Coronavirus disease 2019 in chronic kidney disease

The clinical spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic infection to severe pneumonia with respiratory failure and even death. More severe cases with higher mortality have been reported in older patients and in those with chronic illness such as hypertension, diabetes or cardiovascular diseases. In this regard, patients with chronic kidney disease (CKD) have a higher rate of all-type infections and cardiovascular disease than the general population. A markedly altered immune system and immunosuppressed state may predispose CKD patients to infectious complications. Likewise, they have a state of chronic systemic inflammation that may increase their morbidity and mortality. In this review we discuss the chronic immunologic changes observed in CKD patients, the risk of COVID-19 infections and the clinical implications for and specific COVID-19 therapy in CKD patients. Indeed, the risk for severe COVID-19 is 3-fold higher in CKD than in non-CKD patients; CKD is 12-fold more frequent in intensive care unit than in non-hospitalized COVID-19 patients, and this ratio is higher than for diabetes or cardiovascular disease; and acute COVID19 mortality is 15-25% for haemodialysis patients even when not developing pneumonia

Pilot multi-omic analysis of human bile from benign and malignant biliary strictures: a machine-learning approach

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (1H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.This research was funded by: Instituto de Salud Carlos III (ISCIII) co-financed by Fondo Europeo de Desarrollo Regional (FEDER) Una manera de hacer Europa, grant numbers: PI16/01126 (M.A.A.), PI19/00819 (M.J.M. and J.J.G.M.), PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 (J.M.B.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation), grant name: Rare Cancers 2017 (J.M.U., M.L.M., J.M.B., M.J.M., R.I.R.M., M.G.F.-B., C.B., M.A.A.); Gobierno de Navarra Salud, grant number 58/17 (J.M.U., M.A.A.); La Caixa Foundation, grant name: HEPACARE (C.B., M.A.A.); AMMF The Cholangiocarcinoma Charity, UK, grant number: 2018/117 (F.J.C. and M.A.A.); PSC Partners US, PSC Supports UK, grant number 06119JB (J.M.B.); Horizon 2020 (H2020) ESCALON project, grant number H2020-SC1-BHC-2018–2020 (J.M.B.); BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia, grant numbers BIO15/CA/016/BD (J.M.B.) and BIO15/CA/011 (M.A.A.). Department of Health of the Basque Country, grant number 2017111010 (J.M.B.). La Caixa Foundation, grant number: LCF/PR/HP17/52190004 (M.L.M.), Mineco-Feder, grant number SAF2017-87301-R (M.L.M.), Fundación BBVA grant name: Ayudas a Equipos de Investigación Científica Umbrella 2018 (M.L.M.). MCIU, grant number: Severo Ochoa Excellence Accreditation SEV-2016-0644 (M.L.M.). Part of the equipment used in this work was co-funded by the Generalitat Valenciana and European Regional Development Fund (FEDER) funds (PO FEDER of Comunitat Valenciana 2014–2020). Gobierno de Navarra fellowship to L.C. (Leticia Colyn); AECC post-doctoral fellowship to M.A.; Ramón y Cajal Program contracts RYC-2014-15242 and RYC2018-024475-1 to F.J.C. and M.G.F.-B., respectively. The generous support from: Fundación Eugenio Rodríguez Pascual, Fundación Echébano, Fundación Mario Losantos, Fundación M Torres and Mr. Eduardo Avila are acknowledged. The CNB-CSIC Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0001 (F.J.C.). Comunidad de Madrid Grant B2017/BMD-3817 (F.J.C.).Peer reviewe

SARS-CoV-2-spike antibody and T-cell responses elicited by a homologous third mRNA COVID-19 dose in hemodialysis and kidney transplant recipients

This article belongs to the Section Medical Microbiology.The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.This research work was supported by funding from the Instituto de Salud Carlos III, Madrid, Spain (FIS, PI21/00563) to DN and by funding from the European Commission NextGenerationEU fund (EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global), to RG, and funding from the Valencian Society of Neprology. The project received the Isabel Burches grant from the Valencian Society of Nephrology (2/2/21).Peer reviewe

Tejido adiposo epicárdico, adiponectina y leptina: Una fuente potencial de riesgo cardiovascular en Enfermedad renal crónica

The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT

Iron replacement therapy in the management of anaemia in non-dialysis Chronic kidney disease patients: Perspective of the Spanish Nephrology Society Anaemia Group

This work presents an update on the management of iron deficiency in patients with chronic kidney disease (CKD), either with or without anaemia. A review is made of the recommendations of the guidelines for the treatment of iron deficiency in CKD. It also presents new studies on iron deficiency in patients with CKD, as well as new findings about iron therapy and its impact on clinical outcomes.Anaemia is a common complication of CRF, and is associated with a decrease in the quality of life of the patients, as well as an increase in morbidity and mortality. Iron deficiency (absolute or functional) is common in non-dialysis chronic kidney disease patients, and may cause anaemia or a low response to erythropoiesis-stimulating agents. For this reason, the clinical guidelines for the treatment of the anaemia in Nephrology indicate the correction of the deficiency in the presence of anaemia. Iron replacement therapy is indicated in patients with CKD and anaemia (Hb  12 g/dl, regardless of whether they have an absolute or functional iron deficiency.Intravenous iron replacement therapy is safe, more efficient and rapid than oral therapy for achieving an increase haemoglobin lels and reducing the dose of erythropoiesis-stimulating agents. For the administration of intravenous iron in non-dialysis chronic renal failure patients a strategy of high doses and low frequency would be preferred on being more convenient for the patient, preserves better the venous capital, and is safe and cost-effective. Iron plays an essential role in energy metabolism and other body functions beyond the synthesis of haemoglobin, for which the iron deficiency, even in the absence of anaemia, could have harmful effects in patients with CKD. The correction of the iron deficiency, in the absence of anaemia is associated with functional improvement in patients with heart failure, and in muscle function or fatigue in patients without CKD.Despite the evidence of benefits in the correction of iron deficiency in patients with CKD, more studies are required to evaluate the impact of the correction of the iron deficiency in the absence of anaemia on morbidity and mortality, quality of life and physical capacity, as well as the long-term effect of oral and intravenous iron replacement therapy in this population. Resumen: Este trabajo realiza una actualización sobre el manejo del déficit de hierro en pacientes con enfermedad renal crónica (ERC), ya sea con o sin anemia. Se revisan las recomendaciones de las guías para el tratamiento de la ferropenia en la ERC. Además, muestra los nuevos estudios sobre ferroterapia en pacientes con ERC, así como los nuevos conocimientos sobre el déficit férrico y su impacto en los resultados clínicos.La anemia es una complicación frecuente de la ERC y se asocia con una disminución en la calidad de vida de los pacientes, así como un aumento de la morbimortalidad. El déficit de hierro (absoluto o funcional) es frecuente en pacientes con ERC que no reciben diálisis, y puede causar anemia e hiporrespuesta a los agentes estimuladores de la eritropoyesis. Por ello las guías clínicas para el tratamiento de la anemia en Nefrología aconsejan la corrección del déficit de hierro en presencia de anemia. La ferroterapia está indicada en pacientes con ERC y anemia (Hb  12 independientemente de que presenten déficit férrico absoluto o funcional.La ferroterapia intravenosa es segura, más eficaz y rápida que la oral para conseguir aumentar los niveles de hemoglobina, reducir las dosis de agentes estimulantes de la eritropoyesis. Ante la administración de hierro intravenoso en los pacientes con ERC no en diálisis se preferirá una estrategia de altas dosis y baja frecuencia por ser más conveniente para el paciente, preservar mejor el árbol venoso, ser segura y coste-efectiva. El hierro juega un papel esencial en el metabolismo energético y otras funciones del organismo más allá de la síntesis de la hemoglobina, por lo que el déficit de hierro, aun en ausencia de anemia, podría tener un efecto deletéreo en los pacientes con ERC. La corrección de déficit de hierro en ausencia de anemia se asocia con mejoría funcional en pacientes con insuficiencia cardíaca, y de función muscular o de la fatiga en pacientes sin ERC.A pesar de las evidencias del beneficio en la corrección de déficit de hierro en pacientes con ERC se requieren mas estudios para evaluar el impacto de la corrección del déficit de hierro en ausencia de anemia sobre la morbimortalidad, calidad de vida y capacidad física, así como el efecto a largo plazo de la ferroterapia oral e intravenosa en esta población

Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and their Combination in Patients with Chronic Kidney Disease:A Randomized Cross-Over Clinical Trial

BACKGROUND: SGLT2 inhibitors and MRAs reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with chronic kidney disease (CKD). We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and mineralocorticoid receptor antagonists (MRA) eplerenone alone and in combination in patients with CKD. METHODS: We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hours, eGFR 30-90 ml/min per 1.73 m2, who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. RESULTS: Of 57 patients screened, 46 were randomly assigned (mean eGFR 58.1 ml/min per 1.73 m2, median UACR 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was -19.6% (95% CI, -34.3 to -1.5), -33.7% (95% CI, -46.1 to -18.5), and -53% (95% CI, -61.7 to -42.4; P<0.001 versus dapagliflozin; P=0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone (r=-0.13; P=0.47; r=-0.08; P=0.66, respectively). Hyperkalemia was more frequently reported with eplerenone (n=8; 17.4%) compared with dapagliflozin (n=0; 0%) or dapagliflozin-eplerenone (n=2; 4.3%; P between-groups=0.003). CONCLUSIONS: Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: European Union Clinical Trials Register, EU 2017-004641-25

COVID-19 Vaccination Improved Psychological Distress (Anxiety and Depression Scores) in Chronic Kidney Disease Patients: A Prospective Study

The purpose of the study is to analyze the impact of vaccination against SARS-CoV-2 on anxiety and depression scores in patients with different modalities of chronic kidney disease. One hundred and seventeen renal patients (50 hemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants, and 22 advanced chronic kidney disease patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL), and perceived fears and resources with standardized (Hospital Anxiety and Depression Scale (HADS)) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination. The main finding of the study was that there was a decrease in the global mean of normal scores for anxiety and depression symptoms in chronic kidney disease patients post-vaccination. We did not find statistically significant differences in depression or anxiety scores, nor any HRQOL differences between the treatment groups. The three main fears reported by the participants at baseline were those of adverse effects, not getting the vaccine, and lack of information. These findings highlight the potential interest of assessing psychological variables related to the impact of vaccination against SARS-CoV-2. New studies will be required to assess the impact of comprehensive vaccine coverage and its psychological impact