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1. Economic evaluation of intravenous iron treatments in the management of anemia patients in Greece

Author

Fragoulakis V, Kourlaba G, Goumenos D, Konstantoulakis M, and Maniadakis N

Subjects
Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Vassilis Fragoulakis1, Georgia Kourlaba1, Dimitris Goumenos2, Manousos Konstantoulakis3, Nikolaos Maniadakis11Department of Health Services Management, National School of Public Health, Athens, 2Department of Medicine University Hospital of Patras, Patras, 3Department of Medicine, Athens Medical School, Athens, GreecePurpose: To conduct an economic evaluation comparing Ferinject® (ferric carboxymaltose [FCM]) with Venofer® (iron sucrose [IS]) and CosmoFer® (low-molecular-weight iron dextran [LMWID]) in the management of iron deficiency anemia in Greece.Patients and methods: A cost-minimization analysis was conducted since there are no clear data indicating that one of these regimens is superior to the others in terms of efficacy. Main data inputs were based on bibliography and validated by clinicians. The economic evaluation was conducted for inpatients (ie, surgical patients or patients hospitalized due to a disease related to chronic or acute blood loss) and outpatients (eg, nondialysis chronic kidney disease patients), separately. Analysis was carried out from a National Health Service (NHS) perspective and also from a patient perspective. Total cost treatment reflects the cost of drugs, the cost of all resources expended in patient management such as the cost of disposables for each infusion, the monitoring costs during infusion (salaries of personnel), other hospital expenses, the cost for management of adverse events, the productivity loss, and the traveling cost for patients.Results: In the case of outpatients, the mean total cost per patient in the FCM arm was €198.6, in the IS arm €627.7, and in the LMWID arm, €510.5. For inpatients the mean total cost was estimated at €189.2 for FCM while it was €419.9 and €228.8 for IS and LMWID, respectively. Budget impact analysis for a typical Greek hospital with 100 patients revealed that the total cost of FCM (inpatients analysis) was 113% and 15.4% lower against their comparators. In an outpatient situation, the total cost of FCM was 201.1% and 151.8% lower compared with IS and LMWID, respectively.Conclusion: Ferric carboxymaltose may represent a cost-saving option compared with the most likely alternative existing therapies used for the management of anemia in the National Health Service of Greece.Keywords: economic evaluation, cost minimization, ferric carboxymaltose, anemia, iron therapy

Published
2012

2. Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy

Author

Coppo, R., Feehaly, J., Troyanov, S., Cattran, D.C., Cook, H.T., Roberts, I., Radcliffe, John, Russo, M.L., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Papagianni, K., Stangou, M., Giacchino, F., Goumenos, D., Papasotirious, M., Kalliakmani, P., Gerolymos, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Hryszko, T., Klinger, M., Kamińska, D., Krajewska, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Cambier, A., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Diomedi-Casadei, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Royal, V., Bellur, Shubha S., Troyanov, Stéphan, Vorobyeva, Olga, Coppo, Rosanna, and Roberts, Ian S.D.

Published
2024
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3. Application of the International IgA Nephropathy Prediction Tool one or two years post-biopsy

Author

Russo, M.L., Troyanov, S., Cook, H.T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Papachristou, E., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Ljubanovic, D. Galesic, Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Cook, T., Alpers, C., Berthoux, F., Bonsib, S., D’Agati, V., D’Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, C.-H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Barbour, Sean J., Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Er, Lee, Reich, Heather N., Barratt, Jonathan, and Cattran, Daniel C.

Published
2022
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4. Development and testing of an artificial intelligence tool for predicting end-stage kidney disease in patients with immunoglobulin A nephropathy

Author

Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Coppo, R., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., Feehally, J., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Papasotiriou, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Rauen, T., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Grinyo, J.M. Boria, Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Canton, A. Dal, Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Mazzucco, Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., GalesicLjubanovic, D., Gakiopoulou, H., Bertoni, E., Ortiz, P. Cannata, Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., FulladosaOliveras, X., Maldyk, J., Ioachim, E., Abbrescia, Daniela, Kouri, Nikoleta, Stangou, Maria, Papagianni, Aikaterini, Scolari, Francesco, Delbarba, Elisa, Bonomini, Mario, Piscitani, Luca, Stallone, Giovanni, Infante, Barbara, Godeas, Giulia, Madio, Desiree, Biancone, Luigi, Campagna, Marco, Zaza, Gianluigi, Squarzoni, Isabella, Cangemi, Concetta, Schena, Francesco Paolo, Anelli, Vito Walter, Trotta, Joseph, Di Noia, Tommaso, Manno, Carlo, Tripepi, Giovanni, D’Arrigo, Graziella, Chesnaye, Nicholas C., Russo, Maria Luisa, Zoccali, Carmine, Tesar, Vladimir, and Coppo, Rosanna

Published
2021
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5. Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool

Author

Russo, M.L., Troyanov, S., Cook, H.T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Cook, T., Alpers, C., Berthoux, F., Bonsib, S., D’Agati, V., D’Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa N, N., Zeng, C.-H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Barbour, Sean J., Canney, Mark, Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Katafuchi, Ritsuko, Induruwage, Dilshani, Er, Lee, Reich, Heather N., Feehally, John, Barratt, Jonathan, and Cattran, Daniel C.

Published
2020
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6. Brain dysfunction in tubular and tubulointerstitial kidney diseases

Author

Viggiano D, Bruchfeld A, Carriazo S, de Donato A, Endlich N, Ferreira AC, Figurek A, Fouque D, Franssen CFM, Giannakou K, Goumenos D, Hoorn EJ, Nitsch D, Arduan AO, Pešić V, Rastenyté D, Soler MJ, Rroji M, Trepiccione F, Unwin RJ, Wagner CA, Wiecek A, Zacchia M, Zoccali C, Capasso G, CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target)., Viggiano, D, Bruchfeld, A, Carriazo, S, de Donato, A, Endlich, N, Ferreira, Ac, Figurek, A, Fouque, D, Franssen, Cfm, Giannakou, K, Goumenos, D, Hoorn, Ej, Nitsch, D, Arduan, Ao, Pešić, V, Rastenyté, D, Soler, Mj, Rroji, M, Trepiccione, F, Unwin, Rj, Wagner, Ca, Wiecek, A, Zacchia, M, Zoccali, C, Capasso, G, CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative, Target)., NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), CarMeN, laboratoire, University of the Study of Campania Luigi Vanvitelli, Karolinska University Hospital [Stockholm], Linköping University (LIU), IIS‑Fundación Jiménez Diaz‑Autonoma University [Madrid, Spain], University of Medicine Greifswald, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Universität Zürich [Zürich] = University of Zurich (UZH), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), University of Groningen [Groningen], European University of Cyprus, General University Hospital of Patras, Erasmus University Medical Center [Rotterdam] (Erasmus MC), London School of Hygiene and Tropical Medicine (LSHTM), University of Belgrade [Belgrade], Lithuanian University of health Sciences [Kaunas], Vall d’Hebron Research Institute (VHIR), University Hospital Center 'Mother Tereza' [Tirana, Albania] (UHCMT), University College of London [London] (UCL), Medical University of Silesia (SUM), Renal Research Institute [New York, NY, USA] (2RI), CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target): Giovambattista Capasso, Alexandre Andrade, Maie Bachmann, Inga Bumblyte, Adrian Constantin Covic, Pilar Delgado, Nicole Endlich, Andreas Engvig, Denis Fouque, Casper Franssen, Sebastian Frische, Liliana Garneata, Loreto Gesualdo, Konstantinos Giannakou, Dimitrios Goumenos, Ayşe Tuğba Kartal, Laila-Yasmin Mani, Hans-Peter Marti, Christopher Mayer, Rikke Nielsen, Vesna Pšić, Merita Rroji Molla, Giorgos Sakkas, Goce Spasovski, Kate I Stevens, Evgueniy Vazelov, Davide Viggiano, Lefteris Zacharia, Ana Carina Ferreira, Jolanta Malyszko, Ewout Hoorn, Andreja Figurek, Robert Unwin, Carsten A Wagner, Christoph Wanner, Annette Bruchfeld, Marion Pépin, Andrzej Wieçek, Dorothea Nitsch, Ivo Fridolin, Gaye Hafez, Maria José Soler, Michelangela Barbieri, Bojan Batinić, Laura Carrasco, Sol Carriazo, Ron Gansevoort, Gianvito Martino, Francesco Mattace Raso, Ionut Nistor, Alberto Ortiz, Giuseppe Paolisso, Daiva Rastenytė, Gabriel Stefan, Gioacchino Tedeschi, Ziad A Massy, Boris Bikbov, Karl Hans Endlich, Olivier Godefroy, Jean-Marc Chillon, Anastassia Kossioni, Justina Kurganaite, Norberto Perico, Giuseppe Remuzzi, Tomasz Grodzicki, Francesco Trepiccione, Carmine Zoccali, Mustafa Arici, Peter Blankestijn, Kai-Uwe Eckardt, Danilo Fliser, Eugenio Gutiérrez Jiménez, Maximilian König, Ivan Rychlik, Michela Deleidi, George Reusz, and Internal Medicine

Subjects
ACIDOSIS, [SDV]Life Sciences [q-bio], Review, Disease, electrolyte, 030204 cardiovascular system & hematology, urologic and male genital diseases, 0302 clinical medicine, Child, 610 Medicine & health, MUTATION, 0303 health sciences, Kidney, Proteinuria, Reabsorption, female genital diseases and pregnancy complications, 3. Good health, [SDV] Life Sciences [q-bio], BARTTER-SYNDROME, medicine.anatomical_structure, Nephrology, Child, Preschool, GITELMANS-SYNDROME, Kidney Diseases, medicine.symptom, Glomerular Filtration Rate, medicine.medical_specialty, brain, chronic kidney disease, cognitive function, tubulointerstitial, Urology, Renal function, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Renal Insufficiency, Chronic, AcademicSubjects/MED00340, NEPHRITIS, 030304 developmental biology, Rheumatology and Autoimmunity, Transplantation, Reumatologi och inflammation, HYPONATREMIA, business.industry, urogenital system, AQP2, medicine.disease, Nephrogenic diabetes insipidus, GENE, KLOTHO, MODEL, Nephritis, Interstitial, business, Tubulointerstitial Disease, Kidney disease
Abstract

Funding: This article is published as part of a supplement financially supported by the COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT). Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research. publishersversion published

Published
2022

7. Application of the International IgA Nephropathy Prediction Tool one or two years post-biopsy

Author

Barbour, Sean J., primary, Coppo, Rosanna, additional, Zhang, Hong, additional, Liu, Zhi-Hong, additional, Suzuki, Yusuke, additional, Matsuzaki, Keiichi, additional, Er, Lee, additional, Reich, Heather N., additional, Barratt, Jonathan, additional, Cattran, Daniel C., additional, Russo, M.L., additional, Troyanov, S., additional, Cook, H.T., additional, Roberts, I., additional, Tesar, V., additional, Maixnerova, D., additional, Lundberg, S., additional, Gesualdo, L., additional, Emma, F., additional, Fuiano, L., additional, Beltrame, G., additional, Rollino, C., additional, Amore, A., additional, Camilla, R., additional, Peruzzi, L., additional, Praga, M., additional, Feriozzi, S., additional, Polci, R., additional, Segoloni, G., additional, Colla, L., additional, Pani, A., additional, Piras, D., additional, Angioi, A., additional, Cancarini, G., additional, Ravera, S., additional, Durlik, M., additional, Moggia, E., additional, Ballarin, J., additional, Di Giulio, S., additional, Pugliese, F., additional, Serriello, I., additional, Caliskan, Y., additional, Sever, M., additional, Kilicaslan, I., additional, Locatelli, F., additional, Del Vecchio, L., additional, Wetzels, J.F.M., additional, Peters, H., additional, Berg, U., additional, Carvalho, F., additional, da Costa Ferreira, A.C., additional, Maggio, M., additional, Wiecek, A., additional, Ots-Rosenberg, M., additional, Magistroni, R., additional, Topaloglu, R., additional, Bilginer, Y., additional, D’Amico, M., additional, Stangou, M., additional, Giacchino, F., additional, Goumenos, D., additional, Papachristou, E., additional, Galesic, K., additional, Geddes, C., additional, Siamopoulos, K., additional, Balafa, O., additional, Galliani, M., additional, Stratta, P., additional, Quaglia, M., additional, Bergia, R., additional, Cravero, R., additional, Salvadori, M., additional, Cirami, L., additional, Fellstrom, B., additional, Smerud, H. Kloster, additional, Ferrario, F., additional, Stellato, T., additional, Egido, J., additional, Martin, C., additional, Floege, J., additional, Eitner, F., additional, Lupo, A., additional, Bernich, P., additional, Menè, P., additional, Morosetti, M., additional, van Kooten, C., additional, Rabelink, T., additional, Reinders, M.E.J., additional, Boria Grinyo, J.M., additional, Cusinato, S., additional, Benozzi, L., additional, Savoldi, S., additional, Licata, C., additional, Mizerska-Wasiak, M., additional, Martina, G., additional, Messuerotti, A., additional, Dal Canton, A., additional, Esposito, C., additional, Migotto, C., additional, Triolo, G., additional, Mariano, F., additional, Pozzi, C., additional, Boero, R., additional, Bellur, S., additional, Mazzucco, G., additional, Giannakakis, C., additional, Honsova, E., additional, Sundelin, B., additional, Di Palma, A.M., additional, Gutiérrez, E., additional, Asunis, A.M., additional, Barratt, J., additional, Tardanico, R., additional, Perkowska-Ptasinska, A., additional, Terroba, J. Arce, additional, Fortunato, M., additional, Pantzaki, A., additional, Ozluk, Y., additional, Steenbergen, E., additional, Soderberg, M., additional, Riispere, Z., additional, Furci, L., additional, Orhan, D., additional, Kipgen, D., additional, Casartelli, D., additional, Ljubanovic, D. Galesic, additional, Gakiopoulou, H., additional, Bertoni, E., additional, Cannata Ortiz, P., additional, Karkoszka, H., additional, Groene, H.J., additional, Stoppacciaro, A., additional, Bajema, I., additional, Bruijn, J., additional, Fulladosa Oliveras, X., additional, Maldyk, J., additional, Ioachim, E., additional, Bavbek, N., additional, Cook, T., additional, Alpers, C., additional, Berthoux, F., additional, Bonsib, S., additional, D’Agati, V., additional, D’Amico, G., additional, Emancipator, S., additional, Emmal, F., additional, Fervenza, F., additional, Florquin, S., additional, Fogo, A., additional, Groene, H., additional, Haas, M., additional, Hill, P., additional, Hogg, R., additional, Hsu, S., additional, Hunley, T., additional, Hladunewich, M., additional, Jennette, C., additional, Joh, K., additional, Julian, B., additional, Kawamura, T., additional, Lai, F., additional, Leung, C., additional, Li, L., additional, Li, P., additional, Liu, Z., additional, Massat, A., additional, Mackinnon, B., additional, Mezzano, S., additional, Schena, F., additional, Tomino, Y., additional, Walker, P., additional, Wang, H., additional, Weening, J., additional, Yoshikawa, N., additional, Zeng, C.-H., additional, Shi, S., additional, Nogi, C., additional, Suzuki, H., additional, Koike, K., additional, Hirano, K., additional, Yokoo, T., additional, Hanai, M., additional, Fukami, K., additional, Takahashi, K., additional, Yuzawa, Y., additional, Niwa, M., additional, Yasuda, Y., additional, Maruyama, S., additional, Ichikawa, D., additional, Suzuki, T., additional, Shirai, S., additional, Fukuda, A., additional, Fujimoto, S., additional, and Trimarchi, H., additional

Published
2022
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8. Frequent COL4 mutations in familial microhematuria accompanied by later‐onset Alport nephropathy due to focal segmental glomerulosclerosis

Author

Papazachariou, L., Papagregoriou, G., Hadjipanagi, D., Demosthenous, P., Voskarides, K., Koutsofti, C., Stylianou, K., Ioannou, P., Xydakis, D., Tzanakis, I., Papadaki, A., Kallivretakis, N., Nikolakakis, N., Perysinaki, G., Gale, D.P., Diamantopoulos, A., Goudas, P., Goumenos, D., Soloukides, A., Boletis, I., Melexopoulou, C., Georgaki, E., Frysira, E., Komianou, F., Grekas, D., Paliouras, C., Alivanis, P., Vergoulas, G., Pierides, A., Daphnis, E., and Deltas, C.

Published
2017
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9. Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases: consensus statements from the ERA-IWG and EUVAS

Author

Stevens, K.I., Frangou, E., Shin, J.I., Anders, H.J., Bruchfeld, A., Schonermarck, U., Hauser, T., Westman, K., Fernandez-Juarez, G.M., Floege, J., Goumenos, D., Turkmen, K., Kooten, C. van, McAdoo, S.P., Tesar, V., Segelmark, M., Geetha, D., Jayne, D.R.W., Kronbichler, A., Immunonephrology Working Grp IWG, European Renal Assoc ERA, and European Vasculitis Soc EUVAS

Subjects
immunology, Transplantation, COVID-19 Vaccines, immunosuppression, rituximab, Nephrology, COVID-19, Humans, Kidney Diseases, IgA nephropathy, Mycophenolic Acid, Antibodies, Viral, vasculitis
Abstract

Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. The timing between the use of these agents and administration of vaccines is associated with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine-induced immunity highlight the value of a booster dose and the need to develop mutant-proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or coincidental. Such cases respond to standard management, including the use of immunosuppression. The Immunonephrology Working Group and European Vasculitis Society recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered.

Published
2022

11. Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update

Author

Coppo, R., D'Arrigo, G., Tripepi, G., Russo, M. L., Roberts, I. S. D., Bellur, S., Cattran, D., Cook, T. H., Feehally, J., Tesar, V., Maixnerova, D., Peruzzi, L., Amore, A., Lundberg, S., Di Palma, A. M., Gesualdo, L., Emma, F., Rollino, C., Praga, M., Biancone, L., Pani, A., Feriozzi, S., Polci, R., Barratt, J., Del Vecchio, L., Locatelli, F., Pierucci, A., Caliskan, Y., Perkowska-Ptasinska, A., Durlik, M., Moggia, E., Ballarin, J. C., Wetzels, J. F. M., Goumenos, D., Papasotiriou, M., Galesic, K., Toric, L., Papagianni, A., Stangou, M., Benozzi, L., Cusinato, S., Berg, U., Topaloglu, R., Maggio, M., Ots-Rosenberg, M., D'Amico, M., Geddes, C., Balafa, O., Quaglia, M., Cravero, R., Cirami, C. L., Fellstrom, B., Floege, J., Egido, J., Mallamaci, F., Zoccali, C., Fuiano, L., Beltrame, G., Camilla, R., Segoloni, G., Colla, L., Angioi, A., Piras, L., Cancarini, G., Ravera, S., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Sever, M., Kilicaslan, I., Peters, H., Carvalho, F., Da Costa Ferreira, A. C., Wiecek, A., Magistroni, R., Bilginer, Y., Giacchino, F., Papastirou, M., Siamopoulos, K., Galliani, M., Stratta, P., Bergia, R., Salvadori, M., Cirami, L., Kloster Smerud, H., Ferrario, F., Stellato, T., Martin, C., Eitner, F., Rauen, T., Lupo, A., Bernich, P., Mene, P., Morosetti, M., Van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Gutierrez, E., Asunis, A. M., Tardanico, R., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Akiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., and Internal Medicine

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Adolescent, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, Kidney, Nephropathy, Cohort Studies, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, renal biopsy, Interquartile range, IgA nephropathy, progression, risk factors, Child, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate, Glomerulonephritis, IGA, Humans, Prognosis, Medicine, Endocapillary hypercellularity, IGA, Transplantation, medicine.diagnostic_test, business.industry, medicine.disease, medicine.anatomical_structure, Renal pathology, Nephrology, Cohort, Renal biopsy, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract

Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Published
2020

13. Quantifying duration of proteinuria remission and association with clinical outcome in IgA nephropathy

Author

Canney, M., Barbour, S. J., Zheng, Y., Coppo, R., Zhang, H., Liu, Z. -H., Matsuzaki, K., Suzuki, Y., Katafuchi, R., Reich, H. N., Cattran, D., Russo, M. L., Troyanov, S., Cook, H. T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A. M., Gutierrez, E., Asunis, A. M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Cook, T., Alpers, C., Feehally, J., Berthoux, F., Bonsib, S., D'Agati, V., D'Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, C. -H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Anesthesiology, Pathology, Graduate School, ACS - Heart failure & arrhythmias, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Male, Time Factors, glomerular disease, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, 0302 clinical medicine, Outcome Assessment, Health Care, Clinical endpoint, Medicine, Clinical Epidemiology, Proteinuria, medicine.diagnostic_test, Remission Induction, Hazard ratio, IgA nephropathy, General Medicine, Middle Aged, end stage kidney disease, epidemiology and outcomes, proteinuria, renal function decline, renal pathology, 3. Good health, Renal pathology, Nephrology, Disease Progression, Female, medicine.symptom, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Nephropathy, 03 medical and health sciences, Internal medicine, Biopsy, Humans, Proportional Hazards Models, Retrospective Studies, business.industry, Surrogate endpoint, Glomerulonephritis, IGA, medicine.disease, Confidence interval, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Kidney Failure, Chronic, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract

Contains fulltext : 232930.pdf (Publisher’s version ) (Closed access) BACKGROUND: On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS: In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to

Published
2021

14. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA

Author

Ortiz, A, Cozzolino, M, Duivenvoorden, R, Fliser, D, Fouque, D, Franssen, CFM, Goumenos, D, Hemmelder, MH, Hilbrands, LB, Jager, KJ, Massy, ZA, Noordzij, M, Rosenkranz, AR, Rychlik, I, Soler, MJ, Stevens, K, Torra, R, Tuglular, S, Vart, P, Wanner, C, Gansevoort, RT, ERA-EDTA Council, and Eracoda Working Grp

Subjects
risk factor, prevalence, COVID-19, mortality, renal replacement therapy, chronic kidney disease
Abstract

Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR

Published
2021

15. Quantifying duration of proteinuria remission and association with clinical outcome in IgA nephropathy

Author

Canney, M. Barbour, S.J. Zheng, Y. Coppo, R. Zhang, H. Liu, Z.-H. Matsuzaki, K. Suzuki, Y. Katafuchi, R. Reich, H.N. Cattran, D. Russo, M.L. Troyanov, S. Cook, H.T. Roberts, I. Tesar, V. Maixnerova, D. Lundberg, S. Gesualdo, L. Emma, F. Fuiano, L. Beltrame, G. Rollino, C. Amore, A. Camilla, R. Peruzzi, L. Praga, M. Feriozzi, S. Polci, R. Segoloni, G. Colla, L. Pani, A. Piras, D. Angioi, A. Cancarini, G. Ravera, S. Durlik, M. Moggia, E. Ballarin, J. Di Giulio, S. Pugliese, F. Serriello, I. Caliskan, Y. Sever, M. Kilicaslan, I. Locatelli, F. Del Vecchio, L. Wetzels, J.F.M. Peters, H. Berg, U. Carvalho, F. da Costa Ferreira, A.C. Maggio, M. Wiecek, A. Ots-Rosenberg, M. Magistroni, R. Topaloglu, R. Bilginer, Y. D'Amico, M. Stangou, M. Giacchino, F. Goumenos, D. Kalliakmani, P. Gerolymos, M. Galesic, K. Geddes, C. Siamopoulos, K. Balafa, O. Galliani, M. Stratta, P. Quaglia, M. Bergia, R. Cravero, R. Salvadori, M. Cirami, L. Fellstrom, B. Kloster Smerud, H. Ferrario, F. Stellato, T. Egido, J. Martin, C. Floege, J. Eitner, F. Lupo, A. Bernich, P. Menè, P. Morosetti, M. van Kooten, C. Rabelink, T. Reinders, M.E.J. Boria Grinyo, J.M. Cusinato, S. Benozzi, L. Savoldi, S. Licata, C. Mizerska-Wasiak, M. Martina, G. Messuerotti, A. Dal Canton, A. Esposito, C. Migotto, C. Triolo, G. Mariano, F. Pozzi, C. Boero, R. Bellur, S. Mazzucco, G. Giannakakis, C. Honsova, E. Sundelin, B. Di Palma, A.M. Gutiérrez, E. Asunis, A.M. Barratt, J. Tardanico, R. Perkowska-Ptasinska, A. Arce Terroba, J. Fortunato, M. Pantzaki, A. Ozluk, Y. Steenbergen, E. Soderberg, M. Riispere, Z. Furci, L. Orhan, D. Kipgen, D. Casartelli, D. Galesic Ljubanovic, D. Gakiopoulou, H. Bertoni, E. Cannata Ortiz, P. Karkoszka, H. Groene, H.J. Stoppacciaro, A. Bajema, I. Bruijn, J. Fulladosa Oliveras, X. Maldyk, J. Ioachim, E. Bavbek, N. Cook, T. Alpers, C. Feehally, J. Berthoux, F. Bonsib, S. D'Agati, V. D'Amico, G. Emancipator, S. Emmal, F. Fervenza, F. Florquin, S. Fogo, A. Groene, H. Haas, M. Hill, P. Hogg, R. Hsu, S. Hunley, T. Hladunewich Jennette, C. Joh, K. Julian, B. Kawamura, T. Lai, F. Leung, C. Li, L. Li, P. Liu, Z. Massat, A. Mackinnon, B. Mezzano, S. Schena, F. Tomino, Y. Walker, P. Wang, H. Weening, J. Yoshikawa, N. Zeng, C.-H. Shi, S. Nogi, C. Suzuki, H. Koike, K. Hirano, K. Yokoo, T. Hanai, M. Fukami, K. Takahashi, K. Yuzawa, Y. Niwa, M. Yasuda, Y. Maruyama, S. Ichikawa, D. Suzuki, T. Shirai, S. Fukuda, A. Fujimoto, S. Trimarchi, H. International IgA Nephropathy Network

Abstract

Background On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. Methods In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a $25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to,1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR). Results During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups. Conclusions Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints. Copyright © 2021 by the American Society of Nephrology.

Published
2021

19. Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool

Author

Barbour, Sean J., primary, Canney, Mark, additional, Coppo, Rosanna, additional, Zhang, Hong, additional, Liu, Zhi-Hong, additional, Suzuki, Yusuke, additional, Matsuzaki, Keiichi, additional, Katafuchi, Ritsuko, additional, Induruwage, Dilshani, additional, Er, Lee, additional, Reich, Heather N., additional, Feehally, John, additional, Barratt, Jonathan, additional, Cattran, Daniel C., additional, Russo, M.L., additional, Troyanov, S., additional, Cook, H.T., additional, Roberts, I., additional, Tesar, V., additional, Maixnerova, D., additional, Lundberg, S., additional, Gesualdo, L., additional, Emma, F., additional, Fuiano, L., additional, Beltrame, G., additional, Rollino, C., additional, Amore, A., additional, Camilla, R., additional, Peruzzi, L., additional, Praga, M., additional, Feriozzi, S., additional, Polci, R., additional, Segoloni, G., additional, Colla, L., additional, Pani, A., additional, Piras, D., additional, Angioi, A., additional, Cancarini, G., additional, Ravera, S., additional, Durlik, M., additional, Moggia, E., additional, Ballarin, J., additional, Di Giulio, S., additional, Pugliese, F., additional, Serriello, I., additional, Caliskan, Y., additional, Sever, M., additional, Kilicaslan, I., additional, Locatelli, F., additional, Del Vecchio, L., additional, Wetzels, J.F.M., additional, Peters, H., additional, Berg, U., additional, Carvalho, F., additional, da Costa Ferreira, A.C., additional, Maggio, M., additional, Wiecek, A., additional, Ots-Rosenberg, M., additional, Magistroni, R., additional, Topaloglu, R., additional, Bilginer, Y., additional, D’Amico, M., additional, Stangou, M., additional, Giacchino, F., additional, Goumenos, D., additional, Kalliakmani, P., additional, Gerolymos, M., additional, Galesic, K., additional, Geddes, C., additional, Siamopoulos, K., additional, Balafa, O., additional, Galliani, M., additional, Stratta, P., additional, Quaglia, M., additional, Bergia, R., additional, Cravero, R., additional, Salvadori, M., additional, Cirami, L., additional, Fellstrom, B., additional, Kloster Smerud, H., additional, Ferrario, F., additional, Stellato, T., additional, Egido, J., additional, Martin, C., additional, Floege, J., additional, Eitner, F., additional, Lupo, A., additional, Bernich, P., additional, Menè, P., additional, Morosetti, M., additional, van Kooten, C., additional, Rabelink, T., additional, Reinders, M.E.J., additional, Boria Grinyo, J.M., additional, Cusinato, S., additional, Benozzi, L., additional, Savoldi, S., additional, Licata, C., additional, Mizerska-Wasiak, M., additional, Martina, G., additional, Messuerotti, A., additional, Dal Canton, A., additional, Esposito, C., additional, Migotto, C., additional, Triolo, G., additional, Mariano, F., additional, Pozzi, C., additional, Boero, R., additional, Bellur, S., additional, Mazzucco, G., additional, Giannakakis, C., additional, Honsova, E., additional, Sundelin, B., additional, Di Palma, A.M., additional, Gutiérrez, E., additional, Asunis, A.M., additional, Barratt, J., additional, Tardanico, R., additional, Perkowska-Ptasinska, A., additional, Arce Terroba, J., additional, Fortunato, M., additional, Pantzaki, A., additional, Ozluk, Y., additional, Steenbergen, E., additional, Soderberg, M., additional, Riispere, Z., additional, Furci, L., additional, Orhan, D., additional, Kipgen, D., additional, Casartelli, D., additional, Galesic Ljubanovic, D., additional, Gakiopoulou, H., additional, Bertoni, E., additional, Cannata Ortiz, P., additional, Karkoszka, H., additional, Groene, H.J., additional, Stoppacciaro, A., additional, Bajema, I., additional, Bruijn, J., additional, Fulladosa Oliveras, X., additional, Maldyk, J., additional, Ioachim, E., additional, Bavbek, N., additional, Cook, T., additional, Alpers, C., additional, Berthoux, F., additional, Bonsib, S., additional, D’Agati, V., additional, D’Amico, G., additional, Emancipator, S., additional, Emmal, F., additional, Fervenza, F., additional, Florquin, S., additional, Fogo, A., additional, Groene, H., additional, Haas, M., additional, Hill, P., additional, Hogg, R., additional, Hsu, S., additional, Hunley, T., additional, Hladunewich, M., additional, Jennette, C., additional, Joh, K., additional, Julian, B., additional, Kawamura, T., additional, Lai, F., additional, Leung, C., additional, Li, L., additional, Li, P., additional, Liu, Z., additional, Massat, A., additional, Mackinnon, B., additional, Mezzano, S., additional, Schena, F., additional, Tomino, Y., additional, Walker, P., additional, Wang, H., additional, Weening, J., additional, Yoshikawa N, N., additional, Zeng, C.-H., additional, Shi, S., additional, Nogi, C., additional, Suzuki, H., additional, Koike, K., additional, Hirano, K., additional, Yokoo, T., additional, Hanai, M., additional, Fukami, K., additional, Takahashi, K., additional, Yuzawa, Y., additional, Niwa, M., additional, Yasuda, Y., additional, Maruyama, S., additional, Ichikawa, D., additional, Suzuki, T., additional, Shirai, S., additional, Fukuda, A., additional, Fujimoto, S., additional, and Trimarchi, H., additional

Published
2020
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21. Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

Author

Stangou, M. Marinaki, S. Papachristou, E. Kolovou, K. Sambani, E. Zerbala, S. Papadea, P. Balafa, O. Rapsomanikis, K.-P. Andrikos, A. Manolakaki, P. Papadopoulou, D. Mitsopoulos, E. Liakou, H. Andronikidi, P.-E. Choulitoudi, V. Moustakas, G. Galitsiou, D. Dafnis, E. Stylianou, K. Stefanidis, I. Golfinopoulos, S. Panagoutsos, S. Tsilivigkou, M. Papadogianakis, A. Tzanakis, I. Sioulis, A. Vlachakos, D. Grapsa, E. Spaia, S. Kaperonis, N. Paliouras, C. Dioudis, C. Papoulidou, F. Apostolou, T. Iatrou, C. Boletis, I. Goumenos, D. Papagianni, A.

Abstract

Introduction Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term followup. Aim The aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN. Patients-methods Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens. Results Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14- 87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, p

Published
2019

22. Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: Evidence from the VALidation of IGA study cohort

Author

Bellur, S.S. Roberts, I.S.D. Troyanov, S. Royal, V. Coppo, R. Cook, H.T. Cattran, D. Terroba, Y.A. Asunis, A.M. Bajema, I. Bertoni, E. Bruijn, J.A. Cannata-Ortiz, P. Casartelli, D. Di Palma, A.M. Ferrario, F. Fortunato, M. Furci, L. Gakiopoulou, H. Ljubanovic, D.G. Giannakakis, K. Gomá, M. Gröne, H.-J. Gutiérrez, E. Haider, S.A. Honsova, E. Ioachim, E. Karkoszka, H. Kipgen, D. Maldyk, J. Mazzucco, G. Orhan, D. Ozluk, Y. Pantzaki, A. Perkowska-Ptasinska, A. Riispere, Z. Soderberg, M.P. Steenbergen, E. Stoppacciaro, A. Von Feilitzen, B.S. Tardanico, R. Tesar, V. Maixnerova, D. Lundberg, S. Gesualdo, L. Emma, F. Fuiano, L. Beltrame, G. Rollino, C. Coppo, R. Amore, A. Camilla, R. Peruzzi, L. Praga, M. Feriozzi, S. Polci, R. Segoloni, G. Colla, L. Pani, A. Angioi, A. Piras, L. Feehally, J. Barratt, J. Cancarini, G. Ravera, S. Durlik, M. Moggia, E. Ballarin, J. Di Giulio, S. Pugliese, F. Serriello, I. Caliskan, Y. Sever, M. Locatelli, F. Del Vecchio, L. Wetzels, J.F.M. Peters, H. Berg, U. Carvalho, F. da Costa Ferreira, A.C. Maggio, M. Wiecek, A. Ots-Rosenberg, M. Magistroni, R. Topaloglu, R. Bilginer, Y. D'Amico, M. Stangou, M. Giacchino, F. Goumenos, D. Kalliakmani, P. Gerolymos, M. Galesic, K. Geddes, C. Siamopoulos, K. Balafa, O. Galliani, M. Stratta, P. Quaglia, M. Bergia, R. Cravero, R. Salvadori, M. Cirami, L. Fellstrom, B. Kloster Smerud, H. Ferrario, F. Stellato, T. Egido, J. Martin, C. Floege, J. Eitner, F. Lupo, A. Bernich, P. Menè, P. Morosetti, M. van Kooten, C. Rabelink, T. Reinders, M.E.J. Grinyo, J.M. Fulladosa, X. Cusinato, S. Benozzi, L. Savoldi, S. Licata, C. Mizerska-Wasiak, M. Roszkowska-Blaim, M. Martina, G. Messuerotti, A. Dal Canton, A. Esposito, C. Migotto, C. Triolo, G. Mariano, F. Pozzi, C. Boero, R. Kilicaslan, I.

Abstract

Background: The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results: All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion: We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies. © 2018 The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Published
2019

23. Defective gene expression of the membrane complement inhibitor CD46 in patients with progressive immunoglobulin A nephropathy

Author

Coppo, R, Peruzzi, L, Loiacono, E, Bergallo, M, Krutova, A, Russo, Ml, Cocchi, E, Amore, A, Lundberg, S, Maixnerova, D, Tesar, V, Perkowska-Ptasińska, A, Durlik, M, Goumenos, D, Gerolymos, M, Galesic, K, Toric, L, Papagianni, A, Stangou, M, Mizerska-Wasia Membek, M, Gesualdo, L, Montemurno, E, Benozzi, L, Cusinato, S, Hryszko, T, Klinger, M, Kamińska, D, Krajewska, M, and VALIGA Study Group of the ERA-EDTA Immunonephrology Working Group

Published
2019

24. Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: Evidence from the VALidation of IGA study cohort

Author

Bellur, S. S., Roberts, I. S. D., Troyanov, S., Royal, V., Coppo, R., Cook, H. T., Cattran, D., Terroba, Y. A., Asunis, A. M., Bajema, I., Bertoni, E., Bruijn, J. A., Cannata-Ortiz, P., Casartelli, D., Di Palma, A. M., Ferrario, F., Fortunato, M., Furci, L., Gakiopoulou, H., Ljubanovic, D. G., Giannakakis, K., Goma, M., Grone, H. -J., Gutierrez, E., Haider, S. A., Honsova, E., Ioachim, E., Karkoszka, H., Kipgen, D., Maldyk, J., Mazzucco, G., Orhan, D., Ozluk, Y., Pantzaki, A., Perkowska-Ptasinska, A., Riispere, Z., Soderberg, M. P., Steenbergen, E., Stoppacciaro, A., Von Feilitzen, B. S., Tardanico, R., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., Feehally, J., Barratt, J., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Grinyo, J. M., Fulladosa, X., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., and Kilicaslan, I.

Subjects
medicine.medical_specialty, IgA nephropathy, immunosuppression, kidney biopsy, Oxford classification, proteinuria, medicine.medical_treatment, Biopsy, 030232 urology & nephrology, Disease, 030204 cardiovascular system & hematology, Lesion, 03 medical and health sciences, 0302 clinical medicine, Glomerulonephritis, Models, Internal medicine, medicine, Humans, Endocapillary hypercellularity, Clinical significance, IGA, Retrospective Studies, Observer Variation, Transplantation, Models, Statistical, Proteinuria, medicine.diagnostic_test, business.industry, Patient Selection, Oxford classification, Reproducibility of Results, Glomerulonephritis, IGA, Immunosuppression, Statistical, Prognosis, Nephrology, proteinuria, Glomerular Filtration Rate, Immunosuppressive Agents, Cohort, medicine.symptom, business
Abstract

Background The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.

Published
2019

25. Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

Author

Stangou, M.J. Marinaki, S. Papachristou, E. Liapis, G. Pateinakis, P. Gakiopoulou, H. Nikolaidou, C. Kolovou, K. Lampropoulou, I.-T. Zerbala, S. Papadea, P. Dounousi, E. Balafa, O. Pavlakou, P. Andrikos, A. Balassi, E. Manolakaki, P. Moustakas, G. Galitsiou, D. Mitsopoulos, E. Vourlakou, C. Choulitoudi, V. Andronikidi, P.-E. Stefanidis, I. Golfinopoulos, S. Dafnis, E. Stylianou, K. Panagoutsos, S. Papadogianakis, A. Tzanakis, I. Sioulis, A. Vlahakos, D. Grapsa, I. Tsilivigkou, M. Kaperonis, N. Paliouras, C. Dioudis, C. Spaia, S. Apostolou, T. Iatrou, C. Boletis, J. Goumenos, D. Papagianni, A.

Abstract

Aims: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. Methods and results: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P 50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. Conclusions: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings. © 2019 The Authors. Histopathology published by John Wiley & Sons Ltd

Published
2019

26. Evaluating a New International Risk-Prediction Tool in IgA Nephropathy

Author

Barbour, S.J., Coppo, R., Zhang, H., Liu, Z.H., Suzuki, Y., Matsuzaki, K., Katafuchi, R., Er, L., Espino-Hernandez, G., Kim, S.J., Reich, H.N., Feehally, J., Cattran, D.C., Russo, M.L., Troyanov, S., Cook, H.T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Giulio, S. di, Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Vecchio, L. del, Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., Ferreira, A.C.D., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrorn, B., Smerud, H.K., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, R., Morosetti, M., Kooten, C. van, Rabelink, T., Reinders, M.E.J., Grinyo, J.M.B., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Canton, A. dal, Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Palma, A.M. di, Gutierrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J.A., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Ljubanovic, D.G., Gakiopoulou, H., Bertoni, E., Ortiz, P.C., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Oliveras, X.F., Maldyk, J., Loachim, E., Bavbek, N., Cook, T., Alpers, C., Berthoux, F., Bonsib, S., D'Agati, V., D'Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, C.H., Shi, S.F., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Int IgA Nephropathy Network, and Pathology

Subjects
Adult, Male, medicine.medical_specialty, Risk Assessment, 01 natural sciences, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, 0101 mathematics, business.industry, Proportional hazards model, Clinical study design, 010102 general mathematics, Glomerulonephritis, IGA, Middle Aged, Models, Theoretical, medicine.disease, Clinical trial, Cohort, Female, business, Risk assessment, Kidney disease
Abstract

ImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. ObjectiveTo derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and ParticipantsWe derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and MeasuresCox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R-D(2) measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. ResultsThe study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R-D(2) (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and RelevanceIn this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

Published
2019

27. Evaluating a New International Risk-Prediction Tool in IgA Nephropathy

Author

Barbour, Sean J. Coppo, Rosanna Zhang, Hong Liu, Zhi-Hong and Suzuki, Yusuke Matsuzaki, Keiichi Katafuchi, Ritsuko Er, Lee Espino-Hernandez, Gabriela Kim, S. Joseph Reich, Heather N. Feehally, John Cattran, Daniel C. Russo, M. L. and Troyanov, S. Cook, H. T. Roberts, I. Tesar, V. and Maixnerova, D. Lundberg, S. Gesualdo, L. Emma, F. and Fuiano, L. Beltrame, G. Rollino, C. Amore, A. Camilla, R. Peruzzi, L. Praga, M. Feriozzi, S. Polci, R. and Segoloni, G. Colla, L. Pani, A. Piras, D. Angioi, A. and Cancarini, G. Ravera, S. Durlik, M. Moggia, E. Ballarin, J. Di Giulio, S. Pugliese, F. Serriello, I. Caliskan, Y. and Sever, M. Kilicaslan, I. Locatelli, F. Del Vecchio, L. and Wetzels, J. F. M. Peters, H. Berg, U. Carvalho, F. and da Costa Ferreira, A. C. Maggio, M. Wiecek, A. and Ots-Rosenberg, M. Magistroni, R. Topaloglu, R. Bilginer, Y. and D'Amico, M. Stangou, M. Giacchino, F. Goumenos, D. and Kalliakmani, P. Gerolymos, M. Galesic, K. Geddes, C. and Siamopoulos, K. Balafa, O. Galliani, M. Stratta, P. and Quaglia, M. Bergia, R. Cravero, R. Salvadori, M. Cirami, L. Fellstrorn, B. Smerud, H. Kloster Ferrario, F. and Stellato, T. Egido, J. Martin, C. Floege, J. Eitner, F. and Lupo, A. Bernich, P. Mene, R. Morosetti, M. van Kooten, C. Rabelink, T. Reinders, M. E. J. Boria Grinyo, J. M. Cusinato, S. Benozzi, L. Savoldi, S. Licata, C. and Mizerska-Wasiak, M. Martina, G. Messuerotti, A. Dal Canton, A. Esposito, C. Migotto, C. Triolo, G. Mariano, F. and Pozzi, C. Boero, R. Bellur, S. Mazzucco, G. Giannakakis, C. Honsova, E. Sundelin, B. Di Palma, A. M. Ferrario, F. and Gutierrez, E. Asunis, A. M. Barratt, J. Tardanico, R. and Perkowska-Ptasinska, A. Arce Terroba, J. Fortunato, M. and Pantzaki, A. Ozluk, Y. Steenbergen, E. Soderberg, M. and Riispere, Z. Furci, L. Orhan, D. Kipgen, D. Casartelli, D. Ljubanovic, D. Galesic Gakiopoulou, H. Bertoni, E. and Cannata Ortiz, P. Karkoszka, H. Groene, H. J. Stoppacciaro, A. Bajema, I. Bruijn, J. Fulladosa Oliveras, X. Maldyk, J. Loachim, E. Bavbek, N. Cook, T. Troyanov, S. and Alpers, C. Amore, A. Barratt, J. Berthoux, F. Bonsib, S. and Bruijn, J. D'Agati, V D'Amico, G. Emancipator, S. and Emmal, F. Ferrario, F. Fervenza, F. Florquin, S. Fogo, A. Geddes, C. Groene, H. Haas, M. Hill, P. Hogg, R. and Hsu, S. Hunley, T. Hladunewich Jennette, C. Joh, K. and Julian, B. Kawamura, T. Lai, F. Leung, C. Li, L. and Li, P. Liu, Z. Massat, A. Mackinnon, B. Mezzano, S. and Schena, F. Tomino, Y. Walker, P. Wang, H. Weening, J. and Yoshikawa, N. Zeng, Cai-Hong Shi, Sufang Nogi, C. and Suzuki, H. Koike, K. Hirano, K. Kawamura, T. Yokoo, T. and Hanai, M. Fukami, K. Takahashi, K. Yuzawa, Y. Niwa, M. Yasuda, Y. Maruyama, S. Ichikawa, D. Suzuki, T. and Shirai, S. Fukuda, A. Fujimoto, S. Trimarchi, H. Int IgA Nephropathy Network

Abstract

ImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. ObjectiveTo derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and ParticipantsWe derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and MeasuresCox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R-D(2) measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. ResultsThe study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R-D(2) (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and RelevanceIn this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

Published
2019

28. Normal saline versus balanced crystalloids in patients with prerenal acute kidney injury and pre-existing chronic kidney disease

Author

Papasotiriou Marios, Mpratsiakou Adamantia, Georgopoulou Georgia, Ntrinias Theodoros, Balta Lamprini, Pavlakou Paraskevi, Goumenos Dimitrios S., and Papachristou Evangelos

Subjects
acute kidney injury, balanced solutions, chronic kidney disease, hyperchloremia, normal saline, Internal medicine, RC31-1245
Abstract

Normal saline (N/S) and Ringer’s-Lactate (L/R), are administered in everyday clinical practice. Despite that, N/S increases the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R has lower sodium content, significantly less chloride and contains lactates. In this study we compare the efficacy of L/R versus N/S administration in patients with prerenal acute kidney injury (AKI) and pre-established chronic kidney disease (CKD).

Published
2023
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29. The family of 14-3-3 proteins and specifically 14-3-3σ are up-regulated during the development of renal pathologies

Author

Rizou, M. Frangou, E.A. Marineli, F. Prakoura, N. Zoidakis, J. Gakiopoulou, H. Liapis, G. Kavvadas, P. Chatziantoniou, C. Makridakis, M. Vlahou, A. Boletis, J. Vlahakos, D. Goumenos, D. Daphnis, E. Iatrou, C. Charonis, A.S.

Abstract

Chronic kidney disease, the end result of most renal and some systemic diseases, is a common condition where renal function is compromised due to fibrosis. During renal fibrosis, calreticulin, a multifunctional chaperone of the endoplasmic reticulum (ER) is up-regulated in tubular epithelial cells (TECs) both in vitro and in vivo. Proteomic analysis of cultured TECs overexpressing calreticulin led to the identification of the family of 14-3-3 proteins as key proteins overexpressed as well. Furthermore, an increased expression in the majority of 14-3-3 family members was observed in 3 different animal models of renal pathologies: the unilateral ureteric obstruction, the nephrotoxic serum administration and the ischaemia-reperfusion. In all these models, the 14-3-3σ isoform (also known as stratifin) was predominantly overexpressed. As in all these models ischaemia is a common denominator, we showed that the ischaemia-induced transcription factor HIF1α is specifically associated with the promoter region of the 14-3-3σ gene. Finally, we evaluated the expression of the family of 14-3-3 proteins and specifically 14-3-3σ in biopsies from IgA nephropathy and membranous nephropathy patients. These results propose an involvement of 14-3-3σ in renal pathology and provide evidence for the first time that hypoxia may be responsible for its altered expression. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Published
2018

30. Erythropoietic response to oral iron in patients with nondialysis-dependent chronic kidney disease in the FIND-CKD trial

Author

Macdougall, I. C., Bock, A. H., Carrera, F., Eckardt, K. -U., Gaillard, C., Van Wyck, D., Meier, Y., Larroque, S., Perrin, A., Roger, S. D., Gilles, Auguste, Faull, R., Toussaint, N. D., Mcmahon, L., Suranyi, M., Mudge, D., Hutchison, B., Irish, A., Kerr, P., Kulkarni, H., Elder, G., Jardine, M., Lhotta, K., Mayer, G., Vanholder, R., Maes, B. D., Evenepoel, P., Debelle, F., Jadoul, M., Dratwa, M., Macel, I., Dunaj, M., Kvapil, M., Bucek, P., Rehorova, J., Hruby, A., Honova, V., Malanova, L., Lucak, M., Lecian, D., Jirovec, M., Vlasak, J., Rychlik, I., Surel, S., Kamper, A. -L., Ostergaard, O., Steffensen, G. K., Chenine, L., Choukroun, G., Zaoui, P., Wanner, C., Backs, W., Kraatz, U., Dellanna, F., Busch, K., Marsen, T., Seeger, W., Woitas, R., Obermueller, N., Haak, T., Lueders, S., Pistrosch, F., Mueller, E., Mertens, P. R., Sutermer, W., Grebe, S. -O., Hafezi-Rachti, S., Roeser, S., Tsakiris, D., Memmos, D., Vlachakos, D., Vargemezis, V., Stefanidis, I., Syrganis, C., Alivanis, P., Papadakis, I., Papagalanis, N., Andrikos, A., Goumenos, D., Siamopoulos, K., Gouva, C., Papadakis, G., Boletis, I., Tsimnadi-Spanoudaki, M., Stamatiades, D., Stamatelou, K., Moutafis, S., Locatelli, Federica, Santoro, A., Quarello, F., Remuzzi, G., Coppola, S., Mortellaro, R. F., Icardi, A., Colussi, G., Grotta, F. D., Lombardi, L., Gallieni, M., Villa, G., Grandaliano, Giuseppe, Huisman, S., Barendregt, J., Gregoor, P. J. H., Oien, C., Rutkowski, B., Malecki, R., Nowicki, M., Rutkowski, P., Marczewski, K., Mysliwiec, M., Sydor, A., Rysz, J., Rydzewski, A., Klinger, M., Wnuk, R., Kozminski, P., Nocon, A., Ciechanowski, K., Correia, P., Neves, F., Barata, J., Mircescu, G., Voiculescu, M., Gluhovschi, G., Mota, E., De Francisco, A. L. M., Torre, A., Herreros, A., Luno, J., Gruss, E., Martins, J., Valles, M., Pascual, J., Barany, P., Ambuehl, P. M., Erturk, S., Arici, M., Paydas, S., Soypacaci, Z., Camsari, T., Ustundag, S., Thomas, M. E., D'Souza, R. J., Taylor, J. E., Pritchard, N. R., Jeffery, R., Riley, S. G., Bhatnagar, D., Bhandari, S., Reaich, D., Stevens, P. E., El Kossi, M., Roe, S., Camilleri, B., Ahmed, A., Khwaja, A., Thompson, B., Banerjee, D., Nicholas, J., Hutchison, A., Borrows, R., and Groningen Kidney Center (GKC)

Subjects
0301 basic medicine, Male, 030232 urology & nephrology, Administration, Oral, Gastroenterology, oral, 0302 clinical medicine, DIALYSIS, nondialysis, Settore MED/14 - NEFROLOGIA, Erythropoiesis, SUCROSE, Aged, 80 and over, education.field_of_study, biology, Anemia, General Medicine, Iron deficiency, RANDOMIZED CONTROLLED-TRIAL, Middle Aged, Nephrology, Female, INTRAVENOUS FERRIC CARBOXYMALTOSE, Research Article, Adult, medicine.medical_specialty, Iron, Population, supplement, 03 medical and health sciences, Multicenter trial, Internal medicine, medicine, DEFICIENCY ANEMIA, Humans, Renal Insufficiency, Chronic, education, Aged, Transferrin saturation, business.industry, ferritin, hemoglobin, medicine.disease, Ferritin, 030104 developmental biology, biology.protein, Hemoglobin, business, Kidney disease
Abstract

Aims: To evaluate erythropoietic response rates to oral iron over time in iron-deficient anemic patients with nondialysis-dependent chronic kidney disease (ND-CKD). Materials and methods: FIND-CKD was a 1-year, randomized, multicenter trial of iron therapy in patients with ND-CKD, anemia, and iron deficiency, without erythropoiesis-stimulating agent (ESA) therapy. Patients with active infection or C-reactive protein > 20 mg/L were excluded. In this post-hoc analysis, response was defined as >= 1 g/dL increase in hemoglobin (Hb) from baseline, before initiation of alternative anemia therapy (i.e., ESA, transfusion, or intravenous iron). Results: 308 patients received oral iron (200 mg elemental iron/day). Mean (SD) Hb at baseline was 10.4 (0.7) g/dL. At week 4, Hb data were available from 292 patients without alternative anemia therapy: 63/292 (21.6%) showed a response. Among the 229 nonresponders at week 4, 48.8% showed a cumulative response on >= 1 occasion by week 52 (11.1%, 19.9%, 25.9%, and 28.7% had a response at weeks 8, 12, 24, and 52, respectively), and 27.9% had received alternative iron therapy by week 52. Baseline levels of Hb, ferritin, and transferrin saturation were lower in responders than in nonresponders. Neither concomitant medication nor adherence (as assessed by medication count) was substantially different between early responders and nonresponders. Conclusion: Four weeks after starting oral iron therapy, only 21.6% of anemic patients with ND-CKD and iron deficiency showed an Hb increase of at least 1 g/dL. Among early nonresponders

Published
2017

31. Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis

Author

Papazachariou, L. Papagregoriou, G. Hadjipanagi, D. and Demosthenous, P. Voskarides, K. Koutsofti, C. Stylianou, K. and Ioannou, P. Xydakis, D. Tzanakis, I. Papadaki, A. and Kallivretakis, N. Nikolakakis, N. Perysinaki, G. Gale, D. P. and Diamantopoulos, A. Goudas, P. Goumenos, D. Soloukides, A. Boletis, I. Melexopoulou, C. Georgaki, E. Frysira, E. and Komianou, F. Grekas, D. Paliouras, C. Alivanis, P. and Vergoulas, G. Pierides, A. Daphnis, E. Deltas, C.

Subjects
urologic and male genital diseases
Abstract

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using next generation sequencing (NGS) for 5 genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, 9 of them novel. In 5 families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-years, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies.

Published
2017

32. Development and testing of an artificial intelligence tool for predicting end-stage kidney disease in patients with immunoglobulin A nephropathy

Author

Schena, Francesco Paolo, Anelli, Vito Walter, Trotta, Joseph, Di Noia, Tommaso, Manno, Carlo, Tripepi, Giovanni, D’Arrigo, Graziella, Chesnaye, Nicholas C., Russo, Maria Luisa, Stangou, Maria, Papagianni, Aikaterini, Zoccali, Carmine, Tesar, Vladimir, Coppo, Rosanna, Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Coppo, R., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., Feehally, J., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Papasotiriou, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Rauen, T., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Grinyo, J.M. Boria, Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Canton, A. Dal, Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Mazzucco, Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., GalesicLjubanovic, D., Gakiopoulou, H., Bertoni, E., Ortiz, P. Cannata, Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., FulladosaOliveras, X., Maldyk, J., Ioachim, E., Abbrescia, Daniela, Kouri, Nikoleta, Stangou, Maria, Papagianni, Aikaterini, Scolari, Francesco, Delbarba, Elisa, Bonomini, Mario, Piscitani, Luca, Stallone, Giovanni, Infante, Barbara, Godeas, Giulia, Madio, Desiree, Biancone, Luigi, Campagna, Marco, Zaza, Gianluigi, Squarzoni, Isabella, and Cangemi, Concetta

Abstract

We have developed an artificial neural network prediction model for end-stage kidney disease (ESKD) in patients with primary immunoglobulin A nephropathy (IgAN) using a retrospective cohort of 948 patients with IgAN. Our tool is based on a two-step procedure of a classifier model that predicts ESKD, and a regression model that predicts development of ESKD over time. The classifier model showed a performance value of 0.82 (area under the receiver operating characteristic curve) in patients with a follow-up of five years, which improved to 0.89 at the ten-year follow-up. Both models had a higher recall rate, which indicated the practicality of the tool. The regression model showed a mean absolute error of 1.78 years and a root mean square error of 2.15 years. Testing in an independent cohort of 167patients with IgAN found successful results for 91% of the patients. Comparison of our system with other mathematical models showed the highest discriminant Harrell C index at five- and ten-years follow-up (81% and 86%, respectively), paralleling the lowest Akaike information criterion values (355.01 and 269.56, respectively). Moreover, our system was the best calibrated model indicating that the predicted and observed outcome probabilities did not significantly differ. Finally, the dynamic discrimination indexes of our artificial neural network, expressed as the weighted average of time-dependent areas under the curve calculated at one and two years, were 0.80 and 0.79, respectively. Similar results were observed over a 25-year follow-up period. Thus, our tool identified individuals who were at a high risk of developing ESKD due to IgAN and predicted the time-to-event endpoint. Accurate prediction is an important step toward introduction of a therapeutic strategy for improving clinical outcomes.

Published
2021
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33. Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy

Author

Bellur, Shubha S., Troyanov, Stéphan, Vorobyeva, Olga, Coppo, Rosanna, Roberts, Ian S.D., Coppo, R., Feehaly, J., Troyanov, S., Cattran, D.C., Cook, H.T., Roberts, I., Radcliffe, John, Russo, M.L., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A.C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D’Amico, M., Papagianni, K., Stangou, M., Giacchino, F., Goumenos, D., Papasotirious, M., Kalliakmani, P., Gerolymos, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Boria Grinyo, J.M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Durlik, M., Hryszko, T., Klinger, M., Kamińska, D., Krajewska, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Cambier, A., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Diomedi-Casadei, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., and Royal, V.

Abstract

Evidence from the Oxford IgA nephropathy (IgAN) cohort supports the clinical value of subclassifying focal segmental glomerulosclerosis lesions (S1). Using the larger Validation in IgA (VALIGA) study cohort, we investigated the association between podocytopathic changes and higher proteinuria, kidney outcome and response to immunosuppressive therapy. All biopsies were evaluated for glomeruli with segmental capillary occlusion by matrix (“not otherwise specified”, NOS lesion), simple capsular adhesion without capillary occlusion (Adh), tip lesions, and podocyte hypertrophy (PH). S1 required a NOS lesion and/or Adh. A Chi-Squared Automatic Interaction Detection method was used to identify subgroups of FSGS lesions associated with distinctive proteinuria at biopsy and assessed survival from a combined event (kidney failure or 50% decline in estimated glomerular filtration rate). Finally, we evaluated within each subgroup if immunosuppression was associated with a favorable outcome using propensity analysis. In 1147 patients, S1 was found in 70% of biopsies. Subclassification found NOS lesions in 44%, Adh in 59%, PH in 13%, and tip lesions in 3%, with much overlap. Four subgroups were identified with progressively higher proteinuria: from lowest, S1 without NOS, S1 with NOS but without Adh/PH, to highest, S1 with NOS and Adh but without PH, and S1 with NOS and PH. These four subgroups showed progressively worse kidney survival. Immunosuppression was associated with a better outcome only in the two highest proteinuria subgroups. Propensity analysis in these two groups, adjusted for clinical and pathological findings, found a significant time-dependent hazard of combined outcome with corticosteroids. Podocyte hypertrophy and glomeruli with simple adhesions appeared to reflect active lesions associated with a response to corticosteroids, while other S1 lesions defined chronicity. Thus, our findings support subclassifying S1 lesions in IgAN.

Published
2024
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34. Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy

Author

Feehally, J, Coppo, R, Troyanov, S, Bellur, Ss, Cattran, D, Cook, T, Roberts, Is, Verhave, Jc, Camilla, R, Vergano, L, Egido, J, Wiecek, A, Karkoszka, H, Tesar, V, Maixnerova, D, Ots-Rosenberg, M, Quaglia, M, Rollino, C, Magistroni, R, Cusinato, S, Cravero, R, Peruzzi, L, Lundberg, S, Gesualdo, L, Cancarini, G, Feriozzi, S, Ferrario, F, Emma, F, Fuiano, L, Beltrame, G, Amore, A, Praga, M, Polci, R, Biancone, L, Colla, L, Pani, A, Angioi, A, Piras, D, Ravera, S, Durlik, M, Moggia, E, Ballarin, J, Di Giulio, S, Pierucci, A, Caliskan, Y, Sever, M, Kilicaslan, I, Locatelli, F, Del Vecchio, L, Wetzels, Jf, Peters, H, Berg, U, Carvalho, F, da Costa Ferreira AC, Maggio, M, Topaloglu, R, Bilginer, Y, D'Amico, M, Stangou, M, Giacchino, F, Goumenos, D, Kalliakmani, P, Gerolymos, M, Galesic, K, Geddes, C, Siamopoulos, K, Balafa, O, Galliani, M, Stratta, P, Bergia, R, Salvadori, M, Cirami, L, Fellstrom, B, Kloster Smerud, H, Stellato, T, Cleary, C, Floege, J, Rauen, T, Lupo, A, Bernich, P, Menè, P, Morosetti, M, van Kooten, C, Rabelink, T, Reinders, Me, Boria Grinyo JM, Benozzi, L, Savoldi, S, Licata, C, Mizerska-Wasiak, M, Roszkowska-Blaim, M, Martina, G, Messuerotti, A, Dal Canton, A, Esposito, C, Migotto, C, Triolo, G, Mariano, F, Pozzi, C, Di Palma AM, Boero, R, Mazzucco, G, Giannakakis, C, Honsova, E, Sundelin, B, Gutiérrez, E, Asunis, Am, Barratt, J, Tardanico, R, Perkowska-Ptasinska, A, Arce Terroba, J, Fortunato, M, Pantzaki, A, Ozluk, Y, Steenbergen, E, Soderberg, M, Riispere, Z, Furci, L, Orhan, D, Kipgen, D, Casartelli, D, Galesic Ljubanovic, D, Gakiopoulou, H, Bertoni, E, Cannata Ortiz, P, Groene, Hj, Stoppacciaro, A, Bajema, I, Bruijn, J, Fulladosa Oliveras, X, Maldyk, J, and Ioachim, E.

Subjects
Male, Physiology, medicine.medical_treatment, IgA nephropathy, Tonsillectomy, Risk factors, Progression of chronic renal failure, 030232 urology & nephrology, 030204 cardiovascular system & hematology, urologic and male genital diseases, Gastroenterology, Progression of chronic renal failure, Cohort Studies, Kidney Failure, Glomerulonephritis, 0302 clinical medicine, Ethnicity, Chronic, Proteinuria, medicine.diagnostic_test, Age Factors, IgA nephropathy, Middle Aged, Europe, Treatment Outcome, Nephrology, Cohort, Disease Progression, Female, Renal biopsy, medicine.symptom, Glomerular Filtration Rate, Cohort study, Adult, medicine.medical_specialty, Urology, Renal function, Ethnic Groups, Nephropathy, iga nephropathy, tonsillectomy, risk factors, progression of chronic renal failure, 03 medical and health sciences, Sex Factors, Physiology (medical), Internal medicine, Risk factors, Tonsillectomy, medicine, Humans, Follow-Up Studies, Glomerulonephritis, IGA, Kidney Failure, Chronic, Propensity Score, Retrospective Studies, IGA, business.industry, Retrospective cohort study, medicine.disease, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract

Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

Published
2016

35. FrequentCOL4mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis

Author

Papazachariou, L., primary, Papagregoriou, G., additional, Hadjipanagi, D., additional, Demosthenous, P., additional, Voskarides, K., additional, Koutsofti, C., additional, Stylianou, K., additional, Ioannou, P., additional, Xydakis, D., additional, Tzanakis, I., additional, Papadaki, A., additional, Kallivretakis, N., additional, Nikolakakis, N., additional, Perysinaki, G., additional, Gale, D.P., additional, Diamantopoulos, A., additional, Goudas, P., additional, Goumenos, D., additional, Soloukides, A., additional, Boletis, I., additional, Melexopoulou, C., additional, Georgaki, E., additional, Frysira, E., additional, Komianou, F., additional, Grekas, D., additional, Paliouras, C., additional, Alivanis, P., additional, Vergoulas, G., additional, Pierides, A., additional, Daphnis, E., additional, and Deltas, C., additional

Published
2017
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38. Preclinical cardiorenal interrelationships in essential hypertension

Author

Tsioufis, C. Tsiachris, D. Kasiakogias, A. Dimitriadis, K. Petras, D. Goumenos, D. Siamopoulos, K. Stefanadis, C.

Abstract

A diseased heart causes numerous adverse effects on kidney function, and vice versa renal disease can significantly impair cardiac function. Beyond these heart-kidney interrelationships at the clinical level, a reciprocal association has been suggested to exist even in the early stages of those organs' dysfunction. The aim of the present review is to provide evidence of the presence of a preclinical cardiorenal syndrome in the particular setting of essential hypertension, focusing on the subsequent hypertensive sequelae on heart and kidneys. In particular, a plethora of studies have demonstrated not only the predictive role of kidney damage, as expressed by either decreased glomerular filtration or increased urine albumin excretion, for adverse left ventricular functional and structural adaptations but also preclinical heart disease, i.e. left ventricular hypertrophy that is associated with deterioration of renal function. Notably, these reciprocal interactions seem to exist even at the level of microcirculation, since both coronary flow reserve and renal hemodynamics are strongly related with clinical and preclinical renal and cardiac damage, respectively. In this preclinical setting, common pathophysiological denominators, including the increased hemodynamic load, sympathetic and renin-angiotensin system overactivity, increased subclinical inflammatory reaction, and endothelial dysfunction, account not only for the reported associations between overt cardiac and renal damage but also for the parallel changes that occur in coronary and renal microcirculation. © 2013 S. Karger AG, Basel.

Published
2013

39. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

Author

Parving, Hh, Brenner, Bm, Mcmurray, Jj, de Zeeuw, D, Haffner, Sm, Solomon, Sd, Chaturvedi, N, Persson, F, Desai, As, Nicolaides, M, Richard, A, Xiang, Z, Brunel, P, Pfeffer, Ma, Viberti, G, Lachin, Jm, Zinman, B, Pedersen, Tr, Villamil, As, Juncos, L, Prager, R, Verpooten, G, Zanella, Mt, Leiter, L, Pan, C, Wang, H, Botero, R, Cifkova, R, Christiansen, Js, Groop, Ph, Marre, M, Haller, H, Nickenig, G, Siamopoulos, K, Gero, L, Maggioni, A, Remuzzi, G, Katayama, Ss, Kim, Sg, Petrulioniene, Z, Lok, D, Kooy, A, Jorde, R, Medina, F, Polonia, J, Wong, Ks, Dukat, A, Rayner, Bl, Ruilope, L, Weiss, L, Wuethrich, R, Sheu, W, Sritara, P, Comlekci, A, Bilous, R, Toto, R, Jamerson, K, Carillo, E, Orias, M, Kuschnir, E, Rusculleda, M, Garcia, S, Farias, E, Lema, L, Hominal, M, Montaña, O, Sala, J, Diaz, M, Piskorz, D, Vita, N, Litwak, L, Sinay, I, Marin, M, Massari, P, Majul, C, Aizemberg, D, Azize, Gm, Bartolacci, I, Reboredo, A, Vico, M, Milesi, R, Sessa, H, Wassermann, A, Margulis, F, Zangroniz, P, Watschinger, B, Toplak, H, Paulweber, B, Drexel, H, Francesconi, C, Foeger, B, Mayer, G, Braun, Rk, Brath, H, Gaal, Lv, Niepen, Pv, Persu, A, Vercammen, C, Vriese, Ad, Coucke, F, Mathieu, C, Fery, F, Treille, S, Meeus, G, Acker, Kv, Scheen, A, Tits, J, Ruige, J, Krzesinski, Jm, Hollanders, G, Liénart, F, Dendale, P, Quinonez, M, Arnouts, P, Vanuytsel, J, Zanella, M, Mion D., Jr, Forti, A, Almeida, F, Cunha, R, de Paula RB, Brandao, A, Rocha, J, Krieger, E, Feitosa, G, Saraiva, J, Martin, J, Hissa, Mn, Schmid, H, Felicio, J, Sgarbi, J, Oigman, W, Bowering, K, Garceau, C, Berlingieri, Jc, Weisnagel, Sj, Hardin, P, Powell, C, Turcot, R, Muirhead, N, Aronson, R, Barima, Yt, Steele, Aw, Pandey, S, Woo, V, Cha, J, Dattani, D, Godin, C, Gupta, M, Saunders, K, Tellier, G, Ting, R, Tobe, S, Chouinard, G, Schlosser, R, Khandwala, H, Ekoe, Jm, Harris, Sb, Pichette, V, Lachance, P, Ooi, Tc, Tildesley, H, Barrett, B, Cournoyer, S, Lu, J, Zhang, H, Liu, X, Yan, S, Qi, X, Li, Q, Li, H, Lv, X, Yang, J, Sun, N, Xia, W, Wang, N, Tong, N, Mei, C, Gu, S, Zhang, J, Chen, X, Li, L, Su, B, Wang, L, Qiu, M, Wu, X, Liu, Z, Jia, W, Xu, G, Dong, J, Zhu, D, Zhang, M, Yan, J, Liu, B, Chen, J, Fu, J, Yan, L, Zhan, X, Zhong, L, Yang, T, Ma, J, Xu, M, Xu, X, Shi, B, Ji, Q, Zhong, H, He, R, Yuan, Z, Zhou, Z, Lin, H, Yang, W, Ke, Y, Hong, T, Franco, C, Casas, L, Triana, A, Jaramillo, C, Hernandez, E, Barrera, C, Blanco, D, Stipal, R, Widimsky, P, Dohnalova, L, Komroskova, M, Kvapil, M, Belobradkova, J, Tesar, V, Vodnansky, P, Kocourkova, B, Lervang, Hh, Perrild, H, Rossing, P, Oestergaard, O, Juhl, H, Thorsteinsson, B, Snorgaard, O, Urhammer, S, Egstrup, K, Tikkanen, T, Helin, K, Rinne, J, Lahtela, J, Strand, J, Valtonen, E, Saari, M, Kananen, K, Savela, K, Blacher, J, Aldigier, Jc, Zaoui, P, Fauvel, Jp, Gouet, D, Valensi, Pe, Charpentier, G, Marechaud, R, Penfornis, A, Ovize, M, Kovalchuck, Aa, Dellanna, F, Schoen, N, Groeschel, W, Eickhoff, F, Hanefeld, M, Merke, J, Rambausek, M, Zimmermann, U, Stuetz, W, Vosskuehler, A, Hevendehl, G, Schax, U, Lehmann, G, Haack, A, Hilgenberg, J, Klausmann, G, Adelberger, V, Gessner, S, Fiesselmann, A, Oerter, E, Hohenstatt, T, Groeschel, A, Behnke, T, Sisting, Rt, Schoch, D, Bieler, T, Schleyer, S, Altes, U, Klepzig, C, Rudofsky, G, Mueller, G, Burkhardt, F, Reschke, K, Senftleber, I, Wiesweg, Ck, Herrmann, Hj, Brandstetter, R, Segner, A, Schmitt, H, Rippert, R, Goebel, R, Schreibmueller, F, Pencz, I, Ott, P, Migdalis, I, Pappas, S, Pagkalos, E, Yalouris, A, Tsapas, A, Maltezos, E, Tentolouris, N, Papadakis, I, Ioannidis, G, Goumenos, D, Corona, V, Gonzalez, R, Haase, F, Monterroso, V, Sánchez, V, Turcios, E, Wyss, F, Arango, Jl, Bako, B, Deak, L, Dömötör, E, Dudas, M, Fulop, T, Kiss, I, Koranyi, L, Lengyel, Z, Nyirati, G, Oroszlan, T, Aniko, S, Vörös, P, Kapocsi, J, Wittmann, I, Paragh, G, Abraham, G, Tandon, N, Thomas, N, Mohan, V, Sahay, R, Sethi, B, Rao, V, Kumar, S, Chowdhury, S, Dharmalingam, M, Seshiah, V, Bantwal, G, Viswanathan, V, Yajnik, C, Adhikari, P, Krishnan, U, Varthakavi, P, Hiremath, J, Bhattacharyya, A, Dani, S, Modi, Kk, Glorioso, N, Morosetti, M, Veglio, Franco, Perticone, F, Dotta, F, Quarello, F, Sesti, G, Aiello, A, D'Ospina, A, Giordano, C, Novo, S, Santoro, A, Ferri, C, Capuano, V, Trimarco, B, Tonolo, G, Villa, G, De Pellegrin, A, Zanette, G, Federici, M, Aucello, G, Piatti, P, Vinciguerra, A, Mannarino, E, Taddei, S, Filetti, S, Grandaliano, G, Marchionni, N, Lambiase, C, Locatelli, F, Scanferla, F, Lembo, G, Leotta, S, Mos, L, Calatola, P, Fogari, R, David, S, Pedrinelli, R, Pignone, Am, Cozzolino, D, Bevilacqua, Mt, Catena, C, Del Prato, S, Cerasola, G, Frontoni, S, Falcone, C, Porta, A, Bonora, E, Cocchi, R, Fucili, A, Frisinghelli, A, Volpe, M, Carugo, S, Gambardella, S, Spagnuolo, V, Maglia, G, D'Angelo, Ar, Corsi, A, Limone, Pp, Guarnieri, A, Ghigo, Ezio, Ronchi, E, Ravera, M, Scioli, Ga, Sekiguchi, M, Aoki, S, Ogawa, Y, Seino, H, Onishi, Y, Tojo, A, Narimiya, M, Iwaita, Y, Takeda, H, Shimizu, H, Yamada, T, Kojima, S, Zushi, S, Kaneko, S, Matsumoto, A, Kajiyama, S, Fujita, H, Shikata, K, Tone, A, Matsubayashi, S, Tanaka, S, Sekigami, T, Tatsukawa, Y, Abe, N, Kawahara, K, Kasahara, H, Maeda, Y, Suzuki, Y, Okamoto, H, Tachi, K, Yamada, K, Uzu, T, Itou, T, Fukui, T, Kim, S, Kim, Y, Cho, W, Kwak, I, Chae, D, Oh, H, Ha, S, Shin, Y, Cha, D, Kang, S, Lim, C, Song, J, Kwon, Y, Badariene, J, Labutiniene, Ip, Zabuliene, L, Poteliuniene, V, Miglinas, M, van den Meiracker AH, Gregoor, Pj, Luik, Aj, van Loon BJ, Feenstra, Hj, Kaasjager, Ha, Viergever, Pp, Woittiez, Aj, van Bemmel, T, Lieverse, Ag, Simsek, S, Gaillard, Ca, van der Zwaan, C, Lok, Dj, Spiering, W, Nierop, Pr, Baggen, Mg, Leendert, Rj, de Jong, A, Leurs, Pb, Vincent, Hh, Wins, Eh, Voors, Aa, Ronner, E, Heeg, Je, van Hal JM, Boermans, T, Feis, Wl, Mostard, G, Bakker, Rc, Dunselman, Ph, Skeie, S, Istad, H, Skjelvan, G, Gronert, J, Tomala, T, Gudnason, S, Torvik, Dt, Risberg, K, Abedini, S, Cabrera, W, Medina, B, Herrada, B, Saavedra, A, Polonia, Dj, Providencia, Dl, Carvalho, D, Vasconcelos, Mp, da Silva GF, Branco, P, Gil, Dv, da Costa AG, da Silva PM, Arez, L, Martins, L, Birne, R, Dzuponova, J, Surovcikova, M, Culak, J, Filipova, S, Andre, I, Stevlik, J, Uhliar, R, Fabryova, L, Benacka, J, Koleny, D, Szentivanyi, M, Spisak, V, Pella, D, Pastrnakova, E, Martinka, E, Chua, T, Lau, T, Ng, Tg, Yeoh, Ly, Bhana, Sa, Rayner, B, Wellmann, H, Amod, A, Ranjith, N, Ahmed, F, Rheeder, P, Makan, H, Naicker, P, Podgorski, G, De Teresa, E, Olivan, J, Fernandez, Vl, Povedano, St, Terns, M, Ricart, W, Gonzalez, Jm, Fernandez, P, Parreño Lde, T, Redon, J, Parra, J, Calvo, C, Lopez, I, Puig, Jg, Calle, A, Garcia, Jc, Lopez, Jm, Jimenez, Ml, Fraile, B, Perez, Js, Nadal, Jj, Guija, E, Calviño, J, Barrios, V, Iglesias, Jn, Armario, P, Garcia, M, Aranda, P, Brotons, C, Gomez, P, Catelao, Am, Cusachs, Ar, Sarro, M, Martinez, V, dell Valle MH, Trias, F, Comas, A, Salvador, N, Martinez, F, Hernandez, F, Martinez, J, Mateos, C, Peral, Jl, Tolosana, J, Sobrino, J, Isart, J, Vizcaino, J, Vega, Ff, Zamorano, Jl, Bacariza, M, Soubriet, A, Fernández Cruz, A, Querejeta, R, Leira, Vm, Iglesias, Fe, Ibrik, O, Martin, D, Nanclares, Ms, Mediavilla, Jd, Galceran, Jm, Lopez, A, Muros, T, Pascual, J, Casalla, F, Tornero, F, Fernandez, G, Pettersson, P, Olsen, H, Franke, F, Stroembom, U, Furuland, H, Larnefelt, H, Allemann, Y, Krapf, R, Gerber, P, Munger, R, Hayoz, D, Graf, Hj, Burnier, M, Petrillo, A, Batt, R, Constam, En, Moccetti, T, Bianda, T, Rickli, H, Bulliard, C, Wu, Kd, Lin, Sh, Wu, Cj, Sheu, Wh, Su, Sl, Chen, Sc, Chou, Cw, Lee, Ct, Yang, Tc, Chen, Hc, Sukonthasarn, A, Sriratanasathavorn, C, Eiam Ong, S, Supasyndh, O, Chanchairujira, T, Kitiyakara, C, Arici, M, Usalan, C, Guneri, S, Koc, M, Kalender, B, Ates, K, Gurgun, C, Araz, M, Demirbas, B, Biernacki, W, Calvert, J, Eavis, P, Kerrane, J, Litchfield, J, Middleton, A, Roberts, J, Simpson, H, Charles, H, Jardine, A, Fisher, M, Banerjee, D, Gallen, I, Gnudi, L, Harvey, J, O'Hare, P, Vora, J, Winocour, P, Soran, H, Browne, D, Darko, D, Mancebo, Jg, de Roa ER, Antepara, N, Carrillo, E, Berrizbeitia, M, Guevara, L, Pernalete, N, Ontiveros, C, Zigrang, W, Blakney, E, Rosenblit, P, Weinstein, R, Klaff, L, Lipetz, R, Busick, E, Tung, P, Cooperman, M, Michael, S, Sun, Ch, Hart, T, Maddux, A, Bowden, R, East, C, Arakaki, R, Villafuerte, B, Mamish, Z, Mendez, R, Connery, L, Nour, K, Wynne, A, Busch, R, Zamora, B, Sachson, R, Prasad, J, Lasala, G, Smith, M, Fitz Patrick, D, Ruiz Rivera, L, Barranco, E, Solomon, R, Woolley, A, Brown, C, Freedman, Z, Schmidt, S, Pollock, J, Ruddy, M, Kopyt, Np, Bazzi, A, Horowitz, B, Feng, W, Wahl, T, Duprez, D, Gilbert, J, Steigerwalt, S, Jacqmein, J, Gorton, S, 3rd, Allison J., Pino, J, Lock, J, Leimbach, W, Anderson, J, Beacom, M, Craig, W, Gorson, D, Kerstein, H, Segal, S, Downey, H, Ledger, G, Mcgill, J, Gabriel, J, Nolen, T, Levinson, L, Williams, T, Levenson, D, Lerman, S, Minehart, C, Agarwal, N, Verma, S, Valitutto, M, Demetry, K, Mersey, J, Koeper, D, Fanti, P, Eng, G, Grimm, R, Fagan, T, Bajaj, M, Katz, L, Portnay, G, Altschuller, A, Desai, V, Bilazarian, S, Ipp, E, Rodelas, R, Burstein, D, Berg, J, Velez, J, Lund, R, Rekhi, A, Martin, E, Robertson, D, Singh, N, Narayan, P, Moustafa, M, Lanier, D, Seidner, M, Phillips, A, Vaughters, B, Sprague, A, Swartz, S, Lopez, R, Kumar, J, Bressler, P, Sadler, L, Wise, J, Kilbane, A., and Groningen Kidney Center (GKC)

Subjects
Male, Hyperkalemia, CARDIOVASCULAR MORTALITY, BLOOD-PRESSURE, Angiotensin-Converting Enzyme Inhibitors, Type 2 diabetes, GLOMERULAR-FILTRATION-RATE, DOUBLE-BLIND, chemistry.chemical_compound, Fumarates, cardiovascular disease, Renin, Treatment Failure, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, 610 Medicine & health, diabetes, Medicine (all), Hazard ratio, aliskiren, diabete, trial clinico, Liter, General Medicine, Middle Aged, hypertension, Cardiovascular Diseases, Combination, HEART-FAILURE, Drug Therapy, Combination, Female, Kidney Diseases, type 2 diabetes, medicine.symptom, Type 2, medicine.medical_specialty, Patient Dropouts, Urology, Hypokalemia, Aliskiren, chronic kidney disease, Placebo, Angiotensin Receptor Antagonists, LEFT-VENTRICULAR DYSFUNCTION, Drug Therapy, Double-Blind Method, Diabetes Mellitus, medicine, Humans, CONVERTING-ENZYME INHIBITORS, Antihypertensive Agents, Aged, Amides, Diabetes Mellitus, Type 2, Follow-Up Studies, business.industry, medicine.disease, Confidence interval, Surgery, Blood pressure, MYOCARDIAL-INFARCTION, chemistry, SYSTOLIC DYSFUNCTION, FOLLOW-UP, business
Abstract

BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P = 0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, = 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P CONCLUSIONS The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.)

Published
2012
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45. Primary and secondary glomerulonephritis II

Author

Valdivia Vega, R. P., primary, Perez Carlos, J., additional, LI, X., additional, Xu, X., additional, Zhang, W., additional, Ren, H., additional, Chen, N., additional, Yorioka, N., additional, Doi, T., additional, Hirashio, S., additional, Arita, M., additional, Hirabayashi, A., additional, Tilkiyan, E., additional, Chonova, E., additional, Ronchev, Y., additional, Kumchev, E., additional, Giamalis, P., additional, Spartalis, M., additional, Stangou, M., additional, Tsouchnikas, I., additional, Moysiades, D., additional, Dimopoulou, D., additional, Garyfalos, A., additional, Efstratiadis, G., additional, Memmos, D., additional, Schonermarck, U., additional, Eichhorn, P., additional, Sitter, T., additional, Wendler, T., additional, Vielhauer, V., additional, Lederer, S., additional, Fechner, K., additional, Fischereder, M., additional, Bantis, C., additional, Heering, P., additional, Kouri, N.-M., additional, Schwandt, C., additional, Kuhr, N., additional, Ivens, K., additional, Rump, L.-C., additional, Matta, V., additional, Melis, P., additional, Conti, M., additional, Cao, R., additional, Binda, V., additional, Altieri, P., additional, Asunis, A. M., additional, Catani, W., additional, Floris, M., additional, Angioi, A., additional, Congia, M., additional, Cucca, F., additional, Minerba, L., additional, Peri, M., additional, Pani, A., additional, Beck, L. H., additional, Fervenza, F. C., additional, Bomback, A. S., additional, Ayalon, R., additional, Irazabal, M. V., additional, Eirin, A., additional, Cattran, D. C., additional, Appel, G. B., additional, Salant, D. J., additional, Santoro, D., additional, Postorino, A., additional, Costantino, G., additional, Bellinghieri, G., additional, Savica, V., additional, Weiner, M., additional, Goh, S. M., additional, Mohammad, A., additional, Eriksson, P., additional, Westman, K., additional, Selga, D., additional, Salama, A., additional, Segelmark, M., additional, Chocova, Z., additional, Hruskova, Z., additional, Mareckova, H., additional, Svobodova, B., additional, Jancova, E., additional, Bednarova, V., additional, Rysava, R., additional, Tesar, V., additional, Hanzal, V., additional, Zamboch, K., additional, Grussmannova, M., additional, Svojanovsky, J., additional, Klaboch, J., additional, Kubisova, M., additional, Sevcik, J., additional, Olsanska, R., additional, Sobotkova, M., additional, Becvar, R., additional, Nemec, P., additional, Kodeda, M., additional, Jilek, D., additional, Hussain, M., additional, Dhaygude, A., additional, Cartery, C., additional, Huart, A., additional, Plaisier, E., additional, Bongard, V., additional, Montastruc, F., additional, Ronco, P., additional, Pourrat, J., additional, Chauveau, D., additional, Prasad, N., additional, Gurjar, D., additional, Bhadauria, D., additional, Sharma, R. K., additional, Gupta, A., additional, Kaul, A., additional, Jain, M., additional, Venning, M., additional, Brown, N., additional, Bruce, I., additional, Noor, S., additional, Bekker, P., additional, Potarca, A., additional, Dairaghi, D., additional, Miao, S., additional, Powers, J. P., additional, Jaen, J. C., additional, Schall, T. J., additional, Kalavrizioti, D., additional, Gerolymos, M., additional, Komninakis, D., additional, Rodi, M., additional, Mouzaki, A., additional, Kalliakmani, P., additional, Goumenos, D., additional, Choi, B. S., additional, Park, C. W., additional, Kim, Y.-S., additional, Yang, C. W., additional, Sun, I. O., additional, Qin, W., additional, Xie, L., additional, Tan, C., additional, Mian, W., additional, Fu, P., additional, Kaminskyy, V., additional, Hao, X., additional, Wang, W., additional, Cengiz, C., additional, Nur, C., additional, Nurdan, Y., additional, Selman, G., additional, Pinar, T., additional, Mehmet, T., additional, Lale, S., additional, Caliskan, S., additional, Shinzawa, M., additional, Yamamoto, R., additional, Nagasawa, Y., additional, Oseto, S., additional, Mori, D., additional, Niihata, K., additional, Fukunaga, M., additional, Yamauchi, A., additional, Tsubakihara, Y., additional, Rakugi, H., additional, Isaka, Y., additional, Chen, J.-S., additional, Lin, Y.-F., additional, Lin, W.-Y., additional, Shu, K.-H., additional, Chen, H.-H., additional, Wu, C.-J., additional, Yang, C.-S., additional, Tseng, T.-L., additional, Zaza, G., additional, Bernich, P., additional, Lupo, A., additional, Panizo, N., additional, Rivera, F., additional, Lopez Gomez, J. M., additional, Regn, S. R. o. G., additional, Ceresini, G., additional, Vaglio, A., additional, Urban, M. L., additional, Corradi, D., additional, Usberti, E., additional, Palmisano, A., additional, Buzio, C., additional, Zineb, H., additional, Ramdani, B., additional, Marques, L. P. J., additional, Rioja, L. D. S., additional, Rocco, R., additional, Nery, A. C. F., additional, Novaes, B. C., additional, Bridoux, F., additional, Sicard, A., additional, Labatut, D., additional, Touchard, G., additional, Sarkozy, C., additional, Vanhille, P., additional, Callard, P., additional, Essig, M., additional, Provot, F., additional, Nony, A., additional, Karras, A., additional, Agustin, C. P., additional, M Belen, H. R., additional, Carmen, C. P., additional, Eliana, O., additional, Elisa, P., additional, Luis, P., additional, Alberto, M.-C., additional, Javier, N., additional, Isabel, F., additional, Atzeni, A., additional, Fois, A., additional, Piras, D., additional, Maxia, S., additional, Sau, G., additional, Pili, G., additional, Porcu, M., additional, Derudas, D., additional, Angelucci, E., additional, Ledda, A., additional, La Nasa, G., additional, Ossareh, S., additional, Asgari, M., additional, Savaj, S., additional, Ataipour, Y., additional, Abdi, E., additional, Malakoutian, T., additional, Rajaa, R., additional, Berkchi, F. Z., additional, Haffane, L., additional, Squalli, Z., additional, Rouass, L., additional, Al Hamany, Z., additional, Ezzaitouni, F., additional, Benamar, L., additional, Bayahya, R., additional, Ouzeddoun, N., additional, Gao-Yuan, H., additional, Yao, X., additional, Xin, C., additional, Zhen, C., additional, Yong-Chun, G., additional, Qing-Wen, W., additional, Hui-Ping, C., additional, Da-XI, J., additional, De-Hua, G., additional, Wei-Xin, H., additional, Zhi-Hong, L., additional, Fatima Zahra, B., additional, Laila, H., additional, Zoubair, S., additional, Naima, O., additional, Smykal-Jankowiak, K., additional, Niemir, Z., additional, Polcyn-Adamczak, M., additional, Szramka-Pawlak, B., additional, Zaba, R., additional, Zhang, C., additional, MA, Y., additional, Shen, P., additional, Ouyang, Y., additional, Pan, X., additional, Wang, Z., additional, Feng, X., additional, and Ni, L., additional

Published
2012
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