Rechallenge in idiosyncratic drug-induced liver injury: an analysis of cases in two large prospective registries according to existing definitions.

INTRODUCTION: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. METHODS: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. RESULTS: Of 1,418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. CONCLUSIONS: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.

El índice de resistencia vascular renal no tiene implicaciones pronósticas en el trasplante renal / Vascular renal resistance index is not related with prognosis in kidney transplantation

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Valoración del flujo de la fístula arteriovenosa en pacientes en tratamiento con quelantes con calcio / Evaluation of arteriovenous fistula blood flow in patients with calcium chelation therapy

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Las calcificaciones valvulares al inicio de diálisis predicen la aparición de eventos cardiovasculares en la evolución / Valvular calcification upon initiating dialysis predict the appearance of cardiovascular events in patient evolution

La calcificación valvular (CV) en la enfermedad renal crónica es frecuente, aunque la mayor parte de la información procede de pacientes prevalentes en diálisis. Son pocos los estudios que analicen la CV en los pacientes que inician diálisis. Objetivo: Analizar la presencia de CV al inicio de diálisis y su relación con eventos y/o muerte cardiovascular en la evolución. Métodos: Incluimos en el estudio los pacientes incidentes en diálisis entre nov/03 y sept/07. En el 1o mes de tratamiento analizamos la presencia de CV mediante Ecocardiograma-doppler, junto a factores demográficos y de riesgo cardiovascular, enfermedad coronaria, accidente cerebrovascular (ACV), fibrilación auricular (FA) y parámetros de electro y ecocardiográficos dimensionales y funcionales cardiacos. Los valores bioquímicos analizados fueron: hemoglobina, metabolismo calcio/fósforo/iPTH, colesterol y fracciones, triglicéridos, troponina I, albúmina, PCR y hemoglobina glicosilada. Analizamos la asociación de la CV con la presentación de infarto de miocardio (IAM), ACV y/o muerte cardiovascular hasta el trasplante, muerte, o fin del estudio (dic/2012). Resultados: De 256 pacientes incluidos (83% hemodiálisis, 17% diálisis peritoneal), 128 (50%) presentaban CV (mitral: 39, aórtica: 20, ambas: 69). En el análisis multivariante la CV se asoció a mayor edad (OR: 1,110; IC 95%: 1,073-1,148; p = 0,000) y menor albúmina (OR: 0,29; IC 95%: 0,14-0,61; p = 0,001). En un seguimiento de 42,1 ± 30,2 meses (898,1 pacientesaño), 68 pacientes presentaron IAM, ACV y/o murieron por causa cardiovascular. En el análisis de regresión de Cox, la mayor edad (HR: 1,028; IC 95%: 1,002-1,055; p = 0,037), la enfermedad coronaria y/o ACV (HR: 1,979; IC95%: 1,111-3,527; p = 0,021), la FA (HR: 2,474; IC 95%: 1,331-4,602; p = 0,004) y la presencia de CV antes de entrar en diálisis (HR: 1,996; IC 95%: 1,077-3,700; p = 0,028), fueron predictores independientes de la presentación de los eventos analizados. Conclusiones: La prevalencia de CV en el momento de iniciar diálisis es alta y su presencia predice la presentación de eventos y/o muerte cardiovascular en la evolución (AU)

The estimated frequency of cardiac valvular calcification (VC) in patients on dialysis is high, although the majority of studies published to date regarding the rate of VC have dealt with prevalent patients in dialysis. There are few studies of VC at the commencement of dialysis and its relationship to future events or cardiovascular mortality. Objective: To establish the prevalence of VC at the start of dialysis and the relationship between VC and the presentation of composite endpoints of acute myocardial infarction (MI), stroke or death from cardiovascular causes in the follow-up of incident dialysis patients. Methods: We conducted an analysis of dialysis patients (haemodialysis or peritoneal dialysis) who commenced dialysis between November 03 and September 07. VC was assessed by Doppler-echocardiography and its association with MI, stroke or cardiovascular mortality in the follow-up until death, transplant, or study end in December 2012 was analysed. Other variables assessed in the first month of dialysis were ECG, age, gender, smoking habit, diabetes, hypertension, previous ischemic stroke, coronary arterial disease and atrial fibrillation. Biochemical analyses included: haemoglobin, urea, creatinine, lipids, calcium, phosphorus, parathyroid hormone, albumin, troponin I, glycosylated haemoglobin and C-reactive protein. Results: Of 256 enrolled patients (83% Haemodialysis, 17% Peritoneal dialysis), 128 (50%) had VC at the commencement of dialysis (aortic 20, mitral 39, both 69). VC was associated with older age (OR: 1.110; CI 95%: 1.073-1.148; P=.000) and lower albumin levels (OR: 0.29; CI 95%: 0.14-0.61; P=.001). In a follow-up lasting a mean of 42.1±30.2 months (898.1 patient-years), 68 patients suffered an MI, a stroke or died from cardiovascular causes. The factors that predicted the presentation of the endpoint (Cox regression analysis) were older age (HR: 1.028; CI 95%: 1.002-1.055; P=.037), previous coronary arterial disease or stroke (HR: 1.979; CI 95%: 1.111-3.527; P=.021), atrial fibrillation (HR: 2.474; CI 95%: 1.331-4.602; P=.004) and VC at the start of dialysis (HR: 1.996; CI 95%: 1.077-3.700; P=.028). Conclusions: The prevalence of VC at the commencement of dialysis is very high and its presence is an independent predictor of event and cardiovascular mortality presentation in the course of follow-up (AU)

Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids.

BACKGROUND: We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding. AIM: To characterise phenotype presentation, outcome and severity of AAS DILI. METHODS: Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin-American (5) DILI Registries were collated and compared with previously published cases. RESULTS: AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001-2009 to 8% in 2010-2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS-induced acute kidney impairment (AKI) [OR 1.26 (95% CI: 1.035-1.526); P = 0.021], with 21.5 ×ULN being the best bilirubin cut-off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred. CONCLUSIONS: Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.

Sudden death in incident dialysis patients.

BACKGROUND: Sudden death (SD) constitutes one of the principal causes of death and is an important problem in healthcare provision. Cardiovascular diseases have a high prevalence in dialysis patients and constitute the principal cause of death. We sought to analyze retrospectively the incidence of SD in patients commencing dialysis and the factors related to its presence. METHODS: We evaluated all the patients who began dialysis in our center between 1/11/2003 and 15/9/2007, and who were followed up until death, transplant, or study completion on 31/12/2012. We determined the presence of SD according to the following criteria: SD at 24 h (SD 24H): unexpected death occurring in the 24 h following the start of symptoms, or when the patient was found dead and had been seen alive 24 h earlier; SD at 1 h (SD 1H): death witnessed as occurring in the first hour following the start of symptoms. RESULTS: We evaluated 285 patients, mean age 65.67 ± 15.7 years. In a follow-up of 39.9 ± 34.2 months (947.6 patient-years of follow-up) 168 died (59%), 28 (10%) patients presented SD 24H (2.9/100 patient-years), and 16 (6%) patients presented SD 1H (1.7/100 patient-years). In the multivariate analysis, having had a myocardial infarction or having had electrocardiographic abnormalities (Q wave, negative T wave, subendocardial lesion or QRS >120 ms) were the principal independent predictors of SD 24H (OR 7.83; 95% CI 2.20-27.86; p = 0.001) and of SD 1H (OR 13.43; 95% CI 1.56-115.42; p = 0.018). CONCLUSIONS: SD on dialysis is very frequent. Two groups can be identified easily, with risk profiles clearly differentiated.

Tratamiento con hemodiálisis larga con filtros de alto cut-off en la nefropatía por cilindros del mieloma: nuestra experiencia / Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience

El mieloma múltiple (MM) consiste en la proliferación incontrolada de células plasmáticas con producción de cantidades variables de inmunoglobulinas o sus cadenas. La insuficiencia renal aguda puede ser un síntoma del MM, y a veces su forma de presentación. Las cadenas ligeras libres circulantes (CLL) pueden dar lugar al fallo renal por la precipitación intratubular de ellas, causando una nefropatía por cilindros. El tratamiento del mieloma, una adecuada hidratación y la eliminación de CLL mediante técnicas de aféresis son los tratamientos admitidos actualmente para esta entidad. Se han intentado diversas técnicas de aféresis para intentar eliminar las CLL, siendo la hemodiálisis de larga duración con filtros para eliminar dichas cadenas ligeras (alto cut-off) la que se postula como el tratamiento más eficaz para la nefropatía del mieloma. MÉTODOS: Presentamos cinco casos de nefropatía de mieloma: tres con nefropatía por cilindros (NC) diagnosticada por biopsia renal y dos con alta probabilidad de NC (niveles de CLL > 500 mg/l) tratados con hemodiálisis larga con membrana de alto cut-off. Todos presentaban insuficiencia renal aguda, en cuatro de ellos con necesidad de terapia sustitutiva y uno en situación de insuficiencia renal avanzada. En todos ellos los niveles de CLL fueron muy elevados. Recibieron tratamiento específico para el mieloma más hemodiálisis de alto cut-off hasta alcanzar niveles de CLL < 500 mg/l. RESULTADOS: Cuatro de los cinco pacientes recuperaron función renal, quedando independientes de diálisis. El tiempo de evolución del mieloma desde el inicio de la clínica fue variable (1-6 m). El número de sesiones varió entre 8-16. El paciente de más tiempo de evolución precisó más sesiones y no recuperó función renal. CONCLUSIONES: La hemodiálisis larga con filtros de alto cut-off más tratamiento con quimioterapia del mieloma parece ser un tratamiento eficaz en la insuficiencia renal aguda debida a nefropatía del mieloma. La precocidad en el inicio del tratamiento puede ser un factor determinante de la respuesta

Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulin or their chains. Acute renal failure can be a symptom of MM, and it is sometimes their presentation form. Circulating free light chains (FLC) could led to renal failure by intratubular precipitation of themselves causing a cast nephropathy. Myeloma's treatment, an adequate hydration and FLC's elimination by aphaeresis treatments are currently eligible therapy for this entity. Several aphaeresis techniques have been tried to eliminate the FLC being long-term hemodialysis with filters to remove these light chains (High Cut-Off filters). This treatment is postulated as the most effective treatment for myeloma nephropathy. METHODS: We report 5 cases of myeloma nephropathy: three of them with cast nephropathy (CN) diagnosed by renal biopsy and another two with high probability of NC (FLC levels >500mg/L). All of them were treated by hemodialysis with membrane high Cut-Off. The five patients had had an acute renal failure; in four of them need replacement renal therapy. The fifth patient only had an advanced renal failure. In all patients, FLC levels were very high. All patients received specific treatment for myeloma in addiction on hemodialysis high Cut-Off until the FLC levels were <500mg/ L. RESULTS: Four of the five patients recovered renal function, being independent of dialysis. The evolution time of myeloma since the first symptoms appeared was variable (1-6 months). The number of treatment sessions ranged from 8-16. The patient whose evolution time was the longest one required more sessions and did not recovered the renal function. CONCLUSIONS: Length hemodialysis with filters high cut-off plus specific myeloma chemotherapy seems to be an effective treatment in acute renal failure due to cast myeloma. The early initiation of treatment could be an important factor for the response

Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience.

UNLABELLED: Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains. Acute renal failure can be a symptom of MM, and it is sometimes its form of presentation. Circulating free light chains (FLC) could lead to renal failure due to their intratubular precipitation, causing a cast nephropathy. The treatment of myeloma, adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease. Several apheresis techniques have been attempted for the removal of FLC, with long haemodialysis sessions with filters for the removal of these light chains (high cut-off filters) being proposed as the most effective treatment for myeloma nephropathy. METHODS: We report 5 cases of myeloma nephropathy: three had cast nephropathy (CN) diagnosed by renal biopsy and the other two had a high probability of CN (FLC levels >500 mg/l). They were treated with long haemodialysis sessions with a high cut-off membrane. All patients had suffered acute renal failure; four required renal replacement therapy and one patient had advanced renal failure. In all patients, FLC levels were very high. They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of <500 mg/l. RESULTS: Four of the five patients recovered renal function, and became independent of dialysis. The progression time for myeloma from the time the first symptoms appeared varied (1-6 months). The number of treatment sessions ranged from 8-16. The patient with the longest progression time required more sessions and did not recover renal function. CONCLUSIONS: Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy. The early initiation of treatment could be a determining factor for the response.

Incidencia del infarto agudo de miocardio en la evolución de los pacientes en tratamiento con diálisis / Incidence of acute myocardial infarction in the evolution of dialysis patients

Introducción: Aunque la frecuencia de la enfermedad coronaria (EAC) en los pacientes en diálisis se estima muy elevada, existe una gran variabilidad en los estudios en la tasa de infarto agudo de miocardio (IAM). Objetivo: Establecer la incidencia IAM y analizar sus características y repercusión en la evolución de los pacientes incidentes en diálisis. Métodos: Estudiamos los pacientes incidentes en diálisis entre el 1/1/1999 y el 31/12/2007, y analizamos la presentación del primer IAM en diálisis. Valoramos diagnósticos previos de diabetes, hipertensión arterial, EAC (IAM o lesiones en coronariografía), accidente cerebrovascular isquémico, arteriopatía periférica avanzada y tabaquismo. Se analizaron urea, creatinina, hematocrito, calcio/fósforo, hormona paratiroidea intacta, lípidos y albúmina. El seguimiento fue hasta trasplante, muerte, pérdida o cierre del estudio el 31/12/2010. Resultados: De 576 pacientes incluidos (64,6 ± 16 años; 24,7% diabéticos; 82,3% hemodiálisis/17,7% diálisis peritoneal), 34 (5,9%) (..) (AU)

Background: Although the estimated frequency of coronary artery disease (CAD) in patients on dialysis is very high, there is considerable variation in the studies published to date regarding the rate of acute myocardial infarction (AMI) in these patients. Objective: To establish the incidence of AMI and to analyse the characteristics and consequences of this entity on the clinical progression of incident dialysis patients. Methods: We recorded AMI in the patients treated in our dialysis unit between 01/01/1999 and 31/12/07. The variables assessed were: prior diagnosis of diabetes, hypertension, CAD (AMI or lesions observed in coronary angiography), ischaemic cerebrovascular accident, advanced peripheral artery disease (PAD), atrial fibrillation and tobacco use. Biochemical analyses included: urea, creatinine, haematocrit, calcium, phosphorous, iPTH, lipids and albumin. Follow-up lasted until transplant, death, loss to follow-up or study end in Dec. 2010. Results: Of the 576 patients recruited (aged 64.6±16 years), 24.7% had diabetes, 82.3% were on haemodialysis (17.7% on peritoneal dialysis), and 34 (5.9%) had a previous diagnosis of CAD. In a follow-up lasting a mean of 40.2±32 months (1931.5 patient-years), 40 patients (6.9%) suffered an AMI. The incidence was 2.13/100 patient-years. The patients without CAD had an incidence of 1.84/100 patient-years and those with a previous (..) (AU)

Incidence of acute myocardial infarction in the evolution of dialysis patients.

BACKGROUND: Although the estimated frequency of coronary artery disease (CAD) in patients on dialysis is very high, there is considerable variation in the studies published to date regarding the rate of acute myocardial infarction (AMI) in these patients. OBJECTIVE: To establish the incidence of AMI and to analyse the characteristics and consequences of this entity on the clinical progression of incident dialysis patients. METHODS: We recorded AMI in the patients treated in our dialysis unit between 01/01/1999 and 31/12/07. The variables assessed were: prior diagnosis of diabetes, hypertension, CAD (AMI or lesions observed in coronary angiography), ischaemic cerebrovascular accident, advanced peripheral artery disease (PAD), atrial fibrillation and tobacco use. Biochemical analyses included: urea, creatinine, haematocrit, calcium, phosphorous, iPTH, lipids and albumin. Follow-up lasted until transplant, death, loss to follow-up or study end in Dec. 2010. RESULTS: Of the 576 patients recruited (aged 64.6 ± 16 years), 24.7% had diabetes, 82.3% were on haemodialysis (17.7% on peritoneal dialysis), and 34 (5.9%) had a previous diagnosis of CAD. In a follow-up lasting a mean of 40.2 ± 32 months (1931.5 patient-years), 40 patients (6.9%) suffered an AMI. The incidence was 2.13/100 patient-years. The patients without CAD had an incidence of 1.84/100 patient-years and those with a previous diagnosis of CAD had an incidence of 7.53/100 patient-years. In 22.5% of patients, AMI happened in the first 3 months of dialysis, and 37.5% in the 1st year. Of the 40 AMI, 15 were with ST-segment elevation (incidence: 0.79/100 patient-years) and 25 were non ST-segment elevation (incidence: 1.33/100 patient-years). The factors that predicted the occurrence of AMI in dialysis were older age (OR: 1.037; 95% CI: 1.009-1.067; P=.011), previous CAD (OR: 3.35; 95% CI: 1.48-7.16; P=.004), and diabetes as a cause of nephropathy (OR: 2.96; 95% CI: 1.49-5.86; P=.002). In-hospital mortality was 30%, with 72.5% of deaths occurring in the 1st year and 82.5% in the 2nd; 80% of the patients who underwent a coronary angiography had multi-vessel disease. CONCLUSIONS: The incidence of AMI in incident dialysis patients is high. In previous coronary disease patients, the incidence is 3-fold higher. Post-infarction mortality is very high and multi-vessel disease is very frequent.

How do disorders related to hospitalisation influence haemodialysis patients' nutrition?

INTRODUCTION: Hospitalizations are frequent in hemodialysis patients and is often accompanied by nutritional deterioration showed by a loss of weight and a reduction of albumin serum levels. This phenomenon is related with length of stay having its origin in a complex interplay of factors. Our aim in this study was to analyze if changes in body weight and other nutritional parameters are influenced by the illnesses presented during hospitalization. PATIENTS AND METHODS: Over a period of three years, we retrospectively chose chronic haemodialysis patients that were admitted for more than four days, excluding those cases that died in the hospital. We randomly chose one admission episode per patient so as to avoid excessive weighing of repeated admissions. We took data concerning weight changes, pre-admission and post-discharge analytical results, analytical results following first week of hospital stay, disorders causing hospital admission and those that developed during the hospital stay. We created a point score system to record the total of illnesses presented. RESULTS: The study included 77 patients, aged 67±12 years and having undergone haemodialysis for 31±34 months. Hospital stay was 17.8±12.6 days (median, 12 days). We observed that many patients admitted for digestive and osteoarticular disorders, heart failure or coronary syndrome lost more weight during their hospital stay, although no significant differences were reached. The total number of disorders suffered during the hospital stay was independent of the cause of hospitalisation. Anaemia,heart arrhythmias and signs of heart failure were associated with longer hospital stays, however it was only anaemia that was significantly related to greater weight loss. Weight loss was not related to surgery or infections. Albumin levels during the first week of hospital stay were different depending on the disorder upon admission. It was lower when the patients were admitted for digestive disorders (ANOVA, P=.05). Changes in albumin and creatinine levels before and after the hospital stay did not differ among disorders. We observed a relationship between having presented with more disorders during the stay and a longer stay, lower initial albumin and greater weight loss following discharge. In the multivariate analysis, we found the following weight loss predictors: stay, anaemia, and sepsis. We also found the following hospital stay predictors:Charlson's comorbidity index, heart arrhythmias, anaemia, sepsis and surgery. CONCLUSIONS: Malnutrition during the hospital stay depends on the duration and the number of disorders that develop during this time, the cause of admission having less impact on this. Albumin levels decrease earlier in patients that are going to develop more disorders during hospital stay.

[Loss of weight in hemodialysis patients after hospitalization is related with length of stay and degree of inflammation]. / La pérdida de peso en pacientes en hemodiálisis tras su hospitalización tiene relación con la duración de la estancia y con el grado de inflamación.

BACKGROUND: It is frequent to observe that hemodialysis patients suffer important loss of weight during hospital stay. This issue has not been investigated previously. Our aim in this study was to analyze factors associated with this loss of weight and what changes occur after admission in biochemical parameters with nutritional interest. PATIENTS AND METHODS: We retrospectively selected patients undergoing chronic hemodialysis who were admitted at hospital for acute or chronic pathologies, with a minimum length of stay of 4 days, taking only one episode of admission per patient. We chose loss of weight observed at hospital discharge, at 2 and 4 weeks later and we also collected routine laboratory data and adequacy parameters before and after the hospital admission and basic biochemical parameters in the first week of hospital stay. RESULTS: We included 77 patients, with 67±12 years and 30±34 months in dialysis. Forty (51.9%) were female (51.9%) and 22 diabetics (28.6%). Length of stay was 17.8±12.6 days (median 12). There were 70.4% patients who suffered a loss of weight at discharge and 81.4% at 4 weeks, without differences in sex or diabetes. Weight decreased significantly with a mean of -1.09 kg (95%CI -0.73 to -1.44). After 2 weeks the loss of weight was -1.64 kg (95%CI -1.21 a -2.07 kg) and after 4 weeks was -1.94 kg (95%CI -1.47 a -2.42 kg). Comparing parameters before and after admission, we observed a significantly decrease in serum urea levels (before 134±40 vs after 119±36 mg/dl; p= 0.001), creatinine (before 8.1±2.6 vs after 7.5±2.6 mg/dl; p < 0.001), phosphate (before 5.2±1.7 vs after 4.3±1.5 mg/dl; p < 0.001) and albumin (before 3.70±0.48 vs after 3.56±0.58 g/dl; p=0.05), without changes in adequacy parameters. Greater loss of weight at 4 weeks from discharge was correlated with larger length of stay (r= 0.41; p < 0.001), greater body mass index at admission (r= -0.23; p=0.05) and lower serum albumin at admission (r= 0.39; p= 0.012). It was also correlated with a lower serum albumin (r= 0.27; p=0.05), lower creatinine (r= 0.30; p= 0.02) and lower protein intake (nPNA) (r= 0.47; p= 0.002) after discharge. Lower serum albumin levels at admission were correlated with greater decreases of creatinine after discharge (r= 0.42; p= 0.009) and larger length of stay (r= -0.61; p < 0.001). Employing multivariate analysis we found that loss of weight was associated to length of stay and serum potassium levels before admission. CONCLUSIONS: Hospitalization of hemodialysis patients have a negative nutritional impact causing a significant loss of weight, probably reflecting a reduction of muscle mass. We found that length of stay in hospital is a basic factor associated with this nutritional impairment. The pathologies promoting hospitalization could influence this derangement through inflammation but this hypothesis should be investigated.

Análisis de la eficacia y de los factores que influyen en la respuesta del hiperparatiroidismo secundario de pacientes en hemodiálisis a cinacalcet / Analysis of the efficacy and factors influencing the response of secondary hyperparathyroidism patients on hemodialysis to cinacalcet

Introducción: Aunque el cinacalcet ha mejorado el control del hiperparatiroidismo secundario en hemodiálisis, todavía un 50% de los pacientes no alcanzan las cifras de PTH recomendadas por las guías K/DOQI. El objetivo de este estudio fue analizar la eficacia del tratamiento del hiperparatiroidismo secundario con cinacalcet en pacientes no seleccionados en hemodiálisis crónica, de acuerdo con los objetivos marcados por las guías K/DOQI y KDIGO. Además, investigamos qué factores pueden influir en el grado de respuesta del hiperparatiroidismo secundario a cinacalcet. Material y métodos: Recogimos retrospectivamente la evolución de 74pacientes en hemodiálisis con hiperparatiroidismo secundario que fueron tratados con cinacalcet durante al menos 6 meses. Resultados: De acuerdo con las guías K/DOQI, la proporción de pacientes con PTHi >300 pg/ml se redujo al 50%, la presencia de hiperfosforemia descendió del 38,4 al 23,3% y el producto Ca x P >55 mg2/dl2 bajó de 37,8 a 15,1%. La prevalencia de hipocalcemia aumentó de 2,7 al 12,3%. Con respecto a las guías KDIGO, la proporción con PTHi >600 pg/mlse redujo desde 41,1 al 16,4% y la de hiperfosforemia del68,5 al 52,1%; pero al considerar a pacientes con PTHi inicial>600 pg/ml, la prevalencia de P >4,5 mg/dl descendió de 83,3 del 55,2%. Observamos un incremento de la dosis de carbonato cálcico (basal 0,61 ± 1,53 g de calcio elemento/día frente a final 0,95 ± 1,98 g de calcio elementto/día; p = 0,03), debido más a la hipocalcemia que a la necesidad de quelar el fósforo. Encontramos menores descensos de la PTHi entre los pacientes que tenían prescrito inicialmente más sevelamer, y al final del seguimiento presentan mayores niveles séricos de PTHi (no sevelamer: 312 ± 245 pg/ml; sevelamer < _ 6,4 g/día: 510 ± 490 pg/ml; sevelamer >6,4 g/día: 526 ± 393 pg/ml; p = 0,04) y de fósforo (no sevelamer: 4,5 ± 1,2 mg/dl; sevelamer < _ 6,4 g/día: 4,2 ± 1,5 mg/dl; sevelamer >6,4 g/día: 5,7 ± 0,9 mg/dl; p = 0,01). El tratamiento asociado con paricalcitol no mostró ninguna in- fluencia en el grado de respuesta. Los pacientes que alcanzaron los objetivos de PTH mostraron ya a los 3 meses de tratamiento un mayor descenso en los niveles séricos de PTHi (159 ± 84 frente a 630 ± 377 pg/ml; p <0,001), con dosis significativamente menores de cinacalcet (33,8 ± 22,5 frente a 51,1 ± 25,1 mg/día; p = 0,003). Con análisis multivariante, el grado de reducción de la PTHi dependió de sus cifras séricas iniciales y de la dosis inicial de sevelamer. Conclusiones: Ci- nacalcet mejora el control del hiperparatiroidismo secunda- rio, si bien la respuesta es menor en los casos de mayor gra- vedad, representados por niveles más altos de PTH y mayores dosis iniciales de sevelamer. Por el contrario, un descenso im- portante de PTH a los 3 meses con dosis relativamente bajas de cinacalcet sería un marcador pronóstico de buena respuesta (AU)

Background: Treatment of secondary hyperparathyroidism with cinacalcet improves control of PTH, phosphorus, calcium and Ca X P product, enabling to achieve targets recommended by K/DOQI guidelines for PTHi in only 30-50%of patients, in studies with a very selected population. The aim of this study was to analyze its effectiveness in real clinical practice, comparing results with targets recommended by K/DOQI and KDIGO guidelines and to investigate factors having influence on PTH responsiveness to cinacalcet. Methods: We collected data of evolution of 74 patients on hemodialysis with secondary hyperparathyroidism who were treated with cinacalcet for at least 6months. Results: According K/DOQI targets we observed a reduction of proportion of patients with PTHi >300 pg/mlto 50%, a decrease of hyperphosphoremia from 38.4% to23.3% and proportion of patients with Ca x P product >55mg2/dl2 from 37.8% to 15.1%. By contrast, presence of hypocalcemia increases from 2.7% to 12.3%. Comparing with KDIGO targets, proportion of patients with PTHi >600pg/ml decreased from 41.1% to 16.4% and with hyperphosphoremia from 68.5% to 52.1%. However, when considering patients with baseline PTHi >600 pg/ml prevalence of P >4.5 mg/dl decreased from 83.3% to 55.2%. We observed significant changes of phosphate binders after cinacalcet treatment with an increase in calcium carbonate doses (pre 0.61 ± 1.53 g of calcium/day vs post-cinacalcet (..) (AU)

[Analysis of the efficacy and factors influencing the response of secondary hyperparathyroidism patients on hemodialysis to cinacalcet]. / Análisis de la eficacia y de los factores que influyen en la respuesta del hiperparatiroidismo secundario de pacientes en hemodiálisis a cinacalcet.

BACKGROUND: Treatment of secondary hyperparathyroidism with cinacalcet improves control of PTH, phosphorus, calcium and Ca x P product, enabling to achieve targets recommended by K/DOQI guidelines for PTHi in only 30-50% of patients, in studies with a very selected population. The aim of this study was to analyze its effectiveness in real clinical practice, comparing results with targets recommended by K/DOQI and KDIGO guidelines and to investigate factors having influence on PTH responsiveness to cinacalcet. METHODS: We collected data of evolution of 74 patients on hemodialysis with secondary hyperparathyroidism who were treated with cinacalcet for at least 6 months. RESULTS: According K/DOQI targets we observed a reduction of proportion of patients with PTHi > 300 pg/ml to 50%, a decrease of hyperphosphoremia from 38.4% to 23.3% and proportion of patients with Ca x P product > 55 mg2/dl2 from 37.8% to 15.1%. By contrast, presence of hypocalcemia increases from 2.7% to 12.3%. Comparing with KDIGO targets, proportion of patients with PTHi > 600 pg/ml decreased from 41.1% to 16.4% and with hyperphosphoremia from 68.5% to 52.1%. However, when considering patients with baseline PTHi > 600 pg/ml prevalence of P > 4.5 mg/dl decreased from 83.3% to 55.2%. We observed significant changes of phosphate binders after cinacalcet treatment with an increase in calcium carbonate doses (pre 0.61 +/- 1.53 g of calcium/day vs post-cinacalcet 0.95 +/- 1.98 g of calcium/day; p = 0.03) that was prescribed to prevent hypocalcemia and not as phosphate binder. Responsiveness were lower in patients who were taking higher doses of sevelamer at baseline, showing at the end of the study higher PTHi (no-sevelamer: 312 +/- 245 pg/ml; sevelamer < 6.4 g/day: 510 +/- 490 pg/ml; sevelamer > 6.4 g/day: 526 +/- 393 pg/ml; p = 0.04) and phosphorus (no-sevelamer: 4.5 +/- 1.2 mg/dl; sevelamer < 6.4 g/day: 4.2 +/- 1.5 mg/dl; sevelamer > 6.4 g/day: 5.7 +/- 0.9 mg/dl; p=0.01) serum levels. Use of paricalcitol did not show any influence on PTH response. Patients achieving targets for PTH at the end of the study showed a good response early, with a significant decrease of PTHi levels at three months (159 +/- 84 vs 630 +/- 377 pg/ml; p < 0.001) with significantly lower doses of cinacalcet (33.8 +/- 22.5 vs 51.1 +/- 25.1 mg/day; p = 0.003). Using multivariate analysis we found that percent of PTHi reduction was related with baseline PTHi levels and taking sevelamer as phosphate binder at baseline. CONCLUSION: Use of cinacalcet improves grade of control of secondary hyperparathyroidism in non-selected patients in hemodialysis, showing poor response in population with higher PTHi levels and who takes higher doses of sevelamer at baseline. By contrast, a reduction of PTHi levels at 3 months of treatment with relatively lower doses is a pronostic marker of good response to cinacalcet treatment.

Ischaemic stroke in incident dialysis patients.

BACKGROUND: Despite the high frequency of cardiovascular disease among the population on dialysis, there are few studies on ischaemic stroke and associated factors. The objective of the present study is to assess the prevalence of ischaemic stroke at the start of dialysis, its incidence in the course of follow-up and possible factors associated in its presentation. METHODS: All patients in our dialysis programme between 1 January 1999 and 31 December 2005 were included in the study and followed up until death, transplant, transfer out of our catchment area, or conclusion of the study on 31 December 2008. Factors analysed were age, gender, smoking habit, diabetes, hypertension, previous ischaemic stroke, ischaemic coronary disease, peripheral vascular disease and atrial fibrillation. Other factors measured in the first month of dialysis were haematocrit, urea, creatinine, lipids, calcium, phosphorus, parathyroid hormone and albumin. RESULTS: Of 449 patients included in the study (age 64.4 ± 16 years), 30 commenced dialysis having had previous stroke (prevalence 6.7%). In a follow-up of 38.77 ± 29 months, 34 patients presented with one or more strokes; an incidence of 2.41/100 patient-years. Greater age [odds ratio (OR): 1.05; 95% confidence interval (CI): 1.01-1.09; P = 0.007], diabetes (OR: 2.29; 95% CI: 1.15-4.55; P = 0.018) and presence of atrial fibrillation (OR: 3.11; 95% CI: 1.53-6.32; P = 0.002) were independent predictors of stroke occurrence. Conclusions. The prevalence of ischaemic stroke is high at the commencement of dialysis, and its incidence is elevated in the course of follow-up. As with the general population, atrial fibrillation is an important factor predictive of ischaemic stroke, and as such, the clinical implication is that prophylactic anti-coagulation therapy needs to be considered for these individuals.

Hepatotoxicidad secundaria a “productos naturales”: análisis de los casos notificados al Registro Español de Hepatotoxicidad / No disponible

Introducción: la toxicidad hepática asociada al uso crecientede productos de “remedios naturales” es un fenómeno emergente.Objetivos: valoración de las características epidemiológicas,clínicas y demográficas de los casos de hepatotoxicidad secundariosa productos herbales (PH) y suplementos dietéticos(SD).Pacientes y métodos: análisis de los casos de hepatotoxicidaddebida a PH y SD incluidos en el Registro Español de Hepatotoxicidad.Resultados: trece casos de un total de 521 casos (2%) dereacciones adversas hepáticas incluidas en el registro entre1994 y 2006, eran secundarios a PH/SD, representando el décimogrupo terapéutico responsable por orden de frecuencia,por delante de analgésicos, ansiolíticos y antipsicóticos. Nuevepacientes (69%) eran mujeres y la edad media fue de 45 años.Nueve pacientes (69%) presentaron ictericia. El tipo de dañomás frecuente fue el hepatocelular (12; 92%) y un 31% de loscasos presentaron datos de hipersensibilidad. La sustancia máscomúnmente involucrada en los casos de daño hepático fue laCamellia sinensis (23%) seguida de Rhamnus purshianus eisoflavonas (Fitosoja®, Biosoja®) con dos casos cada uno (15%).Tres casos (23%) presentaron re-exposición positiva.Conclusiones: la hepatotoxicidad originada por PH/SD noes excepcional, y su perfil es la hepatitis aguda hepatocelular ictéricapredominantemente en mujeres. La frecuente ocurrenciade reexposición positiva en estos pacientes indica un bajo índicede sospecha y un retraso o ausencia de diagnóstico de estetipo de reacción adversa

Background: toxic liver damage associated with the use ofnatural remedies is a growing health problem.Objectives: to analyze the demographics, and clinical andepidemiological characteristics of patients developing liver injuryrelated to these remedies.Patients and methods: all DILI cases associated with the useof herbal remedies (HR) or dietary supplements (DS) submitted tothe Spanish Registry were analyzed. Type of liver damage, severity,and outcome were specifically evaluated.Results: thirteen cases out of 521 DILI cases (2%) submittedto the Spanish Liver Toxicity Registry between 1994 and2006 were related to HR/DS, which ranked as the 10th therapeuticgroup with a greater number of cases and above painkillers, anxiolytics, and antipsychotic drugs. Nine patients (69%)were female (mean age 45 years). Nine cases (69%) had jaundiceat presentation. The predominating type of liver damagewas hepatocellular (12; 92%), and 31% of cases exhibited thecommon features of hypersensitivity. Camellia sinensis (3,23%) was the main causative herb, followed by Rhamnus purshianusand isoflavones (Fitosoja®, Biosoja®) (2 cases each,15%). Three cases (23%) were rechallenged with the offendingproduct.Conclusions: the incidence of hepatic damage related toHR/DS is not so rare, the most common profile of affected patientsbeing a woman with acute hepatocellular hepatitis. Lowsuspicion regarding the putative role of herbs in hepatotoxicitymakes diagnosis more difficult, and probably increases the incidenceof inadvertent rechallenge in these patients

[An analysis of the causes, characteristics, and consequences of reexposure to a drug or compound responsible for a hepatotoxicity event]. / Análisis de las causas, características y consecuencias de la reexposición al fármaco o compuesto responsable de un episodio de hepatotoxidad.

INTRODUCTION: reexposure to a causal agent represents a potentially serious event in hepatotoxicity. OBJECTIVES: to assess the characteristics and outcome of cases with positive reexposure. MATERIAL AND METHODS: a retrospective study of cases with evidence of positive reexposure included in Registro Español de Hepatopatías Asociadas a Medicamentos, and an analysis of their relation to demographic and clinical variables, causality, course, and consequences. RESULTS: of a total of 520 cases 31 (6%) met reexposure criteria. Fatal outcomes, needs for admission, and mean recovery time were all higher for hepatocellular-type toxic injury. The most commonly identified drug class was antibiotics. On most occasions (73%) reexposure to the causal compound escaped notice because of: absence of index case diagnosis, lack of information to patients and their physicians, and (12%) development of cross reactions between structurally similar drugs. CONCLUSIONS: accidental reexposure to a drug or a structurally-related compound after an initial hepatotoxicity event is common and may have serious consequences, particularly in hepatocellular-type toxicity. Careful history taking and reflecting diagnostic suspicion in the initial episode s record may reduce the incidence of this iatrogenic event.

Análisis de las causas, características y consecuencias de la reexposición al fármaco o compuesto responsable de un episodio de hepatotoxicidad / No disponible

Introducción: la reexposición al agente causal constituye unincidente potencialmente grave en hepatotoxicidad.Objetivos: evaluar las características y la evolución de los casoscon reexposición positiva.Material y métodos: estudio retrospectivo de una serie decasos con evidencia de reexposición positiva incluidos en el RegistroEspañol de Hepatopatías Asociadas a Medicamentos, analizandosu relación con variables demográficas y clínicas, causalidad,evolución y consecuencias.Resultados: de un total de 520 casos, 31 (6%) cumplían loscriterios de reexposición. La evolución fatal, la necesidad de hospitalizacióny el tiempo medio de recuperación fueron mayores enla lesión tóxica de tipo hepatocelular. El grupo farmacológicoidentificado con mayor frecuencia fue el de los antibióticos. En lamayoría de los casos la reexposición con el compuesto responsablefue inadvertida (73%) debido a: la ausencia de diagnóstico delcaso índice, la carencia de información al paciente o a su médicoy también (12%) por el desarrollo de una reacción cruzada entrefármacos estructuralmente similares.Conclusiones: la reexposición accidental a un mismo fármacoo a otro estructuralmente relacionado tras un primer episodiode hepatotoxicidad no es infrecuente y sus consecuencias puedenser graves, especialmente en el tipo de lesión hepatocelular. Unaminuciosa historia clínica y la sospecha diagnóstica reflejada en elinforme del primer episodio podrían disminuir la incidencia deeste evento iatrogénico

Introduction: reexposure to a causal agent represents a potentiallyserious event in hepatotoxicity.Objectives: to assess the characteristics and outcome of caseswith positive reexposure.Material and methods: a retrospective study of cases withevidence of positive reexposure included in Registro Español deHepatopatías Asociadas a Medicamentos, and an analysis of theirrelation to demographic and clinical variables, causality, course,and consequences.Results: of a total of 520 cases 31 (6%) met reexposure criteria.Fatal outcomes, needs for admission, and mean recovery timewere all higher for hepatocellular-type toxic injury. The most commonlyidentified drug class was antibiotics. On most occasions(73%) reexposure to the causal compound escaped notice becauseof: absence of index case diagnosis, lack of information topatients and their physicians, and (12%) development of cross reactionsbetween structurally similar drugs.Conclusions: accidental reexposure to a drug or a structurally-related compound after an initial hepatotoxicity event is commonand may have serious consequences, particularly in hepatocellular-type toxicity. Careful history taking and reflectingdiagnostic suspicion in the initial episode’s record may reduce the incidence of this iatrogenic event (AU)