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1. 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

4. The nature of water: Greek thought from Homer to Acusilaos

Author

Santo, R. M., Bisaccia, C., Massimo Cirillo, Pollastro, R. M., Raiola, I., Santo, L. S., De Santo, Rm, Bisaccia, C, Cirillo, M, Pollastro, Rosa Maria, Raiola, I, De Santo, L. S., Cirillo, Massimo, Pollastro, Rm, and De Santo, Ls

Subjects
Water, Greek World, Mythology, History, Ancient
Abstract

Greek philosophy finds its roots in the myth of Homer's and Hesiod's poems and especially in Orphism which introduced the concept of a soul separated from the body with an independent principle, psichē (soul), to be rewarded or punished after death. Orphism was an important step in Greek culture. It introduced the divine into man, the soul which does not die with the body and reincarnates. From Orphism started the need of rituals capable of separating the spirit from the body. From Homer to Acusilaos, water was a very important element which connected humans and gods, long before Thales of Miletus defined it the arche.

Published
2009

7. Pathophysiology and clinical studies in CKD 1-5

Author

Gerakis, A., primary, Halapas, A., additional, Chrissoheris, M., additional, Giatras, I., additional, Andritsou, R., additional, Nikolaou, I., additional, Bouboulis, N., additional, Pattakos, E., additional, Spargias, K., additional, Kalaitzidis, R., additional, Karasavvidou, D., additional, Pappas, K., additional, Katatsis, G., additional, Tatsioni, A., additional, Siamopoulos, K., additional, de Borst, M. H., additional, Hajhosseiny, R., additional, Tamez, H., additional, Wenger, J., additional, Thadhani, R., additional, Goldsmith, D. J., additional, Zanoli, L., additional, Rastelli, S., additional, Marcantoni, C., additional, Blanco, J., additional, Tamburino, C., additional, Castellino, P., additional, Larsen, T., additional, Jensen, J., additional, Bech, J., additional, Pedersen, E., additional, Mose, F., additional, Leckstrom, D., additional, Bhuvanakrishna, T., additional, McGrath, A., additional, Goldsmith, D., additional, Muras, K., additional, Masajtis-Zagajewska, A., additional, Nowicki, M., additional, Rayner, H. C., additional, Baharani, J., additional, Smith, S., additional, Suresh, V., additional, Dasgupta, I., additional, Zarzoulas, F., additional, Balafa, O., additional, Di Lullo, L., additional, Floccari, F., additional, Rivera, R., additional, Gorini, A., additional, Malaguti, M., additional, Barbera, V., additional, Granata, A., additional, Santoboni, A., additional, Luczak, M., additional, Formanowicz, D., additional, Pawliczak, E., additional, Wanic-Kossowska, M., additional, Koziol, L., additional, Figlerowicz, M., additional, Bommer, J., additional, Fliser, M., additional, Roth, P., additional, Saure, D., additional, Vettoretti, S., additional, Alfieri, C., additional, Floreani, R., additional, Regalia, A., additional, Bonanomi, C., additional, Meazza, R., additional, Magrini, F., additional, Messa, P., additional, Jankowski, V., additional, Zidek, W., additional, Joachim, J., additional, Lee, K., additional, Hwang, I. H., additional, Lee, S. B., additional, Lee, D. W., additional, Kim, I. Y., additional, Kwak, I. S., additional, Seong, E. Y., additional, Shin, M. J., additional, Rhee, H., additional, Yang, B. Y., additional, Dattolo, P., additional, Michelassi, S., additional, Sisca, S., additional, Allinovi, M., additional, Amidone, M., additional, Mehmetaj, A., additional, Pizzarelli, F., additional, Filiopoulos, V., additional, Manolios, N., additional, Hadjiyannakos, D., additional, Arvanitis, D., additional, Panagiotopoulos, K., additional, Vlassopoulos, D., additional, Kim, J. S., additional, Han, B. G., additional, Choi, S. O., additional, Yang, J. W., additional, Shojai, S., additional, Babu, A., additional, Boddana, P., additional, Dipankar, D., additional, Alvarado, R., additional, Garcia-Pino, G., additional, Ruiz-Donoso, E., additional, Chavez, E., additional, Luna, E., additional, Caravaca, F., additional, Geiger, H., additional, Buttner, S., additional, Lv, L.-L., additional, Cao, Y., additional, Zheng, M., additional, Liu, B.-C., additional, Kouvelos, G. N., additional, Raikou, V. D., additional, Arnaoutoglou, E. M., additional, Milionis, H. J., additional, Boletis, J. N., additional, Matsagkas, M. I., additional, Raiola, I., additional, Trepiccione, F., additional, Pluvio, M., additional, Raiola, R., additional, Capasso, G., additional, Kaykov, I., additional, Kukoleva, L., additional, Zverkov, R., additional, Smirnov, A., additional, Hammami, S., additional, Frih, A., additional, Hajem, S., additional, Hammami, M., additional, and Wan, L., additional

Published
2013
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8. Hydrogen Sulfide, a Toxic Gas with Cardiovascular Properties in Uremia: How Harmful Is It?

Author

Alessandra F. Perna, Immacolata Sepe, Ilaria Raiola, Rosanna Capasso, Natale G. De Santo, Diego Ingrosso, Diana Lanza, Perna, Alessandra, Lanza, D, Sepe, I, Raiola, I, Capasso, R, De Santo, Ng, and Ingrosso, Diego

Subjects
Hydrogen sulfide, Cystathionine γ lyase, Inorganic chemistry, chemistry.chemical_element, Diabete, Cardiovascular System, Nitric oxide, Cystathionine γ-lyase, chemistry.chemical_compound, Renal Dialysis, medicine, Humans, Organic chemistry, Gasotransmitters, Uremia, Chemistry, fungi, Cystathionine gamma-Lyase, food and beverages, Hematology, General Medicine, equipment and supplies, medicine.disease, Toxic gas, Nephrology, Hypertension, Hemodialysi, Carbon
Abstract

Hydrogen sulfide (H(2)S) is a poisonous gas which can be lethal. However, it is also produced endogenously, thus belonging to the family of gasotransmitters along with nitric oxide and carbon monoxide. H(2)S is in fact involved in mediating several signaling and cytoprotective functions, for example in the nervous, cardiovascular, and gastrointestinal systems, such as neuronal transmission, blood pressure regulation and insulin release, among others. When increased, it can mediate inflammation and apoptosis, with a role in shock. When decreased, it can be involved in atherosclerosis, hypertension, myocardial infarction, diabetes, sexual dysfunction, and gastric ulcer; it notably interacts with the other gaseous mediators. Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are the principal enzymes involved in H(2)S production. We have recently studied H(2)S metabolism in the plasma of chronic hemodialysis patients and reported that its levels are significantly decreased. The plausible mechanism lies in the transcription inhibition of the cystathionine γ-lyase gene. The finding could be of importance considering that hypertension and high cardiovascular mortality are characteristic in these patients. Hydrogen sulfide (H2S) is a poisonous gas which can be lethal. However, it is also produced endogenously, thus belonging to the family of gasotransmitters along with nitric oxide and carbon monoxide. H2S is in fact involved in mediating several signaling and cytoprotective functions, for example in the nervous, cardiovascular, and gastrointestinal systems, such as neuronal transmission, blood pressure regulation and insulin release, among others. When increased, it can mediate inflammation and apoptosis, with a role in shock. When decreased, it can be involved in atherosclerosis, hypertension, myocardial infarction, diabetes, sexual dysfunction, and gastric ulcer; it notably interacts with the other gaseous mediators. Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are the principal enzymes involved in H2S production. We have recently studied H2S metabolism in the plasma of chronic hemodialysis patients and reported that its levels are significantly decreased. The plausible mechanism lies in the transcription inhibition of the cystathionine γ-lyase gene. The finding could be of importance considering that hypertension and high cardiovascular mortality are characteristic in these patients. Copyright © 2011 S. Karger AG, Basel.

Published
2011

9. Hydrogen Sulfide, the Third Gaseous Signaling Molecule With Cardiovascular Properties, Is Decreased in Hemodialysis Patients

Author

Diego Ingrosso, Cinzia Lombardi, Paola Pulzella, Rosanna Capasso, Diana Lanza, Ilaria Raiola, Alessandra F. Perna, Maria Grazia Luciano, Immacolata Sepe, Natale G. De Santo, Eleonora Violetti, Perna, Alessandra, Luciano, Mg, Ingrosso, Diego, Raiola, I, Pulzella, P, Sepe, I, Lanza, D, Violetti, E, Capasso, R, Lombardi, C, and DE SANTO, Ng

Subjects
medicine.medical_specialty, Hyperhomocysteinemia, Vasodilator Agents, medicine.medical_treatment, Hydrogen sulfide, Cystathionine beta-Synthase, Medicine (miscellaneous), Sulfurtransferase, Nitric oxide, Pathogenesis, chemistry.chemical_compound, Renal Dialysis, Internal medicine, medicine, Humans, Hydrogen Sulfide, Uremia, Nutrition and Dietetics, biology, business.industry, Cystathionine gamma-Lyase, equipment and supplies, medicine.disease, Cystathionine beta synthase, Endocrinology, chemistry, Cardiovascular Diseases, Nephrology, Sulfurtransferases, Hypertension, biology.protein, Kidney Failure, Chronic, Hemodialysis, business, Kidney disease
Abstract

Hydrogen sulfide, H2S, is the third endogenous gas with cardiovascular properties, after nitric oxide and carbon monoxide. H2S is a potent vasorelaxant, and its deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase, cystathionine gamma- lyase, and 3-mercaptopyruvate sulfurtransferase catalyze H2S formation. Chronic kidney disease is characterized by high prevalence of hyperhomocysteinemia, hypertension, and high cardiovascular mortality, especially in hemodialysis patients. H2S levels are decreased in hemodialysis patients through transcriptional deregulation of genes encoding for the H2S-producing enzymes. Potential implications relate to the pathogenesis of the manifestations of the uremic syndrome, such as hypertension and atherosclerosis. (C) 2010 by the National Kidney Foundation, Inc. All rights reserved.

Published
2010

10. Hyperhomocysteinemia in Uremia-A Red Flag in a Disrupted Circuit

Author

Alessandra F. Perna, Rosanna Capasso, Maria Grazia Luciano, Elisabetta Ascione, Natale G. De Santo, Ilaria Raiola, Diego Ingrosso, Cinzia Lombardi, Immacolata Sepe, Ziad A. Massy, Diana Lanza, Peter Stenvinkel, Eleonora Violetti, Perna, Alessandra, Ingrosso, Diego, Violetti, E, Luciano, Mg, Sepe, I, Lanza, D, Capasso, R, Ascione, E, Raiola, I, Lombardi, C, Stenvinkel, P, Massy, Z, and DE SANTO, Ng

Subjects
medicine.medical_specialty, Hyperhomocysteinemia, Methyltransferase, Homocysteine, Population, chemistry.chemical_compound, Risk Factors, Internal medicine, Mendelian randomization, medicine, Humans, Epigenetics, education, Uremia, education.field_of_study, biology, business.industry, medicine.disease, Endocrinology, Biochemistry, chemistry, Cardiovascular Diseases, Nephrology, Methylenetetrahydrofolate reductase, biology.protein, business
Abstract

Hyperhomocysteinemia is an independent cardiovascular risk factor, according to most observational studies and to studies using the Mendelian randomization approach, utilizing the common polymorphism C677T of methylene tetrahydrofolate reductase. In contrast, the most recent secondary preventive intervention studies, in the general population and in chronic kidney disease (CKD) and uremia, which are all negative (with the possible notable exception of stroke), point to other directions. However, all trials use folic acid in various dosages as a means to reduce homocysteine levels, with the addition of vitamins B6 and B12. It is possible that folic acid has negative effects, which offset the benefits; alternatively, homocysteine could be an innocent by-stander, or a surrogate of the real culprit. The latter possibility leads us to the search for potential candidates. First, the accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which by itself is considered a predictor of cardiovascular events. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, show. In CKD and in uremia, hyperhomocysteinemia and high intracellular AdoHcy are present and are associated with abnormal allelic expression of genes regulated through methylation, such as imprinted genes, and pseudoautosomal genes, thus pointing to epigenetic dysregulation. These alterations are susceptible to reversal upon homocysteine-lowering therapy obtained through folate administration. Second, it has to be kept in mind that homocysteine is mainly protein-bound, and its effects could be linked therefore to protein homocysteinylation. In this respect, increased protein homocysteinylation has been found in uremia, leading to alterations in protein function. © 2009 Wiley Periodicals, Inc.

Published
2009

11. Therapy of Hyperhomocysteinemia in Hemodialysis Patients: Effects of Folates and N-Acetylcysteine

Author

Ilaria Raiola, S Coppola, Massimo Cirillo, Paolino Raiola, Antonio Lupo, Diego Ingrosso, Cataldo Abaterusso, Immacolata Sepe, Diana Lanza, Guido Bellinghieri, Alessandra F. Perna, Satta E, Giuseppina Tirino, Giovanni Cirillo, Domenico Santoro, Biagio Di Iorio, Vincenzo Savica, Eleonora Violetti, Natale G. De Santo, Perna, Af, Violetti, E, Lanza, D, Sepe, I, Bellinghieri, G, Savica, V, Santoro, D, Satta, E, Cirillo, G, Lupo, A, Abaterusso, C, Raiola, I, Raiola, P, Coppola, S, Di Iorio, B, Tirino, G, Cirillo, M, Ingrosso, D, De Santo, Ng, Perna, Alessandra, Ingrosso, Diego, and De Santo, N. G.

Subjects
Male, Nephrology, medicine.medical_specialty, Hyperhomocysteinemia, Homocysteine, medicine.medical_treatment, Population, Medicine (miscellaneous), Gastroenterology, hemodialyis, chemistry.chemical_compound, Folic Acid, Pharmacotherapy, Renal Dialysis, Internal medicine, medicine, Humans, education, Dialysis, Aged, education.field_of_study, Nutrition and Dietetics, business.industry, homocysteine, Middle Aged, medicine.disease, Acetylcysteine, N-acetilcisteina, Surgery, nephrology, chemistry, Ambulatory, Kidney Failure, Chronic, Drug Therapy, Combination, Female, Hemodialysis, business
Abstract

Objective: Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients. Design: The study is an open, parallel, intervention study. Setting: Ambulatory chronic hemodialysis patients. Subjects: Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50). Intervention: One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47). Main Outcome Measure: Plasma homocysteine measured before and after dialysis at the first and the last treatment. Results: At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 μmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level

Published
2012

12. [A narrative review on arteriovenous fistula for hemodialysis].

Author

Satta E, Romano C, Alfarone C, Raiola I, Scarpati L, Lo Iacono F, Di Maio M, Russo L, Russo D, and Pagliuca MM

Subjects
Humans, Quality of Life, Renal Dialysis methods, Arteriovenous Fistula, Arteriovenous Shunt, Surgical methods, Central Venous Catheters
Abstract

Vascular access is the lifeline for hemodialysis patients. Autologous artero-venous fistula (AVF) is still the most popular vascular access for hemodialysis even if declining during the last decades. Compared to central venous catheters and vascular grafts, AVF is characterized by a lower risk of infection and lower number of hospitalizations, and by a better quality of life, higher dialysis efficiency, and more prolonged life expectancy for patients. Since the year 1966 when the two surgeons Cimino and Brescia had the idea of connecting the forearm vein and artery for chronic dialysis, several data have accumulated on surgical procedures, positioning of AVF (distal vs proximal), time for the first use, monitoring and surveilling. All guidelines suggest that special care should be given by monitoring and surveilling AVF to avoid its failure or fatal closing. Attention should be paid to the patient's vasculature before surgery, through the "maturation" phase and chronic use. Indeed, AVF requires constant and careful care. The crucial role is played by the patient itself in cooperation with devoted clinical staff participated by skilled nurses, nephrologists, surgeons, radiologists, and sonographers. Literature on AVF is evaluated and guidelines suggestions reported as well as the data attained by the Accesso Vascolare per Emodialisi (AVE) project. This project aimed to evaluate the benefits of monitoring and surveilling, operated by a multidisciplinary team on dialysis adequacy, AVF longevity, and patient's mortality., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Published
2022

13. Renal phenotype in Bardet-Biedl syndrome: a combined defect of urinary concentration and dilution is associated with defective urinary AQP2 and UMOD excretion.

Author

Zacchia M, Zacchia E, Zona E, Capolongo G, Raiola I, Rinaldi L, Trepiccione F, Ingrosso D, Perna A, Di Iorio V, Simonelli F, Moe OW, and Capasso G

Subjects
Adolescent, Adult, Bardet-Biedl Syndrome urine, Child, Child, Preschool, Female, Humans, Kidney Concentrating Ability physiology, Male, Middle Aged, Phenotype, Young Adult, Aquaporin 2 urine, Bardet-Biedl Syndrome physiopathology, Glomerular Filtration Rate physiology, Kidney physiopathology, Uromodulin urine
Abstract

The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The present study describes renal findings in 41 BBS patients and analyzes the pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41 patients (12%) showed an estimated glomerular filtration rate < 60 ml·min -1 ·1.73 m -2 Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin. Interestingly, water loading (WL) did not result in a significant reduction of Uosm, indicating combined concentrating and diluting defects. dDAVP infusion induced a significant increase of plasma Factor VIII and von Willebrand Factor levels, supporting normal function of the type 2 vasopressin receptor at least in endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and the WL-induced reduction of u-AQP2 were blunted in patients with a combined concentrating and diluting defect, suggesting a potential role of AQP2 in the defective regulation of water absorption. Urine Uromodulin excretion was reduced in all hyposthenuric patients, suggesting a thick ascending limb defect. Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL but not at basal. In summary, BBS patients show combined urinary concentration and dilution defects; a thick ascending limb and collecting duct tubulopathy may underlie impaired water handling., (Copyright © 2016 the American Physiological Society.)

Published
2016
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14. [Next Generation Sequencing and ADPKD].

Author

Restivo A, Di Fruscio G, Masella C, Rinaldi L, Capolongo G, Raiola I, and Capasso G

Abstract

Autosomal Dominant Polycistic Kidney Disease (ADPKD) is the most common inherited genetic disorder in the word, caused by mutations in PKD1 gene in 85% of cases and PKD 2 gene in the remaining 15%. Although diagnosis is usually based on ultrasound, MRI and CT scans, in some cases genetic testing is necessary, for example, in patients with atypical phenotype or with a negative family history, or in cases of donation from relatives. The presence of pseudogenes in PKD1, the size of the gene, the costs of the Sanger sequencing and genetic heterogeneity underlying kidney disease make genetic analysis particularly difficult to be performed. Next Generation Sequencing (NGS) represents the last frontier of innovation among diagnostic tools for molecular diagnosis of inherited cystic kidney disease thanks to the ability to analyze several genes at the same time. In this regard, we have developed a NGS platform, called Nephroplex, with the aim of identifying variations in 115 genes responsible for numerous kidney diseases, including cystic and polycystic disease, achieving, overall, a target region of 338.8 kbps. The technology used for the enrichment is HaloPlex system, based on the digestion of genomic DNA with restriction enzymes and the capture of the regions of interest with specific hybridization probes. With our platform, we have analyzed 9 patients with clinical diagnosis of ADPKD. We have obtained a depth coverage of 100x for 96.5% of the target, while the region not covered accounted for only 3% of the region of interest. In 6 patients, we found causative mutations in the genes PKD1 and PKD2, achieving a detection rate of 66%. In conclusion, the NephroPlex platform has proved to be an excellent device for molecular diagnosis of kidney disease and could clarify the mechanisms underlying genetic heterogeneity observed in kidney disease., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Published
2015

15. Therapy of hyperhomocysteinemia in hemodialysis patients: effects of folates and N-acetylcysteine.

Author

Perna AF, Violetti E, Lanza D, Sepe I, Bellinghieri G, Savica V, Santoro D, Satta E, Cirillo G, Lupo A, Abaterusso C, Raiola I, Raiola P, Coppola S, Di Iorio B, Tirino G, Cirillo M, Ingrosso D, and De Santo NG

Subjects
Aged, Drug Therapy, Combination, Female, Folic Acid administration & dosage, Homocysteine blood, Humans, Hyperhomocysteinemia etiology, Kidney Failure, Chronic complications, Kidney Failure, Chronic therapy, Male, Middle Aged, Acetylcysteine administration & dosage, Folic Acid analogs & derivatives, Hyperhomocysteinemia drug therapy, Renal Dialysis
Abstract

Objective: Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients., Design: The study is an open, parallel, intervention study., Setting: Ambulatory chronic hemodialysis patients., Subjects: Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50)., Intervention: One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47)., Main Outcome Measure: Plasma homocysteine measured before and after dialysis at the first and the last treatment., Results: At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 μmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level <12 μmol/L, compared with 19% in the MTHF group and 16% in the control group., Conclusions: NAC therapy induces a significant additional decrease in homocysteine removal during dialysis. The advantage is limited to the time of administration., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Published
2012
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16. Hydrogen sulfide, a toxic gas with cardiovascular properties in uremia: how harmful is it?

Author

Perna AF, Lanza D, Sepe I, Raiola I, Capasso R, De Santo NG, and Ingrosso D

Subjects
Cystathionine gamma-Lyase metabolism, Humans, Hypertension metabolism, Renal Dialysis, Cardiovascular System metabolism, Hydrogen Sulfide adverse effects, Hydrogen Sulfide metabolism, Uremia metabolism
Abstract

Hydrogen sulfide (H(2)S) is a poisonous gas which can be lethal. However, it is also produced endogenously, thus belonging to the family of gasotransmitters along with nitric oxide and carbon monoxide. H(2)S is in fact involved in mediating several signaling and cytoprotective functions, for example in the nervous, cardiovascular, and gastrointestinal systems, such as neuronal transmission, blood pressure regulation and insulin release, among others. When increased, it can mediate inflammation and apoptosis, with a role in shock. When decreased, it can be involved in atherosclerosis, hypertension, myocardial infarction, diabetes, sexual dysfunction, and gastric ulcer; it notably interacts with the other gaseous mediators. Cystathionine γ-lyase, cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase are the principal enzymes involved in H(2)S production. We have recently studied H(2)S metabolism in the plasma of chronic hemodialysis patients and reported that its levels are significantly decreased. The plausible mechanism lies in the transcription inhibition of the cystathionine γ-lyase gene. The finding could be of importance considering that hypertension and high cardiovascular mortality are characteristic in these patients., (Copyright © 2011 S. Karger AG, Basel.)

Published
2011
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17. Hydrogen sulfide, the third gaseous signaling molecule with cardiovascular properties, is decreased in hemodialysis patients.

Author

Perna AF, Luciano MG, Ingrosso D, Raiola I, Pulzella P, Sepe I, Lanza D, Violetti E, Capasso R, Lombardi C, and De Santo NG

Subjects
Cardiovascular Diseases etiology, Cystathionine beta-Synthase metabolism, Cystathionine gamma-Lyase metabolism, Humans, Hydrogen Sulfide metabolism, Hyperhomocysteinemia etiology, Hypertension etiology, Kidney Failure, Chronic complications, Sulfurtransferases metabolism, Uremia blood, Uremia enzymology, Hydrogen Sulfide blood, Kidney Failure, Chronic blood, Renal Dialysis, Vasodilator Agents
Abstract

Hydrogen sulfide, H(2)S, is the third endogenous gas with cardiovascular properties, after nitric oxide and carbon monoxide. H(2)S is a potent vasorelaxant, and its deficiency is implicated in the pathogenesis of hypertension and atherosclerosis. Cystathionine beta-synthase, cystathionine gamma-lyase, and 3-mercaptopyruvate sulfurtransferase catalyze H(2)S formation. Chronic kidney disease is characterized by high prevalence of hyperhomocysteinemia, hypertension, and high cardiovascular mortality, especially in hemodialysis patients. H(2)S levels are decreased in hemodialysis patients through transcriptional deregulation of genes encoding for the H(2)S-producing enzymes. Potential implications relate to the pathogenesis of the manifestations of the uremic syndrome, such as hypertension and atherosclerosis., (Copyright 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Published
2010
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18. The nature of water: Greek thought from Homer to Acusilaos.

Author

De Santo RM, Bisaccia C, Cirillo M, Pollastro RM, Raiola I, and De Santo LS

Subjects
History, Ancient, Greek World history, Mythology, Water
Abstract

Greek philosophy finds its roots in the myth of Homer's and Hesiod's poems and especially in Orphism which introduced the concept of a soul separated from the body with an independent principle, psiche (soul), to be rewarded or punished after death. Orphism was an important step in Greek culture. It introduced the divine into man, the soul which does not die with the body and reincarnates. From Orphism started the need of rituals capable of separating the spirit from the body. From Homer to Acusilaos, water was a very important element which connected humans and gods, long before Thales of Miletus defined it the arche.

Published
2009

19. Hyperhomocysteinemia in uremia--a red flag in a disrupted circuit.

Author

Perna AF, Ingrosso D, Violetti E, Luciano MG, Sepe I, Lanza D, Capasso R, Ascione E, Raiola I, Lombardi C, Stenvinkel P, Massy Z, and De Santo NG

Subjects
Cardiovascular Diseases etiology, Cardiovascular Diseases metabolism, Cardiovascular Diseases physiopathology, Humans, Hyperhomocysteinemia metabolism, Hyperhomocysteinemia physiopathology, Risk Factors, Uremia metabolism, Uremia physiopathology, Hyperhomocysteinemia complications, Uremia etiology
Abstract

Hyperhomocysteinemia is an independent cardiovascular risk factor, according to most observational studies and to studies using the Mendelian randomization approach, utilizing the common polymorphism C677T of methylene tetrahydrofolate reductase. In contrast, the most recent secondary preventive intervention studies, in the general population and in chronic kidney disease (CKD) and uremia, which are all negative (with the possible notable exception of stroke), point to other directions. However, all trials use folic acid in various dosages as a means to reduce homocysteine levels, with the addition of vitamins B6 and B12. It is possible that folic acid has negative effects, which offset the benefits; alternatively, homocysteine could be an innocent by-stander, or a surrogate of the real culprit. The latter possibility leads us to the search for potential candidates. First, the accumulation of homocysteine in blood leads to an intracellular increase of S-adenosylhomocysteine (AdoHcy), a powerful competitive methyltransferase inhibitor, which by itself is considered a predictor of cardiovascular events. DNA methyltransferases are among the principal targets of hyperhomocysteinemia, as studies in several cell culture and animal models, as well as in humans, show. In CKD and in uremia, hyperhomocysteinemia and high intracellular AdoHcy are present and are associated with abnormal allelic expression of genes regulated through methylation, such as imprinted genes, and pseudoautosomal genes, thus pointing to epigenetic dysregulation. These alterations are susceptible to reversal upon homocysteine-lowering therapy obtained through folate administration. Second, it has to be kept in mind that homocysteine is mainly protein-bound, and its effects could be linked therefore to protein homocysteinylation. In this respect, increased protein homocysteinylation has been found in uremia, leading to alterations in protein function.

Published
2009
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