Tratamiento del virus de la hepatitis C con antivirales de acción directa: aspectos prácticos y situación actual / Treatment of hepatitis C virus with direct-acting antivirals: practical aspects and current situation

La infección por el virus de la hepatitis C constituye un problema importante de salud pública. La introducción de los antivirales de acción directa, cuya eficacia es superior al 90% en todos los grupos de pacientes, incluidos los cirróticos, ha supuesto un cambio muy relevante respecto al tratamiento con las terapias clásicas basadas en interferón. Además, la tolerancia de estos antivirales es significativamente mejor, y la duración del tratamiento más corta. Esta revisión pretende actualizar el tratamiento de la infección por el virus hepatitisC con los nuevos antivirales de acción directa (AU)

Hepatitis C virus infection is a significant public health problem. The introduction of direct-acting antiviral agents, whose efficacy is greater than 90% in all patient groups (including those with cirrhosis), has represented a highly relevant change compared with classical interferon-based therapies. Tolerance for these antiviral agents is significantly better, and the treatment duration is shorter. This review updates the treatment of hepatitisC virus infection with the new direct-acting antiviral agents (AU)

Treatment of hepatitisC virus with direct-acting antivirals: Practical aspects and current situation. / Tratamiento del virus de la hepatitisC con antivirales de acción directa: Aspectos prácticos y situación actual.

HepatitisC virus infection is a significant public health problem. The introduction of direct-acting antiviral agents, whose efficacy is greater than 90% in all patient groups (including those with cirrhosis), has represented a highly relevant change compared with classical interferon-based therapies. Tolerance for these antiviral agents is significantly better, and the treatment duration is shorter. This review updates the treatment of hepatitisC virus infection with the new direct-acting antiviral agents.

Incidence and prognosis of immune reconstitution inflammatory syndrome in HIV-associated progressive multifocal leucoencephalopathy.

BACKGROUND AND PURPOSE: Progressive multifocal leucoencephalopathy-associated immune reconstitution inflammatory syndrome (PML-IRIS) is the paradoxical worsening or unmasking of preexisting infection with JC virus attributable to a rapid recovery of the immune system after highly active antiretroviral therapy (HAART) initiation. We investigated the incidence and factors associated with PML-IRIS in HIV-infected patients. We also studied its influence on mortality of PML and the effect of corticosteroid therapy. METHODS: Single-center retrospective analysis of HIV-infected patients diagnosed with PML from 1996 to 2012 who received HAART. RESULTS: Among 59 PML patients treated with HAART, 18 (30.51%) developed PML-IRIS (five delayed PML-IRIS, 13 simultaneous PML-IRIS). Patients who developed IRIS had lower CD4 counts prior to treatment (102 vs. 68.5, P < 0.05) and experienced a greater decline in HIV-RNA levels in response to HAART (2.5log vs. 2.95log, P < 0.05). Gadolinium enhancement on MRI was observed in 31.25% of PML-IRIS cases versus 2.56% of PML non-IRIS (P < 0.01). Survival rates were higher in patients with PML-IRIS compared to those with PML non-IRIS. Eight patients received corticosteroids, five of which had a good outcome. Patients who died were severely ill when treatment was initiated whereas patients who survived were treated before major neurological deterioration occurred. CONCLUSIONS: Nearly one-third of HIV-infected patients with PML develop IRIS after initiating HAART. Patients severely immunocompromised who experience a rapid virological response to HAART have a higher risk for PML-IRIS. There was a trend for lower mortality in patients with IRIS. Early treatment with corticosteroids might be useful.

Liver toxicity and risk of discontinuation in HIV/hepatitis C virus-coinfected patients receiving an etravirine-containing antiretroviral regimen: influence of liver fibrosis.

OBJECTIVES: The aim of the study was to establish the risk of liver toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving etravirine, according to the degree of liver fibrosis. METHODS: A prospective cohort study of 211 HIV-infected patients initiating an etravirine-containing regimen was carried out. HCV coinfection was defined as a positive HCV RNA test, and baseline liver fibrosis was assessed by transient elastography. Hepatotoxicity was defined as clinical symptoms, or an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value > 5-fold higher than the upper limit of normal if baseline values were normal, or 3.5-fold higher if values were altered at baseline. RESULTS: Overall, 145 patients (69%) were HCV coinfected, with a lower nadir (165 versus 220 cells/µL, respectively; p = 0.03) and baseline (374 versus 498 cells/µL, respectively; p = 0.04) CD4 count than monoinfected patients. Etravirine was mainly used with two nucleoside reverse transcriptase inhibitors (129; 61%) or with a boosted protease inhibitor (PI) (28%), with no significant differences according to HCV serostatus. Transient elastography in 117 patients (81%) showed a median (range) stiffness value of 8.25 (3.5-69) kPa, with fibrosis stage 1 in 43 patients (37%) and fibrosis stage 4 in 28 patients (24%). During an accumulated follow-up time of 449.3 patient-years (median 548 days), only one patient with advanced fibrosis (50.8 kPa) had grade 3-4 liver toxicity (0.7%). Transaminases changed slightly, with no significant differences compared with baseline fibrosis, and nine and six patients had grade 1 and 2 transaminase increases, respectively. Also, HCV coinfection was not associated with a higher risk of discontinuation (25% discontinued versus 21% of monoinfected patients; p = 0.39, log-rank test) or virological failure (8% versus 12%, respectively; p = 0.4). CONCLUSIONS: Our data suggest that etravirine is a safe option for HIV/HCV-coinfected patients, including those with significant liver fibrosis.

Afectación del sistema nervioso central en la infección invasiva por Streptococcus agalactiae en adultos / Central nervous system involvement in adult patients with invasive infection caused by Streptococcus agalactiae

Introducción: El Streptococcus agalactiae (S. agalactiae) es un germen frecuentemente colonizador asintomático y causante de sepsis neonatal y puerperal. Las infecciones en adultos, fuera del embarazo, son poco frecuentes. No se conoce la frecuencia de complicaciones neurológicas en adultos con infección invasiva por este microorganismo. Hemos estudiado la frecuencia y las características de la afectación del sistema nervioso central (SNC) en pacientes adultos con infección invasiva por S. agalactiae. Pacientes y métodos: Se revisó a todos los pacientes adultos con infección invasiva por S. agalactiae en un hospital terciario entre 2003 y 2011. Resultados: En 75 pacientes se aisló S. agalactiae en sangre, líquido cefalorraquídeo o líquido articular. De ellos, 7 (9,3%) tuvieron afectación neurológica: 5 hombres y 2 mujeres no embarazadas, con edades entre 20 y 62 años. Los diagnósticos fueron: absceso epidural secundario a espondilodiscitis con compresión medular, meningitis bacteriana aguda, ictus isquémico como presentación de endocarditis bacteriana (2 pacientes cada uno) y meningoventriculitis tras neurocirugía y derivación ventricular. Un paciente con endocarditis por S. agalactiae y S. aureus falleció en la fase aguda y otra a los 3 meses por neoplasia metastásica. El resto se recuperó sin secuelas. En todos los casos, hubo factores predisponentes sistémicos para la infección y 5 (71,4%) tenían rotura de barrera mucocutánea como posible origen de la infección. Conclusiones: La afectación del SNC es relativamente frecuente en pacientes adultos con infección invasiva por S. agalactiae. El aislamiento de S. agalactiae debe hacer investigar causas predisponentes sistémicas y causas de rotura de barrera mucocutánea, sobre todo en meningitis

Introduction: Streptococcus agalactiae is frequently an asymptomatic coloniser and a cause of neonatal and puerperal sepsis. Infections in nonpregnant adults are uncommon. The frequency of neurological complications caused by invasive infection with this microorganism in adults remains unknown. Here, we study the frequency and characteristics of central nervous system (CNS) involvement in adults with invasive S. agalactiae infection. Patients and methods: Review of all adults with invasive S. agalactiae infection between 2003 and 2011 in a tertiary hospital. Results: S. agalactiae was isolated from blood, CSF or synovial fluid in 75 patients. Among them, 7 (9,3%) displayed neurological involvement: 5 men and 2 nonpregnant women, aged between 20 and 62 years. Diagnoses were spinal epidural abscess due to spondylodiscitis with spinal cord compression; acute bacterial meningitis; ischemic stroke as presentation of bacterial endocarditis (2 patients each); and meningoventriculitis after neurosurgery and ventricular shunting. One patient with endocarditis caused by S. agalactiae and S. aureus died in the acute phase, and another died 3 months later from metastatic cancer. The other patients recovered without sequelae. All patients had systemic predisposing factors for infection and 5 (71,4%) had experienced disruption of the mucocutaneous barrier as a possible origin of the infection. Conclusions: CNS involvement is not uncommon in adult patients with invasive infection caused by S. agalactiae. Isolating S. agalactiae, especially in cases of meningitis, should lead doctors to search for predisposing systemic disease and causes of mucocutaneous barrier disruption

Central nervous system involvement in adult patients with invasive infection caused by Streptococcus agalactiae.

INTRODUCTION: Streptococcus agalactiae is frequently an asymptomatic coloniser and a cause of neonatal and puerperal sepsis. Infections in nonpregnant adults are uncommon. The frequency of neurological complications caused by invasive infection with this microorganism in adults remains unknown. Here, we study the frequency and characteristics of central nervous system (CNS) involvement in adults with invasive S. agalactiae infection. PATIENTS AND METHODS: Review of all adults with invasive S. agalactiae infection between 2003 and 2011 in a tertiary hospital. RESULTS: S. agalactiae was isolated from blood, CSF or synovial fluid in 75 patients. Among them, 7 (9,3%) displayed neurological involvement: 5 men and 2 nonpregnant women, aged between 20 and 62 years. Diagnoses were spinal epidural abscess due to spondylodiscitis with spinal cord compression; acute bacterial meningitis; ischemic stroke as presentation of bacterial endocarditis (2 patients each); and meningoventriculitis after neurosurgery and ventricular shunting. One patient with endocarditis caused by S. agalactiae and S. aureus died in the acute phase, and another died 3 months later from metastatic cancer. The other patients recovered without sequelae. All patients had systemic predisposing factors for infection and 5 (71,4%) had experienced disruption of the mucocutaneous barrier as a possible origin of the infection. CONCLUSIONS: CNS involvement is not uncommon in adult patients with invasive infection caused by S. agalactiae. Isolating S. agalactiae, especially in cases of meningitis, should lead doctors to search for predisposing systemic disease and causes of mucocutaneous barrier disruption.

Documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH / Consensus document on the management of renal disease in HIV-infected patients

OBJETIVO: Actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el virus de la inmunodeficiencia humana (VIH). MÉTODOS: Este documento ha sido consensuado por un panel de expertos del Grupo de Estudio de Sida (GESIDA) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), de la Sociedad Española de Nefrología (S.E.N.) y de la Sociedad Española de Química Clínica y Patología Molecular (SEQC). Para la valoración de la calidad de la evidencia y la graduación de las recomendaciones se ha utilizado el sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTADOS: La evaluación renal debe incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación chronic kidney disease epidemiological collaboration [CKD-EPI]), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. En este documento se revisan las indicaciones de derivación del paciente a Nefrología y las de la biopsia renal, así como las indicaciones y la evaluación y el manejo del paciente en diálisis o del trasplante renal. CONCLUSIONES: La función renal debe monitorizarse en todos los pacientes con infección por el VIH y este documento pretende optimizar la evaluación y el manejo de la afectación renal.(AU)

OBJECTIVE: To update the 2010 recommendations on the evaluation and management of renal disease in HIV-infected patients. METHODS: This document was approved by a panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Nephrology (S.E.N.), and the Spanish Society of Clinical Chemistry and Molecular Pathology (SEQC). The quality of evidence and the level of recommendation were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, Urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glucosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document advises on the optimal time for referral of a patient to the nephrologist and provides indications for renal biopsy. The indications for and evaluation and management of dialysis and renal transplantation are also addressed. CONCLUSIONS: Renal function should be monitored in all HIV-infected patients. The information provided in this document should enable clinicians to optimize the evaluation and management of HIV-infected patients with renal disease.(AU)

Regression of liver fibrosis is progressive after sustained virological response to HCV therapy in patients with hepatitis C and HIV coinfection.

There are few data about the long-term histological outcome of HIV-/HCV-coinfected patients after therapy with interferon and ribavirin. We performed an observational study of 216 patients who received therapy against HCV and who had at least three successive transient elastographies (TE) during the follow-up. The primary endpoint was confirmed fibrosis regression, defined as a reduction of at least 1 point in Metavir fibrosis score, confirmed and without worsening in successive TE. At baseline, 23% had fibrosis stage 4 or cirrhosis. Overall, 82 (38%) achieved sustained virological response (SVR), without differences in baseline fibrosis or time of follow-up. Confirmed fibrosis regression was observed in 55% of patients, higher for SVR (71% vs 44%; P < 0.01), and the likelihood of achieving fibrosis regression at 3, 5 and 7 years was 0.17, 0.51 and 0.67, respectively, for SVR patients, in comparison with 0.02, 0.23 and 0.41 for no SVR patients (P < 0.01, log-rank test at any time point). Progressive regression, defined as continuous improvement in successive TE, was observed in 62% of patients with advanced liver fibrosis or cirrhosis who achieved SVR. In a Cox regression model, only SVR (HR, 4.01; 95% CI, 2.33-7.57; P < 0.01) and a younger age (HR, 1.14; 95% CI, 1.05-1.25; P < 0.01; per year) were associated with fibrosis regression. This study confirms that the rate of liver fibrosis regression increases during the follow-up after SVR to interferon therapy in HIV-/HCV-coinfected patients.

Non-diphtheriae Corynebacterium species: an emerging respiratory pathogen.

The purpose of the study was to describe the microbiological and clinical features of ten cases of lower respiratory tract infection due to Corynebacterium striatum, Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum. Respiratory samples were recovered from hospitalised patients who were diagnosed of pneumonia and exacerbations of chronic respiratory infections. The samples were Gram-stained and seeded on conventional bacterial growing media. Bacteria were identified by matrix-assisted linear desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility was tested by the disk diffusion method. All patients presented an acute respiratory onset, most of them in the context of an underlying disease and/or immunosuppression. In all patients, the microscopical examination of Gram-stained respiratory samples showed numerous polymorphonuclear cells and Gram-positive bacilli, suggestive of the Corynebacterium morphotype. A pure culture growth of Corynebacterium was obtained in the majority (72 %) of samples. The conclusions are that non-diphtheriae Corynebacterium species are an emerging cause of respiratory infection among patients with chronic respiratory disease and/or immunosuppression, and cannot always be considered as mere colonisers. The microorganism's predominance in Gram-stained purulent respiratory samples together with abundant growth in the culture is the key for the microbiological diagnosis.

The effects of mineral metabolism markers on renal transplant outcomes.

BACKGROUND: Hyperparathyroidism is a common complication of chronic renal failure. A functioning kidney graft improves hyperparathyroidism but it can persist to some degree for years. Persistent hyperparathyroidism associated with hypercalcemia and hyperphosphatemia have been associated with poor graft and patient survivals. The purpose of the present work was to assess the association between calcium/phosphate mineral metabolism markers and graft outcomes. PATIENTS AND METHODS: Among 389 renal transplantations performed in our center between January 2000 and June 2008, 331 patients had functioning grafts at 12 months, the subjects of this study. Measurements of intact parathyroid hormone (iPTH), serum calcium and phosphate, tubular phosphate reabsorption, and urinary calcium excretion were performed at 1, 3, 6, and 12 months. The mean follow-up was 84.0 ± 31.8 months. RESULTS: During the follow-up period, 63 grafts (19.0%) were lost, 30 patients (9.0%) died, and 80 recipients (24.2%) presented at least one cardiovascular event. Univariate Cox proportional analysis showed high iPTH levels at 1 and 12 months after transplantation to not be associated with worse patient or graft survival or an higher risk of cardiovascular events. Serum phosphate and calcium concentrations as well as calcium-phosphate products during the first year after transplantation were not associated with graft and patient outcomes or cardiovascular events. However, serum calcium at 12 months showed an inverse association with graft survival after adjusting for other variables (hazard ratio 0.61; 95% confidence interval 0.40-0.94; P = .026). CONCLUSIONS: iPTH levels and serum phosphate concentrations and calcium-phosphate products during the first year after transplantation were not associated with graft outcomes. The inverse association between adjusted calcium and graft survival should be studied further.

Anemia at 1 year after kidney transplantation has a negative long-term impact on graft and patient outcomes.

BACKGROUND: Anemia, a common complication after kidney transplantation, has a controversial impact on graft or patient survivals or the appearance of cardiovascular disease. The present study investigated the incidence and risk factors for anemia in the first year after transplantation and its effects on graft and patient outcomes. PATIENTS AND METHODS: Among 389 patients transplanted between January 2000 and June 2008, the 331 with functioning grafts at 1 year were included in the study. The mean follow-up was 84 ± 31.8 months. Anemia was defined according to the World Health Organization as a hemoglobin < 13 g/dL in men and < 12 g/dL in women. RESULTS: The 88 patients (26.6%) with anemia included 21 (6.3%) who were receiving erythropoiesis stimulant agents. The predictive factors for anemia were: initial immunosuppression with cyclosporine (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.25-3.47; P = .005), serum creatinine (mg/dL) at discharge (OR 1.7; CI 95% 1.26-2.15 P = .000), and 1-year serum albumin (g/dL; OR 0.21; CI 95% 0.10-0.71 P = .001). Donor age in years (OR 1.02; CI 95% 1.00-1.03, P = .054) was close to significance. Cox multivariate analysis showed 1-year hemoglobin (g/dL) to be associated with graft (hazard ratio [HR] 0.81, 95% CI 0.69-0.96, P = .003) and patient survivals after adjusting for other variables (HR 0.74; 95% CI 0-59-0.96, P = .023). But it was only a cardiovascular risk factor when serum creatinine was not included in the model. CONCLUSIONS: Approximately one quarter of patients with functioning grafts show anemia at 1-year. Graft function, initial immunosuppression, serum albumin, and perhaps donor age were risk factors for anemia, which had a negative impact on graft and patient survival, and could be a risk factor for cardiovascular disease.

Validation of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in advanced chronic renal failure.

INTRODUCTION: The aim of this work was to study the accuracy of the CKD-EPI equation to estimate the glomerular filtrate in patients with advanced chronic renal failure. OBJECTIVE: We compared the estimations of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations to a glomerular filtration rate measured as the arithmetic mean of the urea and creatinine clearances (ClUrCr). MATERIAL AND METHODS: The study was made in 89 nondialyzed patients with chronic renal disease in stage 4 or 5. Serum creatinine values were recalibrated to standardized creatinine measurements. In each patient, the difference between each estimating equation and the measured glomerular filtration rate was calculated. The absolute difference expressed as a percentage of the measured glomerular filtration rate indicates the intermethod variability. RESULTS: Overall, the glomerular filtration rate measured as the ClUrCr was 14.5 ± 5.5 ml/min/1.73 m(2); and the results of the estimating equations were: MDRD 14.3 ± 5.5 (p = NS); CKD-EPI 13.6 ± 5.4 (p <0.01) and CG 16.8 ± 6.5 ml/min/1.73 m(2) (p <0.001). The variability of the estimating equations was 16 ± 12.2%, 16.7 ± 12,1% and 22 ± 15.6% (p <0.05), for MDRD, CKD-EPI and CG. The percentage of estimates within 30% above or below the measured glomerular filtration rate was 85% for MDRD, 88% for CKD-EPI and 70% for CG. The CG variability, but not MDRD variability or CKD-EPI variability, was influenced by gender (19.3 ± 15.1% in males vs 27.3 ± 15.5% in females, p <0.05) and showed a negative correlation with the glomerular filtration rate (r = -0.23, p <0.05) and the age (r = -0.24, p <0.05) and positive correlation with the body mass index (r = 0.37, p <0.001). In patients with chronic renal disease in stage 5, the variability of the different estimating equations was similar. CONCLUSIONS: We conclude that in our population with advanced chronic renal failure, the CKD-EPI equation is as accuracy as the MDRD equation. With standardized creatinine the CG equation has a lower accuracy and its utilization may be reconsiderated.

Validación de la fórmula Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) en la insuficiencia renal crónica avanzada / Validation of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in advanced chronic renal failure

Introducción: La ecuación clásica Modification of Diet in Renal Disease (MDRD) subestima el filtrado glomerular en los valores más altos. Para aumentar su concordancia en los estadios 1 y 2 de la enfermedad renal crónica se ha establecido una nueva fórmula: la ecuación Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Objetivo: El objetivo del presente estudio es comprobar si la nueva ecuación es mejor que la MDRD en la estimación del filtrado glomerular en la insuficiencia renal crónica avanzada, en una población como la nuestra que tiene unas características antropométricas distintas de las de la población norteamericana. Material y métodos: En 89 pacientes con enfermedad renal crónica en estadios 4 y 5, hemos estudiado el grado de concordancia entre el filtrado glomerular medido como la media de los aclaramientos de urea y creatinina (AclUrCr) y el estimado por las ecuaciones MDRD, CKD-EPI y Cockcroft-Gault (CG). La concentración de creatinina corresponde a creatinina estandarizada. La variabilidad de cada una de las ecuaciones fue estudiada mediante la diferencia relativa (diferencia absoluta con el AclUrCr expresada como porcentaje de la media entre el AclUrCr y la (..) (AU)

Introduction: The aim of this work was to study the accuracy of the CKD-EPI equation to estimate the glomerular filtrate in patients with advanced chronic renal failure. Objective: We compared the estimations of Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault (CG) equations to a glomerular filtration rate measured as the arithmetic mean of the urea and creatinine clearances (ClUrCr). Material and methods: The study was made in 89 nondialyzed patients with chronic renal disease in stage 4 or 5. Serum creatinine values were recalibrated to standardized creatinine measurements. In each patient, the difference between each estimating equation and the measured glomerular filtration rate was calculated. The (..) (AU)

Melamine toxicity: one more culprit in calcium kidney lithiasis.

An outbreak of uric acid and melamine kidney stones and obstructive acute renal failure in children appeared recently in China due to the ingestion of melamine-tainted formula. Liu and colleagues show that calcium urolithiasis is also strongly associated with urine melamine in adults in Taiwan. Although its effect measure is still uncertain, such an association is likely to be causal. These findings prompt further research into the source of exposure, impact in other settings, and changes over time.

Utilization of elderly kidney donors (>70 years) does not affect graft survival in the medium term.

BACKGROUND: The need for organs for renal transplantation has encouraged the use of grafts from increasingly older donors. Earlier studies performed in Spain have shown the suitability of donors aged 60-65 years. In this single-center study, we evaluated our results using donors >70 years old. METHODS: We evaluated 401 primary transplantations performed from January 2000 to December 2009. Their initial immunosuppression was a tacrolimus-based (n = 324), cyclosporine-based (n = 70) or calcineurin inhibitor-free (n = 7) regimen patients. Recipients were classified according to the donors age: <50 (42.6%); 50-70 (39.7%) and >70 (17.5%) years. RESULTS: There were no differences in recipient or donor gender, time on dialysis, cold ischemia, delayed graft function, or acute rejection episodes. However, the mean age was higher among patients who received grafts from donors >70 years old; 42.5 ± 12.4 years for <50, 58.1 ± 8.2 years for 50-70, and 65.7 ± 7.2 years for >70; (P = .000). The serum creatinine at 12 months was increased according to the age of the donor; 1.4 ± 0.6, 1.8 ± 0.6, 70 and 1.7 ± 0.5 mg/dL, respectively (P = .001). The graft survival rates at 5 years were 81%, 74%, and 70%, respectively (P = .519). Upon multivariate analysis only HLA-DR mismatches, delayed graft function, and acute rejection episodes were associated with graft loss. Patient survival rates (86%) at 5 years were similar among recipients from donors aged 50-70 and >70 years, but higher (96%) for those who received a graft from a donor <50 years (P = .003). CONCLUSIONS: Nearly 20% of donors were >70 years old in our study. Their kidneys displayed excellent short-term outcomes.

Tratamiento de la anorexia urémica con acetato de megestrol / Treatment of uremic anorexia with megestrol acetate

Introducción: La anorexia es un trastorno frecuente en el enfermo tratado con hemodiálisis periódica, y factor contribuyente de la malnutrición. El objetivo del presente trabajo es comprobar la eficacia del acetato de megestrol, un estimulador del apetito utilizado en enfermos con cáncer, como tratamiento de la anorexia del enfermo sometido a diálisis. Material y métodos: En el año 2009, 16 enfermos de nuestra unidad de hemodiálisis, tres de ellos con diabetes mellitus, fueron tratados con acetato de megestrol (160 mg/día en dosis única), por anorexia definida según una escala Likert de apetito. La pauta y la dosis de diálisis no fueron modificadas durante el estudio. Resultados: Al tercer mes de tratamiento se objetivó, en el grupo total, un aumento del peso seco (60,8 frente a 58,9 kg; p <0,01), de la concentración de albúmina (4,02 frente a 3,8 g/dl; p <0,05), de la concentración de creatinina (9,73 frente a 8,26 mg/dl; p <0,01) y de la tasa de catabolismo proteico (1,24 frente a 0,97 g/kg/día; p <0,001). No hemos constatado variaciones significativas en la concentración de hemoglobina, dosis de eritropoyetina y concentración de lípidos. En un enfermo con diabetes mellitus hubo que aumentar la dosis de insulina y en otros 2 enfermos se detectó una hiperglucemia leve. El acetato de megestrol no suprimió la secreción de hormonas sexuales hipofisarias, pero en 3 de 10 enfermos estudiados se constató una inhibición de la secreción de corticotropina. La respuesta no fue homogénea: un enfermo no respondió y disminuyó su peso seco, en cinco el incremento de peso fue discreto (inferior a 1 kg) y en los 10 restantes la respuesta fue buena, con un incremento de peso seco que osciló entre 1,5 y 5,5 kg. Conclusiones: El acetato de megestrol puede mejorar el apetito y los parámetros nutricionales en enfermos tratados con hemodiálisis periódica que refieran anorexia. El acetato de megestrol puede inducir hiperglucemia e inhibir la secreción de corticotropina en algunos pacientes. Estos efectos secundarios deben ser valorados cuando se administre este tratamiento (AU)

Background: Anorexia is a common disorder in patients treated with regular haemodialysis and is a contributing factor to malnutrition. The aim of this study was to evaluate the effectiveness of megestrol acetate, an appetite stimulant used in cancer patients, as a treatment for anorexia in dialysis patients. Material and method: In 2009, 16 patients in our haemodialysis unit, three with diabetes mellitus, were treated with megestrol (160 mg/day single dose) for anorexia defined according to a Likert scale of appetite. The schedule and dialysis dose were not changed during the study. Results: In the third month of treatment there was, in the overall group, an increase in dry weight (60.8 vs 58.9 kg, P<.01), in albumin concentration (4.02 vs 3.8 g/dl, P<.05), in creatinine concentration (9.73 vs 8.26 mg/dl, P<.01), and protein catabolic rate (1.24 vs. 0.97 g/kg/day, P<.0001). Non-significant variations in the concentration of haemoglobin, erythropoietin dose, and lipid concentrations were found. One patient with diabetes mellitus had to increase the dose of insulin and two other patients suffered mild hyperglycaemia. Megestrol acetate did not suppress the secretion of pituitary sex hormones, but in 3 of 10 patients studied inhibition of ACTH secretion was found. The response was not homogeneous: one patient did not respond and reduced his dry weight, in 5 the weight gain was minimal (less than 1 kg) and in the remaining ten the response was good, with an increase in dry weight ranging between 1.5 and 5.5 kg. Conclusions: Megestrol acetate can improve appetite and nutritional parameters in patients treated with periodic haemodialysis who report anorexia. Megestrol acetate may induce hyperglycaemia and inhibit the secretion of ACTH in some patients. These side effects should be assessed when administering this treatment (AU)