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1. 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

2. 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., 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 G., 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., and Ronco C.

Subjects
Male, Contextual analysis, medicine.medical_treatment, Population, 030232 urology & nephrology, Recursive partitioning, 030204 cardiovascular system & hematology, Rate ratio, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Classification tree, COVID-19, Renal replacement therapy, Risk Factors, Medical, Surveys and Questionnaires, Health care, medicine, Settore MED/14 - NEFROLOGIA, Humans, education, Pandemics, Societies, Medical, Female, Italy, Nephrology, education.field_of_study, business.industry, Multilevel model, Decision rule, Confidence interval, Original Article, Hemodialysis, business, Contextual analysi, Societies, Demography
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

9. Increased cancer risk in patients undergoing dialysis: A population-based cohort study in North-Eastern Italy

Author

Taborelli, M., Toffolutti, F., Del Zotto, S., Clagnan, E., Furian, L., Piselli, P., Citterio, Franco, Zanier, L., Boscutti, G., Serraino, D., Shalaby, S., Petrara, R., Burra, P., Zanus, G., Zanini, S., Rigotti, P., Rendina, M., Di Leo, A., Schena, F. P., Grandaliano, Giuseppe, Fiorentino, M., Lauro, A., Pinna, A. D., Di Gioia, P., Pellegrini, S., Zanfi, C., Scolari, M. P., Stefoni, S., Todeschini, P., Panicali, L., Valentini, C., Baccarani, U., Risaliti, A., Adani, G. L., Lorenzin, D., Ettorre, G. M., Vennarecci, G., Colasanti, M., Coco, M., Ettorre, F., Santoro, R., Miglioresi, L., Nudo, F., Rossi, M., Mennini, G., Toti, L., Tisone, G., Casella, A., Fazzolari, L., Sforza, D., Iaria, G., Gazia, C., Belardi, C., Cimaglia, C., Agresta, A., D'Offizi, G., Comandini, U. V., Lionetti, R., Montalbano, M., Taibi, C., Fantola, G., Zamboni, F., Piredda, G. B., Michittu, M. B., Murgia, M. G., Onano, B., Fratino, L., Maso, L. D., De Paoli, P., Verdirosi, D., Vaccher, E., Pisani, F., Famulari, A., Delreno, F., Iesari, S., De Luca, L., Iaria, M., Capocasale, E., Cremaschi, E., Sandrini, S., Valerio, F., Mazzucotelli, V., Bossini, N., Setti, G., Veroux, M., Veroux, P., Giaquinta, A., Zerbo, D., Busnach, G., Di Leo, L., Perrino, M. L., Querques, M., Colombo, V., Sghirlanzoni, M. C., Messa, P., Leoni, A., Galatioto, L., Gruttadauria, S., Sparacino, V., Caputo, F., Buscemi, B., Spagnoletti, Gionata, Salerno, Maria Paola, Favi, E., Segoloni, G. P., Biancone, L., Lavacca, A., Maresca, M. C., Cascone, C., Virgilio, B., Donati, D., Dossi, F., Fontanella, A., Ambrosini, A., Di Cicco, M., Citterio F. (ORCID:0000-0003-0489-6337), Grandaliano G. (ORCID:0000-0003-1213-2177), Spagnoletti G. (ORCID:0000-0003-2626-8147), Salerno M. P., Taborelli, M., Toffolutti, F., Del Zotto, S., Clagnan, E., Furian, L., Piselli, P., Citterio, Franco, Zanier, L., Boscutti, G., Serraino, D., Shalaby, S., Petrara, R., Burra, P., Zanus, G., Zanini, S., Rigotti, P., Rendina, M., Di Leo, A., Schena, F. P., Grandaliano, Giuseppe, Fiorentino, M., Lauro, A., Pinna, A. D., Di Gioia, P., Pellegrini, S., Zanfi, C., Scolari, M. P., Stefoni, S., Todeschini, P., Panicali, L., Valentini, C., Baccarani, U., Risaliti, A., Adani, G. L., Lorenzin, D., Ettorre, G. M., Vennarecci, G., Colasanti, M., Coco, M., Ettorre, F., Santoro, R., Miglioresi, L., Nudo, F., Rossi, M., Mennini, G., Toti, L., Tisone, G., Casella, A., Fazzolari, L., Sforza, D., Iaria, G., Gazia, C., Belardi, C., Cimaglia, C., Agresta, A., D'Offizi, G., Comandini, U. V., Lionetti, R., Montalbano, M., Taibi, C., Fantola, G., Zamboni, F., Piredda, G. B., Michittu, M. B., Murgia, M. G., Onano, B., Fratino, L., Maso, L. D., De Paoli, P., Verdirosi, D., Vaccher, E., Pisani, F., Famulari, A., Delreno, F., Iesari, S., De Luca, L., Iaria, M., Capocasale, E., Cremaschi, E., Sandrini, S., Valerio, F., Mazzucotelli, V., Bossini, N., Setti, G., Veroux, M., Veroux, P., Giaquinta, A., Zerbo, D., Busnach, G., Di Leo, L., Perrino, M. L., Querques, M., Colombo, V., Sghirlanzoni, M. C., Messa, P., Leoni, A., Galatioto, L., Gruttadauria, S., Sparacino, V., Caputo, F., Buscemi, B., Spagnoletti, Gionata, Salerno, Maria Paola, Favi, E., Segoloni, G. P., Biancone, L., Lavacca, A., Maresca, M. C., Cascone, C., Virgilio, B., Donati, D., Dossi, F., Fontanella, A., Ambrosini, A., Di Cicco, M., Citterio F. (ORCID:0000-0003-0489-6337), Grandaliano G. (ORCID:0000-0003-1213-2177), Spagnoletti G. (ORCID:0000-0003-2626-8147), and Salerno M. P.

Abstract

Background: In southern Europe, the risk of cancer in patients with end-stage kidney disease receiving dialysis has not been well quantified. The aim of this study was to assess the overall pattern of risk for de novo malignancies (DNMs) among dialysis patients in the Friuli Venezia Giulia region, north-eastern Italy. Methods: A population-based cohort study among 3407 dialysis patients was conducted through a record linkage between local healthcare databases and the cancer registry (1998-2013). Person-years (PYs) were calculated from 30 days after the date of first dialysis to the date of DNM diagnosis, kidney transplant, death, last follow-up or December 31, 2013, whichever came first. The risk of DNM, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results: During 10,798 PYs, 357 DNMs were diagnosed in 330 dialysis patients. A higher than expected risk of 1.3-fold was found for all DNMs combined (95% CI: 1.15-1.43). The risk was particularly high in younger dialysis patients (SIR = 1.88, 95% CI: 1.42-2.45 for age 40-59 years), and it decreased with age. Moreover, significantly increased DNM risks emerged during the first 3 years since dialysis initiation, especially within the first year (SIR = 8.52, 95% CI: 6.89-10.41). Elevated excess risks were observed for kidney (SIR = 3.18; 95% CI: 2.06-4.69), skin non-melanoma (SIR = 1.81, 95% CI: 1.46-2.22), oral cavity (SIR = 2.42, 95% CI: 1.36-4.00), and Kaposi's sarcoma (SIR = 10.29, 95% CI: 1.25-37.16). Conclusions: The elevated risk for DNM herein documented suggest the need to implement a targeted approach to cancer prevention and control in dialysis patients.

Published
2019

18. Insufficienza renale acuta in corso di sepsi

Author

Mene', Paolo, DE BLASI, Roberto Alberto, Principe, F, Luciani, R, Sacco, F, Punzo, G, CURA DI FERRARIO F, IN NEFROPATIE CON INSUFFICIENZA RENALE ACUTA O. A. RAPIDA P. R. O. G. R. E. S. S. I. O. N. E. A., Battaglia, G, Boscutti, G, Rollino, C, Menè, P, Editore, CAGNOLI L., and Milano, Pp

Published
2009

25. Cardiovascular complications in CKD 5D

Author

Fusaro, M., primary, Fusaro, M., additional, Noale, M., additional, Tripepi, G., additional, D'angelo, A., additional, Miozzo, D., additional, Gallieni, M., additional, Study Group, P.-V., additional, Tsamelesvili, M., additional, Dimitriadis, C., additional, Papagianni, A., additional, Raidis, C., additional, Efstratiadis, G., additional, Memmos, D., additional, Mutluay, R., additional, Konca Degertekin, C., additional, Derici, U., additional, Deger, S. M., additional, Akkiyal, F., additional, Gultekin, S., additional, Gonen, S., additional, Tacoy, G., additional, Arinsoy, T., additional, Sindel, S., additional, Sanchez-Perales, C., additional, Vazquez, E., additional, Merino, E., additional, Perez Del Barrio, P., additional, Borrego, F. J., additional, Borrego, M. J., additional, Liebana, A., additional, Krzanowski, M., additional, Janda, K., additional, Dumnicka, P., additional, Krasniak, A., additional, Sulowicz, W., additional, Kim, Y.-O., additional, Yoon, S.-A., additional, Yun, Y.-S., additional, Song, H.-C., additional, Kim, B.-S., additional, Cheong, M. A., additional, Pasch, A., additional, Farese, S., additional, Floege, J., additional, Jahnen-Dechent, W., additional, Ohtake, T., additional, Furuya, R., additional, Iwagami, M., additional, Tsutsumi, D., additional, Mochida, Y., additional, Ishioka, K., additional, Oka, M., additional, Maesato, K., additional, Moriya, H., additional, Hidaka, S., additional, Kobayashi, S., additional, Guedes, A., additional, Malho Guedes, A., additional, Pinho, A., additional, Fragoso, A., additional, Cruz, A., additional, Mendes, P., additional, Morgado, E., additional, Bexiga, I., additional, Silva, A. P., additional, Neves, P., additional, Oyake, N., additional, Suzuki, K., additional, Itoh, S., additional, Yano, S., additional, Turkmen, K., additional, Kayikcioglu, H., additional, Ozbek, O., additional, Saglam, M., additional, Toker, A., additional, Tonbul, H. Z., additional, Gelev, S., additional, Trajceska, L., additional, Srbinovska, E., additional, Pavleska, S., additional, Amitov, V., additional, Selim, G., additional, Dzekova, P., additional, Sikole, A., additional, Bouarich, H., additional, Lopez, S., additional, Alvarez, C., additional, Arribas, I., additional, DE Sequera, P., additional, Rodriguez, D., additional, Tanaka, S., additional, Kanemitsu, T., additional, Sugahara, M., additional, Kobayashi, M., additional, Uchida, L., additional, Ishimoto, Y., additional, Kotera, N., additional, Tanimoto, S., additional, Tanabe, K., additional, Hara, K., additional, Sugimoto, T., additional, Mise, N., additional, Goldstein, B., additional, Turakhia, M., additional, Arce, C., additional, Winkelmayer, W., additional, Zayed, B. E.-D., additional, Said, K., additional, Nishimura, M., additional, Okamoto, Y., additional, Tokoro, T., additional, Nishida, M., additional, Hashimoto, T., additional, Iwamoto, N., additional, Takahashi, H., additional, Ono, T., additional, Sato, N., additional, Raimann, J., additional, Usvyat, L. A., additional, Sands, J., additional, Levin, N. W., additional, Kotanko, P., additional, Iwasaki, M., additional, Joki, N., additional, Tanaka, Y., additional, Ikeda, N., additional, Hayashi, T., additional, Kubo, S., additional, Imamura, T.-A., additional, Takahashi, Y., additional, Hirahata, K., additional, Imamura, Y., additional, Hase, H., additional, Claes, K., additional, Meijers, B., additional, Bammens, B., additional, Kuypers, D., additional, Naesens, M., additional, Vanrenterghem, Y., additional, Evenepoel, P., additional, Boscutti, G., additional, Calabresi, L., additional, Bosco, M., additional, Simonelli, S., additional, Boer, E., additional, Vitali, C., additional, Martone, M., additional, Mattei, P. L., additional, Franceschini, G., additional, Baligh, E., additional, El-Shafey, E., additional, Ezaat, A., additional, Zawada, A., additional, Rogacev, K., additional, Hummel, B., additional, Grun, O., additional, Friedrich, A., additional, Rotter, B., additional, Winter, P., additional, Geisel, J., additional, Fliser, D., additional, Heine, G. H., additional, Makino, J.-I., additional, Makino, K.-S., additional, Ito, T., additional, Genovesi, S., additional, Santoro, A., additional, Fabbrini, P., additional, Rossi, E., additional, Pogliani, D., additional, Stella, A., additional, Bonforte, G., additional, Remuzzi, G., additional, Bertoli, S., additional, Pozzi, C., additional, Pasquali, S., additional, Cagnoli, L., additional, Conte, F., additional, Buzadzic, I., additional, Tosic, J., additional, Dimkovic, N., additional, Djuric, Z., additional, Popovic, J., additional, Pejin Grubisa, I., additional, Barjaktarevic, N., additional, DI Napoli, A., additional, DI Lallo, D., additional, Salvatori, M. F., additional, Franco, F., additional, Chicca, S., additional, Guasticchi, G., additional, Onofriescu, M., additional, Hogas, S., additional, Luminita, V., additional, Mugurel, A., additional, Gabriel, V., additional, Laura, F., additional, Irina, M., additional, Adrian, C., additional, Bosch, E., additional, Baamonde, E., additional, Culebras, C., additional, Perez, G., additional, El Hayek, B., additional, Ramirez, J. I., additional, Ramirez, A., additional, Garcia, C., additional, Lago, M., additional, Toledo, A., additional, Checa, M. D., additional, Taira, T., additional, Hirano, T., additional, Nohtomi, K., additional, Hyodo, T., additional, Chiba, T., additional, Saito, A., additional, Kim, Y. K., additional, Choi, E. J., additional, Yang, C. W., additional, Kim, Y.-S., additional, Lim, P. S., additional, Ming Ying, W., additional, Ya-Chung, J., additional, Zaripova, I., additional, Kayukov, I., additional, Essaian, A., additional, Nimgirova, A., additional, Young, H., additional, Dungey, M., additional, Watson, E. L., additional, Baines, R., additional, Burton, J. O., additional, Smith, A. C., additional, Yamazaki, K., additional, Bossola, M., additional, Colacicco, L., additional, Scribano, D., additional, Vulpio, C., additional, Tazza, L., additional, Okada, T., additional, Okada, N., additional, Michibata, I., additional, Yura, T., additional, Montero, N., additional, Soler, M., additional, Pascual, M., additional, Barrios, C., additional, Marquez, E., additional, Rodriguez, E., additional, Orfila, M. A., additional, Cao, H., additional, Arcos, E., additional, Comas, J., additional, Pascual, J., additional, Ferrario, M., additional, Garzotto, F., additional, Sironi, T., additional, Monacizzo, S., additional, Basso, F., additional, Cruz, D. N., additional, Moissl, U., additional, Tetta, C., additional, Signorini, M. G., additional, Cerutti, S., additional, Ronco, C., additional, Mostovaya, I., additional, Grooteman, M., additional, Van den Dorpel, M., additional, Penne, L., additional, Van der Weerd, N., additional, Mazairac, A., additional, Den Hoedt, C., additional, Levesque, R., additional, Nube, M., additional, Ter Wee, P., additional, Bots, M., additional, Blankestijn, P., additional, Liu, J., additional, MA, K. L., additional, Zhang, X., additional, Liu, B. C., additional, Vladu, I.-D., additional, Mustafa, R., additional, Cana-Ruiu, D., additional, Vaduva, C., additional, Grauntanu, C., additional, Mota, E., additional, Singh, R., additional, Abbasian, N., additional, Stover, C., additional, Brunskill, N., additional, Burton, J., additional, Herbert, K., additional, Bevington, A., additional, Wu, M., additional, Tang, R.-N., additional, Gao, M., additional, Liu, H., additional, Chen, L., additional, LV, L.-L., additional, Liu, B.-C., additional, Nikodimopoulou, M., additional, Liakos, S., additional, Kapoulas, S., additional, Karvounis, C., additional, Fedak, D., additional, Kuzniewski, M., additional, Paulina, D., additional, Kusnierz-Cabala, B., additional, Kapusta, M., additional, Solnica, B., additional, Junque, A., additional, Vicent, E. S., additional, Moreno, L., additional, Fulquet, M., additional, Duarte, V., additional, Saurina, A., additional, Pou, M., additional, Macias, J., additional, Lavado, M., additional, Ramirez de Arellano, M., additional, Ryuzaki, M., additional, Nakamoto, H., additional, Kinoshita, S., additional, Kobayashi, E., additional, Takimoto, C., additional, Shishido, T., additional, Enia, G., additional, Torino, C., additional, Tripepi, R., additional, Panuccio, V., additional, Postorino, M., additional, Clementi, A., additional, Garozzo, M., additional, Bonanno, G., additional, Boito, R., additional, Natale, G., additional, Cicchetti, T., additional, Chippari, A., additional, Logozzo, D., additional, Alati, G., additional, Cassani, S., additional, Sellaro, A., additional, Zoccali, C., additional, Quiroga, B., additional, Verde, E., additional, Abad, S., additional, Vega, A., additional, Goicoechea, M., additional, Reque, J., additional, Lopez-Gomez, J. M., additional, Luno, J., additional, Cabre Menendez, C., additional, Moles, V., additional, Vives, J. P., additional, Villa, D., additional, Vinas, J., additional, Compte, T., additional, Arruche, M., additional, Diaz, C., additional, Soler, J., additional, Aguilera, J., additional, Martinez Vea, A., additional, De Mauri, A., additional, David, P., additional, Conte, M. M., additional, Chiarinotti, D., additional, Ruva, C. E., additional, De Leo, M., additional, Bargnoux, A.-S., additional, Morena, M., additional, Jaussent, I., additional, Chalabi, L., additional, Bories, P., additional, Dion, J.-J., additional, Henri, P., additional, Delage, M., additional, Dupuy, A.-M., additional, Badiou, S., additional, Canaud, B., additional, Cristol, J.-P., additional, Sironi, E., additional, Pieruzzi, F., additional, Galbiati, E., additional, Vigano, M. R., additional, Anpalakhan, S., additional, Rocha, S., additional, Chitalia, N., additional, Sharma, R., additional, Kaski, J. C., additional, Chambers, J., additional, Goldsmith, D., additional, Banerjee, D., additional, Cernaro, V., additional, Lacquaniti, A., additional, Lupica, R., additional, Lucisano, S., additional, Fazio, M. R., additional, Donato, V., additional, Buemi, M., additional, Segalen, I., additional, Vinsonneau, U., additional, Tanquerel, T., additional, Quiniou, G., additional, Le Meur, Y., additional, Seibert, E., additional, Girndt, M., additional, Zohles, K., additional, Ulrich, C., additional, Kluttig, A., additional, Nuding, S., additional, Swenne, C., additional, Kors, J., additional, Werdan, K., additional, Fiedler, R., additional, Van der Weerd, N. C., additional, Grooteman, M. P., additional, Van den Dorpel, M. A., additional, Nube, M. J., additional, Wetzels, J., additional, Swinkels, D. W., additional, Ter Wee, P. M., additional, Khandekar, A., additional, Khandge, J., additional, Lee, J. E., additional, Moon, S. J., additional, Choi, K. H., additional, Lee, H. Y., additional, Kim, B. S., additional, Tuaillon, E., additional, Rodriguez, A., additional, Chenine, L., additional, Vendrell, J.-P., additional, Sue, Y.-M., additional, Tang, C.-H., additional, Chen, Y.-C., additional, Segura, P., additional, Garcia Cortes, M. J., additional, Gil, J. M., additional, Biechy, M. M., additional, Poulikakos, D., additional, Shah, A., additional, Persson, M., additional, Dattolo, P., additional, Amidone, M., additional, Michelassi, S., additional, Moriconi, L., additional, Betti, G., additional, Conti, P., additional, Rosati, A., additional, Mannarino, A., additional, Panichi, V., additional, Pizzarelli, F., additional, Klejna, K., additional, Naumnik, B., additional, Koc-Zorawska, E., additional, Mysliwiec, M., additional, Dimitrie, S., additional, Simona, H., additional, Mihaela, O., additional, Gabriela, O., additional, Radu, S., additional, Octavian, P., additional, Akdam, H., additional, Akar, H., additional, Yenicerioglu, Y., additional, Kucuk, O., additional, Kurt Omurlu, I., additional, Thambiah, S., additional, Roplekar, R., additional, Manghat, P., additional, Fogelman, I., additional, Fraser, W., additional, Hampson, G., additional, Likaj, E., additional, Caco, G., additional, Seferi, S., additional, Rroji, M., additional, Barbullushi, M., additional, Thereska, N., additional, Serban, A., additional, Carmen, V., additional, Cristian, S., additional, Silvia, L., additional, and Covic, A., additional

Published
2012
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27. Functional Lecithin: Cholesterol Acyltransferase Is Not Required for Efficient Atheroprotection in Humans

Author

Calabresi, L., primary, Baldassarre, D., additional, Castelnuovo, S., additional, Conca, P., additional, Bocchi, L., additional, Candini, C., additional, Frigerio, B., additional, Amato, M., additional, Sirtori, C. R., additional, Alessandrini, P., additional, Arca, M., additional, Boscutti, G., additional, Cattin, L., additional, Gesualdo, L., additional, Sampietro, T., additional, Vaudo, G., additional, Veglia, F., additional, Calandra, S., additional, and Franceschini, G., additional

Published
2009
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34. Balance of non-metabolizable base in continuous peritoneal dialysis patients.

Author

Mioni, G, Messa, P, Mioni, R, Boscutti, G, Cruciatti, A, and D'Angelo, A

Subjects
CONTINUOUS ambulatory peritoneal dialysis, ACID-base chemistry, HEMODIALYSIS, ACID-base equilibrium, ORGANIC acids
Abstract

Acid generation and elimination processes compared to titratable non-metabolizable base (NaOH equivalents, NB) turnover in end-stage renal disease patients are examined in the light of the Law of electroneutrality. The application over 2 days of the whole-body NB balance technique to 18 patients undergoing continuous ambulatory peritoneal dialysis is evaluated. The results show that the mean rate of NB loss with peritoneal effluent (as bicarbonate and organic acid anions) exceeded the mean rate of NB gain with the dialysis fluid (as salts of lactic acid) by 24 (27), m (SD), mmol per 2 days. In spite of this, the bicarbonate and pH of the plasma remained stable and within normal limits. The concurrent mean rate of the intestinal NB absorption was about 61 (27) mmol per 2 days, as calculated from the whole body balances of the several electrolytes in the metabolic steady-state. This intestinal absorption was more than sufficient to restore the body base consumed in neutralizing endogenous acid generation: 37 (14), 2H[sub 2]SO[sub 4] mmol per 2 days, the remaining NB being eliminated as bicarbonate and organic acid anions. The ample spectrum of plasma acid-base (A-B) values appears to some extent influenced by patient-related factors, such as the rate of drinking water intake and the set point deviation for organic acid turnover. [ABSTRACT FROM AUTHOR]

Published
1999
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37. [Effects of Dose of Erythropoiesis Stimulating Agents on Cardiovascular Outcomes, Quality of Life and Costs of Haemodialysis. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) Trial]

Author

Saglimbene V, D'Alonzo D, Ruospo M, Vecchio M, Natale P, Gargano L, Nicolucci A, Pellegrini F, Jc, Craig, Triolo G, Da, Procaccini, Santoro A, Giulio S, Rosa S, Murgo A, Mammarella R, Sambati M, D'Ambrosio N, Greco V, Giannoccaro G, Flammini A, Boccia E, Montalto G, Pagano S, Amarù S, Fici M, Lumaga G, Mancini E, Veronesi M, Patregnani L, Querques M, Schiavone P, Chimienti S, Palumbo R, Franco D, Volpe M, Gori E, Salomone M, Iacono A, Moscoloni M, Treglia A, Casu D, Am, Piras, Silva A, Mandreoli M, Lopez A, Quarello F, Catizone L, Russo G, Forcellini S, Maccarone M, Catucci G, Paolo B, Stingone A, D'Angelo B, Guastoni C, Pasquali S, Minoretti C, Bellasi A, Boscutti G, Martone M, David S, Schito F, Urban L, Iorio B, Caruso F, Mazzoni A, Musacchio R, Andreoli D, Cossu M, Cavoli G, Cornacchiari M, Granata A, Clementi A, Giordano R, Barzaghi W, Miriam Valentini, Hegbrant J, Tognoni G, and Gf, Strippoli

Subjects
Risk, Dose-Response Relationship, Drug, Disease Management, Anemia, Middle Aged, Hemoglobins, Observational Studies as Topic, Double-Blind Method, Meta-Analysis as Topic, Renal Dialysis, Research Design, Outcome Assessment, Health Care, Hematinics, Quality of Life, Humans, Kidney Failure, Chronic, Diabetic Nephropathies, Female
Abstract

Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested.We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

38. [Surgical complications after kidney transplantation]

Author

Risaliti A, Sainz-Barriga M, Baccarani U, Gl, Adani, Montanaro D, Gropuzzo M, Tullissi P, Boscutti G, Dario LORENZIN, Mioni G, and Bresadola F

Subjects
Urologic Diseases, Arteritis, Rupture, Spontaneous, Incidence, Lymphocele, Thrombosis, Renal Artery Obstruction, Kidney Transplantation, Renal Veins, Postoperative Complications, Renal Artery, Italy, Mycoses, Cadaver, Humans, Retrospective Studies
Abstract

Chronic renal failure needs substitutive treatment such as haemodialysis and peritoneal dialysis for the patient to survive. Kidney transplantation (KTx) improves survival of the patient with chronic renal failure. Since the first KTx, performed by Merrill in Boston in 1959, advances in medical therapy, immunosuppressive therapy and refinements in surgical technique have improved the quality of life of the transplant patient. We present a review of the incidence, diagnosis and therapy of surgical complications after KTx reported in the literature and a retrospective analysis of 297 consecutive cadaveric donor kidney transplants done in our institution from September 1993 to September 2002. Vascular complications represent 5-10% of postoperative complications. Our experience showed an incidence of 1.7% renal artery thrombosis, 1.4% renal vein thrombosis, 1.7% renal artery stenosis, 1.4% arterial rupture due to fungal arteritis, 0.7% spontaneous graft ruptures and 12% lymphoceles. Urological complications account for 10-15% of postoperative complications. In our series we found an incidence of 7.4% urinary leakage, 2.7% urinary obstruction and 3% urinary reflux. Gastrointestinal complications represent 16% of postoperative complications. Our series showed 1% pancreatitis with an overall mortality of 33% and an incidence of 1.7% intestinal perforations. Surgical complications still represent a challenge that increments morbidity and mortality among kidney transplant recipients. Data shown may offer some guidance on how to deal with early and late post-transplant surgical complications.

39. Effects of dose of erythropoiesis stimulating agents on cardiovascular outcomes, quality of life and costs of haemodialysis. the clinical evaluation of the DOSe of erythropoietins (C.E. DOSE) Trial | Effetti della dose degli agenti stimolanti l'eritropoiesi su esiti cardio-cerebrovascolari, qualità di vita e costi in emodialisi

Author

Saglimbene, V., D Alonzo, D., Ruospo, M., Vecchio, M., Natale, P., Gargano, L., Nicolucci, A., Pellegrini, F., Craig, J. C., Triolo, G., Procaccini, D. A., Santoro, A., Di Giulio, S., La Rosa, S., Murgo, A., Di Toro Mammarella, R., Sambati, M., D Ambrosio, N., Greco, V., Giannoccaro, G., Flammini, A., Boccia, E., Giuseppe MONTALTO, Pagano, S., Amarù, S., Fici, M., Lumaga, G. B., Mancini, E., Veronesi, M., Patregnani, L., Querques, M., Schiavone, P., Chimienti, S., Palumbo, R., Di Franco, D., Della Volpe, M., Gori, E., Salomone, M., Iacono, A., Moscoloni, M., Treglia, A., Casu, D., Piras, A. M., Di Silva, A., Mandreoli, M., Lopez, A., Quarello, F., Catizone, L., Russo, G., Forcellini, S., Maccarone, M., Catucci, G., Di Paolo, B., Stingone, A., D Angelo, B., Guastoni, C., Pasquali, S., Minoretti, C., Bellasi, A., Boscutti, G., Martone, M., David, S., Schito, F., Urban, L., Di Iorio, B., Caruso, F., Mazzoni, A., Musacchio, R., Andreoli, D., Cossu, M., Li Cavoli, G., Cornacchiari, M., Granata, A., Clementi, A., Giordano, R., Barzaghi, W., Valentini, M., Hegbrant, J., Tognoni, G., and Strippoli, G. F.

45. Functional Lecithin: Cholesterol Acyltransferase Is Not Required for Efficient Atheroprotection in Humans

Author

Laura Calabresi, Damiano Baldassarre, Samuela Castelnuovo, Paola Conca, Letizia Bocchi, Chiara Candini, Beatrice Frigerio, Mauro Amato, Cesare R. Sirtori, Paola Alessandrini, Marcello Arca, Giuliano Boscutti, Luigi Cattin, Loreto Gesualdo, Tiziana Sampietro, Gaetano Vaudo, Fabrizio Veglia, Sebastiano Calandra, Guido Franceschini, Calabresi, L., Baldassarre, D., Castelnuovo, S., Conca, P., Bocchi, L., Candini, C., Frigerio, B., Amato, M., Sirtori, C. R., Alessandrini, P., Arca, M., Boscutti, G., Cattin, Luigi, Gesualdo, L., Sampietro, T., Vaudo, G., Veglia, F., Calandra, S., and Franceschini, G.

Subjects
lipoproteins, atherosclerosi, atherosclerosis, genetics, imaging, Physiology (medical), atherosclerosis • genetics • imaging • lipoproteins, genetic, Cardiology and Cardiovascular Medicine
Abstract

Background— Mutations in the LCAT gene cause lecithin:cholesterol acyltransferase (LCAT) deficiency, a very rare metabolic disorder with 2 hypoalphalipoproteinemia syndromes: classic familial LCAT deficiency (Online Mendelian Inheritance in Man No. 245900), characterized by complete lack of enzyme activity, and fish-eye disease (Online Mendelian Inheritance in Man No. 136120), with a partially defective enzyme. Theoretically, hypoalphalipoproteinemia cases with LCAT deficiency should be at increased cardiovascular risk because of high-density lipoprotein deficiency and defective reverse cholesterol transport. Methods and Results— The extent of preclinical atherosclerosis was assessed in 40 carriers of LCAT gene mutations from 13 Italian families and 80 healthy controls by measuring carotid intima-media thickness (IMT). The average and maximum IMT values in the carriers were 0.07 and 0.21 mm smaller than in controls ( P =0.0003 and P =0.0027), respectively. Moreover, the inheritance of a mutated LCAT genotype had a remarkable gene-dose–dependent effect in reducing carotid IMT ( P =0.0003 for average IMT; P =0.001 for maximum IMT). Finally, no significant difference in carotid IMT was found between carriers of LCAT gene mutations that cause total or partial LCAT deficiency (ie, familial LCAT deficiency or fish-eye disease). Conclusions— Genetically determined low LCAT activity in Italian families is not associated with enhanced preclinical atherosclerosis despite low high-density lipoprotein cholesterol levels. This finding challenges the notion that LCAT is required for effective atheroprotection and suggests that elevating LCAT expression or activity is not a promising therapeutic strategy to reduce cardiovascular risk.

Published
2009
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46. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens

Author

Bénédicte Stengel, Vladimir Tesar, Gerald B. Appel, Anne Boland, Gian Marco Ghiggeri, Maurizio Garozzo, Cristina Barlassina, Krzysztof Mucha, Dita Maixnerova, Giuliano Boscutti, Francesco Scolari, Marco Galliani, Monica Bodria, Rosanna Coppo, Marie Metzger, Daniele Cusi, Ali G. Gharavi, Claudio Ponticelli, Małgorzata Mizerska-Wasiak, Yifu Li, Emanuela Boer, Holly J. Snyder, Battista Fabio Viola, Sneh Lata, Krzysztof Kiryluk, Giovanni Giorgio Battaglia, Maddalena Gigante, Guillaume Canaud, Erika Salvi, Silvana Chicca, Rosaria Polci, Antonio Amoroso, Richard P. Lifton, Maria Roszkowska-Blaim, Sindhuri Prakash, Riccardo Magistroni, Hong Zhang, Andrea Magnano, Francesca Bertinetto, Ulf Panzer, Lise Thibaudin, Pasquale Zamboli, Giovanni M. Frascà, Leszek Pączek, Jürgen Floege, Loreto Gesualdo, Murim Choi, Robert J. Wyatt, Ping Hou, John Feehally, David Fasel, Frank Eitner, Nadia Dallera, Daniel P. Gale, Domenico Santoro, Thomas Rauen, Gianluca Caridi, Clara Fischman, Jingyuan Xie, Jan Novak, Yasar Caliskan, Pietro Ravani, Sandro Feriozzi, Lucia Del Vecchio, Jonathan Barratt, Renzo Mignani, Judit Nagy, Francesca Lugani, Marco Delsante, Tibor Kovács, Carmelita Marcantoni, Licia Peruzzi, Antonello Pani, Hitoshi Suzuki, Maurizio Salvadori, Simone Sanna-Cherchi, Silvana Savoldi, Miguel Verbitsky, Alessandro Amore, Nan Chen, Claudia Izzi, Ichiei Narita, Krzysztof Pawlaczyk, Bruce A. Julian, Samantha Shapiro, Mariarosa Maiorana, Landino Allegri, Marcin Zaniew, Marcella Rocchietti, Domenico Di Landro, François Berthoux, Shin Goto, Kiryluk, K, Li, Y, Scolari, F, Sanna Cherchi, S, Choi, M, Verbitsky, M, Fasel, D, Lata, S, Prakash, S, Shapiro, S, Fischman, C, Snyder, Hj, Appel, G, Izzi, C, Viola, Bf, Dallera, N, Del Vecchio, L, Barlassina, C, Salvi, E, Bertinetto, Fe, Amoroso, A, Savoldi, S, Rocchietti, M, Amore, A, Peruzzi, L, Coppo, R, Salvadori, M, Ravani, P, Magistroni, R, Ghiggeri, Gm, Caridi, G, Bodria, M, Lugani, F, Allegri, L, Delsante, M, Maiorana, M, Magnano, A, Frasca, G, Boer, E, Boscutti, G, Ponticelli, C, Mignani, R, Marcantoni, C, Di Landro, D, Santoro, D, Pani, A, Polci, R, Feriozzi, S, Chicca, S, Galliani, M, Gigante, M, Gesualdo, L, Zamboli, Pasquale, Battaglia, Gg, Garozzo, M, Maixnerová, D, Tesar, V, Eitner, F, Rauen, T, Floege, J, Kovacs, T, Nagy, J, Mucha, K, Pączek, L, Zaniew, M, Mizerska Wasiak, M, Roszkowska Blaim, M, Pawlaczyk, K, Gale, D, Barratt, J, Thibaudin, L, Berthoux, F, Canaud, G, Boland, A, Metzger, M, Panzer, U, Suzuki, H, Goto, S, Narita, I, Caliskan, Y, Xie, J, Hou, P, Chen, N, Zhang, H, Wyatt, Rj, Novak, J, Julian, Ba, Feehally, J, Stengel, B, Cusi, D, Lifton, Rp, and Gharavi, A. G.

Subjects
030232 urology & nephrology, Population genetics, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Inflammatory bowel disease, Article, Nephropathy, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, Polymorphism (computer science), Immunity, Ig Nephropathy, GWAS, Genetics, medicine, Humans, Age of Onset, Antigens, Polymorphism, Proto-Oncogene Proteins c-vav, IGA, 030304 developmental biology, HLA-D Antigens, 0303 health sciences, CD11b Antigen, CD11b, Glomerulonephritis, IGA, Genetic Pleiotropy, Antigens, CD11b, CARD Signaling Adaptor Proteins, Genetic Loci, Genome-Wide Association Study, Host-Pathogen Interactions, Intestines, Single Nucleotide, medicine.disease, 3. Good health, Immunology, Age of onset
Abstract

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.

Published
2014

47. Podocyte Developmental Defects Caused by Adriamycin in Zebrafish Embryos and Larvae: A Novel Model of Glomerular Damage

Author

Piergiorgio Messa, Massimo Mariotti, Sara Pasqualetti, Masami Ikehata, Silvia Armelloni, Michele Carraro, Mary Artero, Cristina Zennaro, Maria Pia Rastaldi, Milan Clai, Alessandro Corbelli, Min Li, G. Boscutti, Zennaro, Cristina, Mariotti, M, Carraro, Michele, Pasqualetti, S, Corbelli, A, Armelloni, S, Li, M, Ikehata, M, Clai, M, Artero, M, Messa, P, Boscutti, G, and Rastaldi, Mp

Subjects
Glomerulu, medicine.medical_specialty, Nephrotic Syndrome, Kidney Glomerulus, lcsh:Medicine, Embryonic Development, Podocyte, Permeability, Nephrin, Adriamycin, In vivo, Internal medicine, Chronic Kidney Disease, Medicine and Health Sciences, medicine, Animals, lcsh:Science, Zebrafish, Basement membrane, Multidisciplinary, Dose-Response Relationship, Drug, Heart development, biology, Podocytes, Pediatric Nephrology, lcsh:R, Biology and Life Sciences, Heart, Developmental Nephrology, biology.organism_classification, Cell biology, Pronephros, Endocrinology, medicine.anatomical_structure, Doxorubicin, Nephrology, Larva, Embryogenesis, Toxicity, Glomerulus, biology.protein, lcsh:Q, Research Article, Developmental Biology
Abstract

The zebrafish pronephros is gaining popularity in the nephrology community, because embryos are easy to cultivate in multiwell plates, allowing large number of experiments to be conducted in an in vivo model. In a few days, glomeruli reach complete development, with a structure that is similar to that of the mammalian counterpart, showing a fenestrated endothelium and a basement membrane covered by the multiple ramifications of mature podocytes. As a further advantage, zebrafish embryos are permeable to low molecular compounds, and this explains their extensive use in drug efficacy and toxicity experiments. Here we show that low concentrations of adriamycin (i.e. 10 and 20 µM), when dissolved in the medium of zebrafish embryos at 9 hours post-fertilization and removed after 48 hours (57 hpf), alter the development of podocytes with subsequent functional impairment, demonstrated by onset of pericardial edema and reduction of expression of the podocyte proteins nephrin and wt1. Podocyte damage is morphologically confirmed by electron microscopy and functionally supported by increased clearance of microinjected 70 kDa fluorescent dextran. Importantly, besides pericardial edema and glomerular damage, which persist and worsen after adriamycin removal from the medium, larvae exposed to adriamycin 10 and 20 µM do not show any myocardiocyte alterations nor vascular changes. The only extra-renal effect is a transient delay of cartilage formation that rapidly recovers once adriamycin is removed. In summary, this low dose adriamycin model can be applied to analyze podocyte developmental defects, such as those observed in congenital nephrotic syndrome, and can be taken in consideration for pharmacological studies of severe early podocyte injury.

Published
2014
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48. The safety of corticosteroid therapy in IGA nephropathy: analysis of a real-life Italian cohort.

Author

Baragetti I, Del Vecchio L, Ferrario F, Alberici F, Amendola A, Russo E, Ponti S, Di Palma AM, Pani A, Rollino C, Giannese D, Boscutti G, Sorrentino A, Colturi C, Brunori G, Lazzarin R, Catapano F, Cozzolino M, Feriozzi S, and Pozzi C

Abstract

Background: Systemic steroids are recommended for patients with IgA nephropathy (IgAN) and proteinuria. However, there are concerns about their safety due to an excess of serious adverse events (SAEs) in previous randomised trials. This study evaluates the incidence of SAEs in IgAN patients receiving different treatment regimens in clinical practice., Methods: Multicentre, retrospective, observational cohort study of 1209 patients (M/F: 864/345, mean age: 41.73 ± 14.92 years) with biopsy-proven IgAN treated with renin angiotensin system (RAS) inhibitors (RASI) (n = 285), intravenous + oral steroids (n = 633), oral steroids (n = 99), steroids + immunosuppressants (n = 192)., Results: A total of 119 (9.8%) adverse events were reported, of which 67 (5.5%) were considered treatment-emergent, and 36 (2.9%) were SAEs (n = 23, 63.8% were infections). One patient died due to sepsis. A significant association was observed between AEs and immunosuppression [8 (2.8%) in RASI, 60 (9.4%) in steroids + immunosuppressants, 14 in oral steroids (14.1%) and 37 pts (19.2%) in steroids + immunosuppressants (p < 0.01)], age and estimated glomerular filtration rate (eGFR), but not with proteinuria and sex. On multivariate analysis, only older age was associated with the occurrence of SAEs., Conclusions: According to our findings, the incidence of SAEs during therapy with steroids alone or associated with immunosuppressors is lower in everyday clinical practice than in randomised clinical trials., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Published
2024
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49. Development of a PET Tracer for OGA with Improved Kinetics in the Living Brain.

Author

Cook BE, Nag S, Arakawa R, Lin EY, Stratman N, Guckian K, Hering H, Lulla M, Choi J, Salinas C, Genung NE, Morén AF, Bolin M, Boscutti G, Plisson C, Martarello L, Halldin C, and Kaliszczak MA

Subjects
Humans, Rats, Animals, Pyrans, beta-N-Acetylhexosaminidases, Brain
Abstract

O -GlcNAcylation is thought to play a role in the development of tau pathology in Alzheimer's disease because of its ability to modulate tau's aggregation propensity. O -GlcNAcylation is regulated by 2 enzymes: O -GlcNAc transferase and O -GlcNAcase (OGA). Development of a PET tracer would therefore be an essential tool for developing therapeutic small-molecule inhibitors of OGA, enabling clinical testing of target engagement and dose selection. Methods: A collection of small-molecule compounds was screened for inhibitory activity and high-affinity binding to OGA, as well as favorable PET tracer attributes (multidrug resistance protein 1 efflux, central nervous system PET multiparameter optimization, etc.). Two lead compounds with high affinity and selectivity for OGA were selected for further profiling, including OGA binding to tissue homogenate using a radioligand competition binding assay. In vivo pharmacokinetics were established using a microdosing approach with unlabeled compounds in rats. In vivo imaging studies were performed in rodents and nonhuman primates (NHPs) with 11 C-labeled compounds. Results: Two selected candidates, BIO-735 and BIO-578, displayed promising attributes in vitro. After radiolabeling with tritium, [ 3 H]BIO-735 and [ 3 H]BIO-578 binding in rodent brain homogenates demonstrated dissociation constants of 0.6 and 2.3 nM, respectively. Binding was inhibited, concentration-dependently, by homologous compounds and thiamet G, a well-characterized and structurally diverse OGA inhibitor. Imaging studies in rats and NHPs showed both tracers had high uptake in the brain and inhibition of binding to OGA in the presence of a nonradioactive compound. However, only BIO-578 demonstrated reversible binding kinetics within the time frame of a PET study with a 11 C-labeled molecule to enable quantification using kinetic modeling. Specificity of tracer uptake was confirmed with a 10 mg/kg blocking dose of thiamet G. Conclusion: We describe the development and testing of 2 11 C PET tracers targeting the protein OGA. The lead compound BIO-578 demonstrated high affinity and selectivity for OGA in rodent and human postmortem brain tissue, leading to its further testing in NHPs. NHP PET imaging studies showed that the tracer had excellent brain kinetics, with full inhibition of specific binding by thiamet G. These results suggest that the tracer [ 11 C]BIO-578 is well suited for further characterization in humans., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Published
2023
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50. Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.

Author

Kiryluk K, Sanchez-Rodriguez E, Zhou XJ, Zanoni F, Liu L, Mladkova N, Khan A, Marasa M, Zhang JY, Balderes O, Sanna-Cherchi S, Bomback AS, Canetta PA, Appel GB, Radhakrishnan J, Trimarchi H, Sprangers B, Cattran DC, Reich H, Pei Y, Ravani P, Galesic K, Maixnerova D, Tesar V, Stengel B, Metzger M, Canaud G, Maillard N, Berthoux F, Berthelot L, Pillebout E, Monteiro R, Nelson R, Wyatt RJ, Smoyer W, Mahan J, Samhar AA, Hidalgo G, Quiroga A, Weng P, Sreedharan R, Selewski D, Davis K, Kallash M, Vasylyeva TL, Rheault M, Chishti A, Ranch D, Wenderfer SE, Samsonov D, Claes DJ, Akchurin O, Goumenos D, Stangou M, Nagy J, Kovacs T, Fiaccadori E, Amoroso A, Barlassina C, Cusi D, Del Vecchio L, Battaglia GG, Bodria M, Boer E, Bono L, Boscutti G, Caridi G, Lugani F, Ghiggeri G, Coppo R, Peruzzi L, Esposito V, Esposito C, Feriozzi S, Polci R, Frasca G, Galliani M, Garozzo M, Mitrotti A, Gesualdo L, Granata S, Zaza G, Londrino F, Magistroni R, Pisani I, Magnano A, Marcantoni C, Messa P, Mignani R, Pani A, Ponticelli C, Roccatello D, Salvadori M, Salvi E, Santoro D, Gembillo G, Savoldi S, Spotti D, Zamboli P, Izzi C, Alberici F, Delbarba E, Florczak M, Krata N, Mucha K, Pączek L, Niemczyk S, Moszczuk B, Pańczyk-Tomaszewska M, Mizerska-Wasiak M, Perkowska-Ptasińska A, Bączkowska T, Durlik M, Pawlaczyk K, Sikora P, Zaniew M, Kaminska D, Krajewska M, Kuzmiuk-Glembin I, Heleniak Z, Bullo-Piontecka B, Liberek T, Dębska-Slizien A, Hryszko T, Materna-Kiryluk A, Miklaszewska M, Szczepańska M, Dyga K, Machura E, Siniewicz-Luzeńczyk K, Pawlak-Bratkowska M, Tkaczyk M, Runowski D, Kwella N, Drożdż D, Habura I, Kronenberg F, Prikhodina L, van Heel D, Fontaine B, Cotsapas C, Wijmenga C, Franke A, Annese V, Gregersen PK, Parameswaran S, Weirauch M, Kottyan L, Harley JB, Suzuki H, Narita I, Goto S, Lee H, Kim DK, Kim YS, Park JH, Cho B, Choi M, Van Wijk A, Huerta A, Ars E, Ballarin J, Lundberg S, Vogt B, Mani LY, Caliskan Y, Barratt J, Abeygunaratne T, Kalra PA, Gale DP, Panzer U, Rauen T, Floege J, Schlosser P, Ekici AB, Eckardt KU, Chen N, Xie J, Lifton RP, Loos RJF, Kenny EE, Ionita-Laza I, Köttgen A, Julian BA, Novak J, Scolari F, Zhang H, and Gharavi AG

Subjects
Animals, Mice, Genome-Wide Association Study, Immunoglobulin A genetics, Glomerulonephritis, IGA drug therapy, Glomerulonephritis, IGA genetics, Glomerulonephritis, IGA diagnosis
Abstract

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum IgA levels. High polygenic score for IgAN was associated with earlier onset of kidney failure. In a comprehensive functional annotation analysis of candidate causal genes, we observed convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2023
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