Safe and Successful Treatment With Pcsk9 Inhibitors in Hypercholesterolemia and Renal Transplantation: A Case Report.

BACKGROUND: Patients with chronic kidney disease (CKD) are more prone to cardiovascular disease (CVD) risks, including CVD-derived sudden death. Additionally, patients with CKD also develop lipid metabolism abnormalities. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) are drugs capable of reducing CVD risk in patients with CKD, but their efficacy is scarcely assessed in transplant patients. CASE PRESENTATION: Here, we report a case of a 74-year-old man undergoing nephrology follow-up for a cadaver donor kidney transplant. The patient described an atorvastatin allergic reaction after an acute coronary syndrome. Because the patient had a very high risk for CVD, alirocumab was substituted for atorvastatin. The patient showed a well-tolerated and effective response and stable everolimus levels. CONCLUSION: PCSK9i may be considered a pharmacologic option for treating lipid metabolism disorder and reducing low-density lipoprotein cholesterol in transplant recipients.

Estudio observacional retrospectivo de persistencia de infección por SARS-CoV-2 en pacientes tratados previamente con rituximab / Retrospective observational study of the persistence of SARS-CoV-2 infection in patients previously treated with rituximab

Introducción. La inmunodepresión inducida por rituximabpodría ser un factor de riesgo de mortalidad por COVID-19. Elobjetivo del estudio fue describir la prevalencia de infecciónpor SARS-CoV-2 en pacientes que habían recibido rituximab yconocer si conduce a una mayor persistencia del virus.Material y métodos. Estudio observacional retrospectivo depacientes que recibieron rituximab en los 6 meses previos al inicio dela pandemia, analizándose la presencia de infección. Se recogieronlas siguientes variables: edad, sexo, enfermedades previas, factoresde riesgo para COVID-19, dosis recibidas de rituximab, resultados delos test diagnósticos, hospitalización, tipo de soporte ventilatorio,desarrollo de eventos tromboembólicos y tratamiento recibido. Serealizó un análisis descriptivo de todas las variables y se compararonpacientes que se habían infectado (C+) y los que no (C-).Resultados. 68 pacientes habían recibido rituximab (mediana de dosis acumulada: 4.161mg (2.611–8.187,5)), 54,4%hombres con edad media de 60,8 años (15,7; 25-87). Se confirmó C+ en 22 pacientes, entre los cuales existían los siguientes antecedentes: 45,5% hipertensión arterial, 36,4% DiabetesMellitus, 31,8% tabaquismo/exfumador, 22,7% neumopatía,13,6% cardiopatía y 4,5% obesidad. No se apreciaron diferencias estadísticamente significativas entre C+ y C-. Sólo 2 pacientes C+ desarrollaron inmunidad y 10 de ellos (45,5%) nonegativizaron PCR a la finalización del seguimiento. No se encontró asociación con la dosis acumulada de rituximab. La tasade mortalidad en la C+ fue de 22,7%.Conclusiones. En nuestros pacientes tratados con rituximab y con infección por SARS-CoV2 se observó una peorevolución y una mayor persistencia de la infección, por lo quedebería valorarse el uso de otras alternativas durante la pandemia, ya que la disminución de la función de células B podríaproducir un mayor riesgo de evolución fatal por COVID-19. (AU)

Introduction. Rituximab-induced immunosuppressioncould be a risk factor for mortality from COVID-19. The aimof the study was to describe the prevalence of SARS-CoV-2infection in patients who have received rituximab and its association with a persistent viral infectionMaterial and methods. Retrospective observationalstudy of patients who received rituximab in the 6 monthsbefore to the onset of the pandemic. We analyzed thepresence of infection and associated them with demographicvariables, pathological history related to an increased riskof developing severe COVID-19, the doses of rituximabreceived, the type of ventilatory support, thromboembolicevents, and the treatment received. A descriptive analysis ofall the variables was carried out and infected and uninfectedpatients were compared.Results. We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611–8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C +was confirmed for 22 patients. Of these, 45.5% had high bloodpressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker,22.7% lung disease, 13.6% heart disease and 4.5% obesity.There were no statistically significant differences between C+and C-. Only 2 patients developed immunity. For 10 patients(45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose ofrituximab. The mortality rate was 22.7% in the C+.Conclusions. We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, becauseof patients with decreased B-cell function may have high riskof fatal progression from COVID-19. (AU)

Vacunación sublingual con bacterias inactivadas en pacientes nefrológicos con infección urinaria recurrente: experiencia en un centro de España / Sublingual vaccination with inactivated bacteria in recurrent urinary tract infection of nephrologic patients: experience in a center in Spain

Resumen Introducción: las infecciones del tracto urinario (ITU) son frecuentes en pacientes con enfermedad renal crónica (ERC). Una opción de tratamiento cuando estas infecciones son recurrentes es la vacunación bacteriana sublingual. Objetivo: determinar la respuesta a la vacunación bacteriana sublingual en pacientes nefrológicos con ITU recurrente. Materiales y métodos: estudio cuasi experimental en el que se evaluó la evolución en 15 meses de los pacientes con ITU recurrente que asistieron a consulta externa de nefrología. Tras recibir tratamiento antibiótico según antibiograma para cada ITU, los participantes tomaron un ciclo de la vacuna sublingual bacteriana Uromune® durante tres meses. Se recogieron datos sociodemográficos y sobre factores de riesgo asociados, análisis de sangre y orina, episodios de ITU en los seis meses previos y posteriores, microorganismos causantes, tratamiento antibiótico concomitante, respuesta al tratamiento y resolución de la ITU. Resultados: se incluyeron 26 pacientes (80,8 % mujeres) con una media de edad de 61,9±18,4 años, de los cuales el 46,2 % tenía diabetes y el 47,7 %, afectación de la función renal. La media de ITU fue 3,62±1,77 (rango: 1 -7) antes de la vacuna y de 1,69±1,77 (rango: 0-5) después. Se recogieron 184 urocultivos: 74,9 % positivos, 16,9 % negativos y 8,2 % contaminados. Las bacterias más frecuentes fueron Escherichia coli (55,4 %), Enterococcus faecalis (6 %) y Enterobacter cloacae (2,7 %). El 50 % de los participan- tes presentó síndrome miccional, que se asoció inversamente con la edad (p<0,05). El 26,9 % no volvió a tener ITU y el 73,1 % tuvo menos episodios. Los pacientes con ERC avanzada (estadios IV-V) respondieron peor a la vacuna (92,9 % vs 50 %, p=0,025). Conclusiones: la vacunación bacteriana sublingual es una buena opción de tratamiento para la ITU recurrente de pacientes con ERC, siendo más eficaz en los que presentan mejor función renal.

Abstract Introduction: Urinary tract infections (UTIs) are common in patients with chronic kidney disease. A treatment option in recurrent UTI is sublingual bacterial vaccination. The objective of this study was to determine the response to vaccination in nephrologic patients with recurrent UTI. Method: Quasi-experimental study before-after (15 months) in patients with recurrent UTI from the outpatient nephrology consultation. After receiving antibiotic treatment for each UTI, patients took one cycle of the sublingual bacterial vaccine Uromune? for three months. Sociodemographic data, associated risk factors, analysis, UTI in the previous and subsequent six months, microorganisms, concomitant antibiotic treatment, response to treatment and resolution of UTI were collected. Results: Twenty-six patients (80.8% female) of 61.9 ±18.4 years, 46.2% with diabetes and 47.7% with impaired renal function were included. The episodes of UTI were 3.62 ±1.77 (1-7) before and 1.69 ± 1.77 (0-5) after vaccination. In total, 184 urine cultures were collected: 74.9% positive, 16.9% negative and 8.2% contaminated. The most frequent bacteria were Escherichia coli (55.4%), Enterococcus faecalis (6%) and Enterobacter cloacae (2.7%). Fifty percent had voiding syndrome, which was inversely associated with age (p < 0.05); 26.9% did not have a UTI again and 73.1% had fewer episodes. Patients with advanced chronic disease (stages 4-5) reponded worse to the vaccine (92.9% vs 50%, p =0.025). Conclusions: Sublingual bacterial vaccination is a good treatment option in recurrent UTI of nephrologic patients, being more effective in those with better renal function.

Lesiones gastrointestinales en pacientes con enfermedad renal crónica y anemia / Gastrointestinal lesions in chronic kidney disease patients with anaemia

Introducción: A pesar de la frecuencia con que la anemia está presente en los pacientes con enfermedad renal crónica (ERC), su relación con lesiones gastrointestinales no ha sido estudiada. Método: Estudio observacional analítico transversal de un año de reclutamiento para determinar la prevalencia de lesiones gastrointestinales endoscópicas y los factores de riesgo asociados en pacientes asintomáticos con ERC estadios 1-5 y anemia que presentaban un test inmunoquímico cualitativo de sangre oculta en heces positivo. Resultados: Se analizaron 9.658 pacientes con ERC, de los que 286 (2,9%) presentaban anemia; 198 tuvieron un test de sangre oculta en heces positivo (47% varones, 71,1 ± 11,8 años). El estudio endoscópico reveló 255 lesiones, con al menos una lesión en el 68,2%, siendo las más prevalentes: pólipos colorrectales adenomatosos (39,6%), lesiones agudas de la mucosa gástrica (22,6%), lesiones neoplásicas (15,1%), angiodisplasias (14,4%), esofagitis (8,4%), enfermedad inflamatoria intestinal (4,8%) y colitis isquémica (3,1%). La uremia y el ácido acetilsalicílico fueron identificados como factores de riesgo de lesiones agudas de la mucosa gástrica. Las angiodisplasias se relacionaron con el enolismo, el mayor estadio de ERC, la anemia y la ausencia de respuesta a agentes estimulantes de la eritropoyesis. La edad y la anemia refractaria constituyeron factores de riesgo de pólipos adenomatosos y cáncer colorrectal. Conclusión: Los pacientes renales con anemia podrían beneficiarse de un estudio endoscópico debido a la alta prevalencia de lesiones gastrointestinales que presentan, particularmente pólipos adenomatosos y cáncer colorrectal, más frecuentes en los mayores de 50 años con ERC estadios 3-5

Introduction: Despite the frequency with which anaemia is present in patients with chronic kidney disease (CKD), its relationship with gastrointestinal lesions has not been studied. Method: A cross-sectional, analytical, observational study involving one year of recruitment was carried out to determine the prevalence of endoscopic gastrointestinal lesions and associated risk factors in asymptomatic patients with chronic kidney disease stages 1-5 and anaemia who had a positive qualitative immunochemical faecal occult blood test. Results: A total of 9,658 patients with CKD were analysed, of which 286 (2.9%) had anaemia; 198 had a positive faecal occult blood test (47% male, 71.1 ± 11.8 years). The endoscopic study revealed 255 lesions, with at least one lesion in 68.2% of patients, with the most prevalent being: adenomatous colorectal polyps (39.6%), acute lesions of the gastric mucosa (22.6%), neoplastic lesions 15.1%), angiodysplasia (14.4%), oesophagitis (8.4%), inflammatory bowel disease (4.8%) and ischaemic colitis (3.1%). Uraemia and acetylsalicylic acid were identified as risk factors for acute gastric mucosal lesions. Angiodysplasia was associated with alcoholism, a more advanced stage of chronic kidney disease, anaemia, and lack of response to erythropoiesis-stimulating agents. Age and refractory anaemia were risk factors for adenomatous polyps and colorectal cancer. Conclusion: Renal patients with anaemia could benefit from an endoscopic study due to their high prevalence of gastrointestinal lesions, particularly adenomatous polyps and colorectal cancer, which are more common in those over 50 years of age with CKD stages 3-5

Gastrointestinal lesions in chronic kidney disease patients with anaemia. / Lesiones gastrointestinales en pacientes con enfermedad renal crónica y anemia.

INTRODUCTION: Despite the frequency with which anaemia is present in patients with chronic kidney disease (CKD), its relationship with gastrointestinal lesions has not been studied. METHOD: A cross-sectional, analytical, observational study involving one year of recruitment was carried out to determine the prevalence of endoscopic gastrointestinal lesions and associated risk factors in asymptomatic patients with chronic kidney disease stages 1-5 and anaemia who had a positive qualitative immunochemical faecal occult blood test. RESULTS: A total of 9,658 patients with CKD were analysed, of which 286 (2.9%) had anaemia; 198 had a positive faecal occult blood test (47% male, 71.1±11.8 years). The endoscopic study revealed 255 lesions, with at least one lesion in 68.2% of patients, with the most prevalent being: adenomatous colorectal polyps (39.6%), acute lesions of the gastric mucosa (22.6%), neoplastic lesions 15.1%), angiodysplasia (14.4%), oesophagitis (8.4%), inflammatory bowel disease (4.8%) and ischaemic colitis (3.1%). Uraemia and acetylsalicylic acid were identified as risk factors for acute gastric mucosal lesions. Angiodysplasia was associated with alcoholism, a more advanced stage of chronic kidney disease, anaemia, and lack of response to erythropoiesis-stimulating agents. Age and refractory anaemia were risk factors for adenomatous polyps and colorectal cancer. CONCLUSION: Renal patients with anaemia could benefit from an endoscopic study due to their high prevalence of gastrointestinal lesions, particularly adenomatous polyps and colorectal cancer, which are more common in those over 50 years of age with CKD stages 3-5.

Estudio multicéntrico español PIBHE: prevalencia e inmunización de la infección crónica por el virus de la hepatitis B en pacientes en hemodiálisis en España / Spanish multicentre PIBHE study: Prevalence and immunization of chronic hepatitis B in haemodialysis patients in Spain

Introducción: El estudio PIBHE, promovido por la Asociación Española de Hígado y Riñón y el Grupo de Virus en Diálisis de la Sociedad Española de Nefrología, es el primer estudio que determina la situación de los pacientes en hemodiálisis con infección crónica por el VHB y la inmunización frente a la vacuna. Método: Estudio nacional multicéntrico, observacional, de corte transversal, entre enero de 2013 y de 2014. Se envió un cuaderno de recogida de datos a todos los servicios de nefrología y unidades extrahospitalarias de hemodiálisis de España, para que lo cumplimentaran a partir de la historia clínica del paciente, tras consentimiento informado. Los datos se incluyeron en una base central. Resultados: Participaron 215 centros (15.645 pacientes), con una prevalencia del VHB del 1,03%. El 7,2% de los pacientes VHB(+) estaba coinfectado por el VHC o VIH. La carga viral era inferior a 2.000 UI/ml en el 80%. Los niveles de GOT y GPT fueron de 19,1±10,1 y 15,9±9,6 UI/ml, respectivamente. La biopsia hepática se había realizado en el 7,1%. El 30% había recibido tratamiento antiviral, que se había suspendido en el 12,5%. El más empleado había sido entecavir (13,3%), seguido de lamivudina (10%), adefovir y tenofovir (6,7%) e interferón (3,3%). El 34,5% era candidato a trasplante renal y el 6,9% no había sido evaluado. Se encontraban en seguimiento por un digestólogo el 64,3%. No había sido vacunado el 27,2% de los pacientes VHB(−) sin inmunización. Se emplearon 14 pautas distintas de vacunación, con un 58,8% de inmunización. La media de anti-HBs se situaba en 165,7±297,8mUI/ml. El 72,7% de los pacientes había recibido un ciclo de vacunación; el 26,4%, 2 ciclos; el 1,0%, 3 ciclos y el 11,6%, una dosis de recuerdo. El 28,3% tuvo una respuesta pobre (anti-HBs 10-99mUI/ml); el 22,4%, una respuesta óptima (anti-HBs 100-999mUI/ml); y el 7,9%, una respuesta excelente (anti-HBs≥1.000mUI/ml). La edad se asoció significativamente con la respuesta a la vacunación, de manera que los pacientes que no respondieron tenían una edad media significativamente mayor que los pacientes que obtuvieron cualquier tipo de respuesta (p<0,05). La mayor probabilidad de conseguir una respuesta inmunitaria se alcanzaba con 4 dosis de 40mcg de vacuna adyuvada (OR: 7,3; IC 95%: 3,4-15,7), a igualdad de edad y número de revacunaciones y recuerdos. La edad, la vacuna adyuvada, la dosis y el esquema de vacunación influían en la respuesta inmunitaria y en el título de anti-HBs alcanzado (p<0,05). Conclusión: La prevalencia de la infección crónica por el VHB en hemodiálisis en España es baja, así como las tasas de inmunización frente a este virus. Los esquemas de vacunación empleados son muy diversos y se han correlacionado con la respuesta inmunitaria, por lo que sería necesario protocolizar la pauta más eficaz para aumentar la inmunización en estos pacientes (AU)

Introduction: The PIBHE study, promoted by the Spanish Liver and Kidney Association and the Dialysis Virus Group of the Spanish Society of Nephrology, is the first study to determine the status of haemodialysis patients with chronic HBV infection and the immunisation against the vaccine. Method: The study has a national multicentre, observational, cross-sectional design and was carried out between January 2013 and 2014. A data collection folder was sent to all the nephrology departments and outpatient haemodialysis units in Spain, to be completed based on patient medical files after informed consent. The data were recorded in a central database. Results: A total of 215 centres participated (15,645 patients), with an HBV prevalence of 1.03%. HCV or HIV was present in 7.2% of the HBV(+) patients. Viral load was below 2,000 IU/ml in 80%. GOT and GPT levels were 19.1±10.1 and 15.9±9.6 IU/ml, respectively. Liver biopsy was performed in 7.1%. Antiviral treatment was prescribed in 30% and suspended in 12.5%: entecavir (13.3%), lamivudine (10%), adefovir and tenofovir (6.7%), and interferon (3.3%). A total of 34.5% were candidates for renal transplantation and 6.9% had not been evaluated; 64.3% were followed up by a gastroenterologist; 27.2% of HBV(−) patients without immunisation had not been vaccinated. Fourteen different immunisation schedules had been used, with an immunisation rate of 58.8%. Mean anti-HBs stood at 165.7±297.8mIU/ml. A total of 72.7% of patients had received a vaccination course; 26.4%, 2 cycles; 1.0%, 3 cycles; and 11.6%, a booster dose. A total of 28.3% had a poor response (anti-HBs 10-99mIU/ml); 22.4%, an optimal response (anti-HBs 100-999mIU/ml); and 7.9%, an excellent response (anti-HBs ≥ 1,000mIU/ml). Age was significantly associated with response to vaccination; the mean age of nonresponders was significantly higher than patients who had a response of any kind (P<.05). The highest probability of an immune response was achieved with 4 doses of 40 mcg of adjuvanted vaccine (OR: 7.3; 95% CI 3.4 to 15.7), for the same age and number of cycles and boosters. Age, adjuvanted vaccine, dose and vaccination schedule influenced the immune response and the anti-HBs titres reached (P<.05). Conclusion: The prevalence of chronic HBV infection in haemodialysis in Spain is low and so are the rates of immunisation against the virus. The vaccination schedules used are very diverse and have been observed to correlate with the immune response. It would therefore be necessary to establish a protocol for the most effective vaccination schedule to increase immunisation in these patients (AU)

Spanish multicentre PIBHE study: Prevalence and immunization of chronic hepatitis B in haemodialysis patients in Spain.

INTRODUCTION: The PIBHE study, promoted by the Spanish Liver and Kidney Association and the Dialysis Virus Group of the Spanish Society of Nephrology, is the first study to determine the status of haemodialysis patients with chronic HBV infection and the immunisation against the vaccine. METHOD: The study has a national multicentre, observational, cross-sectional design and was carried out between January 2013 and 2014. A data collection folder was sent to all the nephrology departments and outpatient haemodialysis units in Spain, to be completed based on patient medical files after informed consent. The data were recorded in a central database. RESULTS: A total of 215 centres participated (15,645 patients), with an HBV prevalence of 1.03%. HCV or HIV was present in 7.2% of the HBV(+) patients. Viral load was below 2,000 IU/ml in 80%. GOT and GPT levels were 19.1±10.1 and 15.9±9.6 IU/ml, respectively. Liver biopsy was performed in 7.1%. Antiviral treatment was prescribed in 30% and suspended in 12.5%: entecavir (13.3%), lamivudine (10%), adefovir and tenofovir (6.7%), and interferon (3.3%). A total of 34.5% were candidates for renal transplantation and 6.9% had not been evaluated; 64.3% were followed up by a gastroenterologist; 27.2% of HBV(-) patients without immunisation had not been vaccinated. Fourteen different immunisation schedules had been used, with an immunisation rate of 58.8%. Mean anti-HBs stood at 165.7±297.8mIU/ml. A total of 72.7% of patients had received a vaccination course; 26.4%, 2 cycles; 1.0%, 3 cycles; and 11.6%, a booster dose. A total of 28.3% had a poor response (anti-HBs 10-99mIU/ml); 22.4%, an optimal response (anti-HBs 100-999mIU/ml); and 7.9%, an excellent response (anti-HBs ≥ 1,000mIU/ml). Age was significantly associated with response to vaccination; the mean age of nonresponders was significantly higher than patients who had a response of any kind (P<.05). The highest probability of an immune response was achieved with 4 doses of 40 mcg of adjuvanted vaccine (OR: 7.3; 95% CI 3.4 to 15.7), for the same age and number of cycles and boosters. Age, adjuvanted vaccine, dose and vaccination schedule influenced the immune response and the anti-HBs titres reached (P<.05). CONCLUSION: The prevalence of chronic HBV infection in haemodialysis in Spain is low and so are the rates of immunisation against the virus. The vaccination schedules used are very diverse and have been observed to correlate with the immune response. It would therefore be necessary to establish a protocol for the most effective vaccination schedule to increase immunisation in these patients.

On the clinical evidence leading to tetrazepam withdrawal.

INTRODUCTION: In July 2013, the European Medicines Agency suspended the marketing authorizations of tetrazepam across the European Union. Herein, we examine the various kinds of adverse drug reactions (ADRs) reported to be associated with tetrazepam. AREAS COVERED: We undertook a two-sided systematic approach. First, we conducted a search in Medline for all studies that have published about tetrazepam ADRs in peer-reviewed journals. Second, we collected tetrazepam ADRs from pharmacovigilance system databases. Our study reveals discrepancies in the information provided by these two different sources, both in the number of cases reported as well as in the kind of reported ADRs. Whereas cutaneous alterations are the only ADRs reported in peer-reviewed journals, pharmacovigilance system databases include others (hepatobiliary, neurological and psychiatric). EXPERT OPINION: We noted the lack of randomized controlled clinical trials evaluating tetrazepam efficiency and safety. We failed to find a turning point in the amount of ADRs reported following tetrazepam withdrawal to underpin the validity of the withdrawal. We stress the importance of a better communication of knowledge in scientific literature, pharmacovigilance agencies, and from doctors to prevent marketed usage of drugs with well-established side effects during long periods.

Réquiem por el tetracepam / Requiem for tetrazepam

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Requiem for tetrazepam.

TITLE: Requiem por el tetracepam.