.0 (105.0, 109.0) vs. 105.0 (102.0, 107.0), P = 0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, P = 0.02). Patients experienced mainly slight ΔBP (< 10 mmHg). The primary outcome was not associated (P = 0.79) with the study treatment (129 received NaHCO 3 and 27 received citrate). We subsequently developed three different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO 3 is no longer associated with an ECV increase compared to citrate in real-life settings., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Survivors of out-of-hospital cardiac arrest undergoing percutaneous coronary intervention are at high thrombotic and bleeding risk. The type of antiplatelet that should be used in these patients remains controversial., Aim: To compare the impact of the use of more potent P2Y 12 receptor inhibitors on thrombotic and bleeding events with that of clopidogrel in survivors of out-of-hospital cardiac arrest undergoing percutaneous coronary intervention., Methods: This was an observational study including consecutive patients treated for out-of-hospital cardiac arrest associated with acute coronary syndrome by percutaneous coronary intervention with stent implantation and dual antiplatelet therapy between January 2007 and December 2017. Baseline characteristics, mortality and in-hospital haemorrhagic and thrombotic events were compared between patients who received clopidogrel and those who received more potent P2Y 12 receptor inhibitors., Results: Among the 359 included patients, 197 received clopidogrel and 162 received ticagrelor or prasugrel. The primary composite endpoint of death, definite stent thrombosis or major bleeding was similar in the two groups (57.4% in the clopidogrel group vs. 53.7% in the new P2Y 12 receptor inhibitors group; P=0.49). Fewer haemorrhagic events occurred in the clopidogrel group (21.8% vs. 31.5%; P=0.04), whereas similar rates of definite stent thrombosis were observed (5.1% vs. 6.2%; P=0.65). The use of more potent P2Y 12 receptor inhibitors was an independent predictor of major bleeding (odds ratio 2.69, 95% confidence interval 1.37-5.25; P=0.004)., Conclusions: In this specific population, the use of more potent P2Y 12 receptor inhibitors was not associated with a reduced thrombosis rate compared with clopidogrel, but with a higher haemorrhagic risk. Prospective studies should be performed on the optimal antithrombotic therapy in this subset of patients., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength., Methods/design: VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient's autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective., Discussion: In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient's muscle strength., Trial Registration: ClinicalTrials.gov NCT04262934 . Registered on 10 February 2020 - Retrospectively registered.

Introduction: Prevalence of chronic kidney disease (CKD) varies around the world. Little is known about the discrepancy between the general population's needs and nephrology care offered. We aimed to contribute to filling this gap and propose a means to infer the number of patients needing follow-up., Methods: All patients undergoing at least one nephrology consultation in 2019 were enrolled. We used the ratio between CKD Stages 3 and 4 reported in the literature, and considered that only 25-50% of CKD Stage 3 patients have progressive CKD, to hypothesize different scenarios to estimate the number of CKD Stage 3 patients still needing nephrology follow-up., Results: The 1992 CKD patients were followed-up in our centre (56.93% males; age 66.71 ± 18.32 years; 16.82% Stage 1; 14.66% Stage 2; 39.46% Stage 3; 19.88% Stage 4; 7.68% Stage 5). The ratio between Stages 3 and 4 in population studies ranged from 7.72 to 51.29, being 1.98 in our centre. Hypothesizing that we followed-up 100, 70 or 50% of CKD Stage 4 patients, 528-2506 CKD Stage 3 patients in our area would need nephrology follow-up [1885-8946 per million population (p.m.p.)]. Three to 17 additional nephrologists p.m.p. would be necessary to fully cover the need for care., Conclusions: The number of patients with CKD Stage 3 who would benefit from nephrology care is high. Considering that one patient-year of delay of dialysis could cover a nephrologist's annual salary, interventions aimed to improve the care of advanced CKD may be economically sound., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Out of hospital cardiac arrest (OHCA) patients requiring percutaneous coronary intervention (PCI) are at higher risk of both stent thrombosis and bleeding. The use of aggressive antiplatelet therapy could lead to a higher risk of bleeding in these patients. Indeed, data on glycoprotein IIb/IIIa inhibitor (GPi) use in this specific indication is scarce., Aim: We sought to evaluate the benefit and safety of GPi use in OHCA patients requiring PCI., Methods and Results: Between January 2007 and December 2017, we retrospectively included all consecutive patients treated with PCI for an OHCA from cardiac cause. Clinical, procedural data and in-hospital outcomes were collected. Three hundred and eighty-five patients were included. GPi were administrated in 41.3% of cases (159 patients). Patients who received GPi were younger, had less prior PCI, more often a TIMI 0 or 1 flow before PCI and thromboaspiration use. There were no differences regarding in-hospital definite stent thrombosis among the two groups (11.9% in the GPi group vs 7.1% in the non-GPi group, p = 0.10) or in-hospital mortality (48.6% vs 49.3%, p = 0.68). The incidence of any bleeding (33.3% vs. 19.6%; p = 0.002), and major bleeding (BARC 3-5) (21.9% vs. 16.8%; p = 0.007) was significantly higher in patients receiving GPi. Indeed, using multivariate analysis, GPi use was predictor of major bleeding (OR: 1.81; 95% CI: 1.06-3.08; p = 0.03)., Conclusions: In patients treated with PCI for OHCA from cardiac cause, GPi use was associated with an increased risk of major bleeding events, without difference on in-hospital stent thrombosis or death., (Copyright © 2020 Elsevier B.V. All rights reserved.)