IgA-Dominant Infection-Associated Glomerulonephritis Following SARS-CoV-2 Infection

The renal involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has been reported. The etiology of kidney injury appears to be tubular, mainly due to the expression of angiotensin-converting enzyme 2, the key joint receptor for SARS-CoV-2; however, cases with glomerular implication have also been documented. The multifactorial origin of this renal involvement could include virus-mediated injury, cytokine storm, angiotensin II pathway activation, complement dysregulation, hyper-coagulation, and microangiopathy. We present the renal histological findings from a patient who developed acute kidney injury and de novo nephrotic syndrome, highly suggestive of acute IgA-dominant infection-associated glomerulonephritis (IgADIAGN) after SARS-CoV-2 infection, as evidenced by the presence of this virus detected in the renal tissue of the patient via immunohistochemistry assay. In summary, we document the first case of IgA-DIAGN associated to SARS-CoV-2. Thus, SARS-CoV-2 S may act as a super antigen driving the development of multisystem inflammatory syndrome as well as cytokine storm in patients affected by COVID-19, reaching the glomerulus and leading to the development of this novel IgA-DIAGN

POS-255 EFFECT OF DAPAGLIFLOZIN ON BLOOD PRESSURE IN PATIENTS WITH CKD: A PRE-SPECIFIED ANALYSIS FROM DAPA-CKD

Introduction: Hypertension is common in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors decrease blood pressure in patients with type 2 diabetes, but the consistency and magnitude of blood pressure lowering with dapagliflozin in patients with CKD is unknown. We performed a pre-specified analysis of the DAPA-CKD trial to investigate the effect of dapagliflozin on systolic blood pressure in patients with CKD, with and without type 2 diabetes. Methods: We randomized 4,304 adults with baseline eGFR 25–75 mL/min/1.73m2and urinary albumin-to-creatinine ratio (UACR) 200–5,000 mg/g to either dapagliflozin 10 mg or placebo once daily; median follow-up was 2.4 years. The primary outcome was a composite of sustained ≥50% eGFR decline, end-stage kidney disease, or death from a kidney or cardiovascular cause. Change in systolic blood pressure was a pre-specified endpoint. Subgroup analyses were performed according to baseline type 2 diabetes status. Results: Baseline mean (SD) systolic blood pressure was 137.1 mmHg (17.4); in participants with and without type 2 diabetes 139.2 mmHg (17.3) and 132.6 mmHg (16.7), respectively. By week 2, dapagliflozin compared to placebo reduced systolic blood pressure by 3.6 mmHg (95%CI 2.8, 4.4; p\u3c0.001), an effect maintained over the duration of the trial, with similar reductions in patients with and without type 2 diabetes (Table). The reduction in systolic blood pressure with dapagliflozin explained 7.6% (95%CI 1.8, 20.9) of the effect on the primary composite outcome, with similar proportions explained in patients with and without type 2 diabetes. Conclusions: In participants with CKD, dapagliflozin lowered systolic blood pressure with a consistent effect in participants with and without type 2 diabetes. The modest reduction in blood pressure explained a small proportion of the benefit of dapagliflozin on the primary outcome. Conflict of interest Potential conflict of interest: HLH received grant funding and honoraria for consultancy as a member of the steering committee of the DAPA-CKD trial from AstraZeneca. Honoraria for steering committee membership paid to his institution from Janssen, Gilead, Bayer, Chinook, CSL Pharma honoraria for consultancy paid to his institution from Abbvie, Boehringer Ingleheim, Retrophin, Novo Nordisk honoraria for advisory board participation paid to his institution from Janssen, Merck, Mitsubishi Tanabe and Munipharma lecture fees received from AstraZeneca and Mitsubishi Tanabe and grant support received from Boehringer Ingelheim

Antithrombotic Therapy in Elderly Patients with Acute Coronary Syndromes

The treatment of acute coronary syndrome (ACS) in elderly patients continues to be a challenge because of the characteS.G.B.ristics of this population and the lack of data and specific recommendations. This review summarizes the current evidence about critical points of oral antithrombotic therapy in elderly patients. To this end, we discuss the peculiarities and differences reported referring to dual antiplatelet therapy (DAPT) in ACS management in elderly patients and what might be the best option considering these population characteristics. Furthermore, we analyze antithrombotic strategies in patients with atrial fibrillation (AF), with a particular focus on those cases that also present coronary artery disease (CAD). It is imperative to deepen our knowledge regarding the management of these challenging patients through real-world data and specifically designed geriatric studies to help resolve the questions remaining in their disease management

Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO2 study

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Efecto de la forma de presentación de los resultados en los ensayos clínicos en la intención de prescribir en atención primaria: un ensayo clínico ruzado en Ourense

Fundamento: Actualmente se acepta que el mayor nivel de evidencia científica lo proporcionan los metaanálisis y los ensayos clínicos aleatorios. Dada la existencia de diversas formas de presentación de los resultados de ensayos clínicos, el objetivo de este trabajo es determinar si dicha presentación influye en la intención de prescripción de los médicos de Atención Primaria. Métodos: Ensayo clínico aleatorizado, multicéntrico y cruzado. Tras un muestreo aleatorio de 8 Equipos de Atención Primaria de la provincia de Ourense (España), se entrevistó a dos grupos de médicos de familia (nA = 45 y nB = 51) con un cuestionario en el que se reflejaban los datos de cinco ensayos clínicos publicados (tres sobre prevención de patología cardiovascular, uno sobre beneficio cognitivo en un síndrome demencial y otro sobre prevención de fracturas en ancianos). A un grupo se le presentaban los datos como reducción relativa del riesgo y al otro como número necesario de personas a tratar. Se preguntaban además edad, sexo y años de ejercicio. Tras un período de blanqueo de 3 semanas se invirtió la intervención. La intención de prescribir se recogió en una escala tipo Likert graduada de 0 a 10. Se utilizaron pruebas de c2, t de Student simple o para datos apareados y correlación de Pearson según cumpliera, con un error a de 0,05. Resultados: No se observaron diferencias respecto a sexo, edad o experiencia profesional. Respecto al efecto global, excepto en uno de los ensayos presentados, no se encontraron diferencias significativas en la intención de prescripción de los fármacos implicados en función de la forma de presentación de los datos: ensayo A: IC95% (- 1,55~0,17), B: IC95% (-2,75 ~ -1,20), C: IC95% (-0,16~1,65), D: IC95% (-0,30~1,44), E: IC95% (-1,22 ~ 0,35). Conclusiones: La presentación de los datos de los ensayos clínicos no influye por sí sola en la intención de prescripción de medicamentos

Efecto de la forma de presentación de los resultados en los ensayos clínicos en la intención de prescribir en atención primaria: un ensayo clínico ruzado en Ourense

Fundamento: Actualmente se acepta que el mayor nivel de evidencia científica lo proporcionan los metaanálisis y los ensayos clínicos aleatorios. Dada la existencia de diversas formas de presentación de los resultados de ensayos clínicos, el objetivo de este trabajo es determinar si dicha presentación influye en la intención de prescripción de los médicos de Atención Primaria. Métodos: Ensayo clínico aleatorizado, multicéntrico y cruzado. Tras un muestreo aleatorio de 8 Equipos de Atención Primaria de la provincia de Ourense (España), se entrevistó a dos grupos de médicos de familia (nA = 45 y nB = 51) con un cuestionario en el que se reflejaban los datos de cinco ensayos clínicos publicados (tres sobre prevención de patología cardiovascular, uno sobre beneficio cognitivo en un síndrome demencial y otro sobre prevención de fracturas en ancianos). A un grupo se le presentaban los datos como reducción relativa del riesgo y al otro como número necesario de personas a tratar. Se preguntaban además edad, sexo y años de ejercicio. Tras un período de blanqueo de 3 semanas se invirtió la intervención. La intención de prescribir se recogió en una escala tipo Likert graduada de 0 a 10. Se utilizaron pruebas de c2, t de Student simple o para datos apareados y correlación de Pearson según cumpliera, con un error a de 0,05. Resultados: No se observaron diferencias respecto a sexo, edad o experiencia profesional. Respecto al efecto global, excepto en uno de los ensayos presentados, no se encontraron diferencias significativas en la intención de prescripción de los fármacos implicados en función de la forma de presentación de los datos: ensayo A: IC95% (- 1,55~0,17), B: IC95% (-2,75 ~ -1,20), C: IC95% (-0,16~1,65), D: IC95% (-0,30~1,44), E: IC95% (-1,22 ~ 0,35). Conclusiones: La presentación de los datos de los ensayos clínicos no influye por sí sola en la intención de prescripción de medicamentos

Cumplimiento de los objetivos de control metabólico en diabetes mellitus en el medio rural de Ourense.

Fundamento: Valorar el cumplimiento de los objetivos de control metabólico en el paciente diabético tipo 2 en la atención primaria de ámbito rural, comparándolo con los valores recomendados por la American Diabetes Association (ADA) y el Grupo de estudio de la diabetes en atención primaria de salud (GEDAPS). Métodos: Estudio descriptivo transversal. Se calculó un tamaño muestral, basándose en la determinación de la hemoglobina glicosilada (HbA1c), de 119 individuos. Participaron 253 personas diabéticas tipo 2 con al menos 2 años de seguimiento en su centro de salud. Fueron seleccionados de forma aleatoria de 17 cupos médicos de 11 centros de salud rurales de la provincia de Ourense. A partir de la historia clínica se recogieron variables demográficas, factores de riesgo cardiovascular, tratamiento farmacológico, realización de autoanálisis, fondo de ojo, sensibilidad táctil, HbA1c, perfil lipídico, presión arterial e índice de masa corporal. Resultados: En el 44,3% de las personas de la muestra se había determinado HbA1c en los últimos 6 meses y presentaba un valor inferior a 7%. Un 21,2% tenía la presión arterial por debajo de 130/80, y el 19,8% un colesterol LDL menor de 100 mg/dl. Entre los pacientes con colesterol LDL mayor de 100 el 40,7% no recibía tratamiento hipolipemiante. El 20,4% de los que tenían cifras elevadas de presión arterial no recibía tratamiento hipotensor. Considerando estos tres factores el 2,5% alcanzaba los 3 objetivos de control. Un 36% realizaba tratamiento antiagregante con ácido acetil salicilico. Conclusiones: Se constata un importante déficit tanto en la frecuencia de los controles realizados por los profesionales sanitarios como en el número de intervenciones realizadas para conseguir los objetivos propuestos, con resultados muy inferiores a lo recomendado en las guías de práctica clínica