Non-valvular atrial fibrillation in CKD : role of vitamin K antagonists and direct oral anticoagulants. A narrative review

Atrial fibrillation (AF) is the most common arrhythmia in chronic kidney disease (CKD), with a close bidirectional relationship between the two entities. The presence of CKD in AF increases the risk of thromboembolic events, mortality and bleeding. Vitamin K antagonists (VKA) have been the mainstay of treatment for the prevention of thromboembolic events in AF until recently, with confirmed benefits in AF patients with stage 3 CKD. However, the risk-benefit profile of VKA in patients with AF and stages 4-5 CKD is controversial due to the lack of evidence from randomized controlled trials. Treatment with VKA in CKD patients has been associated with conditions such as poorer anticoagulation quality, increased risk of bleeding, faster progression of vascular/valvular calcification and higher risk of calciphylaxis. Direct oral anticoagulants (DOACs) have shown equal or greater efficacy in stroke/systemic embolism prevention, and a better safety profile than VKA in post-hoc analysis of the pivotal randomized controlled trials in patients with non-valvular AF and stage 3 CKD, yet evidence of its risk-benefit profile in more advanced stages of CKD is scarce. Observational studies associate DOACs with a good safety/effectiveness profile compared to VKA in non-dialysis CKD patients. Further, DOACs have been associated with a lower risk of acute kidney injury and CKD development/progression than VKA. This narrative review summarizes the evidence of the efficacy and safety of warfarin and DOACs in patients with AF at different CKD stages, as well as their effects on renal function, vascular/valvular calcification and bone health

Cardiorenal benefits of finerenone: protecting kidney and heart

Albuminuria; Enfermedad renal crónica; FinerenonaAlbuminúria; Malaltia renal crònica; FinerenonaAlbuminuria; Chronic kidney disease; FinerenonePersons with diabetes and chronic kidney disease (CKD) have a high residual risk of developing cardiovascular (CV) complications despite treatment with renin-angiotensin system blockers and sodium-glucose cotransporter type 2 inhibitors. Overactivation of mineralocorticoid receptors plays a key role in the progression of renal and CV disease, mainly by promoting inflammation and fibrosis. Finerenone is a nonsteroidal selective mineralocorticoid antagonist. Recent clinical trials, such as FIDELIO-DKD and FIGARO-DKD and the combined analysis FIDELITY have demonstrated that finerenone decreases albuminuria, risk of CKD progression, and CV risk in subjects with type 2 diabetes (T2D) and CKD. As a result, finerenone should thus be considered as part of a holistic approach to kidney and CV risk in persons with T2D and CKD. In this narrative review, the impact of finerenone treatment on the CV system in persons with type 2 diabetes and CKD is analyzed from a practical point of view

Insulin withdrawal in diabetic kidney disease : What are we waiting for?

The prevalence of type 2 diabetes mellitus worldwide stands at nearly 9.3% and it is estimated that 20-40% of these patients will develop diabetic kidney disease (DKD). DKD is the leading cause of chronic kidney disease (CKD), and these patients often present high morbidity and mortality rates, particularly in those patients with poorly controlled risk factors. Furthermore, many are overweight or obese, due primarily to insulin compensation resulting from insulin resistance. In the last decade, treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to be beneficial in renal and cardiovascular targets; however, in patients with CKD, the previous guidelines recommended the use of drugs such as repaglinide or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), plus insulin therapy. However, new guidelines have paved the way for new treatments, such as SGLT2i or GLP1-RA in patients with CKD. Currently, the new evidence supports the use of GLP1-RA in patients with an estimated glomerular filtration rate (eGFR) of up to 15 mL/min/1.73 m2 and an SGLT2i should be started with an eGFR > 60 mL/min/1.73 m2. Regarding those patients in advanced stages of CKD, the usual approach is to switch to insulin. Thus, the add-on of GLP1-RA and/or SGLT2i to insulin therapy can reduce the dose of insulin, or even allow for its withdrawal, as well as achieve a good glycaemic control with no weight gain and reduced risk of hypoglycaemia, with the added advantage of cardiorenal benefits

Practical approaches to building up a cardiorenal clinic

Cardiorenal clinics; Cardiorenal disease; Cardiorenal programClínicas cardiorrenales; Enfermedad cardiorrenal; Programa cardiorrenalClíniques cardiorenals; Malaltia cardiorenal; Programa cardiorenalThe population with concomitant heart and kidney disease (often termed ‘cardiorenal’ disease) is expected to grow, significantly impacting public health and healthcare utilization. Moreover, the cardiorenal nexus encompasses a bidirectional relationship that worsens prognosis and may complicate pharmacological management in often elderly and frail patients. Therefore, a more cohesive multidisciplinary team approach aiming to provide holistic, coordinated and specialized care would be a positive shift towards improving patient outcomes and optimizing healthcare resources. This article aims to define the organizational aspects and key elements for setting up a multidisciplinary cardiorenal clinical program as a potential healthcare model adapted to the particular characteristics of patients with cardiorenal disease

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

Background: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). Methods: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. Results: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. Conclusions: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patientsThis study was partially supported by a grant from Amgen S.A., Barcelona, Spain, through the Spanish Society of Nephrology

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

Background: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). Methods: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. Results: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. Conclusions: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patientsThis study was partially supported by a grant from Amgen S.A., Barcelona, Spain, through the Spanish Society of Nephrology

Gender differences related to the presence of atrial fibrillation in older hypertensive patients.

AIM: To determine whether there are gender differences in the epidemiological profile of atrial fibrillation(AF) and to characterise the clinical, biochemical, and therapeutic factors associated with AF. METHODS: Each investigator (primary care physicians or physicians based in hospital units for hypertension treatment) recruited the first 3 patients with an ageof ≥ 65 years and a clinical diagnosis of hypertension(ambulatory blood pressure monitoring and an electrocardiogram,were performed) on the first working day of the week for 5 wk and identified those individuals with atrial fibrillation. A binary logistic regression was performed, including all of the variables that were significant in the univariate analysis, to establish the variables that were associated with the presence of arrhythmia.CONCLUSION: In patients with hypertension over 65 years of age, there are relevant gender differences in the factors associated with AF

Mineral and Bone Metabolism Markers and Mortality in Diabetic Patients on Haemodialysis

© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.BACKGROUND: Diabetic patients on haemodialysis have a higher risk of mortality than non-diabetic patients. The aim of this COSMOS analysis was to assess whether bone and mineral laboratory values (calcium, phosphorus, and PTH) contribute to such risk. METHODS: COSMOS is a multicentre, open-cohort, 3-year prospective study, which includes 6797 patients from 227 randomly selected dialysis centres from 20 European countries. The association between mortality and calcium, phosphate or PTH was assessed using Cox proportional hazard regression models using both penalized splines smoothing and categorization according to KDIGO guidelines. The effect modification of the association between the relative risk of mortality and serum calcium, phosphate or PTH by diabetes was assessed. RESULTS: There was a statistically significant effect modification of the association between the relative risk of mortality and serum PTH by diabetes (p = 0.011). The slope of the curve of the association between increasing values of PTH and relative risk of mortality was steeper for diabetic compared with non-diabetic patients, mainly for high levels of PTH. In addition, high serum PTH (> 9 times the normal values) was significantly associated with a higher relative risk of mortality in diabetic patients but not in non-diabetic patients (1.53[95%CI:1.07-2.19] and 1.17[95%CI:0.91-1.52]). No significant effect modification of the association between the relative risk of mortality and serum calcium or phosphate by diabetes was found (p = 0.2 and p = 0.059, respectively). CONCLUSION: The results show a different association of PTH with the relative risk of mortality in diabetic and non-diabetic patients. These findings could have relevant implications for the diagnosis and treatment of CKD-MBD.publishersversionpublishe

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe