Eligibility test for advanced chronic kidney disease: Revision and proposal.

Nowadays, chronic kidney disease (CKD) prevalence keeps increasing worldwide. The management of these patients usually requires renal replacement therapy (RRT). However, the complexity of patients' profiles comprises a great challenge to overcome. During the last decades, CKD units have been developed to offer multidisciplinary and coordinated attention to patients, helping in the decision-making of the RRT. Nevertheless, there is a huge variability in the performance and organization of care practice, implying an existing necessity to homogenize the RRT modality chosen. We propose a test composed of two parts: one to be completed by the medical staff (to evaluate contraindications for the different RRT techniques) and another by the patient or nursing staff (to consider patients' preferences). In this sense, it would be possible to have a common and useful tool to complement patient education in RRT, as well as sharing decision-making in the ACKD units taking into account patient preferences.

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.

COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry.

Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN. Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use. Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR. Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.

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.

Infección del tracto urinario en la enfermedad renal crónica / Urinary tract infection in chronic kidney disease patients

Resumen Las infecciones en personas con enfermedad renal crónica son una causa importante de morbimortalidad. Los pacientes renales presentan factores de riesgo específicos para la adquisición de infecciones, que además suelen ser más graves, de progresión más rápida y de resolución más lenta que en sujetos sanos. La infección del tracto urinario en esta población es a menudo complicada debido a la presencia de diabetes, microorganismos multirresistentes, anomalías anatómicas o funcionales del tracto urinario, alteraciones metabólicas y el uso frecuente de sonda vesical. Las infecciones urinarias ocasionan una de las tasas más altas de hospitalización en diálisis y son muy prevalentes en el trasplante renal. Este trabajo tiene como objetivo revisar la literatura publicada sobre la etiología, el diagnóstico microbiológico y el tratamiento de las infecciones del tracto urinario en pacientes con enfermedad renal crónica.

Abstract Infections in chronic kidney disease patients are a major cause of morbidity and mortality. Renal patients have specific risk factors for acquiring infections, which also tend to be more severe and have a more rapid progression and slower resolution than in the healthy individuals. Urinary tract infection in renal patients is often complicated due to the presence of diabetes, multiresistant microorganisms, anatomic or functional abnormalities of the urinary tract, metabolic disturbances and the frequent use of urinary catheters. It causes one of the highest rates of hospitalization among dialysis patients and is highly prevalent in kidney transplantation. The aim of this work is to review the etiology, microbiological diagnosis and treatment of urinary tract infections in chronic kidney disease patients.

Adjuvanted recombinant HBV vaccine (HBV-AS04) is effective over extended follow-up in dialysis population. An open-label non randomized trial.

BACKGROUND: Patients on regular dialysis show a poor response to hepatitis B vaccine due to uremia. A recombinant HB vaccine (containing an improved adjuvant system AS04, HBV-AS04) has been licensed but the evidence on its efficacy and safety in dialysis population over the long term is extremely limited. AIM: We have measured antibody (anti-HBs) persistence for up to 72 months in a large cohort of patients on long-term dialysis (with susceptibility to HBV infection) who underwent vaccination with HBV-AS04 vaccine. METHODS: Patients were prospectively recruited to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle). Two vaccine schedules were adopted: 0,1,2, and 3 month (n=217 patients) and 0,1,2, and 6 month (n=31 patients). Anti-HBs antibody concentrations were tested at 1,2,3, 4, 7 and 12 months and then every year up to 72 months. Multivariate analysis was made to find the baseline parameters that were associated with the immune response to HBV-AS04 vaccine. RESULTS: Two hundred and seventy-two patients were included and 248 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 81.5% (202/248) (mean anti-HBs antibody titers, 384.9±391.9mIU/mL), according to per-protocol analysis. On the grounds of univariate analysis, age was lower in responder than non- responder patients to HBV AS04 even if no statistical significance was achieved (P=0.09). The sero-protection rate at month 72 was 77% (7/9) (anti-HBs antibody titers, 184.9±360.1mIU/mL, P=0.001). Multivariate analysis found a relationship between sero-response rate and age (P=0.04). No major side effects and no de novo HBV episodes were observed. CONCLUSIONS: Our open-label nonrandomized trial performed in a 'real-world' practice showed the persistence of anti-HBs antibody among responder patients over a very long follow-up. Studies with longer observation periods are under way.

Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease / Eficacia y seguridad de los antivíricos de acción directa para el VHC en la nefropatía crónica de leve a moderada

BACKGROUND AND AIMS: The advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' cohort of patients with CKD. METHODS: We performed an observational single-arm multi-centre study in a large (n = 198) cohort of patients with stage 1-3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities. RESULTS: The average baseline eGFR (CKD-EPI equation) was 70.06 ± 20.1 mL/min/1.72 m2; the most common genotype was HCV 1b (n = 93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n = 40), simeprevir ± daclatasvir (n = 2), and sofosbuvir-based combinations (n = 147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures - eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n = 12), which required discontinuation or dose reduction of ribavirin in some cases (n = 6); deterioration of kidney function occurred in three (1.7%). CONCLUSIONS: All-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a 'real-world' clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population

ANTECEDENTES Y OBJETIVOS: La aparición de los antivíricos de acción directa (AAD) promete cambiar el tratamiento de la infección por el virus de la hepatitis C (VHC) en los pacientes con nefropatía crónica (NC), un grupo de pacientes en el que el tratamiento de la hepatitis C siempre supuso una dificultad. Se investiga la seguridad y la eficacia de los antivíricos de acción directa, sin interferones orales, en todos los casos para el tratamiento de la hepatitis C en una cohorte en condiciones reales de pacientes con NC. MÉTODOS: Se llevó a cabo un estudio multicéntrico, de un solo grupo y observacional en una cohorte amplia (n = 198) de pacientes con NC en estadio 1-3 a los que se administró tratamiento antivírico con AAD para el VHC. El criterio principal de valoración fue la respuesta virológica sostenida (ARN sérico del VHC < 15 UI/ml, 12 semanas después de la finalización del tratamiento) (RVS12). Se recogieron los datos sobre acontecimientos adversos (AA) surgidos durante el tratamiento, AA graves y anomalías analíticas. RESULTADOS: La FGe inicial media (ecuación de CKD-EPI) fue de 70,06 ± 20,1 ml/min/1,72 m2; el genotipo más frecuente fue VHC 1b (n = 93; 51%). Se observó cicatrización hepática avanzada en 58 (46%) pacientes mediante elastografía transitoria. Se adoptaron 5 pautas: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), pauta de paritaprevir/ombitasvir/dasabuvir (PrOD) potenciada con ritonavir (n = 40), simeprevir ± daclatasvir (n = 2) y combinaciones basadas en sofosbuvir (n = 147). La tasa de RVS12 fue del 95,4% (IC del 95%: 93,8; 96,8%). Hubo 9 fracasos virológicos, 8 de ellos recidivantes. Se produjeron acontecimientos adversos en el 30% (51/168) de los pacientes, que se trataron clínicamente sin suspensión del tratamiento ni hospitalización. Uno de los AA más frecuentes fue la anemia (n = 12), que precisó la suspensión o la reducción de la dosis de ribavirina en algunos casos (n = 6); se produjo deterioro de la función renal en 3 casos (1,7%). CONCLUSIONES: El tratamiento sin interferón oral en todos los casos con AAD para el VHC crónico en la NC de leve a moderada fue eficaz y bien tolerado en un contexto de la práctica clínica real. Hay estudios en curso para abordar si la respuesta viral sostenida se traduce en una mejor supervivencia en esta población

Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease.

BACKGROUND AND AIMS: The advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' cohort of patients with CKD. METHODS: We performed an observational single-arm multi-centre study in a large (n=198) cohort of patients with stage 1-3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities. RESULTS: The average baseline eGFR (CKD-EPI equation) was 70.06±20.1mL/min/1.72m2; the most common genotype was HCV 1b (n=93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n=5), glecaprevir/pibrentasvir (n=4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n=40), simeprevir±daclatasvir (n=2), and sofosbuvir-based combinations (n=147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures - eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n=12), which required discontinuation or dose reduction of ribavirin in some cases (n=6); deterioration of kidney function occurred in three (1.7%). CONCLUSIONS: All-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a 'real-world' clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population.

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.

'Real-life' experience with direct-acting antiviral agents for hepatitis C virus in end-stage renal disease.

BACKGROUND AND AIMS: The advent of direct-acting antiviral agents promises to change the management of hepatitis C in patients with end-stage renal disease, a patient group where the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a 'real-world' group of patients with end-stage renal disease. METHODS: We performed a single-arm, multi-centre study in a cohort (n=30) of patients with advanced chronic kidney disease (mostly on dialysis) who underwent antiviral therapy with direct-acting antiviral agents. The primary end-point was sustained virologic response (serum hepatitis C virus RNA < 15 mIU/mL, 12 weeks after treatment ended). We collected data on on-treatment adverse events, serious adverse events and laboratory abnormalities. RESULTS: In total, 23 (77%) and 7 (23%) patients underwent regular dialysis and had chronic kidney disease at pre-dialysis stage, respectively. Six regimens were adopted: elbasvir/grazoprevir ( n = 6), ledipasvir/sofosbuvir ± ribavirin ( n = 4), PrOD regimens ± ribavirin ( n = 10), simeprevir + daclatasvir ( n = 3), sofosbuvir + daclatasvir ± ribavirin ( n = 3), sofosbuvir + ribavirin ( n = 4). The SVR12 rate was 90% (95% confidence interval, 74%; 96%). A total of 27 (90%) patients achieved SVR12; there were three virologic failures - two were non-responders and one had a viral breakthrough while on therapy. Adverse events occurred in 53% (16/30) (95% confidence interval, 0.39; 0.73) of patients and were managed clinically without discontinuation of therapy or hospitalization. The most common adverse event was anaemia ( n = 12) that required blood transfusions in seven individuals; deterioration of kidney function occurred in one (14%). CONCLUSION: All-oral, interferon-free therapy with direct-acting antiviral agents for chronic hepatitis C virus in advanced chronic kidney disease was effective and well tolerated in a 'real-life' clinical setting. Careful monitoring of haemoglobin and serum creatinine during therapy with direct-acting antiviral agents is suggested. Studies are under way to address whether sustained viral response translates into better survival in this population.

Recommendations for the treatment of hepatitis C virus infection in chronic kidney disease: a position statement by the Spanish association of the liver and the kidney.

Hepatitis C virus (HCV) infection is one of the main causes of liver cirrhosis worldwide. The long-term impact of HCV infection is highly variable, ranging from minimal histological changes to extensive fibrosis with hepatocellular carcinoma. The development of HCV drugs has increased dramatically in recent years, even in special populations such as chronic kidney disease patients. Classical treatment of chronic hepatitis C was based on the administration of interferon and ribavirin for 24-48 weeks, which was associated with a poor viral response and a high rate of side effects, especially in patients with a lower estimated glomerular filtration rate. The current high availability of the new direct-acting antivirals renders the classification of these agents for this special population necessary. The Spanish Association of the Liver and the Kidney has produced a position statement on the treatment of HCV infection in chronic kidney disease patients since the evidence to guide this treatment is scant and what evidence does exist is weak. The recommendations are based on the results of clinical trials and controlled studies conducted to date, with data published hitherto by the authors of these studies. Since the indications for treatment have been evaluated by other societies or are dependent on internal clinical protocols, the main goal of this position statement is to assist in decision-making when choosing a therapeutic option.

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.

Impact of isolated hepatitis C virus (HCV) core-specific antibody detection and viral RNA amplification among HCV-seronegative dialysis patients at risk for infection.

Amplification of hepatitis C virus (HCV) RNA from blood detected occult HCV infections in 30.9% of 210 HCV-seronegative dialysis patients with abnormal liver enzyme levels that had evaded standard HCV testing practices. Isolated HCV core-specific antibody detection identified three additional anti-HCV screening-negative patients lacking HCV RNA amplification in blood who were considered potentially infectious. Together, these findings may affect management of the dialysis setting.

Exocrine pancreatic insufficiency and chronic pancreatitis in chronic alcoholic liver disease: coincidence or shared toxicity?

OBJECTIVES: The aims of this study were to determine the prevalence of exocrine pancreatic insufficiency (EPI) and chronic pancreatitis (CP) in patients with chronic alcoholic liver disease and to analyze the possible associated factors. METHODS: This is an analytical observational study of cases and controls for a sample of patients with chronic alcoholic and nonalcoholic liver disease. Exocrine pancreatic insufficiency was diagnosed using the C mixed-triglyceride breath test. Patients with abdominal pain underwent endoscopic ultrasonography for CP evaluation using the Wiersema criteria. RESULTS: A total of 154 patients were included, 129 with alcoholic liver disease (83 with cirrhosis) and 25 with nonalcoholic liver disease. Exocrine pancreatic insufficiency was found in 55.2% versus 16.7% (P < 0.001), 70% of patients without cirrhosis compared with 46.2% of patients with cirrhosis had pancreatic insufficiency (P = 0.017), and 82.7% of patients with alcoholic liver disease and abdominal pain had CP (P < 0.001). Exocrine pancreatic insufficiency was associated with the male sex, alcohol intake, abdominal pain, degree of liver failure, and the absence of portal hypertension. Chronic pancreatitis was correlated with age younger than 55 years and abdominal pain. CONCLUSIONS: Patients with alcoholic liver disease had a high prevalence of EPI and CP; this prevalence was even higher in patients who have not yet developed cirrhosis with liver failure or portal hypertension.

Tratamiento con adalimumab en la amiloidosis secundaria a artritis reumatoide: a propósito de dos casos / Treatment with adalimumab in amyloidosis secondary to rheumatoid arthritis: two case reports

Las patologías reumatológicas, y en primer lugar la artritis reumatoidea (AR), siguen siendo unas de las principales causas de amiloidosis secundaria. La aparición de agentes biológicos como el adalimumab en el tratamiento precoz de la AR puede ser una alternativa eficaz para frenar el desarrollo y la progresión de la amiloidosis secundaria. No todos los pacientes responderán igual al tratamiento; debemos considerar la comorbilidad asociada, los factores de mal pronóstico para predecir la repuesta terapéutica y los posibles efectos adversos. Dentro de los efectos adversos de las terapias biológicas, hay que destacar el aumento de la tasa de infecciones letales y cuadros de insuficiencia cardíaca. Presentamos dos casos clínicos con amiloidosis renal secundaria a AR que han seguido un curso clínico diferente: nuestro primer caso tuvo una buena repuesta al adalimumab, mientras que el segundo caso evolucionó desfavorablemente después del inicio del tratamiento, falleciendo por complicaciones cardiovasculares (AU)

Rheumatological diseases and, firstly, rheumatoid arthritis (RA) remain a major cause of secondary amyloidosis. The emergence of biological agents such as adalimumab in the early treatment of RA can be an effective alternative to stop the development and progression of secondary amyloidosis. Not all patients will respond the same way to treatment; we must consider associated comorbidity, the poor prognosis factors for predicting therapeutic response and possible adverse effects. In the adverse effects of biological therapies, there has been an increase in the rate of lethal infections and congestive heart failure. We present two cases with renal amyloidosis secondary to RA who had a different clinical course: our 1st case had a good response to Adalimumab while the 2nd case evolved unfavourably after treatment, and died from cardiovascular complications (AU)

SHECTS multi-centre Spanish study: liver situation of patients with chronic hepatitis from HCV on renal replacement therapy with haemodialysis.

INTRODUCTION: The SHECTS study, approved by the Spanish Society of Nephrology, has the goal of analysing the level of examination and follow-up of patients with chronic hepatitis C virus (HCV) infections on haemodialysis, and to determine the current prevalence of these patients. METHOD: A national, multi-centre, cohort study carried out between September 2010 and September 2011. We sent a data collection folder to all Spanish haemodialysis units to include information regarding each centre and the nephrological/hepatological situation of their HCV-positive patients. RESULTS: A total of 187 haemodialysis units (71 hospital-based) participated in the study. The global prevalence of HCV was estimated at 5.6%. The most common cause of chronic kidney disease was glomerular (25%); of the 72.1% of patients who had undergone a renal biopsy, 23.2% had glomerulonephritis that could have been associated with HCV. Genotyping had not been carried out in 64%, liver ultrasound had not been applied in 61.3%, and liver biopsies were not performed in 87.7%. One-third of all patients received care from a gastroenterologist. Antiviral treatment was administered to 26.6% of patients, with a sustained viral response in 35.3% and suspension of treatment in 67.4%. CONCLUSION: The prevalence of HCV in patients on haemodialysis in Spain has decreased to the point of reaching similar rates to those of neighbouring countries. These patients receive incomplete analyses of liver condition, and individuals who receive antiviral treatment and untreated patients constitute a large proportion, despite having low viral loads and being candidates for kidney transplants.

Treatment with adalimumab in amyloidosis secondary to rheumatoid arthritis: two case reports.

Rheumatological diseases and, firstly, rheumatoid arthritis (RA) remain a major cause of secondary amyloidosis. The emergence of biological agents such as adalimumab in the early treatment of RA can be an effective alternative to stop the development and progression of secondary amyloidosis. Not all patients will respond the same way to treatment; we must consider associated comorbidity, the poor prognosis factors for predicting therapeutic response and possible adverse effects. In the adverse effects of biological therapies, there has been an increase in the rate of lethal infections and congestive heart failure. We present two cases with renal amyloidosis secondary to RA who had a different clinical course: our 1st case had a good response to Adalimumab while the 2nd case evolved unfavourably after treatment, and died from cardiovascular complications.

Microalbuminuria e insuficiencia renal en la infección crónica por el virus de la hepatitis C / Microalbuminuria and renal insufficiency in chronic hepatitis C virus infection

Introducción La infección crónica por el virus de la hepatitis C (VHC) se ha asociado a enfermedad glomerular, que se manifiesta mediante proteinuria con o sin disfunción renal. Método Estudio observacional analítico transversal con 120 pacientes infectados por el VHC y 145 controles VHC-negativos para determinar la prevalencia de daño renal asociada al VHC y su relación con factores de riesgo. Se recogieron datos de la historia clínica y anamnesis y se realizaron al menos 3 análisis de sangre y orina en un año. La insuficiencia renal se definió por un filtrado glomerular estimado inferior a 60ml/min/1,73 m2 y/o una microalbuminuria superior a 20mg/l o un índice microalbuminuria/creatinina mayor de 30 μg/mg. Resultados La prevalencia de microalbuminuria e insuficiencia renal se estimó en el 19,3 y 11,7% en los VHC-positivos vs el 10,5 y 0,7% en los VHC-negativos (p = 0,04), respectivamente. El 26,1% de los pacientes VHC-positivos tenía algún signos de daño renal vs el 11,8% de los VHC-negativos (p = 0,003). La infección por el VHC se asoció de forma independiente y significativa con la probabilidad de deterioro de la función renal. La prevalencia de microalbuminuria e insuficiencia renal se incrementó progresivamente con el aumento de edad. Conclusión Los pacientes VHC-positivos presentan una alta prevalencia de microalbuminuria e insuficiencia renal en comparación con sujetos VHC-negativos. El riesgo de insuficiencia renal asociado al VHC es independiente en presencia de otros factores predisponentes como hipertensión arterial y diabetes (AU)

Introduction Chronic hepatitis C virus (HCV) infection is associated with glomerular disease, which is manifested by proteinuria with or without renal dysfunction. Method To determine the prevalence of HCV-associated renal injury and associated risk factors, we performed an observational, analytic, cross-sectional study of 120 HCV-positive patients and 145 HCV-negative controls. Data were gathered from medical records and history-taking and at least three blood and urine analyses were performed over a 1-year period. Renal insufficiency was defined as an estimated glomerular filtration rate of less than 60ml/min/1.73 m2 and/or microalbuminuria of more than 20mg/l or a microalbumin/creatinine ratio higher than 30 mcg/mg. Results The prevalence of microalbuminuria and renal insufficiency was 19.3% and 11.7% in HCV-positive patients versus 10.5% and 0.7% in HCV-negative controls (p 0.04), respectively. A total of 26.1% of HCV-positive patients had signs of renal injury compared with 11.8% of HCV-negative controls (p 0.003). HCV infection was independently and significantly associated with the probability of worsening of renal function. The prevalence of microalbuminuria and renal insufficiency progressively increased with greater age. Conclusion HCV-positive patients show a high prevalence of microalbuminuria and renal insufficiency compared with HCV-negative individuals. The risk of HCV-associated renal insufficiency is independent of the presence of other predisposing factors such hypertension and diabetes (AU)