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

Optimizing the timing of nephrology referral for patients with diabetic kidney disease

Diabetis mellitus; Malaltia renal diabètica; Atenció multidisciplinàriaDiabetes mellitus; Diabetic kidney disease; Multidisciplinary careDiabetes mellitus; Enfermedad renal diabética; Atención multidisciplinariaAge-standardized rates of diabetes mellitus (DM)-related complications, such as acute myocardial infarction, stroke or amputations, have decreased in recent years, but this was not associated with a clear reduction of the incidence of advanced chronic kidney disease (CKD) requiring renal replacement therapy. The early detection of diabetic kidney disease (DKD) is a key to reduce complications, morbidity and mortality. Consensus documents and clinical practice guidelines recommend referral of DM patients to nephrology when the estimated glomerular filtration rate falls below 30 mL/min/1.73 m2 or when albuminuria exceeds 300 mg/g urinary creatinine. Conceptually, it strikes as odd that patients with CKD are referred to the specialist caring for the prevention and treatment of CKD only when >70% of the functioning kidney mass has been lost. The increasing global health burden of CKD, driven in large part by DKD, the suboptimal impact of routine care on DKD outcomes as compared with other DM complications, the realization that successful therapy of CKD requires early diagnosis and intervention, the advances in earlier diagnosis of kidney injury and the recent availability of antidiabetic drugs with a renal mechanism of action and lack of hypoglycaemia risk, which additionally are cardio- and nephroprotective, all point towards a paradigm shift in the care for DM patients in which they should be referred earlier to nephrology as part of a coordinated and integrated care approach.Sources of support: FIS/Fondos FEDER PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM

Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus

Gastrointestinal adverse events; Obesity; Type 2 diabetesEsdeveniments adversos gastrointestinals; Obesitat; Diabetis tipus 2Eventos adversos gastrointestinales; Obesidad; Diabetes tipo 2Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are indicated in type 2 diabetes and obesity for their high efficacy in controlling glycaemia and inducing body weight loss, respectively. Patients may develop gastrointestinal adverse events (GI AEs), namely nausea, vomiting, diarrhoea and/or constipation. To minimize their severity and duration, healthcare providers (HCPs) and patients must be aware of appropriate measures to follow while undergoing treatment. An expert panel comprising endocrinologists, nephrologists, primary care physicians, cardiologists, internists and diabetes nurse educators convened across virtual meetings to reach a consensus regarding these compelling recommendations. Firstly, specific guidelines are provided about how to reach the maintenance dose and how to proceed if GI AEs develop during dose-escalation. Secondly, specific directions are set about how to avoid/minimize nausea, vomiting, diarrhoea and constipation symptoms. Clinical scenarios representing common situations in daily practice, and infographics useful to guide both HCPs and patients, are included. These recommendations may prevent people with T2D and/or obesity from withdrawing from GLP-1 RAs treatment, thus benefitting from their superior effect on glycaemic control and weight loss.This work has been funded by Novo-Nordisk

Association of renin–angiotensin system blockers with COVID-19 diagnosis and prognosis in patients with hypertension: a population-based study

COVID-19; Angiotensin receptor blockers; HypertensionCOVID-19; Bloqueadores de los receptores de angiotensina; HipertensiónCOVID-19; Bloquejadors dels receptors d'angiotensina; HipertensióBackground The effect of renin–angiotensin system (RAS) blockade either by angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) susceptibility, mortality and severity is inadequately described. We examined the association between RAS blockade and COVID-19 diagnosis and prognosis in a large population-based cohort of patients with hypertension (HTN). Methods This is a cohort study using regional health records. We identified all individuals aged 18–95 years from 87 healthcare reference areas of the main health provider in Catalonia (Spain), with a history of HTN from primary care records. Data were linked to COVID-19 test results, hospital, pharmacy and mortality records from 1 March 2020 to 14 August 2020. We defined exposure to RAS blockers as the dispensation of ACEi/ARBs during the 3 months before COVID-19 diagnosis or 1 March 2020. Primary outcomes were: COVID-19 infection and severe progression in hospitalized patients with COVID-19 (the composite of need for invasive respiratory support or death). For both outcomes and for each exposure of interest (RAS blockade, ACEi or ARB) we estimated associations in age-, sex-, healthcare area- and propensity score-matched samples. Results From a cohort of 1 365 215 inhabitants we identified 305 972 patients with HTN history. Recent use of ACEi/ARBs in patients with HTN was associated with a lower 6-month cumulative incidence of COVID-19 diagnosis {3.78% [95% confidence interval (CI) 3.69–3.86%] versus 4.53% (95% CI 4.40–4.65%); P < 0.001}. In the 12 344 patients with COVID-19 infection, the use of ACEi/ARBs was not associated with a higher risk of hospitalization with need for invasive respiratory support or death [OR = 0.91 (0.71–1.15); P = 0.426]. Conclusions RAS blockade in patients with HTN is not associated with higher risk of COVID-19 infection or with a worse progression of the disease.The study was partially funded by ‘CIBER de Epidemiología y Salud Pública (CIBERESP)’

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?

International audienceAbstract Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins’ putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care

Acidosis, cognitive dysfunction and motor impairments in patients with kidney disease

International audienceMetabolic acidosis, defined as a plasma or serum bicarbonate concentration &lt;22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10–30% of patients with advanced stages of CKD. Likewise, in patients with a kidney transplant, prevalence rates of metabolic acidosis range from 20% to 50%. CKD has recently been associated with cognitive dysfunction, including mild cognitive impairment with memory and attention deficits, reduced executive functions and morphological damage detectable with imaging. Also, impaired motor functions and loss of muscle strength are often found in patients with advanced CKD, which in part may be attributed to altered central nervous system (CNS) functions. While the exact mechanisms of how CKD may cause cognitive dysfunction and reduced motor functions are still debated, recent data point towards the possibility that acidosis is one modifiable contributor to cognitive dysfunction. This review summarizes recent evidence for an association between acidosis and cognitive dysfunction in patients with CKD and discusses potential mechanisms by which acidosis may impact CNS functions. The review also identifies important open questions to be answered to improve prevention and therapy of cognitive dysfunction in the setting of metabolic acidosis in patients with CKD

Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor

International audiencePeople living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood–brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics