Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.
The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain. flmedrano@yahoo.es.
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López-Medrano
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.
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Fernández-Ruiz
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.
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Silva
University of Michigan Health System, Ann Harbor, MI.
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Carver
Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva, Geneva, Switzerland.
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van Delden
Unit of Infectious Diseases, Hospital Universitario General, Alicante, Spain.
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Merino
Department of Nephrology, Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
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Pérez-Saez
Department of Infectious Diseases, Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
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Montero
Department of Nephrology, Dialysis and Kidney Transplantation, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
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Coussement
Division of Nephology, Department of Medicine, Universidade Federal de São Paulo-UNIFESP and Hospital do Rim e Hipertensão, Fundação Oswaldo Ramos, São Paulo, Brazil.
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de Abreu Mazzolin
Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain.
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Cervera
Unit of Renal Transplantation, Department of Urology and Kidney Transplantation, Coimbra Hospital and University Centre, Coimbra, Portugal.
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Santos
Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
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Sabé
Service de Néphrologie et Transplantation Adulte, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, RTRS Centaure, Paris, France.
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Scemla
Unit of Infectious Diseases, Hospitales Universitarios "Vigen del Rocío", Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain.
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Cordero
Department of Nephrology, Hospital Universitario "La Fe", Valencia, Spain.
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Cruzado-Vega
Department of Nephrology, Clínica Universitaria de Navarra, Pamplona, Spain.
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Martín-Moreno
Department of Infectious Diseases, Hospital Universitari Vall d'Hebrón, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
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Len
Department of Nephrology, Hospital Universitario "Carlos Haya", Málaga, Spain.
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Rudas
Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México DF, México.
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de León
Clínica de Nefrología, Urología y Enfermedades Cardiovasculares, Santa Fe, Argentina.
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Arriola
Department of Nephrology, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
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Lauzurica
Department of Microbiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
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David
Department of Infectious Diseases, University Hospital "Marqués de Valdecilla", Santander, Spain.
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González-Rico
Department of Nephrology, University Hospital "Doctor Negrín", Las Palmas de Gran Canaria, Spain.
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Henríquez-Palop
Department of Infectious Diseases, University Hospital "Ramón y Cajal", Madrid, Spain.
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Fortún
Department of Internal Medicine, Hematology Service and Mycology Laboratory, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
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Nucci
Department of Infectious Diseases and Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
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Manuel
Department of Internal Medicine, Hospital Universitario "La Paz", School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
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Paño-Pardo
Department of Infectious Diseases, Hospital Universitario Cruces, Barakaldo, Bilbao, Spain.
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Montejo
Department of Microbiology and Infectious Diseases, Hospital General Universitario "Gregorio Marañón", Madrid, Spain.
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Muñoz
Department of Nephrology, Hospital Universitario Puerta de Hierro-Majadahonda, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
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Sánchez-Sobrino
Department of Nephrology, Hospital Universitario "Puerta del Mar", Cádiz, Spain.
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Mazuecos
Department of Nephrology, Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
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Pascual
Department of Infectious Diseases, Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
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Horcajada
Service of Infectious Diseases, Department of Medical Specialities, University Hospitals Geneva, Geneva, Switzerland.
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Lecompte
Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Spain.
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Moreno
Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Barcelona, Spain.
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Carratalà
Unit of Infectious Diseases, Hospital Universitario "La Fe", Valencia, Spain.
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Blanes
Department of Nephrology, Hospital Universitario "Carlos Haya", Málaga, Spain.
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Hernández
Department of Infectious Diseases, University Hospital "Marqués de Valdecilla", Santander, Spain.
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Fariñas
Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.
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Andrés
Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), Department of Medicine, School of Medicine, Universidad Complutense, Madrid, Spain.
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Aguado
D001230:Aspergillus; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007390:International Agencies; D055744:Invasive Pulmonary Aspergillosis / Q000209:etiology / Q000401:mortality* / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000401:mortality*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D066027:Transplant Recipients
antibiotic: antifungal; clinical research/practice; complication: infectious; fungal; infection and infectious agents; infectious disease; kidney transplantation/nephrology