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1. Clinical triage of patients on kidney replacement therapy presenting with COVID-19: An ERACODA registry analysis

Author

Mitra, S., Jayanti, A., Vart, P., Coca, A., Gallieni, M., Ovrehus, M. A., Midtvedt, K., Abd Elhafeez, S., Gandolfini, I., Buttner, S., Franssen, C. F. M., Hemmelder, M. H., Van Der Net, J. B., Essig, M., Du Buf-Vereijken, P. W. G., Van Ginneken, B., Maas, N., Vogt, L., Van Jaarsveld, B. C., Jager, K. J., Bemelman, F. J., Klingenberg-Salahova, F., Heenan-Vos, F., Vervloet, M. G., Nurmohamed, A., Abramowicz, D., Verhofstede, S., Maoujoud, O., Malfait, T., Fialova, J., Melilli, E., Fava, A., Cruzado, J. M., Perez, N. M., Lips, J., Krepel, H., Adilovic, H., Hengst, M., Rydzewski, A., Gellert, R., Oliveira, J., Alferes, D. G., Zakharova, E. V., Ambuehl, P. M., Walker, A., Winzeler, R., Lepeytre, F., Rabate, C., Rostoker, G., Marques, S., Azasevac, T., Katicic, D., Dam, M. T., Kruger, T., Brzosko, S., Zanen, A. L., Logtenberg, S. J. J., Fricke, L., Slebe, J. J. P., Kemlin, D., Van De Wetering, J., Reinders, M. E. J., Eiselt, J., Kielberger, L., El-Wakil, H. S., Verhoeven, M. A. M., Canal, C., Facundo, C., Ramos, A. M., Debska-Slizien, A., Veldhuizen, N. M. H., Tigka, E., Konsta, M. A. P., Panagoutsos, S., Mallamaci, F., Postorino, A., Cambareri, F., Covic, A., Matceac, I., Nistor, I., Cordos, M., Groeneveld, J. H. M., Jousma, J., Marjolijn Van Buren, Diekmann, F., Tiago Assis Pereira, Santos, A. C. S., Arias-Cabrales, C., Crespo, M., Llinas-Mallol, L., Buxeda, A., Tarrega, C. B., Redondo-Pachon, D., Jimenez, M. D. A., Hofstra, J. M., Franco, A., Arroyo, D., Rodriguez-Ferrero, M. L., Manzanos, S. B., Barrios, R. H. S., Avila, G., Laranjinha, I., Mateus, C., Lemahieu, W., Bartelet, K., Dirim, A. B., Sever, M. S., Demir, E., Safak, S., Turkmen, A., Hollander, D. A. M. J., De Vries, A. P. J., Meziyerh, S., Van Der Helm, D., Mallat, M., Bouwsma, H., Sridharan, S., Petruliene, K., Maloney, S. -R., Verberk, I., Van Der Sande, F. M., Christiaans, M. H. L., Mohankumar, N., Di Luca, M., Tuglular, S. Z., Kramer, A., Beerenhout, C., Luik, P. T., Kerschbaum, J., Tiefenthaler, M., Watschinger, B., Adema, A. Y., Stepanov, V. A., Zulkarnaev, A. B., Turkmen, K., Fliedner, A., Asberg, A., Mjoen, G., Miyasato, H., De Fijter, C. W. H., Mongera, N., Pini, S., De Biase, C., Duivenvoorden, R., Hilbrands, L., Kerckhoffs, A., Van De Logt, A. -E., Maas, R., Lebedeva, O., Lopez, V., Verhave, J., Reichert, L. J. M., Titov, D., Parshina, E. V., Zanoli, L., Marcantoni, C., Van Gils-Verrij, L. E. A., Harty, J. C., Meurs, M., Myslak, M., Battaglia, Y., Lentini, P., Den Deurwaarder, E., Stendahl, M., Rahimzadeh, H., Schouten, M., Rychlik, I., Cabezas-Reina, C. J., Roca, A. M., Nauta, F., Goffin, E., Kanaan, N., Labriola, L., Devresse, A., Diaz-Mareque, A., Meijers, B. K. I., Naesens, M., Kuypers, D., Desschans, B., Tonnelier, A., Wissing, K. M., De Arriba, G., Dedinska, I., Pessolano, G., Maggiore, U., Malik, S., Papachristou, E., Gansevoort, R. T., Noordzij, M., Berger, S. P., Meijer, E., Ozyilmaz, A., Sanders, J. S. F., Ponikvar, J. B., Arnol, M., Pernat, A. M., Kovac, D., Ekart, R., Abrahams, A. C., Molenaar, F. M., Van Zuilen, A. D., Meijvis, S. C. A., Dolmans, H., Tantisattamo, E., Esposito, P., Krzesinski, J. -M., Barahira, J. D., Sabiu, G., Martin-Moreno, P. L., Guglielmetti, G., Guzzo, G., Toapanta, N., Soler, M. J., Luik, A. J., Van Kuijk, W. H. M., Stikkelbroeck, L. W. H., Hermans, M. M. H., Rimsevicius, L., Righetti, M., Islam, M., Braak, N. H. -T., Nephrology, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Interne Geneeskunde, RS: Carim - V02 Hypertension and target organ damage, Groningen Kidney Center (GKC), ACS - Diabetes & metabolism, AII - Inflammatory diseases, AII - Infectious diseases, Internal Medicine, and Clinical sciences

Subjects
kidney, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, Pulmonary insufficiency, infectious diseases, Kidney, Second presentation, Interquartile range, Internal medicine, medicine, Humans, Registries, Mortality, AcademicSubjects/MED00340, Dialysis, Aged, Transplantation, second presentation, business.industry, SARS-CoV-2, COVID-19, medicine.disease, mortality, Triage, Hospitalization, Renal Replacement Therapy, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Nephrology, Oxygen Saturation, dialysis, Original Article, Hemodialysis, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], Presentation (obstetrics), business, transplantation
Abstract

Background Patients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes. Methods The European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage. Results Among 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2–7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage. Conclusions This study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19 to aid clinical triage and optimize resource utilization during the ongoing pandemic.

Published
2021

2. Use and safety of remdesivir in kidney transplant recipients with COVID-19

Author

Maria Luisa Martin, Cristina Canal, Carlos Arias-Cabrales, Antonio Franco, Francesc Moreso, Isabel María Saura, Luis Sanchez-Cámara, Sofía Zárraga, Sheila Cabello Pelegrin, Julio Pascual, Emilio Sánchez-Álvarez, Inmaculada Lorenzo, Anna Buxeda, Raquel Santana-Estupiñán, Edoardo Melilli, María José Aladrén, Esperanza Moral Berrio, Judit Cacho, Marta Crespo, Orlando Siverio, Auxiliadora Mazuecos, José Portolés, Verónica López, Elena González-García, Paloma L Martin-Moreno, Iñigo Moina, María José Pérez-Sáez, Cristina Galeano, María del Carmen Ruiz-Fuentes, Institut Català de la Salut, [Buxeda A, Arias-Cabrales C, Pérez-Sáez MJ] Department of Nephrology, Hospital del Mar, Institute Mar for Medical Research (IMIM), Red de Investigación Renal (REDinREN) (RD16/0009/0013), Barcelona, Spain. [Cacho J] Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. [Cabello Pelegrin S] Department of Nephrology, Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Melilli E] Department of Nephrology, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. [Moreso F] Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
medicine.medical_specialty, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales::insuficiencia renal::lesión renal aguda [ENFERMEDADES], medicine.medical_treatment, Trasplantament renal, Remdesivir, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Injury, Other subheadings::Other subheadings::/drug therapy [Other subheadings], law.invention, Kidney transplantation, SARS-CoV2l, Randomized controlled trial, COVID-19 (Malaltia) - Tractament, law, Clinical Research, Internal medicine, medicine, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Adverse effect, business.industry, SARS-CoV-2, Acute kidney injury, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Immunosuppression, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], medicine.disease, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Acute Kidney Injury [DISEASES], Discontinuation, Insuficiència renal aguda, Nephrology, SARS-CoV2, Cohort, Avaluació de resultats (Assistència sanitària), Acute kidney, business, Cohort study
Abstract

Introduction:Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time torecovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acutekidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidneytransplant recipients.Methods:We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treatedwith remdesivir. Outcomes and safety were assessed.Results:Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) requiredmechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged$65 years(45% vs. 3.2% in younger patients). Acute kidneyinjury was present in 27.7% of patients, but wasdiagnosed in 50% before treatment. No patients required remdesivir discontinuation because ofadverse events. We did notfind significant hepatoxicity or systemicsymptoms resulting from thedrug. Conclusion:In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renaland hepatic toxicity, but randomized trials are needed to assess its efficacy. The authors are indebted to the many physicians andnurses who take care of these patients and are facing theCOVID-19 pandemic in our country. This research wassupported by Rio Hortega contract CM19/00004 (ISCIII)(AB), and RD16/0009/0013 (ISCIII FEDER RedinRen). MJP-S is supported by a Spanish Society of Transplantscholarship

Published
2021

3. Recurrence of FSGS after Kidney Transplantation in Adults

Author

Carlos Arias-Cabrales, Thomas Jouve, María José Pérez-Sáez, Leonardo V. Riella, Enver Akalin, Paolo Cravedi, Stefan P Berger, Kuo-Kai Chin, Carlucci Gualberto Ventura, Xingxing S. Cheng, Paolo Malvezzi, Claudia Bini, Silvia Regina Hokazono, Gilberto M.V. Neto, Audrey Uffing, Mathilde Bugnazet, Saif A. Muhsin, Marilda Mazzali, Anna Buxeda, Roberto Ceratti Manfro, Fabiana Agena, Miguel C. Riella, Nikhil Agrawal, Frederico de Sottomaior Drumond, Gaetano La Manna, Giorgia Comai, Omar Alani, Meredith Haverly, Suraj Sarvode Mothi, Samira S. Farouk, Elias David-Neto, Helio Tedesco-Silva, Michelle M. O’Shaughnessy, Juliana Mansur, Gianna Mastroianni Kirsztajn, Andrea Carla Bauer, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Uffing A., Perez-Saez M.J., Mazzali M., Manfro R.C., Bauer A.C., Drumond F.S., O'shaughnessy M.M., Cheng X.S., Chin K.-K., Ventura C.G., Agena F., David-Neto E., Mansur J.B., Kirsztajn G.M., Tedesco-Silva H., Neto G.M.V., Arias-Cabrales C., Buxeda A., Bugnazet M., Jouve T., Malvezzi P., Akalin E., Alani O., Agrawal N., La Manna G., Comai G., Bini C., Muhsin S.A., Riella M.C., Hokazono S.R., Farouk S.S., Haverly M., Mothi S.S., Berger S.P., Cravedi P., and Riella L.V.

Subjects
Male, Time Factors, Epidemiology, medicine.medical_treatment, kidney disease, 030232 urology & nephrology, graft survival, CHILDREN, 030230 surgery, Critical Care and Intensive Care Medicine, Nephrectomy, DISEASE, FOCAL SEGMENTAL GLOMERULOSCLEROSIS, 0302 clinical medicine, Focal segmental glomerulosclerosis, rituximab, cohort studies, Interquartile range, THERAPEUTIC PLASMA-EXCHANGE, Medicine, risk factors, humans, Kidney transplantation, transplant recipients, Glomerulosclerosis, Focal Segmental, RENAL-TRANSPLANTATION, adult, Hazard ratio, Middle Aged, renal transplantation, kidney diseases, sample size, Europe, risk factor, plasmapheresis, Nephrology, Retreatment, Female, Brazil, Immunosuppressive Agents, Cohort study, medicine.medical_specialty, kidney, recurrence, kidney transplantation, body mass index, ALLOGRAFT, Risk Assessment, 03 medical and health sciences, transplant recipient, Internal medicine, human, Risk factor, Retrospective Studies, plasmapheresi, Transplantation, business.industry, Proportional hazards model, transplant outcomes, Editorials, registries, transplant outcome, medicine.disease, United States, RECIPIENTS, registrie, RESISTANT NEPHROTIC SYNDROME, focal segmental glomerulosclerosi, SAMPLE-SIZE, incidence, treatment outcome, RISK-FACTORS, business, cohort studie
Abstract

Background and objectives FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. Design, setting, participants, & measurements The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. Results Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0–8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. Conclusions Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

Published
2020

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