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1. Clinical and Economic Impact of Early Diagnosis of Chronic Kidney Disease in General Practice: The Endorse Study

Author

Pesce F, Bruno GM, Colombo GL, Di Matteo S, Maurizi AR, Mongelli V, Mele S, Narici L, Bianchi S, Bonomini M, Castellano G, De Nicola L, Gambaro G, Grandaliano G, La Manna G, Pani A, Ranghino A, and Gesualdo L

Subjects
egfr, uacr, awareness, chronic kidney disease, general practice, economic impact, training intervention, early diagnosis, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Francesco Pesce,1 Giacomo Matteo Bruno,2 Giorgio Lorenzo Colombo,2 Sergio Di Matteo,3 Anna Rita Maurizi,4 Valentina Mongelli,4 Silvia Mele,5 Lavinia Narici,5 Stefano Bianchi,6 Mario Bonomini,7 Giuseppe Castellano,8 Luca De Nicola,9 Giovanni Gambaro,10 Giuseppe Grandaliano,11 Gaetano La Manna,12 Antonello Pani,13 Andrea Ranghino,14 Loreto Gesualdo15 1Division of Renal Medicine, “Fatebenefratelli Isola Tiberina—Gemelli Isola”, Rome, 00186, Italy; 2Department of Drug Sciences, University of Pavia, Pavia, Italy; 3S.A.V.E. Studi Analisi Valutazioni Economiche, Milan, Italy; 4Cardiovascular, Renal and Metabolism Medical Affairs, AstraZeneca, Milan, Italy; 5Value & Access, AstraZeneca, Milan, Italy; 6Nephrology and Dialysis Unit, Department of Internal Medicine, ASL Toscana Nordovest, Regione Toscana, Livorno, Italy; 7Department of Medicine, Section of Nephrology and Dialysis, G. D’Annunzio University, Chieti, 66013, Italy; 8UOC of Nephrology, Dialysis, and Kidney Transplant, IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 9Department of Advanced Medical and Surgical Sciences, Nephrology and Dialysis Unit, University Vanvitelli, Naples, Italy; 10Division of Nephrology and Dialysis, Department of Medicine, University of Verona, Verona, Italy; 11Department of Translational Medicine and Surgery, Università Cattolica Sacro Cuore, Rome, Italy; 12Nephrology Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy; 13Department of Nephrology and Dialysis, G. Brotzu Hospital, Cagliari, Italy; 14Nephrology, Dialysis and Kidney Transplant Unit, Ospedali Riuniti Ancona, Ancona, Italy; 15Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (Dimepre-J), University of Bari “aldo Moro”, Bari, ItalyCorrespondence: Giorgio Lorenzo Colombo, Email colombog@unipv.itIntroduction: The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis.Methods: Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases.Results: The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention’s impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure.Discussion: A budget impact analysis projected cumulative five-year savings of € 1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at € 106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression.Conclusion: The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale. Keywords: eGFR, uACR, awareness, chronic kidney disease, general practice, economic impact, training intervention, early diagnosis

Published
2024

2. Effects of empagliflozin on progression of chronic kidney disease: a prespecified secondary analysis from the empa-kidney trial

Author

Staplin, N, Haynes, R, Judge, PK, Wanner, C, Green, JB, Emberson, J, Preiss, D, Mayne, KJ, Ng, SYA, Sammons, E, Zhu, D, Hill, M, Stevens, W, Wallendszus, K, Brenner, S, Cheung, AK, Liu, ZH, Li, J, Hooi, LS, Liu, WJ, Kadowaki, T, Nangaku, M, Levin, A, Cherney, D, Maggioni, AP, Pontremoli, R, Deo, R, Goto, S, Rossello, X, Tuttle, KR, Steubl, D, Petrini, M, Seidi, S, Landray, MJ, Baigent, C, Herrington, WG, Abat, S, Abd Rahman, R, Abdul Cader, R, Abdul Hafidz, MI, Abdul Wahab, MZ, Abdullah, NK, Abdul-Samad, T, Abe, M, Abraham, N, Acheampong, S, Achiri, P, Acosta, JA, Adeleke, A, Adell, V, Adewuyi-Dalton, R, Adnan, N, Africano, A, Agharazii, M, Aguilar, F, Aguilera, A, Ahmad, M, Ahmad, MK, Ahmad, NA, Ahmad, NH, Ahmad, NI, Ahmad Miswan, N, Ahmad Rosdi, H, Ahmed, I, Ahmed, S, Aiello, J, Aitken, A, AitSadi, R, Aker, S, Akimoto, S, Akinfolarin, A, Akram, S, Alberici, F, Albert, C, Aldrich, L, Alegata, M, Alexander, L, Alfaress, S, Alhadj Ali, M, Ali, A, Alicic, R, Aliu, A, Almaraz, R, Almasarwah, R, Almeida, J, Aloisi, A, Al-Rabadi, L, Alscher, D, Alvarez, P, Al-Zeer, B, Amat, M, Ambrose, C, Ammar, H, An, Y, Andriaccio, L, Ansu, K, Apostolidi, A, Arai, N, Araki, H, Araki, S, Arbi, A, Arechiga, O, Armstrong, S, Arnold, T, Aronoff, S, Arriaga, W, Arroyo, J, Arteaga, D, Asahara, S, Asai, A, Asai, N, Asano, S, Asawa, M, Asmee, MF, Aucella, F, Augustin, M, Avery, A, Awad, A, Awang, IY, Awazawa, M, Axler, A, Ayub, W, Azhari, Z, Baccaro, R, Badin, C, Bagwell, B, Bahlmann-Kroll, E, Bahtar, AZ, Bains, D, Bajaj, H, Baker, R, Baldini, E, Banas, B, Banerjee, D, Banno, S, Bansal, S, Barberi, S, Barnes, S, Barnini, C, Barot, C, Barrett, K, Barrios, R, Bartolomei Mecatti, B, Barton, I, Barton, J, Basily, W, Bavanandan, S, Baxter, A, Becker, L, Beddhu, S, Beige, J, Beigh, S, Bell, S, Benck, U, Beneat, A, Bennett, A, Bennett, D, Benyon, S, Berdeprado, J, Bergler, T, Bergner, A, Berry, M, Bevilacqua, M, Bhairoo, J, Bhandari, S, Bhandary, N, Bhatt, A, Bhattarai, M, Bhavsar, M, Bian, W, Bianchini, F, Bianco, S, Bilous, R, Bilton, J, Bilucaglia, D, Bird, C, Birudaraju, D, Biscoveanu, M, Blake, C, Bleakley, N, Bocchicchia, K, Bodine, S, Bodington, R, Boedecker, S, Bolduc, M, Bolton, S, Bond, C, Boreky, F, Boren, K, Bouchi, R, Bough, L, Bovan, D, Bowler, C, Bowman, L, Brar, N, Braun, C, Breach, A, Breitenfeldt, M, Brettschneider, B, Brewer, A, Brewer, G, Brindle, V, Brioni, E, Brown, C, Brown, H, Brown, L, Brown, R, Brown, S, Browne, D, Bruce, K, Brueckmann, M, Brunskill, N, Bryant, M, Brzoska, M, Bu, Y, Buckman, C, Budoff, M, Bullen, M, Burke, A, Burnette, S, Burston, C, Busch, M, Bushnell, J, Butler, S, Büttner, C, Byrne, C, Caamano, A, Cadorna, J, Cafiero, C, Cagle, M, Cai, J, Calabrese, K, Calvi, C, Camilleri, B, Camp, S, Campbell, D, Campbell, R, Cao, H, Capelli, I, Caple, M, Caplin, B, Cardone, A, Carle, J, Carnall, V, Caroppo, M, Carr, S, Carraro, G, Carson, M, Casares, P, Castillo, C, Castro, C, Caudill, B, Cejka, V, Ceseri, M, Cham, L, Chamberlain, A, Chambers, J, Chan, CBT, Chan, JYM, Chan, YC, Chang, E, Chant, T, Chavagnon, T, Chellamuthu, P, Chen, F, Chen, J, Chen, P, Chen, TM, Chen, Y, Cheng, C, Cheng, H, Cheng, MC, Ching, CH, Chitalia, N, Choksi, R, Chukwu, C, Chung, K, Cianciolo, G, Cipressa, L, Clark, S, Clarke, H, Clarke, R, Clarke, S, Cleveland, B, Cole, E, Coles, H, Condurache, L, Connor, A, Convery, K, Cooper, A, Cooper, N, Cooper, Z, Cooperman, L, Cosgrove, L, Coutts, P, Cowley, A, Craik, R, Cui, G, Cummins, T, Dahl, N, Dai, H, Dajani, L, D'Amelio, A, Damian, E, Damianik, K, Danel, L, Daniels, C, Daniels, T, Darbeau, S, Darius, H, Dasgupta, T, Davies, J, Davies, L, Davis, A, Davis, J, Davis, L, Dayanandan, R, Dayi, S, Dayrell, R, De Nicola, L, Debnath, S, Deeb, W, Degenhardt, S, DeGoursey, K, Delaney, M, DeRaad, R, Derebail, V, Dev, D, Devaux, M, Dhall, P, Dhillon, G, Dienes, J, Dobre, M, Doctolero, E, Dodds, V, Domingo, D, Donaldson, D, Donaldson, P, Donhauser, C, Donley, V, Dorestin, S, Dorey, S, Doulton, T, Draganova, D, Draxlbauer, K, Driver, F, Du, H, Dube, F, Duck, T, Dugal, T, Dugas, J, Dukka, H, Dumann, H, Durham, W, Dursch, M, Dykas, R, Easow, R, Eckrich, E, Eden, G, Edmerson, E, Edwards, H, Ee, LW, Eguchi, J, Ehrl, Y, Eichstadt, K, Eid, W, Eilerman, B, Ejima, Y, Eldon, H, Ellam, T, Elliott, L, Ellison, R, Epp, R, Er, A, Espino-Obrero, M, Estcourt, S, Estienne, L, Evans, G, Evans, J, Evans, S, Fabbri, G, Fajardo-Moser, M, Falcone, C, Fani, F, Faria-Shayler, P, Farnia, F, Farrugia, D, Fechter, M, Fellowes, D, Feng, F, Fernandez, J, Ferraro, P, Field, A, Fikry, S, Finch, J, Finn, H, Fioretto, P, Fish, R, Fleischer, A, Fleming-Brown, D, Fletcher, L, Flora, R, Foellinger, C, Foligno, N, Forest, S, Forghani, Z, Forsyth, K, Fottrell-Gould, D, Fox, P, Frankel, A, Fraser, D, Frazier, R, Frederick, K, Freking, N, French, H, Froment, A, Fuchs, B, Fuessl, L, Fujii, H, Fujimoto, A, Fujita, A, Fujita, K, Fujita, Y, Fukagawa, M, Fukao, Y, Fukasawa, A, Fuller, T, Funayama, T, Fung, E, Furukawa, M, Furukawa, Y, Furusho, M, Gabel, S, Gaidu, J, Gaiser, S, Gallo, K, Galloway, C, Gambaro, G, Gan, CC, Gangemi, C, Gao, M, Garcia, K, Garcia, M, Garofalo, C, Garrity, M, Garza, A, Gasko, S, Gavrila, M, Gebeyehu, B, Geddes, A, Gentile, G, George, A, George, J, Gesualdo, L, Ghalli, F, Ghanem, A, Ghate, T, Ghavampour, S, Ghazi, A, Gherman, A, Giebeln-Hudnell, U, Gill, B, Gillham, S, Girakossyan, I, Girndt, M, Giuffrida, A, Glenwright, M, Glider, T, Gloria, R, Glowski, D, Goh, BL, Goh, CB, Gohda, T, Goldenberg, R, Goldfaden, R, Goldsmith, C, Golson, B, Gonce, V, Gong, Q, Goodenough, B, Goodwin, N, Goonasekera, M, Gordon, A, Gordon, J, Gore, A, Goto, H, Gowen, D, Grace, A, Graham, J, Grandaliano, G, Gray, M, Greene, T, Greenwood, G, Grewal, B, Grifa, R, Griffin, D, Griffin, S, Grimmer, P, Grobovaite, E, Grotjahn, S, Guerini, A, Guest, C, Gunda, S, Guo, B, Guo, Q, Haack, S, Haase, M, Haaser, K, Habuki, K, Hadley, A, Hagan, S, Hagge, S, Haller, H, Ham, S, Hamal, S, Hamamoto, Y, Hamano, N, Hamm, M, Hanburry, A, Haneda, M, Hanf, C, Hanif, W, Hansen, J, Hanson, L, Hantel, S, Haraguchi, T, Harding, E, Harding, T, Hardy, C, Hartner, C, Harun, Z, Harvill, L, Hasan, A, Hase, H, Hasegawa, F, Hasegawa, T, Hashimoto, A, Hashimoto, C, Hashimoto, M, Hashimoto, S, Haskett, S, Hauske, SJ, Hawfield, A, Hayami, T, Hayashi, M, Hayashi, S, Hazara, A, Healy, C, Hecktman, J, Heine, G, Henderson, H, Henschel, R, Hepditch, A, Herfurth, K, Hernandez, G, Hernandez Pena, A, Hernandez-Cassis, C, Herzog, C, Hewins, S, Hewitt, D, Hichkad, L, Higashi, S, Higuchi, C, Hill, C, Hill, L, Himeno, T, Hing, A, Hirakawa, Y, Hirata, K, Hirota, Y, Hisatake, T, Hitchcock, S, Hodakowski, A, Hodge, W, Hogan, R, Hohenstatt, U, Hohenstein, B, Hooi, L, Hope, S, Hopley, M, Horikawa, S, Hosein, D, Hosooka, T, Hou, L, Hou, W, Howie, L, Howson, A, Hozak, M, Htet, Z, Hu, X, Hu, Y, Huang, J, Huda, N, Hudig, L, Hudson, A, Hugo, C, Hull, R, Hume, L, Hundei, W, Hunt, N, Hunter, A, Hurley, S, Hurst, A, Hutchinson, C, Hyo, T, Ibrahim, FH, Ibrahim, S, Ihana, N, Ikeda, T, Imai, A, Imamine, R, Inamori, A, Inazawa, H, Ingell, J, Inomata, K, Inukai, Y, Ioka, M, Irtiza-Ali, A, Isakova, T, Isari, W, Iselt, M, Ishiguro, A, Ishihara, K, Ishikawa, T, Ishimoto, T, Ishizuka, K, Ismail, R, Itano, S, Ito, H, Ito, K, Ito, M, Ito, Y, Iwagaitsu, S, Iwaita, Y, Iwakura, T, Iwamoto, M, Iwasa, M, Iwasaki, H, Iwasaki, S, Izumi, K, Izumi, T, Jaafar, SM, Jackson, C, Jackson, Y, Jafari, G, Jahangiriesmaili, M, Jain, N, Jansson, K, Jasim, H, Jeffers, L, Jenkins, A, Jesky, M, Jesus-Silva, J, Jeyarajah, D, Jiang, Y, Jiao, X, Jimenez, G, Jin, B, Jin, Q, Jochims, J, Johns, B, Johnson, C, Johnson, T, Jolly, S, Jones, L, Jones, S, Jones, T, Jones, V, Joseph, M, Joshi, S, Judge, P, Junejo, N, Junus, S, Kachele, M, Kadoya, H, Kaga, H, Kai, H, Kajio, H, Kaluza-Schilling, W, Kamaruzaman, L, Kamarzarian, A, Kamimura, Y, Kamiya, H, Kamundi, C, Kan, T, Kanaguchi, Y, Kanazawa, A, Kanda, E, Kanegae, S, Kaneko, K, Kang, HY, Kano, T, Karim, M, Karounos, D, Karsan, W, Kasagi, R, Kashihara, N, Katagiri, H, Katanosaka, A, Katayama, A, Katayama, M, Katiman, E, Kato, K, Kato, M, Kato, N, Kato, S, Kato, T, Kato, Y, Katsuda, Y, Katsuno, T, Kaufeld, J, Kavak, Y, Kawai, I, Kawai, M, Kawase, A, Kawashima, S, Kazory, A, Kearney, J, Keith, B, Kellett, J, Kelley, S, Kershaw, M, Ketteler, M, Khai, Q, Khairullah, Q, Khandwala, H, Khoo, KKL, Khwaja, A, Kidokoro, K, Kielstein, J, Kihara, M, Kimber, C, Kimura, S, Kinashi, H, Kingston, H, Kinomura, M, Kinsella-Perks, E, Kitagawa, M, Kitajima, M, Kitamura, S, Kiyosue, A, Kiyota, M, Klauser, F, Klausmann, G, Kmietschak, W, Knapp, K, Knight, C, Knoppe, A, Knott, C, Kobayashi, M, Kobayashi, R, Kobayashi, T, Koch, M, Kodama, S, Kodani, N, Kogure, E, Koizumi, M, Kojima, H, Kojo, T, Kolhe, N, Komaba, H, Komiya, T, Komori, H, Kon, SP, Kondo, M, Kong, W, Konishi, M, Kono, K, Koshino, M, Kosugi, T, Kothapalli, B, Kozlowski, T, Kraemer, B, Kraemer-Guth, A, Krappe, J, Kraus, D, Kriatselis, C, Krieger, C, Krish, P, Kruger, B, Ku Md Razi, KR, Kuan, Y, Kubota, S, Kuhn, S, Kumar, P, Kume, S, Kummer, I, Kumuji, R, Küpper, A, Kuramae, T, Kurian, L, Kuribayashi, C, Kurien, R, Kuroda, E, Kurose, T, Kutschat, A, Kuwabara, N, Kuwata, H, La Manna, G, Lacey, M, Lafferty, K, LaFleur, P, Lai, V, Laity, E, Lambert, A, Langlois, M, Latif, F, Latore, E, Laundy, E, Laurienti, D, Lawson, A, Lay, M, Leal, I, Lee, AK, Lee, J, Lee, KQ, Lee, R, Lee, SA, Lee, YY, Lee-Barkey, Y, Leonard, N, Leoncini, G, Leong, CM, Lerario, S, Leslie, A, Lewington, A, Li, N, Li, X, Li, Y, Liberti, L, Liberti, ME, Liew, A, Liew, YF, Lilavivat, U, Lim, SK, Lim, YS, Limon, E, Lin, H, Lioudaki, E, Liu, H, Liu, J, Liu, L, Liu, Q, Liu, X, Liu, Z, Loader, D, Lochhead, H, Loh, CL, Lorimer, A, Loudermilk, L, Loutan, J, Low, CK, Low, CL, Low, YM, Lozon, Z, Lu, Y, Lucci, D, Ludwig, U, Luker, N, Lund, D, Lustig, R, Lyle, S, Macdonald, C, MacDougall, I, Machicado, R, MacLean, D, Macleod, P, Madera, A, Madore, F, Maeda, K, Maegawa, H, Maeno, S, Mafham, M, Magee, J, Mah, DY, Mahabadi, V, Maiguma, M, Makita, Y, Makos, G, Manco, L, Mangiacapra, R, Manley, J, Mann, P, Mano, S, Marcotte, G, Maris, J, Mark, P, Markau, S, Markovic, M, Marshall, C, Martin, M, Martinez, C, Martinez, S, Martins, G, Maruyama, K, Maruyama, S, Marx, K, Maselli, A, Masengu, A, Maskill, A, Masumoto, S, Masutani, K, Matsumoto, M, Matsunaga, T, Matsuoka, N, Matsushita, M, Matthews, M, Matthias, S, Matvienko, E, Maurer, M, Maxwell, P, Mazlan, N, Mazlan, SA, Mbuyisa, A, McCafferty, K, McCarroll, F, McCarthy, T, McClary-Wright, C, McCray, K, McDermott, P, McDonald, C, McDougall, R, McHaffie, E, McIntosh, K, McKinley, T, McLaughlin, S, McLean, N, McNeil, L, Measor, A, Meek, J, Mehta, A, Mehta, R, Melandri, M, Mené, P, Meng, T, Menne, J, Merritt, K, Merscher, S, Meshykhi, C, Messa, P, Messinger, L, Miftari, N, Miller, R, Miller, Y, Miller-Hodges, E, Minatoguchi, M, Miners, M, Minutolo, R, Mita, T, Miura, Y, Miyaji, M, Miyamoto, S, Miyatsuka, T, Miyazaki, M, Miyazawa, I, Mizumachi, R, Mizuno, M, Moffat, S, Mohamad Nor, FS, Mohamad Zaini, SN, Mohamed Affandi, FA, Mohandas, C, Mohd, R, Mohd Fauzi, NA, Mohd Sharif, NH, Mohd Yusoff, Y, Moist, L, Moncada, A, Montasser, M, Moon, A, Moran, C, Morgan, N, Moriarty, J, Morig, G, Morinaga, H, Morino, K, Morisaki, T, Morishita, Y, Morlok, S, Morris, A, Morris, F, Mostafa, S, Mostefai, Y, Motegi, M, Motherwell, N, Motta, D, Mottl, A, Moys, R, Mozaffari, S, Muir, J, Mulhern, J, Mulligan, S, Munakata, Y, Murakami, C, Murakoshi, M, Murawska, A, Murphy, K, Murphy, L, Murray, S, Murtagh, H, Musa, MA, Mushahar, L, Mustafa, R, Mustafar, R, Muto, M, Nadar, E, Nagano, R, Nagasawa, T, Nagashima, E, Nagasu, H, Nagelberg, S, Nair, H, Nakagawa, Y, Nakahara, M, Nakamura, J, Nakamura, R, Nakamura, T, Nakaoka, M, Nakashima, E, Nakata, J, Nakata, M, Nakatani, S, Nakatsuka, A, Nakayama, Y, Nakhoul, G, Naverrete, G, Navivala, A, Nazeer, I, Negrea, L, Nethaji, C, Newman, E, Ng, TJ, Ngu, LLS, Nimbkar, T, Nishi, H, Nishi, M, Nishi, S, Nishida, Y, Nishiyama, A, Niu, J, Niu, P, Nobili, G, Nohara, N, Nojima, I, Nolan, J, Nosseir, H, Nozawa, M, Nunn, M, Nunokawa, S, Oda, M, Oe, M, Oe, Y, Ogane, K, Ogawa, W, Ogihara, T, Oguchi, G, Ohsugi, M, Oishi, K, Okada, Y, Okajyo, J, Okamoto, S, Okamura, K, Olufuwa, O, Oluyombo, R, Omata, A, Omori, Y, Ong, LM, Ong, YC, Onyema, J, Oomatia, A, Oommen, A, Oremus, R, Orimo, Y, Ortalda, V, Osaki, Y, Osawa, Y, Osmond Foster, J, O'Sullivan, A, Otani, T, Othman, N, Otomo, S, O'Toole, J, Owen, L, Ozawa, T, Padiyar, A, Page, N, Pajak, S, Paliege, A, Pandey, A, Pandey, R, Pariani, H, Park, J, Parrigon, M, Passauer, J, Patecki, M, Patel, M, Patel, R, Patel, T, Patel, Z, Paul, R, Paulsen, L, Pavone, L, Peixoto, A, Peji, J, Peng, BC, Peng, K, Pennino, L, Pereira, E, Perez, E, Pergola, P, Pesce, F, Pessolano, G, Petchey, W, Petr, EJ, Pfab, T, Phelan, P, Phillips, R, Phillips, T, Phipps, M, Piccinni, G, Pickett, T, Pickworth, S, Piemontese, M, Pinto, D, Piper, J, Plummer-Morgan, J, 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2024
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3. Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

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Judge, PK, Staplin, N, Mayne, KJ, Wanner, C, Green, JB, Hauske, SJ, Emberson, JR, Preiss, D, Ng, SYA, Roddick, AJ, Sammons, E, Zhu, D, Hill, M, Stevens, W, Wallendszus, K, Brenner, S, Cheung, AK, Liu, ZH, Li, J, Hooi, LS, Liu, WJ, Kadowaki, T, Nangaku, M, Levin, A, Cherney, D, Maggioni, AP, Pontremoli, R, Deo, R, Goto, S, Rossello, X, Tuttle, KR, Steubl, D, Massey, D, Landray, MJ, Baigent, C, Haynes, R, Herrington, WG, Abat, S, Abd Rahman, R, Abdul Cader, R, Abdul Hafidz, MI, Abdul Wahab, MZ, Abdullah, NK, Abdul-Samad, T, Abe, M, Abraham, N, Acheampong, S, Achiri, P, Acosta, JA, Adeleke, A, Adell, V, Adewuyi-Dalton, R, Adnan, N, Africano, A, Agharazii, M, Aguilar, F, Aguilera, A, Ahmad, M, Ahmad, MK, Ahmad, NA, Ahmad, NH, Ahmad, NI, Ahmad Miswan, N, Ahmad Rosdi, H, Ahmed, I, Ahmed, S, Aiello, J, Aitken, A, AitSadi, R, Aker, S, Akimoto, S, Akinfolarin, A, Akram, S, Alberici, F, Albert, C, Aldrich, L, Alegata, M, Alexander, L, Alfaress, S, Alhadj Ali, M, Ali, A, Alicic, R, Aliu, A, 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Nimbkar, T, Nishi, H, Nishi, M, Nishi, S, Nishida, Y, Nishiyama, A, Niu, J, Niu, P, Nobili, G, Nohara, N, Nojima, I, Nolan, J, Nosseir, H, Nozawa, M, Nunn, M, Nunokawa, S, Oda, M, Oe, M, Oe, Y, Ogane, K, Ogawa, W, Ogihara, T, Oguchi, G, Ohsugi, M, Oishi, K, Okada, Y, Okajyo, J, Okamoto, S, Okamura, K, Olufuwa, O, Oluyombo, R, Omata, A, Omori, Y, Ong, LM, Ong, YC, Onyema, J, Oomatia, A, Oommen, A, Oremus, R, Orimo, Y, Ortalda, V, Osaki, Y, Osawa, Y, Osmond Foster, J, O'Sullivan, A, Otani, T, Othman, N, Otomo, S, O'Toole, J, Owen, L, Ozawa, T, Padiyar, A, Page, N, Pajak, S, Paliege, A, Pandey, A, Pandey, R, Pariani, H, Park, J, Parrigon, M, Passauer, J, Patecki, M, Patel, M, Patel, R, Patel, T, Patel, Z, Paul, R, Paulsen, L, Pavone, L, Peixoto, A, Peji, J, Peng, BC, Peng, K, Pennino, L, Pereira, E, Perez, E, Pergola, P, Pesce, F, Pessolano, G, Petchey, W, Petr, EJ, Pfab, T, Phelan, P, Phillips, R, Phillips, T, Phipps, M, Piccinni, G, Pickett, T, Pickworth, S, Piemontese, M, Pinto, D, Piper, J, Plummer-Morgan, J, Poehler, D, Polese, L, Poma, V, Postal, A, Pötz, C, Power, A, Pradhan, N, Pradhan, R, Preiss, E, Preston, K, Prib, N, Price, L, Provenzano, C, Pugay, C, Pulido, R, Putz, F, Qiao, Y, Quartagno, R, Quashie-Akponeware, M, Rabara, R, Rabasa-Lhoret, R, Radhakrishnan, D, Radley, M, Raff, R, Raguwaran, S, Rahbari-Oskoui, F, Rahman, M, Rahmat, K, Ramadoss, S, Ramanaidu, S, Ramasamy, S, Ramli, R, Ramli, S, Ramsey, T, Rankin, A, Rashidi, A, Raymond, L, Razali, WAFA, Read, K, Reiner, H, Reisler, A, Reith, C, Renner, J, Rettenmaier, B, Richmond, L, Rijos, D, Rivera, R, Rivers, V, Robinson, H, Rocco, M, Rodriguez-Bachiller, I, Rodriquez, R, Roesch, C, Roesch, J, Rogers, J, Rohnstock, M, Rolfsmeier, S, Roman, M, Romo, A, Rosati, A, Rosenberg, S, Ross, T, Roura, M, Roussel, M, Rovner, S, Roy, S, Rucker, S, Rump, L, Ruocco, M, Ruse, S, Russo, F, Russo, M, Ryder, M, Sabarai, A, Saccà, C, Sachson, R, Sadler, E, Safiee, NS, Sahani, M, Saillant, A, Saini, J, Saito, C, Saito, S, Sakaguchi, K, Sakai, M, Salim, H, Salviani, C, Sampson, A, Samson, F, Sandercock, P, Sanguila, S, Santorelli, G, Santoro, D, Sarabu, N, Saram, T, Sardell, R, Sasajima, H, Sasaki, T, Satko, S, Sato, A, Sato, D, Sato, H, Sato, J, Sato, T, Sato, Y, Satoh, M, Sawada, K, Schanz, M, Scheidemantel, F, Schemmelmann, M, Schettler, E, Schettler, V, Schlieper, GR, Schmidt, C, Schmidt, G, Schmidt, U, Schmidt-Gurtler, H, Schmude, M, Schneider, A, Schneider, I, Schneider-Danwitz, C, Schomig, M, Schramm, T, Schreiber, A, Schricker, S, Schroppel, B, Schulte-Kemna, L, Schulz, E, Schumacher, B, Schuster, A, Schwab, A, Scolari, F, Scott, A, Seeger, W, Segal, M, Seifert, L, Seifert, M, Sekiya, M, Sellars, R, Seman, MR, Shah, S, Shainberg, L, Shanmuganathan, M, Shao, F, Sharma, K, Sharpe, C, Sheikh-Ali, M, Sheldon, J, Shenton, C, Shepherd, A, Shepperd, M, Sheridan, R, Sheriff, Z, Shibata, Y, Shigehara, T, Shikata, K, Shimamura, K, Shimano, H, Shimizu, Y, Shimoda, H, Shin, K, Shivashankar, G, Shojima, N, Silva, R, Sim, CSB, Simmons, K, Sinha, S, Sitter, T, Sivanandam, S, Skipper, M, Sloan, K, Sloan, L, Smith, R, Smyth, J, Sobande, T, Sobata, M, Somalanka, S, Song, X, Sonntag, F, Sood, B, Sor, SY, Soufer, J, Sparks, H, Spatoliatore, G, Spinola, T, Squyres, S, Srivastava, A, Stanfield, J, Staylor, K, Steele, A, Steen, O, Steffl, D, Stegbauer, J, Stellbrink, C, Stellbrink, E, Stevenson, A, Stewart-Ray, V, Stickley, J, Stoffler, D, Stratmann, B, Streitenberger, S, Strutz, F, Stubbs, J, Stumpf, J, Suazo, N, Suchinda, P, Suckling, R, Sudin, A, Sugamori, K, Sugawara, H, Sugawara, K, Sugimoto, D, Sugiyama, H, Sugiyama, T, Sullivan, M, Sumi, M, Suresh, N, Sutton, D, Suzuki, H, Suzuki, R, Suzuki, Y, Swanson, E, Swift, P, Syed, S, Szerlip, H, Taal, M, Taddeo, M, Tailor, C, Tajima, K, Takagi, M, Takahashi, K, Takahashi, M, Takahashi, T, Takahira, E, Takai, T, Takaoka, M, Takeoka, J, Takesada, A, Takezawa, M, Talbot, M, Taliercio, J, Talsania, T, Tamori, Y, Tamura, R, Tamura, Y, Tan, CHH, Tan, EZZ, Tanabe, A, Tanabe, K, Tanaka, A, Tanaka, N, Tang, S, Tang, Z, Tanigaki, K, Tarlac, M, Tatsuzawa, A, Tay, JF, Tay, LL, Taylor, J, Taylor, K, Te, A, Tenbusch, L, Teng, KS, Terakawa, A, Terry, J, Tham, ZD, Tholl, S, Thomas, G, Thong, KM, Tietjen, D, Timadjer, A, Tindall, H, Tipper, S, Tobin, K, Toda, N, Tokuyama, A, Tolibas, M, Tomita, A, Tomita, T, Tomlinson, J, Tonks, L, Topf, J, Topping, S, Torp, A, Torres, A, Totaro, F, Toth, P, Toyonaga, Y, Tripodi, F, Trivedi, K, Tropman, E, Tschope, D, Tse, J, Tsuji, K, Tsunekawa, S, Tsunoda, R, Tucky, B, Tufail, S, Tuffaha, A, Turan, E, Turner, H, Turner, J, Turner, M, Tye, YL, Tyler, A, Tyler, J, Uchi, H, Uchida, H, Uchida, T, Udagawa, T, Ueda, S, Ueda, Y, Ueki, K, Ugni, S, Ugwu, E, Umeno, R, Unekawa, C, Uozumi, K, Urquia, K, Valleteau, A, Valletta, C, van Erp, R, Vanhoy, C, Varad, V, Varma, R, Varughese, A, Vasquez, P, Vasseur, A, Veelken, R, Velagapudi, C, Verdel, K, Vettoretti, S, Vezzoli, G, Vielhauer, V, Viera, R, Vilar, E, Villaruel, S, Vinall, L, Vinathan, J, Visnjic, M, Voigt, E, von-Eynatten, M, Vourvou, M, Wada, J, Wada, T, Wada, Y, Wakayama, K, Wakita, Y, Walters, T, Wan Mohamad, WH, Wang, L, Wang, W, Wang, X, Wang, Y, Wanninayake, S, Watada, H, Watanabe, K, Watanabe, M, Waterfall, H, Watkins, D, Watson, S, Weaving, L, Weber, B, Webley, Y, Webster, A, Webster, M, Weetman, M, Wei, W, Weihprecht, H, Weiland, L, Weinmann-Menke, J, Weinreich, T, Wendt, R, Weng, Y, Whalen, M, Whalley, G, Wheatley, R, Wheeler, A, Wheeler, J, Whelton, P, White, K, Whitmore, B, Whittaker, S, Wiebel, J, Wiley, J, Wilkinson, L, Willett, M, Williams, A, Williams, E, Williams, K, Williams, T, Wilson, A, Wilson, P, Wincott, L, Wines, E, Winkelmann, B, Winkler, M, Winter-Goodwin, B, Witczak, J, Wittes, J, Wittmann, M, Wolf, G, Wolf, L, Wolfling, R, Wong, C, Wong, E, Wong, HS, Wong, LW, Wong, YH, Wonnacott, A, Wood, A, Wood, L, Woodhouse, H, Wooding, N, Woodman, A, Wren, K, Wu, J, Wu, P, Xia, S, Xiao, H, Xiao, X, Xie, Y, Xu, C, Xu, Y, Xue, H, Yahaya, H, Yalamanchili, H, Yamada, A, Yamada, N, Yamagata, K, Yamaguchi, M, Yamaji, Y, Yamamoto, A, Yamamoto, S, Yamamoto, T, Yamanaka, A, Yamano, T, Yamanouchi, Y, Yamasaki, N, Yamasaki, Y, Yamashita, C, Yamauchi, T, Yan, Q, Yanagisawa, E, Yang, F, Yang, L, Yano, S, Yao, S, Yao, Y, Yarlagadda, S, Yasuda, Y, Yiu, V, Yokoyama, T, Yoshida, S, Yoshidome, E, Yoshikawa, H, Young, A, Young, T, Yousif, V, Yu, H, Yu, Y, Yuasa, K, Yusof, N, Zalunardo, N, Zander, B, Zani, R, Zappulo, F, Zayed, M, Zemann, B, Zettergren, P, Zhang, H, Zhang, L, Zhang, N, Zhang, X, Zhao, J, Zhao, L, Zhao, S, Zhao, Z, Zhong, H, Zhou, N, Zhou, S, Zhu, L, Zhu, S, Zietz, M, Zippo, M, Zirino, F, and Zulkipli, FH

Published
2024
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4. Risk of end-stage kidney disease in kidney transplant recipients versus patients with native chronic kidney disease: multicentre unmatched and propensity-score matched analyses

Author

De Nicola, L., Serra, R., Provenzano, M., Minutolo, R., Michael, A., Ielapi, N., Federico, S., Carrano, R., Bellizzi, V., Garofalo, C., Iodice, C., Borrelli, S., Grandaliano, Giuseppe, Stallone, G., Gesualdo, L., Chiodini, P., Andreucci, M., Grandaliano G. (ORCID:0000-0003-1213-2177), De Nicola, L., Serra, R., Provenzano, M., Minutolo, R., Michael, A., Ielapi, N., Federico, S., Carrano, R., Bellizzi, V., Garofalo, C., Iodice, C., Borrelli, S., Grandaliano, Giuseppe, Stallone, G., Gesualdo, L., Chiodini, P., Andreucci, M., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Background: In kidney transplant recipients (KTR), the end-stage kidney disease (ESKD) risk dependent on the risk factors acting in native chronic kidney disease (CKD) remains undefined. Methods: We compared risk and determinants of ESKD between 757 adult KTR and 1940 patients with native CKD before and after propensity-score (PS) analysis matched for unmodifiable risk factors [(age, sex, diabetes, cardiovascular disease and estimated glomerular filtration rate (eGFR)]. Results: In unmatched cohorts, eGFR was lower in CKD versus KTR (45.9 ± 11.3 versus 59.2 ± 13.4 mL/min/1.73 m2, P < 0.001). During a median follow-up of 5.4 years, the unadjusted cumulative incidence of ESKD was consistently lower in unmatched KTR versus CKD. Conversely, in PS-matched analysis, the risk of ESKD in KTR was 78% lower versus CKD at 1 year of follow-up while progressively increased over time resulting similar to that of native CKD patients after 5 years and 2.3-fold higher than that observed in CKD at 10 years. R2 analysis in unmatched patients showed that the proportion of the outcome variance explained by traditional ESKD determinants was smaller in KTR versus native CKD (31% versus 70%). After PS matching, the risk of ESKD [hazard ratio (HR), 95% confidence interval (95% CI)] was significantly associated with systolic blood pressure (1.02, 1.01-1.02), phosphorus (1.31, 1.05-1.64), 24-h proteinuria (1.11, 1.05-1.17) and haemoglobin (0.85, 0.78-0.93) irrespective of KTR status. Similar data were obtained after matching also for modifiable risk factors. Conclusions: In KTR, when compared with matched native CKD patients, the risk of ESKD is lower in the first 5 years and higher later on. Traditional determinants of ESKD account for one-third of the variability of time-to-graft failure.

Published
2023

7. mTOR inhibition improves mitochondria function/biogenesis and delays cardiovascular aging in kidney transplant recipients with chronic graft dysfunction

Author

Infante, B., Bellanti, F., Correale, M., Pontrelli, P., Franzin, R., Leo, S., Calvaruso, M., Mercuri, S., Netti, G. S., Ranieri, E., Brunetti, N. D., Grandaliano, G., Gesualdo, L., Serviddio, G., Castellano, G., Stallone, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Infante, B., Bellanti, F., Correale, M., Pontrelli, P., Franzin, R., Leo, S., Calvaruso, M., Mercuri, S., Netti, G. S., Ranieri, E., Brunetti, N. D., Grandaliano, G., Gesualdo, L., Serviddio, G., Castellano, G., Stallone, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

CVD remains the major cause of mortality with graft functioning in Kidney transplant recipients (KTRs), with an estimated risk of CV events about 50-fold higher than in the general population. Many strategies have been considered to reduce the CV risk such as the use of mTOR inhibitors. We evaluate whether chronic mTOR inhibition might influence CV aging in KTRs studying the molecular mechanisms involved in this effect. We retrospectively analyzed 210 KTRs with stable graft function on therapy with CNI and mycophenolic acid (Group A, 105 pts.), or with CNI and mTORi (Everolimus, Group B, 105 pts.). The presence of mTOR inhibitor in immunosuppressive therapy was associated to increase serum levels of Klotho with concomitant reduction in FGF-23, with a significant decrease in left ventricular mass. In addition, KTRs with mTORi improved mitochondrial function/biogenesis in PBMC with more efficient oxidative phosphorylation, antioxidant capacity and glutathione peroxidase activity. Finally, group B KTRs presented reduced levels of inflammaging markers such as reduced serum pentraxin-3 and p21ink expression in PBMC. In conclusion, we demonstrated that mTOR inhibition in immunosuppressive protocols prevents the occurrence and signs of CV aging in KTRs.

Published
2021

12. COVID-19 and kidney transplantation: an Italian Survey and Consensus

Author

Vistoli, F., Furian, L., Maggiore, U., Caldara, R., Cantaluppi, V., Ferraresso, M., Zaza, G., Cardillo, M., Biancofiore, G., Menichetti, F., Russo, A., Turillazzi, E., Di Paolo, M., Grandaliano, G., Boggi, U., Brunori, G., Petrini, F., Valenza, F., Lavezzo, B., Bonucchi, D., Capocasale, E., Grossi, P., Ponticelli, C., Sandrini, S., Schena, F. P., Segoloni, G., Biancone, L., Boschiero, L., Rigotti, P., Comai, G., Bossini, N., Minetti, E., Iaria, G., Ambrosini, A., Messa, P. G., Boscutti, G., Carmellini, M., Caputo, F., Ranghino, A., De Rosa, P., Federico, S., Veroux, M., Cirami, C., Nordio, M., Citterio, F., Piredda, G. B., Pretagostini, R., De Paolis, P., Rampino, T., Pisani, F., Cappelli, G., Secchi, A., Salis, P., Gastaldon, F., Mallamaci, F., Strologo, L. D., Taglioni, C., Teresa, P., Peruzzi, L., Gesualdo, L., Gotti, E., Feltracco, P., and Paoletti, E.

Subjects
Nephrology, medicine.medical_specialty, Consensus, Pneumonia, Viral, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Organ transplantation, law.invention, Kidney transplantation, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, law, Intensive care, Internal medicine, Pandemic, medicine, Living Donors, Settore MED/14 - NEFROLOGIA, Antimicrobial stewardship, Humans, Viral, Position papers and Guidelines, Survey, Pandemics, business.industry, SARS-CoV-2, Public health, COVID-19, Pneumonia, medicine.disease, Coronavirus Infections, Kidney Transplantation, Intensive care unit, Family medicine, business
Abstract

Italy was the first Western country to face the COVID-19 pandemic. Here we report the results of a national survey on kidney transplantation activity in February and March 2020, and the results of a three-round Delphi consensus promoted by four scientific societies: the Italian Society of Organ Transplantation, the Italian Society of Nephrology, the Italian Society of Anesthesia and Intensive Care, and the Italian Group on Antimicrobial Stewardship. All 41 Italian transplant centers were invited to express their opinion in the Delphi rounds along with a group of seven experts. The survey revealed that, starting from March 2020, there was a decline in kidney transplantation activity in Italy, especially for living-related transplants. Overall, 60 recipients tested positive for SARS-CoV2 infection, 57 required hospitalization, 17 were admitted to the ICU, and 11 died. The online consensus had high response rates at each round (95.8%, 95.8%, and 89.5%, respectively). Eventually, 27 of 31 proposed statements were approved (87.1%), 12 at the first or second round (38.7%), and 3 at the third (9.7%). Based on the Italian experience, we discuss the reasons for the changes in kidney transplantation activity during the COVID-19 pandemic in Western countries. We also provide working recommendations for the organization and management of kidney transplantation under these conditions. Electronic supplementary material The online version of this article (10.1007/s40620-020-00755-8) contains supplementary material, which is available to authorized users.

Published
2020

13. Eradication of HCV by direct antiviral agents restores mitochondrial function and energy homeostasis in peripheral blood mononuclear cells

Author

Villani, R., Sangineto, M., Pontrelli, P., Bellanti, F., Bukke, V. N., Moola, A., Gesualdo, L., Vendemiale, G., Grandaliano, Giuseppe, Stallone, G., Serviddio, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Villani, R., Sangineto, M., Pontrelli, P., Bellanti, F., Bukke, V. N., Moola, A., Gesualdo, L., Vendemiale, G., Grandaliano, Giuseppe, Stallone, G., Serviddio, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Hepatitis C virus (HCV) adopts several immune evasion mechanisms such as interfering with innate immunity or promoting T-cell exhaustion. However, the recent direct-antiviral agents (DAAs) rapidly eliminate the virus, and the repercussions in terms of immune system balance are unknown. Here we compared the PBMCs transcriptomic profile of patients with HCV chronic infection at baseline (T0) and 12 weeks after the end of the therapy (SVR12) with DAAs. 3862 genes were differently modulated, identifying oxidative phosphorylation as the top canonical pathway differentially activated. Therefore, we dissected PBMCs bioenergetic profile by analyzing mitochondrial respiration and glycolysis at 4 timepoints: T0, 4 weeks of therapy, end of therapy (EoT), and SVR12. Maximal and reserve respiratory capacity considerably increased at EoT, persisting until SVR12. Notably, over time a significant increase was observed in respiratory chain (RC) complexes protein levels and the enzymatic activity of complexes I, II, and IV. Mitochondrial-DNA integrity improved over time, and the expression of mitochondrial biogenesis key regulators such as TFAM, Nrf-1, and PPARGC1A significantly increased at SVR12; hence, RC complexes synthesis and mitochondrial respiration were supported after treatment. HCV clearance with DAAS profoundly changed PBMCs bioenergetic profile, suggesting the immunometabolism study as a new approach to the understanding of viral immune evasion mechanisms and host adaptations during infections and therapies.

Published
2022

15. New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: A multicohort observational study

Author

Minutolo, R., Provenzano, M., Chiodini, P., Borrelli, S., Garofalo, C., Andreucci, M., Liberti, M. E., Bellizzi, V., Conte, G., De Nicola, L., Zamboli, P., Iodice, F. C., Signoriello, S., Gallo, C., Cianciaruso, B., Pota, A., Nappi, F., Avella, F., Di Iorio, B. R., Cestaro, R., Martignetti, V., Morrone, L., Lupo, A., Abaterusso, C., Donadio, C., Bonomini, M., Sirolli, V., Casino, F., Lopez, T., Detomaso, F., Giannattasio, M., Virgilio, M., Tarantino, G., Cristofano, C., Tuccillo, S., Chimienti, S., Petrarulo, F., Giancaspro, V., Strippoli, M., Laraia, E., Gallucci, M., Gigante, B., Lodeserto, C., Santese, D., Montanaro, A., Giordano, R., Caglioti, A., Fuiano, G., Zoccali, C., Caridi, G., Postorino, M., Savica, V., Monardo, P., Bellinghieri, G., Santoro, D., Castellino, P., Rapisarda, F., Fatuzzo, P., Messina, A., Dal Canton, A., Esposito, V., Formica, M., Segoloni, G., Gallieni, M., Locatelli, F., Tarchini, R., Meneghel, G., Oldrizzi, L., Cossu, M., Di Giulio, S., Malaguti, M., Pizzarelli, F., Quintaliani, G., Pisani, A., Bonofiglio, R., Grandaliano, Giuseppe, Russo, D., Di Micco, L., Torraca, S., Sabbatini, M., Grandaliano G. (ORCID:0000-0003-1213-2177), Minutolo, R., Provenzano, M., Chiodini, P., Borrelli, S., Garofalo, C., Andreucci, M., Liberti, M. E., Bellizzi, V., Conte, G., De Nicola, L., Zamboli, P., Iodice, F. C., Signoriello, S., Gallo, C., Cianciaruso, B., Pota, A., Nappi, F., Avella, F., Di Iorio, B. R., Cestaro, R., Martignetti, V., Morrone, L., Lupo, A., Abaterusso, C., Donadio, C., Bonomini, M., Sirolli, V., Casino, F., Lopez, T., Detomaso, F., Giannattasio, M., Virgilio, M., Tarantino, G., Cristofano, C., Tuccillo, S., Chimienti, S., Petrarulo, F., Giancaspro, V., Strippoli, M., Laraia, E., Gallucci, M., Gigante, B., Lodeserto, C., Santese, D., Montanaro, A., Giordano, R., Caglioti, A., Fuiano, G., Zoccali, C., Caridi, G., Postorino, M., Savica, V., Monardo, P., Bellinghieri, G., Santoro, D., Castellino, P., Rapisarda, F., Fatuzzo, P., Messina, A., Dal Canton, A., Esposito, V., Formica, M., Segoloni, G., Gallieni, M., Locatelli, F., Tarchini, R., Meneghel, G., Oldrizzi, L., Cossu, M., Di Giulio, S., Malaguti, M., Pizzarelli, F., Quintaliani, G., Pisani, A., Bonofiglio, R., Grandaliano, Giuseppe, Russo, D., Di Micco, L., Torraca, S., Sabbatini, M., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Background: Anemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known. Methods: We performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR <60 mL/min/1.73 m2 regularly followed in renal clinics. We estimated the incidence of mild anemia (hemoglobin 11-12 g/dL in women and 11-13 g/dL in men) and severe anemia (hemoglobin <11 g/dL or use of erythropoiesis-stimulating agents) during a 3-year follow-up period. Thereafter we estimated the risk of end-stage kidney disease (ESKD) and all-cause death associated with new-onset mild and severe anemia. Results: The mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1-1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR <30 mL/min/1.73 m2 and proteinuria >0.50 g/day. Male sex, moderate CKD (eGFR 30-44 mL/min/1.73 m2) and moderate proteinuria (0.15-0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02-1.98]} and all-cause death [HR 1.55 (95% CI 1.04-2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20-2.51)] and death [HR 1.83 (95% CI 1.05-3.19)].

Published
2022

16. Can SGLT2 inhibitors answer unmet therapeutic needs in chronic kidney disease?

Author

De Nicola, L, Cozzolino, M, Genovesi, S, Gesualdo, L, Grandaliano, G, Pontremoli, R, De Nicola, Luca, Cozzolino, Mario, Genovesi, Simonetta, Gesualdo, Loreto, Grandaliano, Giuseppe, Pontremoli, Roberto, De Nicola, L, Cozzolino, M, Genovesi, S, Gesualdo, L, Grandaliano, G, Pontremoli, R, De Nicola, Luca, Cozzolino, Mario, Genovesi, Simonetta, Gesualdo, Loreto, Grandaliano, Giuseppe, and Pontremoli, Roberto

Abstract

Chronic kidney disease (CKD) is a global health problem, affecting more than 850 million people worldwide. The number of patients receiving renal replacement therapy (dialysis or renal transplantation) has increased over the years, and it has been estimated that the number of people receiving renal replacement therapy will more than double from 2.618 million in 2010 to 5.439 million in 2030, with wide differences among countries. The main focus of CKD treatment has now become preserving renal function rather than replacing it. This is possible, at least to some extent, through the optimal use of multifactorial therapy aimed at preventing end-stage kidney disease and cardiovascular events. Sodium/glucose cotransporter 2 inhibitors (SGLT2i) reduce glomerular hypertension and albuminuria with beneficial effects on progression of renal damage in both diabetic and non-diabetic CKD. SGLT2 inhibitors also show great benefits in cardiovascular protection, irrespective of diabetes. Therefore, the use of these drugs will likely be extended to the whole CKD population as a new standard of care.

Published
2022

17. Crystal-induced colitis

Author

Spasiano, Andrea, Castri, Federica, Giustiniani, Maria Cristina, Riccioni, Maria Elena, Naticchia, Alessandro, Grandaliano, Giuseppe, Panocchia, Nicola, Spasiano A., Castri F., Giustiniani M. C., Riccioni M. E. (ORCID:0000-0002-9239-4312), Naticchia A., Grandaliano G. (ORCID:0000-0003-1213-2177), Panocchia N., Spasiano, Andrea, Castri, Federica, Giustiniani, Maria Cristina, Riccioni, Maria Elena, Naticchia, Alessandro, Grandaliano, Giuseppe, Panocchia, Nicola, Spasiano A., Castri F., Giustiniani M. C., Riccioni M. E. (ORCID:0000-0002-9239-4312), Naticchia A., Grandaliano G. (ORCID:0000-0003-1213-2177), and Panocchia N.

Abstract

A 59-year-old man undergoing dialysis was admitted to our hospital with lower limb ischemia; he had a story of long-term use of phosphate and potassium chelator. Because of anemia and repeated episodes of bowel bleeding, he underwent colonoscopy with a biopsy of the ileocecal valve and ulcerative lesions of the proximal descending colon

Published
2022

21. Modulation of complement activation by pentraxin-3 in prostate cancer

Author

Stallone, G., Netti, G. S., Cormio, L., Castellano, G., Infante, B., Pontrelli, P., Divella, C., Selvaggio, O., Spadaccino, F., Ranieri, E., Sanguedolce, F., Pennella, A., Gesualdo, L., Carrieri, G., Grandaliano, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Stallone, G., Netti, G. S., Cormio, L., Castellano, G., Infante, B., Pontrelli, P., Divella, C., Selvaggio, O., Spadaccino, F., Ranieri, E., Sanguedolce, F., Pennella, A., Gesualdo, L., Carrieri, G., Grandaliano, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Pentraxin 3 (PTX3) is an essential component of the innate immune system and a recognized modulator of Complement cascade. The role of Complement system in the pathogenesis of prostate cancer has been largely underestimated. The aim of our study was to investigate the role of PTX3 as possible modulator of Complement activation in the development of this neoplasia. We performed a single center cohort study; from January 2017 through December 2018, serum and prostate tissue samples were obtained from 620 patients undergoing prostate biopsy. A group of patients with benign prostatic hyperplasia (BPH) underwent a second biopsy within 12–36 months demonstrating the presence of a prostate cancer (Group A, n = 40) or confirming the diagnosis of BPH (Group B, N = 40). We measured tissue PTX3 protein expression together with complement activation by confocal microscopy in the first and second biopsy in group A and B patients. We confirmed that that PTX3 tissue expression in the first biopsy was increased in group A compared to group B patients. C1q deposits were extensively present in group A patients co-localizing and significantly correlating with PTX3 deposits; on the contrary, C1q/PTX3 deposits were negative in group B. Moreover, we found a significantly increased expression of C3a and C5a receptors within resident cells in group A patient. Interestingly, C1q/PTX3 deposits were not associated with activation of the terminal Complement complex C5b-9; moreover, we found a significant increase of Complement inhibitor CD59 in cancer tissue. Our data indicate that PTX3 might play a significant pathogenic role in the development of this neoplasia through recruitment of the early components of Complement cascade with hampered activation of terminal Complement pathway associated with the upregulation of CD59. This alteration might lead to the PTX3-mediated promotion of cellular proliferation, angiogenesis and insensitivity to apoptosis possible leading to cancer cell i

Published
2020

22. The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation

Author

Pontrelli, P., Rascio, F., Castellano, G., Grandaliano, G., Gesualdo, L., Stallone, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Pontrelli, P., Rascio, F., Castellano, G., Grandaliano, G., Gesualdo, L., Stallone, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Natural killer cells (NK) represent a population of lymphocytes involved in innate immune response. In addition to their role in anti-viral and anti-tumor defense, they also regulate several aspects of the allo-immune response in kidney transplant recipients. Growing evidence suggests a key role of NK cells in the pathogenesis of immune-mediated graft damage in kidney transplantation. Specific NK cell subsets are associated with operational tolerance in kidney transplant patients. On the other side, allo-reactive NK cells are associated with chronic antibody-mediated rejection and graft loss. Moreover, NK cells can prime the adaptive immune system and promote the migration of other immune cells, such as dendritic cells, into the graft leading to an increased allo-immune response and, eventually, to chronic graft rejection. Finally, activated NK cells can infiltrate the transplanted kidney and cause a direct graft damage. Interestingly, immunosuppression can influence NK cell numbers and function, thus causing an increased risk of post-transplant neoplasia or infection. In this review, we will describe how these cells can influence the innate and the adaptive immune response in kidney transplantation and how immunosuppression can modulate NK behavior.

Published
2020

23. Altered phosphorylation of cytoskeleton proteins in peripheral blood mononuclear cells characterizes chronic antibody-mediated rejection in kidney transplantation

Author

Rocchetti, M. T., Rascio, F., Castellano, G., Fiorentino, M., Netti, G. S., Spadaccino, F., Ranieri, E., Gallone, A., Gesualdo, L., Stallone, G., Pontrelli, P., Grandaliano, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Rocchetti, M. T., Rascio, F., Castellano, G., Fiorentino, M., Netti, G. S., Spadaccino, F., Ranieri, E., Gallone, A., Gesualdo, L., Stallone, G., Pontrelli, P., Grandaliano, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Chronic antibody-mediated rejection (CAMR) is the major cause of kidney transplant failure. The molecular mechanisms underlying this event are still poorly defined and this lack of knowledge deeply influences the potential therapeutic strategies. The aim of our study was to analyze the phosphoproteome of peripheral blood mononuclear cells (PBMCs), to identify cellular signaling networks differentially activated in CAMR. Phosphoproteins isolated from PBMCs of biopsy proven CAMR, kidney transplant recipients with normal graft function and histology and healthy immunocompetent individuals, have been investigated by proteomic analysis. Phosphoproteomic results were confirmed by Western blot and PBMCs’ confocal microscopy analyses. Overall, 38 PBMCs samples were analyzed. A differential analysis of PBMCs’ phosphoproteomes revealed an increase of lactotransferrin, actin-related protein 2 (ARPC2) and calgranulin-B in antibody-mediated rejection patients, compared to controls. Increased expression of phosphorylated ARPC2 and its correlation to F-actin filaments were confirmed in CAMR patients. Our results are the first evidence of altered cytoskeleton organization in circulating immune cells of CAMR patients. The increased expression of phosphorylated ARPC2 found in the PBMCs of our patients, and its association with derangement of F-actin filaments, might suggest that proteins regulating actin dynamics in immune cells could be involved in the mechanism of CAMR of kidney grafts.

Published
2020

24. Nocturnal haemodialysis is associated with a reduced occurrence of low triiodothyronine serum levels in haemodialysed patients

Author

Netti, GS, Rotondi, M, Di Lorenzo, A, Papantonio, D, Teri, A, Schirone, M, Spadaccino, F, Croce, L, Infante, B, Perulli, R, Coperchini, F, Rocchetti, MT, Iannelli, G, Fortunato, F, Prato, R, Castellano, G, Gesualdo, L, Stallone, G, Ranieri, E, Grandaliano, G, Grandaliano G (ORCID:0000-0003-1213-2177), Netti, GS, Rotondi, M, Di Lorenzo, A, Papantonio, D, Teri, A, Schirone, M, Spadaccino, F, Croce, L, Infante, B, Perulli, R, Coperchini, F, Rocchetti, MT, Iannelli, G, Fortunato, F, Prato, R, Castellano, G, Gesualdo, L, Stallone, G, Ranieri, E, Grandaliano, G, and Grandaliano G (ORCID:0000-0003-1213-2177)

Abstract

Background End-stage renal disease (ESRD) is associated with a broad spectrum of morphological and functional thyroid disorders. Recent studies have shown that low free triiodothyronine (fT3) levels are related to inflammatory status and endothelial activation in ESRD patients on haemodialysis (HD). Limited data exist about a possible relationship between dialysis regimen, namely long nocturnal haemodialysis (LNHD), and thyroid function parameters. The aim of this study was to evaluate the relationship between dialysis regimen and thyroid function, and consequently with the main patient outcomes. Methods To this purpose, we performed a retrospective, single-centre cohort study including 220 incident chronic HD patients treated during an 8-year period (from January 2010 to December 2017). The main clinical and haematochemical parameters, including thyroid function, were evaluated and related to the main patient outcomes. Results Patients with low fT3 levels (<3.05 ng/mL) showed significantly lower survival rates than patients with normal fT3 levels (>3.05 ng/mL) (P < 0.001), although there were no substantial differences in the demographic and clinical characteristics between the two groups. After propensity score 1:3 matching of 25 patients treated with nocturnal HD to 75 patients treated with diurnal HD, LNHD patients showed significantly higher survival rates (88.0% versus 61.3%, P = 0.001) and lower incidence of cardiovascular events than patients on diurnal dialysis (8.0% versus 40.0%, P = 0.001). Moreover, an 8-year time-dependent analysis showed that at any time, except for baseline, the rate of patients with fT3 levels >3.05 ng/mL was significantly higher in LNHD patients than in patients treated with diurnal dialysis. Conclusions Our data suggest that the application of alternative dialysis regimens, also reducing the frequency of low T3, could ameliorate outcomes and therefore reduce the incidence of cardiovascular events in HD patients.

Published
2020

35. LPS removal reduces CD80-mediated albuminuria in critically ill patients with gram-negative sepsis

Author

Netti, G. S., Sangregorio, F., Spadaccino, F., Staffieri, F., Crovace, A., Infante, B., Maiorano, A., Godeas, G., Castellano, G., Palma, A. M. D., Prattichizzo, C., Cotoia, A., Mirabella, L., Gesualdo, L., Cinnella, G., Stallone, G., Ranieri, E., Grandaliano, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Netti, G. S., Sangregorio, F., Spadaccino, F., Staffieri, F., Crovace, A., Infante, B., Maiorano, A., Godeas, G., Castellano, G., Palma, A. M. D., Prattichizzo, C., Cotoia, A., Mirabella, L., Gesualdo, L., Cinnella, G., Stallone, G., Ranieri, E., Grandaliano, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomized to either have coupled plasma filtration and adsorption (CPFA) added to the standard care (n = 35) or not (n = 35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria, and CD80 expression in Gram sepsis, a swine model of LPS-induced AKI was set up. Three hours after LPS infusion, animals were treated or not with CPFA for 6 h. Treatment with CPFA significantly reduced serum cytokines, C-reactive protein, procalcitonin, and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.

Published
2019

36. Recurrent urinary tract infections in kidney transplant recipients during the first-year influence long-term graft function: a single-center retrospective cohort study

Author

Pesce, F., Martino, M., Fiorentino, M., Rollo, T., Simone, S., Gallo, P., Stallone, G., Grandaliano, G., Schena, A., Margiotta, M., Mininni, D., Palieri, R., Lucarelli, G., Battaglia, M., Gesualdo, L., Castellano, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Pesce, F., Martino, M., Fiorentino, M., Rollo, T., Simone, S., Gallo, P., Stallone, G., Grandaliano, G., Schena, A., Margiotta, M., Mininni, D., Palieri, R., Lucarelli, G., Battaglia, M., Gesualdo, L., Castellano, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Urinary tract infections (UTIs) after kidney transplantation are associated with significant morbidity. However, data on the impact of UTI on graft survival are controversial. We conducted a retrospective cohort study of 380 kidney transplant patients. Recipients with symptomatic UTIs during the first year after transplantation were categorized into three groups: early (< 3 episodes from months 1st to 6th), late (< 3 episodes during months 7th to 12th) and recurrent (≥ 3 episodes throughout the whole first year). Graft function at three years was considered the primary outcome. Symptomatic UTIs occurred in 184 (48.4%) kidney transplant recipients during the first year; 83 (21.8%) patients developed early UTIs, 50 (13.2%) late UTIs and 51 (13.4%) recurrent UTIs. We observed a significant improvement in graft function after three years in all patients (P < 0.001) except those who had recurrent UTIs. A Kaplan–Meier analysis showed that recipients with recurrent UTIs had worse graft outcome (eGFR value < 60 mL/min/1.73 m2) (P = 0.01). Recurrent UTIs was an independent predictor of graft function at three years in a model adjusted for DGF and episodes of acute rejection (Hazard Ratio, 2.2; 95% CI, 1.3 to 3.5; P = 0.001). Recurrent symptomatic UTIs during the first year after transplantation have negative impact on long-term graft function.

Published
2019

37. Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial

Author

Morrone, L., Palmer, S. C., Saglimbene, V. M., Perna, A., Cianciolo, G., Russo, D., Gesualdo, L., Natale, P., Santoro, A., Mazzaferro, S., Cozzolino, M., Cupisti, A., Di Luca, M., Di Iorio, B., Strippoli, G. F. M., Massimetti, C., Pennacchiotti, F., Mannarino, A., Grimaldi, C., Savica, V., Schillaci, O., Credentino, O., Casu, M. D., Lomonte, C., Vigo, V., Grandaliano, G., Netti, S., Aucella, F., Morosetti, M., Boero, R., Soleti, F., Fasianos, E., Polidoro, M., Santoro, D., Malberti, F., D'Apice, L., Musacchio, R., Porcu, M. C., Rotondi, S., and Muci, M. L.

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, vitamin D deficiency, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Hyperphosphatemia, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Renal Dialysis, Internal medicine, medicine, Vitamin D and neurology, Humans, Mortality, Vitamin D, Calcifediol, ESKD, business.industry, Hazard ratio, Hemodialysis, Vitamins, medicine.disease, chemistry, Nephrology, Dietary Supplements, business, Kidney disease
Abstract

Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63–1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41–2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62–2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02–1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. NCT01457001

Published
2021

38. POS0110 ASSOCIATION OF miR-155 AND miR-34a EXPRESSION IN LUPUS NEPHRITIS RENAL TISSUE WITH DISEASE ONSET AND OUTCOMES

Author

Di Mario, C., primary, Petricca, L., additional, Gigante, M. R., additional, Costanzi, S., additional, Vischini, G., additional, Paglionico, A., additional, Varriano, V., additional, Bui, L., additional, Tanti, G., additional, Lanzo, L., additional, Federico, F., additional, Grandaliano, G., additional, D’agostino, M. A., additional, Alivernini, S., additional, Tolusso, B., additional, and Gremese, E., additional

Published
2021
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39. Management of the kidney transplant patient with Cancer: Report from a Multidisciplinary Consensus Conference

Author

Romagnoli, Jacopo, Tagliaferri, Luca, Acampora, Anna, Bianchi, V., D'Ambrosio, Viola, D'Aviero, A., Esposito, I., Hohaus, Stefan, Iezzi, Roberto, Lancellotta, V., Maiolo, E., Maiorano, Brigida Anna, Paoletti, Fabio, Peris, Ketty, Posa, Alessandro, Preziosi, Francesco, Rossi, E., Scaletta, Giuseppe, Schinzari, Giovanni, Spagnoletti, Gionata, Tanzilli, A., Scambia, Giovanni, Tortora, Giampaolo, Valentini, Vincenzo, Maggiore, U., Grandaliano, Giuseppe, Romagnoli J. (ORCID:0000-0002-7153-0346), Tagliaferri L. (ORCID:0000-0003-2308-0982), Acampora A., D'Ambrosio V., Hohaus S. (ORCID:0000-0002-5534-7197), Iezzi R. (ORCID:0000-0002-2791-481X), Maiorano B. A., Paoletti F., Peris K. (ORCID:0000-0002-5237-0463), Posa A., Preziosi F., Scaletta G., Schinzari G. (ORCID:0000-0001-6105-7252), Spagnoletti G. (ORCID:0000-0003-2626-8147), Scambia G. (ORCID:0000-0003-2758-1063), Tortora G. (ORCID:0000-0002-1378-4962), Grandaliano G. (ORCID:0000-0003-1213-2177), Romagnoli, Jacopo, Tagliaferri, Luca, Acampora, Anna, Bianchi, V., D'Ambrosio, Viola, D'Aviero, A., Esposito, I., Hohaus, Stefan, Iezzi, Roberto, Lancellotta, V., Maiolo, E., Maiorano, Brigida Anna, Paoletti, Fabio, Peris, Ketty, Posa, Alessandro, Preziosi, Francesco, Rossi, E., Scaletta, Giuseppe, Schinzari, Giovanni, Spagnoletti, Gionata, Tanzilli, A., Scambia, Giovanni, Tortora, Giampaolo, Valentini, Vincenzo, Maggiore, U., Grandaliano, Giuseppe, Romagnoli J. (ORCID:0000-0002-7153-0346), Tagliaferri L. (ORCID:0000-0003-2308-0982), Acampora A., D'Ambrosio V., Hohaus S. (ORCID:0000-0002-5534-7197), Iezzi R. (ORCID:0000-0002-2791-481X), Maiorano B. A., Paoletti F., Peris K. (ORCID:0000-0002-5237-0463), Posa A., Preziosi F., Scaletta G., Schinzari G. (ORCID:0000-0001-6105-7252), Spagnoletti G. (ORCID:0000-0003-2626-8147), Scambia G. (ORCID:0000-0003-2758-1063), Tortora G. (ORCID:0000-0002-1378-4962), and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Introduction: Cancer is the second most common cause of mortality and morbidity in Kidney Transplant Recipients (KTRs). Immunosuppression can influence the efficacy of cancer treatment and modification of the immunosuppressive regimen may restore anti-neoplastic immune responses improving oncologic prognosis. However, patients and transplant physicians are usually reluctant to modify immunosuppression, fearing rejection and potential graft loss. Due to the lack of extensive and recognised data supporting how to manage the immunosuppressive therapy in KTRs, in the context of immunotherapy, chemotherapy, radiotherapy and loco-regional treatments, a Consensus Conference was organised under the auspices of the European Society of Organ Transplantation and the Italian Society of Organ Transplantation. The conference involved a multidisciplinary group of transplant experts in the field across Europe. Methods: The overall process included a) the formulation of 12 specific questions based on the PICO methodology, b) systematic literature review and summary for experts for each question, c) a two-day conference celebration and the collection of experts' agreements. The conference was articulated in three sessions: “Immunosuppressive therapy and immunotherapy”, “Systemic therapy”, “Integrated Therapy”, while the final experts' agreement was collected with a televoting procedure and defined according to the majority criterion. Results: Twenty-six European experts attended the conference and expressed their vote. A total of 14 statements were finally elaborated and voted. Strong agreement was found for ten statements, moderate agreement for two, moderate disagreement for one and uncertainty for the last one. Conclusions: The consensus statements provide guidance to transplant physicians caring for kidney transplant recipients with cancer and indicate key aspects that need to be addressed by future clinical research.

Published
2021

40. Pentraxin-3-mediated complement activation in a swine model of renal ischemia/reperfusion injury

Author

Divella, C., Stasi, A., Franzin, R., Rossini, M., Pontrelli, P., Sallustio, F., Netti, G. S., Ranieri, E., Lacitignola, L., Staffieri, F., Crovace, A. M., Lucarelli, G., Ditonno, P., Battaglia, M., Daha, M. R., van der Pol, P., van Kooten, C., Grandaliano, Giuseppe, Gesualdo, L., Stallone, G., Castellano, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Divella, C., Stasi, A., Franzin, R., Rossini, M., Pontrelli, P., Sallustio, F., Netti, G. S., Ranieri, E., Lacitignola, L., Staffieri, F., Crovace, A. M., Lucarelli, G., Ditonno, P., Battaglia, M., Daha, M. R., van der Pol, P., van Kooten, C., Grandaliano, Giuseppe, Gesualdo, L., Stallone, G., Castellano, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Pentraxins are a family of evolutionarily conserved pattern recognition molecules with pivotal roles in innate immunity and inflammation, such as opsonization of pathogens during bacterial and viral infections. In particular, the long Pentraxin 3 (PTX3) has been shown to regulate several aspects of vascular and tissue inflammation during solid organ transplantation. Our study investigated the role of PTX3 as possible modulator of Complement activation in a swine model of renal ischemia/reperfusion (I/R) injury. We demonstrated that I/R injury induced early PTX3 deposits at peritubular and glomerular capillary levels. Confocal laser scanning microscopy revealed PTX3 deposits co-localizing with CD31+ endothelial cells. In addition, PTX3 was associated with infiltrating macrophages (CD163), dendritic cells (SWC3a) and myofibroblasts (FSP1). In particular, we demonstrated a significant PTX3-mediated activation of classical (C1q-mediated) and lectin (MBL-mediated) pathways of Complement. Interestingly, PTX3 deposits co-localized with activation of the terminal Complement complex (C5b-9) on endothelial cells, indicating that PTX3-mediated Complement activation occurred mainly at the renal vascular level. In conclusion, these data indicate that PTX3 might be a potential therapeutic target to prevent Complement-induced I/R injury.

Published
2021

41. On-line hemodiafiltration modulates atherosclerosis signaling in peripheral lymphomonocytes of hemodialysis patients

Author

Simone, S., Chieti, A., Pontrelli, P., Rascio, F., Castellano, G., Stallone, G., Infante, B., Gesualdo, L., Grandaliano, Giuseppe, Pertosa, G., Grandaliano G. (ORCID:0000-0003-1213-2177), Simone, S., Chieti, A., Pontrelli, P., Rascio, F., Castellano, G., Stallone, G., Infante, B., Gesualdo, L., Grandaliano, Giuseppe, Pertosa, G., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Background: Hemodialysis patients present a dramatic increase in cardiovascular morbidity/mortality. Circulating immune cells, activated by both uremic milieu and dialysis, play a key role in the pathogenesis of dialysis-related vascular disease. The aim of our study was to identify, through a high-throughput approach, differences in gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of patients treated with on-line hemodiafiltration and bicarbonate hemodialysis. Methods: The transcriptomic profile was investigated in PBMCs isolated from eight patients on on-line hemodiafiltration and eight patients on bicarbonate hemodialysis by microarray analysis. The results were evaluated by statistical and functional pathway analysis and validated by real time PCR (qPCR) in an independent cohort of patients (on-line hemodiafiltration N = 20, bicarbonate hemodialysis n = 20). Results: Eight hundred and forty-seven genes were differentially expressed in patients treated with on-line hemodiafiltration and bicarbonate hemodialysis. Thirty-seven functional gene networks were identified and atherosclerosis signaling was the top canonical pathway regulated by on-line hemodiafiltration. Among the genes of this pathway, on-line hemodiafiltration was associated with a reduced expression of Platelet-derived growth factor A chain (PDGF A), Clusterin, Monoamine Oxidase A, Interleukin-6 (IL-6) and Vascular Endothelial GrowthFactor C (VEGF-)C and with an increase of Apolipoprotein E. qPCR confirmed the microarray results. Platelet derived growth factor AA (PDGF-AA), IL-6 and VEGF-C serum levels were significantly lower in the on-line hemodiafiltration group. Finally, 10 patients previously on bicarbonate hemodialysis were switched to on-line hemodiafiltration and PBMCs were harvested after 6 months. The qPCR results from this perspective group confirmed the modulation of atherosclerotic genes observed in

Published
2021

42. Waves of infection and waves of communication: the importance of sharing in the era of Covid-19

Author

Mazzaferro, S., Rocca, A. R., Bagordo, D., Alfarone, C., Baldinelli, G., Boccia, E., Bondatti, F., Casarci, M., Catucci, A. E., Chiappini, M. G., Cioffi, A., Cuzziol, C., De Paolis, P., Della Grotta, B., Daniele, N. D., Di Lullo, L., Di Pietro, G., Di Zazzo, G., Fazzari, L., Feriozzi, S., Ferrazzano, M., Filippini, A., Fini, R., Firmi, G., Flammini, A., Forte, F., Galliani, M., Gamberini, M., Gangeri, F., Grandaliano, Giuseppe, Iamundo, V., Lavini, R., Lonzi, M., Marinelli, R., Marrocco, F., Mene, P., Miglio, L., Morabito, S., Morgia, A., Morosetti, M., Muci, M. L., Nazzaro, L., Nusca, C., Onorato, L., Pace, G., Palumbo, R., Pantano, L., Polito, P., Puliti, M., Rifici, N., Rizzi, E., Rossi, V., Sabry, H., Scabbia, L., Serraiocco, M., Sfregola, P., Simonelli, R., Treglia, A., Umbro, I., Valentini, W., Grandaliano G. (ORCID:0000-0003-1213-2177), Mazzaferro, S., Rocca, A. R., Bagordo, D., Alfarone, C., Baldinelli, G., Boccia, E., Bondatti, F., Casarci, M., Catucci, A. E., Chiappini, M. G., Cioffi, A., Cuzziol, C., De Paolis, P., Della Grotta, B., Daniele, N. D., Di Lullo, L., Di Pietro, G., Di Zazzo, G., Fazzari, L., Feriozzi, S., Ferrazzano, M., Filippini, A., Fini, R., Firmi, G., Flammini, A., Forte, F., Galliani, M., Gamberini, M., Gangeri, F., Grandaliano, Giuseppe, Iamundo, V., Lavini, R., Lonzi, M., Marinelli, R., Marrocco, F., Mene, P., Miglio, L., Morabito, S., Morgia, A., Morosetti, M., Muci, M. L., Nazzaro, L., Nusca, C., Onorato, L., Pace, G., Palumbo, R., Pantano, L., Polito, P., Puliti, M., Rifici, N., Rizzi, E., Rossi, V., Sabry, H., Scabbia, L., Serraiocco, M., Sfregola, P., Simonelli, R., Treglia, A., Umbro, I., Valentini, W., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

No abstract available

Published
2021

43. Risk factors and action thresholds for the novel coronavirus pandemic. Insights from the Italian Society of Nephrology COVID-19 Survey

Author

Nordio, M., Reboldi, G., Di Napoli, A., Quintaliani, G., Alberici, F., Postorino, M., Aucella, F., Messa, P., Brunori, G., Bosco, M., Malberti, F., Mandreoli, M., Mazzaferro, S., Movilli, E., Ravera, M., Salomone, M., Santoro, D., Postorinolimido, M. A., Bonomini, M., Stingone, A., Maccarone, M., Di Loreto, E., Stacchiotti, L., Malandra, R., Chiarella, S., D'Agostino, F., Fuiano, G., Nicodemo, L., Bonofiglio, R., Greco, S., Mallamaci, F., Barreca, E., Caserta, C., Bruzzese, V., Galati, D., Tramontana, D., Viscione, M., Chiuchiolo, L., Tuccillo, S., Sepe, M., Vitale, F., Ciriana, E., Martignetti, V., Caserta, D., Stizzo, A., Romano, A., Iulianiello, G., Cascone, E., Minicone, P., Chiricone, D., Delgado, G., Barbato, A., Celentano, S., Molfino, I., Coppola, S., Raiola, I., Abategiovanni, M., Borrelli, S., Margherita, C., Bruno, F., Ida, M., Aliperti, E., Potito, D., Cuomo, G., De Luca, M., Merola, M., Botta, C., Garofalo, G., Alinei, P., Paglionico, C., Roano, M., Vitale, S., Ierardi, R., Fimiani, V., Conte, G., Di Natale, G., Romano, M., Di Marino, V., Scafarto, A., Meccariello, S., Pecoraro, C., Di Stazio, E., Di Meglio, E., Cuomo, A., Maresca, B., Rotaia, E., Capasso, G., Auricchio, M., Pluvio, C., Maddalena, L., De Maio, A., Palladino, G., Buono, F., Gigliotti, G., Mancini, E., La Manna, G., Storari, A., Mosconi, G., Cappelli, G., Scarpioni, R., Gregorini, M., Rigotti, A., Mancini, W., Bianco, F., Boscutti, G., Amici, G., Tosto, M., Fini, R., Pace, G., Cioffi, A., Boccia, E., Di Lullo, L., Di Zazzo, G., Simonelli, R., Bondatti, F., Miglio, L., Rifici, N., Treglia, A., Muci, M., Baldinelli, G., Rizzi, E., Lonzi, M., De Cicco, C., Forte, F., De Paolis, P., Grandaliano, Giuseppe, Cuzziol, C., Torre, V. M., Sfregola, P., Rossi, V., Fabio, G., Flammini, A., Filippini, A., Onorato, L., Vendola, F., Di Daniela, N., Alfarone, C., Scabbia, L., Ferrazzano, M., Grotta, B. D., Gamberini, M., Fazzari, L., Mene, P., Morgia, A., Catucci, A., Palumbo, R., Puliti, M., Marinelli, R., Polito, P., Marrocco, F., Morabito, S., Rocca, R., Nazzaro, L., Lavini, R., Iamundo, V., Chiappini, M., Casarci, M., Morosetti, M., Hassan, S., Firmi, G., Galliani, M., Serraiocco, M., Feriozzi, S., Valentini, W., Sacco, P., Garibotto, G., Cappelli, V., Saffioti, C., Repetto, M., Rolla, D., Lorenz, M., Pedrini, L., Polonioli, D., Galli, E., Ruggenenti, P., Scolari, F., Bove, S., Costantino, E., Bracchi, M., Mangano, S., Depetri, G., La Milia, V., Farina, M., Zecchini, S., Savino, R., Melandri, M., Guastoni, C., Paparella, M., Gallieni, M., Minetti, E., Bisegna, S., Righetti, M., Badalamenti, S., Alberghini, E., Bertoli, S., Fabbrini, P., Albrizio, P., Rampino, T., Colturi, C., Rombola, G., Lucatello, A., Guerrini, E., Ranghino, A., Lenci, F., Fanciulli, E., Santarelli, S., Damiani, C., Garofalo, D., Sopranzi, F., Santoferrara, A., Di Luca, M., Galiotta, P., Brigante, M., Manganaro, M., Maffei, S., Berto, I., Besso, L., Viglino, G., Cusinato, S., Chiarinottichiappero, D. F., Tognarelli, G., Gianoglio, B., Forneris, G., Biancone, L., Savoldi, S., Vitale, C., Boero, R., Filiberti, O., Borzumati, M., Gesualdo, L., Lomonte, C., Gernone, G., Pallotta, G., Di Paolo, S., Vernaglione, L., Specchio, A., Stallone, G., Dell'Aquila, R., Sandri, G., Russo, F., Napoli, M., Marangi, A., Morrone, L., Di Stratis, C., Fresu, A., Cicu, F., Murtas, S., Manca, O., Pani, A., Pilloni, M., Pistis, R., Cadoni, M., Contu, B., Logias, F., Ivaldi, R., Fancello, S., Cossu, M., Lepori, G., Vittoria, S., Battiati, E., Arnone, M., Rome, M., Barbera, A., Granata, A., Collura, G., Dico, C. L., Pugliese, G., Di Natale, E., Rizzari, G., Cottone, L., Longo, N., Battaglia, G., Marcantoni, C., Giannetto, G., Tumino, G., Randazzo, F., Bellissimo, L., Faro, F. L., Grippaldi, F., Urso, S., Quattrone, G., Todaro, I., Vincenzo, D., Murgo, A., Masuzzo, M., Pisacane, A., Monardo, P., Pontorierro, M., Quari, C., Bauro, A., Chimenz, R. R., Alfio, D., Girasole, F., Cascio, A. L., Caviglia, A., Tornese, F., Sirna, F., Altieri, C., Cusumano, R., Saveriano, V., La Corte, A., Locascio, G., Rotolo, U., Musso, S., Risuglia, L., Blanco, G., Minardo, G., Castellino, S., Zappulla, Z., Randone, S., Di Francesca, M., Cassetti, C. C., Oddo, G., Buscaino, G., Mucaria, F., Barraco, V. I., Di Martino, A., Rallo, D., Dani, L., Campolo, G., Manescalchi, F., Biagini, M., Agate, M., Panichi, V., Casani, A., Traversari, L., Garosi, G., Tabbi, M., Selvi, A., Cencioni, L., Fagugli, R., Timio, F., Leveque, A., Manes, M., Mennella, G., Calo, L., Fiorini, F., Abaterusso, C., Calzavara, P., Meneghel, G., Bonesso, C., Gambaro, G., Gammaro, L., Rugiu, C., Ronco, C., Grandaliano G. (ORCID:0000-0003-1213-2177), Nordio, M., Reboldi, G., Di Napoli, A., Quintaliani, G., Alberici, F., Postorino, M., Aucella, F., Messa, P., Brunori, G., Bosco, M., Malberti, F., Mandreoli, M., Mazzaferro, S., Movilli, E., Ravera, M., Salomone, M., Santoro, D., Postorinolimido, M. A., Bonomini, M., Stingone, A., Maccarone, M., Di Loreto, E., Stacchiotti, L., Malandra, R., Chiarella, S., D'Agostino, F., Fuiano, G., Nicodemo, L., Bonofiglio, R., Greco, S., Mallamaci, F., Barreca, E., Caserta, C., Bruzzese, V., Galati, D., Tramontana, D., Viscione, M., Chiuchiolo, L., Tuccillo, S., Sepe, M., Vitale, F., Ciriana, E., Martignetti, V., Caserta, D., Stizzo, A., Romano, A., Iulianiello, G., Cascone, E., Minicone, P., Chiricone, D., Delgado, G., Barbato, A., Celentano, S., Molfino, I., Coppola, S., Raiola, I., Abategiovanni, M., Borrelli, S., Margherita, C., Bruno, F., Ida, M., Aliperti, E., Potito, D., Cuomo, G., De Luca, M., Merola, M., Botta, C., Garofalo, G., Alinei, P., Paglionico, C., Roano, M., Vitale, S., Ierardi, R., Fimiani, V., Conte, G., Di Natale, G., Romano, M., Di Marino, V., Scafarto, A., Meccariello, S., Pecoraro, C., Di Stazio, E., Di Meglio, E., Cuomo, A., Maresca, B., Rotaia, E., Capasso, G., Auricchio, M., Pluvio, C., Maddalena, L., De Maio, A., Palladino, G., Buono, F., Gigliotti, G., Mancini, E., La Manna, G., Storari, A., Mosconi, G., Cappelli, G., Scarpioni, R., Gregorini, M., Rigotti, A., Mancini, W., Bianco, F., Boscutti, G., Amici, G., Tosto, M., Fini, R., Pace, G., Cioffi, A., Boccia, E., Di Lullo, L., Di Zazzo, G., Simonelli, R., Bondatti, F., Miglio, L., Rifici, N., Treglia, A., Muci, M., Baldinelli, G., Rizzi, E., Lonzi, M., De Cicco, C., Forte, F., De Paolis, P., Grandaliano, Giuseppe, Cuzziol, C., Torre, V. M., Sfregola, P., Rossi, V., Fabio, G., Flammini, A., Filippini, A., Onorato, L., Vendola, F., Di Daniela, N., Alfarone, C., Scabbia, L., Ferrazzano, M., Grotta, B. D., Gamberini, M., Fazzari, L., Mene, P., Morgia, A., Catucci, A., Palumbo, R., Puliti, M., Marinelli, R., Polito, P., Marrocco, F., Morabito, S., Rocca, R., Nazzaro, L., Lavini, R., Iamundo, V., Chiappini, M., Casarci, M., Morosetti, M., Hassan, S., Firmi, G., Galliani, M., Serraiocco, M., Feriozzi, S., Valentini, W., Sacco, P., Garibotto, G., Cappelli, V., Saffioti, C., Repetto, M., Rolla, D., Lorenz, M., Pedrini, L., Polonioli, D., Galli, E., Ruggenenti, P., Scolari, F., Bove, S., Costantino, E., Bracchi, M., Mangano, S., Depetri, G., La Milia, V., Farina, M., Zecchini, S., Savino, R., Melandri, M., Guastoni, C., Paparella, M., Gallieni, M., Minetti, E., Bisegna, S., Righetti, M., Badalamenti, S., Alberghini, E., Bertoli, S., Fabbrini, P., Albrizio, P., Rampino, T., Colturi, C., Rombola, G., Lucatello, A., Guerrini, E., Ranghino, A., Lenci, F., Fanciulli, E., Santarelli, S., Damiani, C., Garofalo, D., Sopranzi, F., Santoferrara, A., Di Luca, M., Galiotta, P., Brigante, M., Manganaro, M., Maffei, S., Berto, I., Besso, L., Viglino, G., Cusinato, S., Chiarinottichiappero, D. F., Tognarelli, G., Gianoglio, B., Forneris, G., Biancone, L., Savoldi, S., Vitale, C., Boero, R., Filiberti, O., Borzumati, M., Gesualdo, L., Lomonte, C., Gernone, G., Pallotta, G., Di Paolo, S., Vernaglione, L., Specchio, A., Stallone, G., Dell'Aquila, R., Sandri, G., Russo, F., Napoli, M., Marangi, A., Morrone, L., Di Stratis, C., Fresu, A., Cicu, F., Murtas, S., Manca, O., Pani, A., Pilloni, M., Pistis, R., Cadoni, M., Contu, B., Logias, F., Ivaldi, R., Fancello, S., Cossu, M., Lepori, G., Vittoria, S., Battiati, E., Arnone, M., Rome, M., Barbera, A., Granata, A., Collura, G., Dico, C. L., Pugliese, G., Di Natale, E., Rizzari, G., Cottone, L., Longo, N., Battaglia, G., Marcantoni, C., Giannetto, G., Tumino, G., Randazzo, F., Bellissimo, L., Faro, F. L., Grippaldi, F., Urso, S., Quattrone, G., Todaro, I., Vincenzo, D., Murgo, A., Masuzzo, M., Pisacane, A., Monardo, P., Pontorierro, M., Quari, C., Bauro, A., Chimenz, R. R., Alfio, D., Girasole, F., Cascio, A. L., Caviglia, A., Tornese, F., Sirna, F., Altieri, C., Cusumano, R., Saveriano, V., La Corte, A., Locascio, G., Rotolo, U., Musso, S., Risuglia, L., Blanco, G., Minardo, G., Castellino, S., Zappulla, Z., Randone, S., Di Francesca, M., Cassetti, C. C., Oddo, G., Buscaino, G., Mucaria, F., Barraco, V. I., Di Martino, A., Rallo, D., Dani, L., Campolo, G., Manescalchi, F., Biagini, M., Agate, M., Panichi, V., Casani, A., Traversari, L., Garosi, G., Tabbi, M., Selvi, A., Cencioni, L., Fagugli, R., Timio, F., Leveque, A., Manes, M., Mennella, G., Calo, L., Fiorini, F., Abaterusso, C., Calzavara, P., Meneghel, G., Bonesso, C., Gambaro, G., Gammaro, L., Rugiu, C., Ronco, C., and Grandaliano G. (ORCID:0000-0003-1213-2177)

Abstract

Background and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.

Published
2021

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