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1. Absence of interaction between rivaroxaban, tacrolimus and everolimus in renal transplant recipients with deep vein thrombosis or atrial fibrillation

Author

Flavia Neri, L. Furian, G.P. Avruscio, E. Bernardi, F. Fabris, M.T. Sartori, G. Camporese, S. Villalta, P. Simioni, D. Bernardi, F. Marchini, and L. Bonfante

Subjects
0301 basic medicine, Male, Physiology, Pilot Projects, 030204 cardiovascular system & hematology, chemistry.chemical_compound, 0302 clinical medicine, Rivaroxaban, Atrial Fibrillation, Drug Interactions, Prospective Studies, Venous Thrombosis, Anticoagulant, Graft Survival, Atrial fibrillation, Middle Aged, Thrombosis, surgical procedures, operative, Treatment Outcome, Immunosuppressants, Pharmacokinetics, Renal transplantation, Venous thromboembolism, Molecular Medicine, Female, Drug Monitoring, Immunosuppressive Agents, medicine.drug, medicine.medical_specialty, medicine.drug_class, Urology, Renal function, Hemorrhage, Tacrolimus, 03 medical and health sciences, medicine, Humans, Everolimus, Blood Coagulation, Aged, Pharmacology, Creatinine, business.industry, medicine.disease, Kidney Transplantation, 030104 developmental biology, chemistry, business, Factor Xa Inhibitors
Abstract

No data are available on rivaroxaban use in renal transplant recipients and on its surmised interaction with immunosuppressants. The aim was to investigate potential interactions between rivaroxaban and immunosuppressants in this setting. Renal transplant recipients with a stable renal function treated with rivaroxaban and tacrolimus with or without everolimus were investigated. All drugs and creatinine concentrations were determined daily for 2 weeks after the start of anticoagulation. Blood samples were drawn at 8.00 am and 3–4 h later for trough and peak concentrations, respectively. Bleeding and thrombotic events were recorded during a minimum follow-up of 6 months. In 8 renal transplant patients, rivaroxaban levels showed a predictable pharmacokinetic trend, both at Ctrough (30–61 μg/L) and at Cpeak (143–449 μg/L), with limited variability in the 25th–75th percentile range. Tacrolimus (Ctrough 3–13 μg/L; Cpeak 3–16 μg/L), everolimus (Ctrough 3–11 μg/L; Cpeak 5–17 μg/L) and creatinine concentrations were stable as well. Immunosuppressors variability before and after rivaroxaban were 30% and 30% for tacrolimus, 27% and 29% for everolimus, respectively, as well as 14% and 3% for creatinine. For rivaroxaban monitoring, the reference change value better performed in identifying significant variations of its concentration. No patient had bleeding or thrombotic events, worsening of renal graft function, and signs of immunosuppressants toxicity during a mean follow-up of 23 (9–28) months. In conclusion, rivaroxaban does not seem to interact with tacrolimus and everolimus in renal transplant recipients. Both anticoagulant and immunosuppressive effects seem warranted, without major bleeding complications and effect on the graft function.

Published
2019

2. Contents, Vol. 56, 1990

Author

M. Monteagudo, Norishi Ueda, Kazuyoshi Watanabe, Aureliano Rocchi, J.V. Barbas, Giuseppe Curatola, Quirino Maggiore, Sojiro Ogino, Miiko Fujisawa, Fumiaki Marumo, Andrea Buscaroli, C. Bru, H. Nohno, C. Ronco, Yutaka Furumitsu, N. Koçak, Dino Docci, Eyal Raz, Salim K. Mujais, P. Conz, Takashi Inoue, Laura Gurioli, K. Nakatsuka, J. Lima, Sisca S, Nicole Ruel, A. Torras, Hideo Nakagawa, Stanley Nahman, H. Kawakami, E. Vilella, J.M. Simó, F. Marumo, G. Buccianti, Tsutomu Tabata, Y.E. Sönmez, P.A. Bevilacqua, Maria Giovanna Cirolla, Anna Cadario, J. Camps, Mikio Okamura, K. Jojima, Daniel G. Bichet, Dos Santos, Mayer Brezis, Alfonso Pacitti, Michèle Lonergan, Yusuke Tsukamoto, G. Valenti, Bruno Balbi, Kazuo Kumano, Zbigniew W. Hruby, Radwan al-Kiek, Marco Forni, Fumitake Gejyo, Sandra McEachrane, Takashi Morita, Carlo Feletti, Naftali Kaminski, S. Cantaro, Richard Dicker, Audrey V. Cybulsky, L. Masana, Earl Nielsen, L. Revert, E. Ponz, H. Iwamoto, Renzo Bilancioni, M.I. Sonnekus, Shigemi Kinoshita, Mhd Zaher Sahloul, Bahrain Azadeh, L. Bonfante, C. Villabona, Yuichiro Maruyama, Masaaki Arakawa, F. Garcia-Bragado, H. Itoh, P.R. Turner, A.E. Smyth, Jun Fujita, M. Vilardell, Saleh H. Abu-Romeh, H. Matsuzaki, Hiroyuki Shimada, Michele Portigliatti, Atsuko Morita, Yoshiharu Kanayama, Noriyuki Honma, M. Feriani, L. Calò, E.N. Wardle, Takami Miki, J. Joven, Takatoshi Inoue, Shinichi Nishi, Tadanao Takeda, Eros Malara, Massimiliano Bianchi, Hiromi Inariba, Carlo Viglino, Carmine Zoccali, Leopoldo Baldrati, S. Meli, Fernando G. Cosio, Maurizio Postorino, M. Valles, R. Dell’Aquila, Sebastiano Cutrupi, A.M. Meyers, G. Pietribiasi, Osamu Ishida, M.M. Praia, F.T. Sousa, M.Ş. Sever, M. Shichiri, Yoshiki Nishizawa, Masanori Emoto, G. La Greca, Silvia Mengozzi, Shigeru Iwanami, D. Cresseri, A. Piccoli, Marie-Françoise Arthus, Satoshi Saka, Rosa Giordano, Giuseppe Enia, A. Brendolan, M. Lorenz, García García, Hirotoshi Morii, Caterina Canavese, Y. Hirata, Robin P. Lowry, Fausto Turci, N.A. Laminski, Claudio Capponcini, Sergio Costantini, Vivette D. D'Agati, Nobuo Negoro, S. Favaro, M. Carrera, A. Borsatti, Peter Ivanovich, T. Murakami, J.M. Campistol, and Awad Rashed

Subjects
Traditional medicine, business.industry, Medicine, business
Published
1990
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3. [Arterial hypertension and oxidative stress induced by cyclosporin. Effect of carvedilol]

Author

E, Pagnin, B, Giacon, F, Zaghetto, D, Vianello, L, Bonfante, W, Huber, A, Antonello, A, Semplicini, and L, Calò

Subjects
Adult, Male, Carbazoles, Middle Aged, Kidney Transplantation, Antioxidants, Propanolamines, Oxidative Stress, Postoperative Complications, Hypertension, Cyclosporine, Humans, Carvedilol, Female
Abstract

Cyclosporin-induced hypertension and endothelial dysfunction have been attributed to the effects of cyclosporin on factors controlling vasomotor tone. Endothelial nitric oxide (NO) regulates basal vasodilation, and an NO-mediated protective mechanism from cyclosporin-induced vasoconstriction has been proposed. In transplanted patients with cyclosporin-induced hypertension, we have recently demonstrated upregulation of the NO system and superoxide and free radical overproduction, which, by increasing NO metabolism, could induce hypertension, vascular remodeling and chronic rejection. In the present work, we have evaluated endothelial constitutive NO synthase (ecNOS), transforming growth factor beta and heme oxygenase-1 (protective against oxidative stress), mRNA production and plasma NO metabolites, peroxynitrite and antioxidant power in 15 kidney transplanted patients before and after 4 months of treatment with carvedilol alpha 1-beta-blocker and potent antioxidant. Our aim was to study the efficacy of the reduction of oxidative stress on complications such as endothelial dysfunction and fibrogenesis. Monocyte ecNOS and plasma NO metabolites remained higher versus those of control subjects and were unchanged by carvedilol, while antioxidant power and heme oxygenase-1 mRNA production increased. Peroxynitrite, as well as transforming growth factor beta mRNA, were reduced by carvedilol. It also normalized blood pressure. In conclusion, carvedilol reduces oxidative stress and normalizes blood pressure; ecNOS remains upregulated while mRNA for transforming growth factor beta, a key fibrogenic cytokine, is reduced by carvedilol, which seems to preserve protective mechanisms such as NO and heme oxygenase-1 against long-term complications of oxidative stress, e.g., endothelial dysfunction, fibrogenesis and chronic rejection.

Published
2001

4. 7-year-follow up (1987-1994) of a population with asymptomatic persistent microhematuria and normal renal function

Author

L, Bonfante, A, D'Angelo, S, Favaro, A, Giacomini, M, Normanno, L, Calò, A, Antonello, V, Bordin, D, Vianello, A, Meani, and A, Borsatti

Subjects
Adult, Cohort Studies, Male, Adolescent, Humans, Female, Follow-Up Studies, Hematuria
Abstract

A group od 129 patients with persistent asymptomatic microhematuria was studied for 7 years (1987-1994). At the beginning of the study, 31 patients showed mild proteinuria (less than 1 g/day) and in the rest of 98 patients, 21 showed microalbuminuria. At the end of the study none of the patients developed renal failure, urological disease, hypertension. Six patients out of 31 with mild proteinuria (less than 1 g/day), developed an increase of proteinuria over 2 and 3/day and underwent a renal biopsy while 2 out of 21 patients with altered microalbuminuria completely recovered after the follow-up period. The rest of 77 patients at the end of the study still showed isolated microhematuria. The results of this study support the hypothesis that in a population with age range between 16 and 28 years, the presence of persistent microhematuria, also associated with mild proteinuria, even for a long time, does not seem to lead to changes of renal function or to urological diseases.

Published
1996

6. Subject Index, Vol. 56, 1990

Author

H. Kawakami, Salim K. Mujais, F. Marumo, Audrey V. Cybulsky, A.M. Meyers, K. Jojima, Masaaki Arakawa, Osamu Ishida, M.M. Praia, M. Valles, Kazuyoshi Watanabe, Fumiaki Marumo, N. Koçak, F. Garcia-Bragado, E. Ponz, Richard Dicker, L. Masana, Marie-Françoise Arthus, Renzo Bilancioni, Mhd Zaher Sahloul, Awad Rashed, G. La Greca, L. Bonfante, Sandra McEachrane, Jun Fujita, Yuichiro Maruyama, Quirino Maggiore, M. Lorenz, J. Lima, Sojiro Ogino, Takami Miki, Sergio Costantini, Yoshiharu Kanayama, Eyal Raz, A. Torras, Hideo Nakagawa, C. Bru, M. Vilardell, M. Feriani, Maria Giovanna Cirolla, Earl Nielsen, L. Revert, G. Buccianti, Tsutomu Tabata, M. Monteagudo, Alfonso Pacitti, Michèle Lonergan, Takatoshi Inoue, Hiromi Inariba, P. Conz, L. Calò, E.N. Wardle, Saleh H. Abu-Romeh, H. Matsuzaki, Hiroyuki Shimada, Dos Santos, Y.E. Sönmez, Marco Forni, Noriyuki Honma, Vivette D. D'Agati, J. Joven, Carlo Feletti, A. Piccoli, Caterina Canavese, Maurizio Postorino, Eros Malara, Takashi Morita, Nobuo Negoro, Leopoldo Baldrati, Peter Ivanovich, S. Favaro, Dino Docci, F.T. Sousa, Carlo Viglino, Sisca S, Kazuo Kumano, P.A. Bevilacqua, Anna Cadario, Fernando G. Cosio, Yoshiki Nishizawa, Masanori Emoto, Silvia Mengozzi, Shigeru Iwanami, D. Cresseri, Satoshi Saka, Rosa Giordano, M. Shichiri, S. Cantaro, T. Murakami, J.M. Campistol, Fausto Turci, A. Brendolan, M. Carrera, N.A. Laminski, Giuseppe Curatola, Claudio Capponcini, A. Borsatti, Yusuke Tsukamoto, Y. Hirata, Zbigniew W. Hruby, Laura Gurioli, Shinichi Nishi, Robin P. Lowry, Yutaka Furumitsu, Shigemi Kinoshita, J. Camps, G. Pietribiasi, Takashi Inoue, Michele Portigliatti, Norishi Ueda, C. Villabona, Giuseppe Enia, C. Ronco, Andrea Buscaroli, G. Valenti, Bruno Balbi, Aureliano Rocchi, J.V. Barbas, K. Nakatsuka, H. Itoh, P.R. Turner, H. Iwamoto, A.E. Smyth, Atsuko Morita, Carmine Zoccali, M.I. Sonnekus, Massimiliano Bianchi, S. Meli, R. Dell’Aquila, Mayer Brezis, Stanley Nahman, Miiko Fujisawa, Nicole Ruel, Mikio Okamura, Daniel G. Bichet, H. Nohno, Fumitake Gejyo, M.Ş. Sever, Bahrain Azadeh, Tadanao Takeda, Sebastiano Cutrupi, García García, Hirotoshi Morii, E. Vilella, J.M. Simó, Radwan al-Kiek, and Naftali Kaminski

Subjects
Index (economics), business.industry, Statistics, Medicine, Subject (documents), business
Published
1990
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