RESUMEN
BACKGROUND AND AIMS: Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can be intensified in high-risk patients. METHODS: Inflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA, and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome-wide association study was then undertaken with these cases and 4109 disease controls. RESULTS: After adjudication, 151 cases of 5-ASA-induced nephrotoxicity were identified. Sixty-eight percent of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6-79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% confidence interval [CI] 2.3-3.7). Only 30% of cases recovered completely after drug withdrawal, with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region (p = 1×10(-7)) with 5-ASA-induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis (n = 55) significantly strengthened this association (p = 4×10(-9), odds ratio 3.1). CONCLUSIONS: This is the largest and most detailed study of 5-ASA-induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to drug-induced renal injury.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , ADN/análisis , Estudio de Asociación del Genoma Completo/métodos , Antígenos HLA/genética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Riñón/patología , Mesalamina/efectos adversos , Lesión Renal Aguda/patología , Adolescente , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Niño , Femenino , Genotipo , Antígenos HLA/metabolismo , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , Riñón/efectos de los fármacos , Masculino , Mesalamina/uso terapéutico , Persona de Mediana Edad , Fenotipo , Adulto JovenRESUMEN
BACKGROUND: Self-expanding metallic stent (SEMS) placement is an important method of dysphagia palliation for patients with inoperable esophageal cancer. In most institutions, it is performed with fluoroscopic guidance; however, in 2001, we described a novel, direct-vision approach to SEMS placement, which does not require fluoroscopy. Here we report an audit of our experience over the last 5 years when using this methodology. OBJECTIVE: To describe our 5-year experience of 98 patients in whom esophageal stents were inserted when using the direct-vision technique and compare outcomes with published series of radiography-guided stents. DESIGN: Retrospective review of single-center experience. SETTING: English National Health Service Cancer Centre Hospital. PATIENTS: All patients who underwent esophageal stent insertion for a primary esophageal malignancy. INTERVENTIONS: SEMS insertion by direct endoscopic vision. RESULTS: Ninety-eight patients underwent SEMS insertion for malignant dysphagia during the study period, 92% of which were inserted without fluoroscopy. The technique had a low complication rate, which was consistent with published fluoroscopic data, and the median survival beyond stent insertion was 100 days (interquartile range, 62, 256; range, 4-921 days). In 59 patients, no further endoscopic palliative procedure was required. LIMITATIONS: Retrospective data collection. CONCLUSIONS: This series confirms direct-vision SEMS placement as a safe and efficacious method of malignant dysphagia palliation, providing definitive treatment in almost two thirds of cases.