A Population-Based Registry Analysis on Hospitalized COVID-19 Patients with Previous Cardiovascular Disease: Clinical Profile, Treatment, and Predictors of Death.

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI.

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., ß-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

Clinical Profile, Pharmacological Treatment, and Predictors of Death Among Hospitalized COVID-19 Patients With Acute Kidney Injury: A Population-Based Registry Analysis.

Introduction: One of the worst clinical outcomes of the coronavirus disease 2019 (COVID-19) pandemic was acute kidney injury (AKI). Methods: This manuscript presents results from a population-based registry study assessing treatment, comorbidities, and predictors of hospital death among COVID-19 patients with AKI from March 1st to May 31th, 2020. Death, oxygen delivery and ventilation, acute dialysis need, use of medications, and various clinical outcomes, in addition to the length of stay in the hospital and intensive care unit (ICU), were evaluated. Results: In Castile and Leon, the largest region of Spain, 10.87% of the patients admitted for COVID-19 (n = 7,307) developed AKI. These patients were known by having hypertension (57.93%), cardiovascular disease (48.99%), diabetes (26.7%) and chronic kidney disease (14.36%), and they used antibiotics (90.43%), antimalarials (60.45%), steroids (48.61%), antivirals (33.38%), anti-systemic inflammatory response syndrome (SIRS) drugs (9.45%), and tocilizumab (8.31%). Mortality among patients with AKI doubled that observed in patients without AKI (46.1 vs. 21.79%). Predictors of hospital death in COVID-19 patients with AKI were ventilation needs (OR = 5.9), treatment with steroids (OR = 1.7) or anti-SIRS (OR = 2.4), severe acute respiratory syndrome (SARS) occurrence (OR = 2.8), and SIRS occurrence (OR = 2.5). Conclusions: Acute kidney injury is a frequent and serious complication among COVID-19 patients, with a very high mortality, that requires more attention by treating physicians, when prescribing medications, by looking for manifestations particular to the disease, such as SARS or SIRS.

Clinical Profile, Treatment and Predictors during the First COVID-19 Wave: A Population-Based Registry Analysis from Castile and Leon Hospitals.

The first wave of the COVID-19 pandemic collapsed the hospitals in Castile and Leon (Spain). An analysis of the clinical characteristics, drug therapies and principal outcome predictors in the COVID-19 hospitalized patients from 1 March to 31 May 2020 is presented through a population-based registry study. Hospital stay variables, ventilation mode data and clinical outcomes were observed. In Castile and Leon hospitals, 7307 COVID-19 patients were admitted, with 57.05% being male and a median of 76 years. The mortality rate was 24.43%, with a high incidence of severe acute respiratory syndrome (SARS) (14.03%) and acute kidney injury (AKI) (10.87%). The most used medicines were antibiotics (90.83%), antimalarials (42.63%), steroids (44.37%) and antivirals, such as lopinavir/ritonavir (42.63%). The use of tocilizumab (9.37%) and anti-SIRS (systemic inflammatory response syndrome) medicines (7.34%) were remarkable. Fundamentally, death occurred more likely over 65 years of age (OR: 9.05). In addition, the need for ventilation was associated with a higher probability of death (OR: 3.59), SARS (OR: 5.14) and AKI (OR: 2.31). The drug-use pattern had been modified throughout the COVID-19 first wave. Multiple factors, such as age, gender and the need for mechanical ventilation, were related to the worst evolution prognosis of the disease.

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies.

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common "off-label" (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

The Impact of Iron Supplementation for Treating Anemia in Patients with Chronic Kidney Disease: Results from Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

After relative erythropoietin deficiency, iron deficiency is the second most important contributing factor for anemia in chronic kidney disease (CKD) patients. Iron supplementation is a crucial part of the treatment of anemia in CKD patients, and intravenous (IV) iron supplementation is considered to be superior to per os (PO) iron supplementation. The differences between the available formulations are poorly characterized. This report presents results from pairwise and network meta-analyses carried out after a comprehensive search in sources of published and unpublished studies, according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations (International prospective register of systematic reviews PROSPERO reference ID: CRD42020148155). Meta-analytic calculations were performed for the outcome of non-response to iron supplementation (i.e., hemoglobin (Hgb) increase of <0.5-1.0 g/dL, or initiation/intensification of erythropoiesis-stimulating agent (ESA) therapy, or increase/change of iron supplement, or requirements of blood transfusion). A total of 34 randomized controlled trials (RCT) were identified, providing numerical data for analyses covering 93.7% (n = 10.097) of the total study population. At the network level, iron supplementation seems to have a more protective effect against the outcome of non-response before the start of dialysis than once dialysis is initiated, and some preparations seem to be more potent (e.g., ferumoxytol, ferric carboxymaltose), compared to the rest of iron supplements assessed (surface under the cumulative ranking area (SUCRA) > 0.8). This study provides parameters for adequately following-up patients requiring iron supplementation, by presenting the most performing preparations, and, indirectly, by making it possible to identify good responders among all patients treated with these medicines.

Cholesterol-Lowering Treatment in Chronic Kidney Disease: Multistage Pairwise and Network Meta-Analyses.

Pairwise and network meta-analyses on the relationship between the efficacy of the use of statins with or without ezetimibe and reductions in low-density lipoprotein cholesterol (LDLc) and C-reactive protein (CRP) in patients with chronic kidney disease (CKD) are presented. In the pairwise meta-analysis, statins with or without ezetimibe were shown to be efficacious in reducing major adverse cardiovascular events (MACE) in patients with CKD and an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2, in the context of both primary prevention [odds ratio (OR)/95% confidence interval (95% CI)/I2/number of studies (n): 0.50/0.40-0.64/0%/6] and primary/secondary prevention (0.66/0.57-0.76/57%/18). However, in the Bayesian network meta-analysis, compared to the placebo, only atorvastatin 80 mg daily and atorvastatin and rosuvastatin at doses equivalent to simvastatin 20 mg daily reduced the odds of MACEs in this patient population. The network meta-analysis for LDLc and CRP treatment objectives also showed that, regardless of eGFR and excluding dialysis patients, the number of MACEs decreased in patients with CKD, with reductions in both LDLc and CRP of less than 50% (surface under the cumulative ranking (SUCRA)/heterogeneity (vague)/n: 0.77/0.14/3). The evaluation of the benefits of drugs may lead to individualized therapy for CKD patients: Cholesterol-lowering treatment for CKD patients with high levels of both LDLc and CRP is suggested.

Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática / Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review

Fundamento y objetivo: Las células T reguladoras circulantes podrían convertirse en un adecuado biomarcador para los trasplantados renales. El objetivo de este estudio es evaluar el efecto de los inhibidores de la mammalian target of rapamycin (I-mTOR, «diana de rapamicina en células de mamífero») en las células reguladoras, y el interés clínico de este efecto. Material y métodos: Revisión sistemática de trabajos publicados y no publicados. Bases de datos y repositorios del mundo entero. Se buscaron ensayos controlados aleatorizados y estudios de cohortes que compararon recuentos de células reguladoras y episodios de rechazo entre trasplantados tratados con y sin I-mTOR. Los trabajos podían medir la correlación células reguladoras-filtrado glomerular. Se evaluó la codependencia células reguladoras-eficacia de los I-mTOR. Resultados: Se incluyeron 5 ensayos y 9 estudios. Las diferencias clínicas no permitieron una estimación cuantitativa del efecto de la inmunosupresión en el número de células reguladoras. Sin embargo, observamos que hay más células reguladoras con sirolimus o everolimus. El número de episodios de rechazo fue similar con anticalcineurínicos que con I-mTOR, a pesar de las diferencias en el número de células reguladoras. La correlación combinada células reguladoras-filtrado glomerular fue prospectivamente de 0,114, con un intervalo de confianza al 95% (IC 95%) de 0,062-0,406, y retrospectivamente, de 0,13 (IC 95% 0,0-0,361). Existen pruebas directas, aunque de bajo nivel (aleatorización estratificada por el biomarcador), respecto a la codependencia células reguladoras-eficacia de los I-mTOR. Conclusión: El número de células reguladoras puede asociarse a buenos resultados o desenlaces en los tratados con I-mTOR (eficacia antirrechazo), considerando la relación entre estas células y la función del injerto. Registro: PROSPERO (CRD42016046285) (AU)

Background and objective: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. Material and methods: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. Results: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. Conclusions: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function Registration: PROSPERO (CRD42016046285) (AU)

Peripheral blood regulatory T cell counts as a predictive biomarker for the outcome of kidney transplant: A systematic review. / Recuentos de células T reguladoras en sangre periférica como biomarcador predictivo del resultado del trasplante renal: revisión sistemática.

BACKGROUND AND OBJECTIVE: Circulating regulatory T cells could become a suitable biomarker for kidney recipients. The objective of this study was to evaluate the effect of mammalian target of rapamycin (mTOR) inhibitors on regulatory T cell numbers, and the clinical interest of this effect. MATERIAL AND METHODS: Systematic review of published and unpublished studies. Worldwide databases or repositories. Randomised controlled trials and cohort studies comparing regulatory T cell counts and rejection episodes between patients with and without mTOR inhibitors were searched. Correlation of regulatory T cells-glomerular filtration rate might be supplied. Co-dependency regulatory T cells-mTOR inhibitors efficacy was evaluated. RESULTS: Five trials and 9 studies were included. Clinical differences made it difficult to obtain quantitative estimates of the effect of immunosuppression on regulatory T cell numbers. Nevertheless, we found that there are higher regulatory T cell numbers under treatment with sirolimus or everolimus. Rejection episodes were similar under calcineurin inhibitors and mTOR inhibitors despite different regulatory T cell numbers. Pooled correlation regulatory T cells-glomerular filtration rate was, prospectively 0.114 (95% confidence interval [95% CI] 0.062-0.406), and retrospectively 0.13 (95% CI 0.0-0.361). There is direct evidence although of low level (biomarker-stratified randomisation) on the co-dependency regulatory T cells-mTOR inhibitors efficacy. CONCLUSIONS: Regulatory T cells counts may be associated with better outcomes under treatment with mTOR inhibitors (anti-rejection efficacy), considering that there is a relationship between these cells and kidney graft function. REGISTRATION: PROSPERO (CRD42016046285).