A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cytotoxicity may involve inhibition of peroxisome proliferator-activated receptor alpha. Fenofibrate activates peroxisome proliferator-activated receptor alpha and inhibits SARS-CoV-2 replication in vitro. Whether fenofibrate can be used to treat coronavirus disease 2019 (COVID-19) infection in humans remains unknown. Here, we randomly assigned inpatients and outpatients with COVID-19 within 14 d of symptom onset to 145 mg of oral fenofibrate nanocrystal formulation versus placebo for 10 d, in a double-blinded fashion. The primary endpoint was a severity score whereby participants were ranked across hierarchical tiers incorporating time to death, mechanical ventilation duration, oxygenation, hospitalization and symptom severity and duration. In total, 701 participants were randomized to fenofibrate (n = 351) or placebo (n = 350). The mean age of participants was 49 ± 16 years, 330 (47%) were female, mean body mass index was 28 ± 6 kg/m2 and 102 (15%) had diabetes. Death occurred in 41 participants. Compared with placebo, fenofibrate had no effect on the primary endpoint. The median (interquartile range) rank in the placebo arm was 347 (172, 453) versus 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in secondary and exploratory endpoints, including all-cause death, across arms. There were 61 (17%) adverse events in the placebo arm compared with 46 (13%) in the fenofibrate arm, with slightly higher incidence of gastrointestinal side effects in the fenofibrate group. Overall, among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes ( NCT04517396 ).

A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019.

Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro . Methods We randomly assigned 701 participants with COVID-19 within 14 days of symptom onset to 145 mg of fenofibrate (nanocrystal formulation with dose adjustment for renal function or dose-equivalent preparations of micronized fenofibrate or fenofibric acid) vs. placebo for 10 days, in a double-blinded fashion. The primary endpoint was a ranked severity score in which participants were ranked across hierarchical tiers incorporating time to death, duration of mechanical ventilation, oxygenation parameters, subsequent hospitalizations and symptom severity and duration. ClinicalTrials.gov registration: NCT04517396. Findings: Mean age of participants was 49 ± 16 years, 330 (47%) were female, mean BMI was 28 ± 6 kg/m 2 , and 102 (15%) had diabetes mellitus. A total of 41 deaths occurred. Compared with placebo, fenofibrate administration had no effect on the primary endpoint. The median (interquartile range [IQR]) rank in the placebo arm was 347 (172, 453) vs. 345 (175, 453) in the fenofibrate arm (P = 0.819). There was no difference in various secondary and exploratory endpoints, including all-cause death, across randomization arms. These results were highly consistent across pre-specified sensitivity and subgroup analyses. Conclusion Among patients with COVID-19, fenofibrate has no significant effect on various clinically relevant outcomes.

Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial.

BACKGROUND: Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. METHODS: The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. FINDINGS: Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; ß-coefficient 8 [95% CI -13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups. INTERPRETATION: Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. FUNDING: REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.

Guía de práctica clínica para el tamizaje, diagnóstico y manejo de la enfermedad renal crónica en estadios 1 al 3 en el Seguro Social del Perú (EsSalud) / Clinical practice guideline for the screening, diagnosis, and management of chronic kidney disease stages 1-3 for the Peruvian Social Security (EsSalud)

RESUMEN El presente artículo resume la guía de práctica clínica (GPC) para tamizaje, diagnóstico y manejo de los pacientes con enfermedad renal crónica (ERC) en los estadios 1 al 3 en el Seguro Social del Perú (EsSalud). Para el desarrollo de esta GPC, se conformó un grupo elaborador de la guía (GEG) que incluyó especialistas clínicos y metodólogos, el cual formuló ocho preguntas clínicas. Para responder cada pregunta se realizaron búsquedas sistemáticas de revisiones sistemáticas y, cuando fue considerado pertinente, de estudios primarios; y se seleccionó la evidencia pertinente. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones periódicas, el GEG usó la metodología GRADE para revisar la evidencia y emitir las recomendaciones. Se emitieron ocho recomendaciones (cuatro fuertes y cuatro condicionales), 29 puntos de buena práctica clínica, y tres flujogramas.

ABSTRACT This paper summarizes the clinical practice guidelines (CPG) for the screening, diagnosis, and management of patients with chronic kidney disease (CKD) stages 1-3 in the Social Security of Peru (EsSalud). A guideline development group (GDG) was established for develop this CPG, which included clinical and methodology specialists, who formulated 08 clinical questions. Systematic searches of systematic reviews and, when considered necessary, primary studies were conducted to answer each question; and relevant evidence was selected. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GDG used the GRADE methodology for reviewing the evidence and for developing recommendations. At the end, this CPG formulated 08 recommendations (04 strong and 04 conditional), 29 points of good clinical practice, and 03 flowcharts were formulated.

Effectiveness of adherence to a renal health program in a health network in Peru.

OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.

Teenager with a Primary Renal Lymphoma: A Case Report.

We report a case of an 18-year-old male patient who was diagnosed with primary renal lymphoma (PRL) through biopsy findings and imaging studies. The patient presented with clinical manifestations of distal renal tubular acidosis including polyuria, polydipsia, lower limb weakness, involuntary weight loss, asthenia and dyspnea. No personal background or relevant medical history was reported. A kidney biopsy showed high grade immature B-cell lymphoproliferative process (Non-Hodgkin's Lymphoma) with a Ki67 value greater than 90%. Complementary studies excluded primary lymphoid migration sites, which confirmed the diagnosis of PRL. The oncology unit initiated treatment with a combination of medications due to lack of protocols for the specific treatment. Besides the fact that this condition is rare, it also shows a unique symptoms presentation and non-typical findings in imaging methods. Also, it is important to underline the fact that the treatment is not yet specified for such type of cancer and different combinations are needed to control the disease.

Effectiveness of adherence to a renal health program in a health network in Peru / Efectividad de la adherencia a un programa de salud renal en una red sanitaria de Perú

ABSTRACT OBJECTIVE To evaluate the effectiveness of adherence to a multidisciplinary renal health program in reducing mortality and progression to hemodialysis. METHODS We used a database that included patient monitoring (2013-2017), dialysis admissions and all cause of mortality in Peru. Adherence to the program was established by meeting minimum visits during the first year of monitoring. The outcome of interest was hemodialysis admissions or all cause-mortality. Kaplan-Meier curves, Log-Rank test and competing survival analysis methods were used to estimate the differential risk between adherent and non-adherent patients. RESULTS A total of 20,354 participants was evaluated; 54.1% were male, 72.1 years old in average, 2.2 years average follow-up, and 15,279 (75.1%) belonged to the early stages (1 to 3a) of Chronic Kidney Disease. Adherence decreased the risk of renal replacement therapy in 41.0% (HR = 0.59, 95%CI 0.41-0.85) in the low-risk group and mortality in the high-risk group was 31.0% (HR = 0.69, 95%CI 0.57-0.83). CONCLUSIONS The multidisciplinary care strategy with standardized assessments by stage is effective in reducing admission to .0when the patient is identified in early stages and in reducing mortality in advanced stages.

RESUMEN OBJETIVO Evaluar la efectividad de la adherencia a un programa de salud renal en la reducción de mortalidad y progresión a hemodiálisis. MÉTODOS Utilizamos una base de datos que condensaba el seguimiento de los pacientes (2013-2017), los ingresos a diálisis de los mismos y la mortalidad por todas las causas en Perú. La adherencia al programa se estableció con el cumplimiento de visitas mínimas durante su primer año de seguimiento. La efectividad de la adherencia al programa se midió en términos de debut a hemodiálisis o muerte por todas las causas. Se utilizaron curvas de Kaplan-Meier, test de diferencias en la distribución (Log-Rank test) y métodos de análisis de supervivencia. Los análisis se realizaron utilizando R estudio 3.5.0 RESULTADOS Fueron evaluados 20.354 participantes, 54,1% varones, edad media de 72,1 años, con un seguimiento medio de 2,2 años; 15.279 (75.1%) tuvieron ERC en estadios tempranos (estadio 1 al 3a). La adherencia disminuyó en un 41,0% el riesgo de terapia de reemplazo renal (HR = 0,59; IC95% 0,41-0,85) en el grupo de bajo riesgo y en un 31,0% (HR = 0,69; IC95% 0,57-0,83) la mortalidad en el grupo de alto riesgo. CONCLUSIONES La estrategia de cuidado multidisciplinario con evaluaciones estandarizadas según estadio es efectiva en reducir el ingreso a terapia de reemplazo renal cuando se identifica al paciente en estadios tempranos y en reducir la mortalidad en estadios avanzados.

Mortalidad precoz en pacientes con enfermedad renal crónica que inician hemodiálisis por urgencia en una población peruana: Incidencia y factores de riesgo / Early mortality in patients with chronic kidney disease who started emergency haemodialysis in a Peruvian population: Incidence and risk factors

OBJETIVOS: Estimar la mortalidad precoz en pacientes con enfermedad renal crónica que iniciaron hemodiálisis por urgencia entre los años 2012-2014 en un hospital de referencia nacional en Lima, Perú, e identificar los factores de riesgo. Diseño, características, participantes y mediciones Se estudió una cohorte retrospectiva mediante la revisión de historias clínicas de todos los pacientes admitidos a la Unidad de Hemodiálisis del hospital en el periodo de tiempo señalado. Se evaluó mortalidad precoz, definida como la muerte dentro de los primeros 90 días luego de iniciar hemodiálisis, así como edad, sexo, etiología de enfermedad renal crónica, comorbilidades, causa de muerte, tasa de filtración glomerular estimada, acceso vascular, entre otras variables, en los pacientes que iniciaron hemodiálisis por urgencia. Se estimó la mortalidad precoz mediante frecuencias y se utilizó regresión de Poisson con varianza robusta para determinar los factores de riesgo. RESULTADOS: Se encontró que el 43,4% fueron mujeres, el 51,5% tenían ≥ 65 años y una mortalidad precoz del 9,3%. Los principales factores de riesgo fueron tasa de filtración glomerular estimada > 10 mL/min/1,73 m2 (RR: 2,72 [IC 95%: 1,60-4,61]); edad ≥ 65 años (RR: 2,51 [IC 95%: 1,41-4,48]); infección de catéter venoso central, RR: 2,25 (IC 95%: 1,08-4,67); sexo femenino, RR: 2,15 (IC 95%: 1,29-3,58); y albúmina < 3,5 g/dL (RR: 1,97 [IC 95%: 1,01-3,82]). CONCLUSIONES: La mortalidad precoz fue del 9,3%. El principal factor de riesgo fue iniciar hemodiálisis con una tasa de filtración glomerular estimada > 10 mL/min/1,73m2

OBJECTIVES: To estimate early mortality in patients with chronic kidney disease who started emergency haemodialysis between 2012 and 2014 in a national referral hospital in Lima, Peru, and to identify risk factors. Design, characteristics, participants and measurements. A retrospective cohort study was conducted by reviewing the medical records of all patients admitted to the hospital's Haemodialysis Unit from 2012 to 2014. Early mortality, defined as death within the first 90 days of starting haemodialysis, as well as age, gender, chronic kidney disease aetiology, comorbidities, cause of death, estimated glomerular filtration rate, vascular access and other variables were evaluated in patients who initiated emergency haemodialysis. Early mortality was estimated using frequencies and risk factors were determined by Poisson regression with robust variance. RESULTS: 43.4% of patients were female, 51.5% were aged ≥ 65 years and the early mortality rate was 9.3%. The main risk factors were estimated glomerular filtration rate > 10 ml/min/1.73 m2 (RR: 2.72 [95% CI: 1.60-4.61]); age ≥ 65 years (RR: 2.51 [95% CI: 1.41-4.48]); central venous catheter infection, RR: 2.25 (95% CI: 1.08-4.67); female gender, RR: 2.15 (95% CI: 1.29-3.58); and albumin < 3.5g/dl (RR: 1.97 [95% CI: 1.01-3.82]). CONCLUSIONS: Early mortality was 9.3%. The main risk factor was starting haemodialysis with an estimated glomerular filtration rate > 10 ml/min/1.73 m2

Early mortality in patients with chronic kidney disease who started emergency haemodialysis in a Peruvian population: Incidence and risk factors. / Mortalidad precoz en pacientes con enfermedad renal crónica que inician hemodiálisis por urgencia en una población peruana: Incidencia y factores de riesgo.

OBJECTIVES: To estimate early mortality in patients with chronic kidney disease who started emergency haemodialysis between 2012 and 2014 in a national referral hospital in Lima, Peru, and to identify risk factors. DESIGN, CHARACTERISTICS, PARTICIPANTS AND MEASUREMENTS: A retrospective cohort study was conducted by reviewing the medical records of all patients admitted to the hospital's Haemodialysis Unit from 2012 to 2014. Early mortality, defined as death within the first 90 days of starting haemodialysis, as well as age, gender, chronic kidney disease aetiology, comorbidities, cause of death, estimated glomerular filtration rate, vascular access and other variables were evaluated in patients who initiated emergency haemodialysis. Early mortality was estimated using frequencies and risk factors were determined by Poisson regression with robust variance. RESULTS: 43.4% of patients were female, 51.5% were aged≥65 years and the early mortality rate was 9.3%. The main risk factors were estimated glomerular filtration rate>10 ml/min/1.73m2 (RR: 2.72 [95% CI: 1.60-4.61]); age≥65 years (RR: 2.51 [95% CI: 1.41-4.48]); central venous catheter infection, RR: 2.25 (95% CI: 1.08-4.67); female gender, RR: 2.15 (95% CI: 1.29-3.58); and albumin<3.5g/dl (RR: 1.97 [95% CI: 1.01-3.82]). CONCLUSIONS: Early mortality was 9.3%. The main risk factor was starting haemodialysis with an estimated glomerular filtration rate>10ml/min/1.73m2.

Risk factors associated to hospital mortality in patients with acute kidney injury on hemodialysis. / Factores de riesgo asociados a mortalidad intrahospitalaria en pacientes con insuficiencia renal aguda en hemodiálisis.

INTRODUCTION: The worldwide incidence of acute kidney injury is 18% and the overall hospital mortality can rise above 50%. In Peru, there are few series about mortality of acute kidney injury in hemodialysis patients. OBJECTIVES: To identify risk factors associated to hospital mortality of acute kidney injury in hemodialysis patients. METHODS: This is a retrospective cohort of patients with acute kidney injury in hemodialysis of Hospital Nacional Edgardo Rebagliati Martins gathered between January 2013 and December 2015. The sample size was 154 patients which allowed a power of 80% and a CI of 95%. ICD-10 codes were used to identify medical records of patients with acute kidney injury (N.17) and hemodialysis (Z.49). The independent variable was oliguria, and the primary outcome was hospital mortality. Poisson regression was used for multivariate analysis. RESULTS: We identified a total of 285 patients; 212 medical records were analyzed and 44 were excluded. Out of the 168 medical records, 129 belonged to living patients and 39 to deceased ones. The overall mortality incidence was 17.2%. The principal etiologies of acute kidney injury while in hemodialysis were sepsis (39.2%), and severe dehydration (10.8%). In the adjusted model, the risk factors associated to hospital mortality of acute kidney injury while in hemodialysis were elevated serum lactate (RR 1.09), elevated serum potassium (RR 0.93), and mean arterial pressure (RR 0.97). CONCLUSIONS: Lactate is an objective parameter that can predict prognosis and contributes to a better management of acute kidney injury in hemodialysis patients.

INTRODUCCIÓN: La incidencia de insuficiencia renal aguda a nivel mundial es 18% y la mortalidad intrahospitalaria puede alcanzar más del 50%. En Perú, existen escasos estudios acerca de la mortalidad en pacientes con insuficiencia renal aguda en hemodiálisis. OBJETIVOS: Identificar los factores de riesgo asociados a mortalidad intrahospitalaria en pacientes con insuficiencia renal aguda en hemodiálisis. MÉTODOS: Es una cohorte retrospectiva, en la cual se estudió a los pacientes con insuficiencia renal aguda en hemodiálisis en el Hospital Nacional Edgardo Rebagliati Martins entre enero de 2013 y diciembre de 2015. Se halló un tamaño de muestra de 154 pacientes con una potencia de 80%, y un intervalo de confianza de 95%. Se utilizaron los códigos de la Clasificación Internacional de Enfermedades-10 para identificar las historias clínicas de pacientes con insuficiencia renal aguda (N.17) y hemodiálisis (Z.49). La variable independiente fue oliguria y la variable dependiente fue mortalidad intrahospitalaria. Para el análisis multivariado, se utilizó regresión de Poisson. RESULTADOS: El universo fue de 285 pacientes. Se revisaron 212 historias clínicas y se excluyeron 44. De las 168 historias clínicas estudiadas, 129 pertenecían a pacientes vivos y 39 a fallecidos. La incidencia de mortalidad fue de 17,2%. Las principales causas de insuficiencia renal aguda en hemodiálisis fueron sepsis (39,2%) y deshidratación severa (10,8%). En el modelo ajustado, los factores de riesgo asociados a mortalidad intrahospitalaria de insuficiencia renal aguda en hemodiálisis fueron lactato (riesgo relativo 1,09), potasio (riesgo relativo 0,93), y presión arterial media (riesgo relativo 0,97). CONCLUSIONES: El lactato es un parámetro objetivo que permite predecir el pronóstico y contribuye a un mejor manejo de los pacientes con insuficiencia renal aguda en hemodiálisis.