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1. Methoxy polyethylene glycol-epoetin beta for anemia with chronic kidney disease

Author

Ohashi N, Sakao Y, Yasuda H, Kato A, and Fujigaki Y

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Naro Ohashi1, Yukitoshi Sakao2, Hideo Yasuda1, Akihiko Kato2, Yoshihide Fujigaki11Internal Medicine 1, 2Blood Purification Unit, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, JapanAbstract: Chronic kidney disease (CKD) is a risk factor for end-stage renal failure and cardiovascular events. In patients with CKD, anemia is often caused by decreased erythropoietin production relative to hemoglobin levels. As correction of anemia is associated with improved cardiac and renal function and quality of life, erythropoiesis-stimulating agents (ESAs) are standard therapy for anemia in CKD patients. However, traditional ESAs such as epoetin or darbepoetin have short half-lives and require frequent administration, dose changes, and close monitoring of hemoglobin concentration to maintain target hemoglobin levels. Methoxy polyethylene glycol-epoetin beta (MPG-EPO) is the only ESA that is generated by chemical modification of glycosylated erythropoietin through the integration of one specific, long, linear chain of polyethylene glycol. This ESA induces continuous erythropoietin receptor activation and has a long half-life (approximately 130 hours). Subcutaneous or intravenous administration of MPG-EPO once every 2 weeks or monthly achieved a high hemoglobin response rate in patients with anemia associated with CKD, regardless of whether the patient was undergoing dialysis. According to data from an observational time and motion study, MPG-EPO maintains hemoglobin levels when the same dose is administered, however infrequently. This suggests that compared with the use of traditional ESAs, administration of MPG-EPO reduces the overall time and cost associated with the management of anemia in CKD patients undergoing dialysis. MPG-EPO is generally well tolerated and most adverse events are of mild to moderate severity. The most commonly reported adverse effects are hypertension, nasopharyngitis, and diarrhea. Subcutaneous injection of MPG-EPO is significantly less painful than subcutaneous injection of darbepoetin. In conclusion, MPG-EPO is as effective and safe as traditional ESAs in managing renal anemia, irrespective of whether the patient is undergoing dialysis.Keywords: methoxy polyethylene glycol-epoetin beta, renal anemia, end-stage renal failure, hemoglobin, erythropoiesis-stimulating agent

Published
2012

11. Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease

Author

Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS, Tempo team, Gross P, Schulze B, Bichet D, Chauveau D, Peeters P, Voiculescu M, Manunta P, Tuazon J, Watnick T, Goral S, Horie S, Nutahara K, Torres V, Chapman A, Gansevoort R, Perrone R, Czerwiec F, Goldstein S, Cowley B, Fukagawa M, Torra R, Wei LJ, Cook T, Toto R, Agarwal R, August P, Bakris G, Beddhu S, Corwin H, Ruilope L, Rosa-Diez G, De La Fuente J, Martin R, Massari P, Novoa P, Rial M, Wasserman A, Faull R, Fraser I, Johnson D, Pedagagos E, Lian M, Pollock C, Cooper B, Rangan G, Russ G, McDonald S, Thomas M, Khoo D, Walker R, Pirson Y, Laecke V, Van der Niepen P, Sennesael J, Barre P, Alam A, Soroka S, Dieperink H, Strandgaard S, Petersen L, Berthoux F, Canaud B, Gontiers-Picard A, Huart A, Combe C, Delmas Y, Dussol B, Laville M, Guebre-Egziabher F, Mignon F, Michel C, Rieu P, Noel N, Ryckelynck J, Lobbedez T, Dellanna F, Kleophas W, Feldkamp T, Witzke O, Nurnberger J, Zeltner R, Walz G, Zeier M, Sommerer C, Bianchi S, Capasso G, Miranda N, Magistroni R, Bracale M, Remuzzi G, Rota S, Villa G, Tilocca P, Asahi K, Kato T, Endo M, Umezono T, Fujigaki Y, Kato A, Fukatsu A, Hasegawa H, Tayama Y, Hasegawa M, Hosoya T, Hanaoka K, Iehara N, Iino Y, Tsuruoka S, Imai E, Isaka Y, Ishimura E, Ito S, Sato H, Kamata K, Sakamoto H, Kamura K, Kusano E, Muto S, Kuwahara M, Matsubara A, Yorioka N, Mochizuki T, Narita I, Naya Y, Nihei N, Yukio N, Nishio S, Nitta K, Tsuchiya K, Okamura M, Sasaki S, Rai T, Seta K, Sugawara A, Shibazaki S, Sugiyama S, Tabei K, Takaichi K, Tomita K, Kitamura K, Tsukamoto Y, Tsuruya K, Nakano T, Ubara Y, Watanabe T, Yamamoto T, Yoshida K, Ishii D, Yuzawa Y, Meijer E, Vervloet M, Ciechanowski K, Wisniewska M, Gutowska-Jablonska M, Marcinkowska-Królewicz M, Klatko W, Wiśniewski T, Klinger M, Krajewska M, Ksiazek A, Orłowska G, Malecki R, Gontarek-Kacprzak J, Nowicki M, Makówka A, Rutkowski B, Wołyniec W, Rydzewski A, Sulowicz W, Jasik P, Covic A, Volovat C, Mircescu G, Petrescu L, Bobeica R, Barbarash O, Chesnokova L, Borovoy S, Demina L, Shostka G, Idovu M, Tkalich L, Geynits O, Tomilina N, Foggensteiner L, Holt S, Kingswood J, Lambie S, Peel R, MacDougall I, Tucker B, MacPhee I, Maxwell A, Brown H, Mikhail A, Bastin L, Turner N, Neary J, Wheeler D, Maxwell P, Wilkie M, Ong A, Zehnder D, Aldridge N, Adler S, Klein M, Battle D, Bennett W, Berger B, Dell K, Blumenfeld J, Donahue S, Bolin P, Browder R, Perry A, Oskoui F, Culpepper M, Dahl N, Edelstein C, Clegg L, Fischer D, Kaplan M, Kaveh K, Pankhaniya R, Koren M, Mansur K, Lafayette R, Lamar W, Lee J, Mahnensmith R, Nachman P, Mottl A, Miskulin D, Petersen J, Radhakrishnan J, Roppolo M, Basireddy M, Rosner M, Bolton W, Schulman G, Steed L, Steinman T, Hogan M, Venuto R, Turban S, Winklhofer F., Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Torres, Ve, Chapman, Ab, Devuyst, O, Gansevoort, Rt, Grantham, Jj, Higashihara, E, Perrone, Rd, Krasa, Hb, Ouyang, J, Czerwiec, F, Tempo, Team, Gross, P, Schulze, B, Bichet, D, Chauveau, D, Peeters, P, Voiculescu, M, Manunta, P, Tuazon, J, Watnick, T, Goral, S, Horie, S, Nutahara, K, Torres, V, Chapman, A, Gansevoort, R, Perrone, R, Goldstein, S, Cowley, B, Fukagawa, M, Torra, R, Wei, Lj, Cook, T, Toto, R, Agarwal, R, August, P, Bakris, G, Beddhu, S, Corwin, H, Ruilope, L, Rosa-Diez, G, De La Fuente, J, Martin, R, Massari, P, Novoa, P, Rial, M, Wasserman, A, Faull, R, Fraser, I, Johnson, D, Pedagagos, E, Lian, M, Pollock, C, Cooper, B, Rangan, G, Russ, G, Mcdonald, S, Thomas, M, Khoo, D, Walker, R, Pirson, Y, Laecke, V, Van der Niepen, P, Sennesael, J, Barre, P, Alam, A, Soroka, S, Dieperink, H, Strandgaard, S, Petersen, L, Berthoux, F, Canaud, B, Gontiers-Picard, A, Huart, A, Combe, C, Delmas, Y, Dussol, B, Laville, M, Guebre-Egziabher, F, Mignon, F, Michel, C, Rieu, P, Noel, N, Ryckelynck, J, Lobbedez, T, Dellanna, F, Kleophas, W, Feldkamp, T, Witzke, O, Nurnberger, J, Zeltner, R, Walz, G, Zeier, M, Sommerer, C, Bianchi, S, Capasso, G, Miranda, N, Magistroni, R, Bracale, M, Remuzzi, G, Rota, S, Villa, G, Tilocca, P, Asahi, K, Kato, T, Endo, M, Umezono, T, Fujigaki, Y, Kato, A, Fukatsu, A, Hasegawa, H, Tayama, Y, Hasegawa, M, Hosoya, T, Hanaoka, K, Iehara, N, Iino, Y, Tsuruoka, S, Imai, E, Isaka, Y, Ishimura, E, Ito, S, Sato, H, Kamata, K, Sakamoto, H, Kamura, K, Kusano, E, Muto, S, Kuwahara, M, Matsubara, A, Yorioka, N, Mochizuki, T, Narita, I, Naya, Y, Nihei, N, Yukio, N, Nishio, S, Nitta, K, Tsuchiya, K, Okamura, M, Sasaki, S, Rai, T, Seta, K, Sugawara, A, Shibazaki, S, Sugiyama, S, Tabei, K, Takaichi, K, Tomita, K, Kitamura, K, Tsukamoto, Y, Tsuruya, K, Nakano, T, Ubara, Y, Watanabe, T, Yamamoto, T, Yoshida, K, Ishii, D, Yuzawa, Y, Meijer, E, Vervloet, M, Ciechanowski, K, Wisniewska, M, Gutowska-Jablonska, M, Marcinkowska-Królewicz, M, Klatko, W, Wiśniewski, T, Klinger, M, Krajewska, M, Ksiazek, A, Orłowska, G, Malecki, R, Gontarek-Kacprzak, J, Nowicki, M, Makówka, A, Rutkowski, B, Wołyniec, W, Rydzewski, A, Sulowicz, W, Jasik, P, Covic, A, Volovat, C, Mircescu, G, Petrescu, L, Bobeica, R, Barbarash, O, Chesnokova, L, Borovoy, S, Demina, L, Shostka, G, Idovu, M, Tkalich, L, Geynits, O, Tomilina, N, Foggensteiner, L, Holt, S, Kingswood, J, Lambie, S, Peel, R, Macdougall, I, Tucker, B, Macphee, I, Maxwell, A, Brown, H, Mikhail, A, Bastin, L, Turner, N, Neary, J, Wheeler, D, Maxwell, P, Wilkie, M, Ong, A, Zehnder, D, Aldridge, N, Adler, S, Klein, M, Battle, D, Bennett, W, Berger, B, Dell, K, Blumenfeld, J, Donahue, S, Bolin, P, Browder, R, Perry, A, Oskoui, F, Culpepper, M, Dahl, N, Edelstein, C, Clegg, L, Fischer, D, Kaplan, M, Kaveh, K, Pankhaniya, R, Koren, M, Mansur, K, Lafayette, R, Lamar, W, Lee, J, Mahnensmith, R, Nachman, P, Mottl, A, Miskulin, D, Petersen, J, Radhakrishnan, J, Roppolo, M, Basireddy, M, Rosner, M, Bolton, W, Schulman, G, Steed, L, Steinman, T, Hogan, M, Venuto, R, Turban, S, Winklhofer, F., University of Zurich, Torres, Vicente E, Feldkamp, Thorsten (Beitragende*r), and Witzke, Oliver (Beitragende*r)

Subjects
Male, Tolvaptan, Medizin, 2700 General Medicine, SIROLIMUS, Kidney, V2 RECEPTOR ANTAGONIST, 10052 Institute of Physiology, Aquaretic, VASOPRESSIN V-2-RECEPTOR ANTAGONIST, Polycystic Kidney, 10035 Clinic for Nephrology, Medicine (all), General Medicine, Organ Size, Middle Aged, Adolescent, Adult, Benzazepines, Double-Blind Method, Female, Glomerular Filtration Rate, Humans, Polycystic Kidney, Autosomal Dominant, Sodium, Young Adult, Antidiuretic Hormone Receptor Antagonists, LONG-ACTING SOMATOSTATIN, Autosomal Dominant, 10076 Center for Integrative Human Physiology, OPC-41061, medicine.symptom, medicine.drug, medicine.medical_specialty, RENAL-FUNCTION, CYST GROWTH, Autosomal dominant polycystic kidney disease, Urology, Renal function, Kidney Volume, 610 Medicine & health, Placebo, Article, VOLUME PROGRESSION, Cystic kidney disease, Internal medicine, medicine, HYPONATREMIA, business.industry, urogenital system, ORAL TOLVAPTAN, medicine.disease, Endocrinology, Albuminuria, 570 Life sciences, biology, business
Abstract

BACKGROUND: The course of autosomal dominant polycystic kidney disease (ADPKD) is often associated with pain, hypertension, and kidney failure. Preclinical studies indicated that vasopressin V 2 -receptor antagonists inhibit cyst growth and slow the decline of kidney function. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V 2 -receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney-function decline. RESULTS: Over a 3-year period, the increase in total kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P

Published
2012

12. EXPERIMENTAL ACUTE KIDNEY INJURY

Author

Kuma, A., primary, Yamada, S., additional, Miyamoto, T., additional, Serino, R., additional, Tamura, M., additional, Otsuji, Y., additional, Kohno, K., additional, Cho, W. Y., additional, Kim, M.-G., additional, Jo, S.-K., additional, Kim, H. K., additional, Jado, J. C., additional, Humanes, B., additional, Lopez-Parra, V., additional, Camano, S., additional, Lara, J. M., additional, Cercenado, E., additional, Tejedor, A., additional, Lazaro, A., additional, Jansen, M., additional, Castellano, G., additional, Stasi, A., additional, Intini, A., additional, Gigante, M., additional, Di Palma, A. M., additional, Divella, C., additional, Netti, G. S., additional, Prattichizzo, C., additional, Pontrelli, P., additional, Crovace, A., additional, Staffieri, F., additional, Fiaccadori, E., additional, Brienza, N., additional, Grandaliano, G., additional, Pertosa, G. B., additional, Gesualdo, L., additional, Xanthopoulou, K., additional, Tsouchnikas, I., additional, Ouzounidis, G., additional, Kokaraki, G., additional, Lagoudaki, R., additional, Simeonidou, C., additional, Karkavelas, G., additional, Spandou, E., additional, Tsakiris, D., additional, Kallaras, K., additional, Schneider, R., additional, Meusel, M., additional, Betz, B. B., additional, Held, C., additional, Moller-Ehrlich, K., additional, Buttner-Herold, M., additional, Wanner, C., additional, Michael, G., additional, Sauvant, C., additional, Hosszu, A., additional, Antal, Z., additional, Hodrea, J., additional, Koszegi, S., additional, Banki, N. F., additional, Wagner, L., additional, Lenart, L., additional, Vannay, A., additional, Szabo, A. J., additional, Fekete, A., additional, Michael, A., additional, Faga, T., additional, Navarra, M., additional, Andreucci, M., additional, Lemoine, S., additional, Pillot, B., additional, Rabeyrin, M., additional, Varennes, A., additional, Ovize, M., additional, Juillard, L., additional, Gomes Santana, L., additional, Silva Almeida, W., additional, Schor, N., additional, Watanabe, M., additional, Fonseca, C. D., additional, Pessoa, E. A., additional, Mendonca, M. H., additional, Fernandes, S. M., additional, Borges, F. T., additional, Vattimo, M. F., additional, Ow, C. P. C., additional, Tassone, F., additional, Koeners, M. P., additional, Malpas, S. C., additional, Evans, R. G., additional, Alfarano, C., additional, Guardia, M.-A., additional, Lluel, P., additional, Palea, S., additional, Young, G.-H., additional, Wu, V.-C., additional, Choi, D. E., additional, Jeong, J. Y., additional, Chang, Y. K., additional, Chung, S., additional, Na, K. R., additional, Kim, S. S., additional, Lee, K. W., additional, Yang, Y., additional, Zhang, L., additional, Fu, P., additional, Zhao, Y., additional, Zhang, X., additional, Jadot, I., additional, Decleves, A.-E., additional, Colombaro, V., additional, Martin, B., additional, Voisin, V., additional, Habsch, I., additional, Deprez, E., additional, Nortier, J., additional, Caron, N., additional, Iwakura, T., additional, Fujikura, T., additional, Ohashi, N., additional, Yasuda, H., additional, Fujigaki, Y., additional, Vasco, C. F., additional, Vattimo, M. D. F. F., additional, Draibe, J., additional, Y ld r m, Y., additional, Aba, O., additional, Y lmaz, Z., additional, Kadiroglu, A. K., additional, Y lmaz, M. E., additional, Gul, M., additional, Ketani, A., additional, Colpan, L., additional, Neiva, L. B. d. M., additional, Suller Garcia, J., additional, Oliveira, A. S. d., additional, Naves, M. A., additional, Van Swelm, R. P. L., additional, Wetzels, J. F. M., additional, Verweij, V. G. M., additional, Laarakkers, C. M. M., additional, Pertijs, J. C. L. M., additional, Swinkels, D. W., additional, Masereeuw, R., additional, Sereno, J., additional, Rodrigues-Santos, P., additional, Vala, H., additional, Rocha-Pereira, P., additional, Fernandes, J., additional, Santos-Silva, A., additional, Teixeira, F., additional, Reis, F., additional, Altuntas, A., additional, Yilmaz, H. R., additional, Uz, E., additional, Demir, M., additional, Gokcimen, A., additional, Bayram, D. S., additional, Aksu, O., additional, Sezer, M. T., additional, Yang, K. H., additional, Jung, Y. J., additional, Kim, D., additional, Lee, A. S., additional, Lee, S., additional, Kang, K. P., additional, Park, S. K., additional, Kim, W., additional, Junglee, N. A., additional, Searell, C. R., additional, Jibani, M. M., additional, Macdonald, J. H., additional, Wu, C.-C., additional, Chen, C.-C., additional, Lu, K.-C., additional, Lin, Y.-F., additional, Estrela, G. R., additional, Wasinski, F., additional, Pereira, R., additional, Malheiros, D., additional, Camara, N. O. S., additional, Araujo, R. C., additional, Ramos, M. F., additional, Passos, C. d. S., additional, Razvickas, C. V., additional, Borges, F., additional, Ormanji, M., additional, Plotnikov, E., additional, Morosanova, M., additional, Pevzner, I., additional, Zorova, L., additional, Manskikh, V., additional, Skulachev, M., additional, Skulachev, V., additional, Zorov, D., additional, Pinto, C. F., additional, and Vattimo, M., additional

Published
2014
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13. AKI - human studies

Author

Kutlay, S., primary, Kurultak, I., additional, Nergizoglu, G., additional, Erturk, S., additional, Karatan, O., additional, Azevedo, P., additional, Pinto, C. T., additional, Pereira, C. M., additional, Marinho, A., additional, Vanmassenhove, J., additional, Hoste, E., additional, Glorieux, G., additional, Dhondt, A., additional, Vanholder, R., additional, Van Biesen, W., additional, Rei, S., additional, Aleksandrova, I., additional, Kiselev, V., additional, Ilynskiy, M., additional, Berdnikov, G., additional, Marchenkova, L., additional, Daher, E. F., additional, Vieira, A. P. F., additional, Souza, J. B., additional, Falcao, F. S., additional, Costa, C. R., additional, Fernandes, A. A. C. S., additional, Mota, R. M. S., additional, Lima, R. S. A., additional, Silva Junior, G. B., additional, Ulusal Okyay, G., additional, Erten, Y., additional, Er, R., additional, Aybar, M., additional, Inal, S., additional, Tekbudak, M., additional, Aygencel, G., additional, Onec, K., additional, Bali, M., additional, Sindel, S., additional, Soto, K., additional, Fidalgo, P., additional, Papoila, A. L., additional, Lentini, P., additional, Zanoli, L., additional, Granata, A., additional, Contestabile, A., additional, Basso, A., additional, Berlingo, G., additional, de Cal, M., additional, Pellanda, V., additional, Dell'Aquila, R., additional, Fortrie, G., additional, Stads, S., additional, van Bommel, J., additional, Zietse, R., additional, Betjes, M. G., additional, Berrada, A., additional, Arias, C., additional, Riera, M., additional, Orfila, M. A., additional, Rodriguez, E., additional, Barrios, C., additional, Peruzzi, L., additional, Chiale, F., additional, Camilla, R., additional, Martano, C., additional, Cresi, F., additional, Bertino, E., additional, Coppo, R., additional, Klimenko, A., additional, Villevalde, S., additional, Efremovtseva, M., additional, Kobalava, Z., additional, Pipili, C., additional, Ioannidou, S., additional, Kokkoris, S., additional, Poulaki, S., additional, Tripodaki, E.-S., additional, Parisi, M., additional, Papastylianou, A., additional, Nanas, S., additional, Wang, Y.-n., additional, Cheng, H., additional, Chen, Y.-p., additional, Wen, Z., additional, Li, X., additional, Shen, P., additional, Zou, Y., additional, Lu, Y., additional, Ma, X., additional, Chen, Y., additional, Ren, H., additional, Chen, X., additional, Chen, N., additional, Yue, T., additional, Elmamoun, S., additional, Wodeyar, H., additional, Goldsmith, C., additional, Abraham, A., additional, Wootton, A., additional, Ahmed, S., additional, Hill, C., additional, Curtis, S., additional, Miller, A., additional, Hine, T., additional, Stevens, K. K., additional, Patel, R. K., additional, Mark, P. B., additional, Delles, C., additional, Jardine, A. G., additional, Wilflingseder, J., additional, Heinzel, A., additional, Mayer, P., additional, Perco, P., additional, Kainz, A., additional, Mayer, B., additional, Oberbauer, R., additional, Huang, T.-M., additional, Wu, V.-C., additional, Park, D. J., additional, Bae, E. J., additional, Kang, Y.-J., additional, Cho, H. S., additional, Chang, S.-h., additional, Stramana, R., additional, Cognolato, D., additional, Baiocchi, M., additional, Chiella, B. M., additional, Pilla, C., additional, Balbinotto, A., additional, Antunes, V. H., additional, Heglert, A., additional, Collares, F. M., additional, Thome, F. S., additional, Gjyzari, A., additional, Thereska, N., additional, Xhango, O., additional, Xue, J., additional, Chen, M. C., additional, Wang, L., additional, Chen, Y. J., additional, Sun, X. Z., additional, An, W. S., additional, Kim, E. S., additional, Son, Y. K., additional, Kim, S. E., additional, Kim, K. H., additional, Oh, Y. J., additional, Tsai, H.-B., additional, Ko, W.-J., additional, Chao, C.-T., additional, Aarnoudse, A.-J. L., additional, Peride, I., additional, Radulescu, D., additional, Niculae, A., additional, Ciocalteu, A., additional, Checherita, A.-I., additional, Kao, C.-C., additional, Wang, C.-Y., additional, Lai, C.-F., additional, Chen, H.-H., additional, Wu, K.-D., additional, Klaus, F., additional, Goldani, J. C., additional, Cantisani, G., additional, Zanotelli, M. L., additional, Carvalho, L., additional, Klaus, D., additional, Garcia, V. D., additional, Keitel, E., additional, Hussaini, S. M., additional, Rao, P. N., additional, Kul, A., additional, Ye, N., additional, Zhang, Y., additional, Baines, R., additional, Westacott, R., additional, Trew, J., additional, Kirtley, J., additional, Selby, N., additional, Carr, S., additional, Xu, G., additional, Steffgen, J., additional, Blaschke, S., additional, Brun-Schulte-Wissing, N., additional, Pagel, P., additional, Huber, F., additional, Mapes, J., additional, Jaehnige, A., additional, Pestel, S., additional, Deray, G., additional, Rouviere, O., additional, Bacigalupo, L., additional, Maes, B., additional, Hannedouche, T., additional, Vrtovsnik, F., additional, Rigothier, C., additional, Billiouw, J.-M., additional, Campioni, P., additional, Marti-Bonmati, L., additional, Gao, Y.-m., additional, Li, D., additional, Woo, S., additional, Lee, J., additional, Noh, H., additional, Kwon, S. H., additional, Han, D. C., additional, Hetherington, L., additional, Valluri, A., additional, McQuarrie, E., additional, Fleming, S., additional, Geddes, C., additional, Bell, S., additional, MacKinnon, B., additional, Patton, A., additional, Sneddon, J., additional, Donnan, P., additional, Vadiveloo, T., additional, Marwick, C., additional, Bennie, M., additional, Davey, P., additional, Yasuda, H., additional, Tsuji, N., additional, Tsuji, T., additional, Iwakura, T., additional, Ohashi, N., additional, Kato, A., additional, Fujigaki, Y., additional, Sasaki, S., additional, Kawarazaki, H., additional, Shibagaki, Y., additional, Kimura, K., additional, Lingaraju, U., additional, Rajanna, S., additional, Radhakrishnan, H., additional, Parekh, A., additional, Sreedhar, C. G., additional, Sarvi, R., additional, Rainone, F., additional, Merlino, L., additional, Ritchie, J. P., additional, Kalra, P. A., additional, Jacinto, C. N., additional, Abreu, K. L. S., additional, Neves, M., additional, Baptista, J. P., additional, Rodrigues, L., additional, Pinho, J., additional, Teixeira, L., additional, Pimentel, J., additional, Gonzalez Sanchidrian, S., additional, Rangel Hidalgo, G., additional, Cebrian Andrada, C., additional, Deira Lorenzo, J., additional, Marin Alvarez, J., additional, Garcia-Bernalt Funes, V., additional, Gallego Dominguez, S., additional, Labrador Gomez, P., additional, Castellano Cervino, I., additional, Novillo Santana, R., additional, Gomez-Martino Arroyo, J., additional, Kim, Y., additional, Choi, B. S., additional, Kim, Y. o., additional, Yoon, S. A., additional, Lin, M.-C., additional, Wang, W.-J., additional, Melo, M. J., additional, Lopes, J. A., additional, Raimundo, M., additional, Fragoso, A., additional, Antunes, F., additional, Martin-Moreno, P. L., additional, Varo, N., additional, Restituto, P., additional, Sayon-Orea, C., additional, Garcia-Fernandez, N., additional, Leite Filho, N. C. V., additional, Souza, L. E. O., additional, Cavalcante, R. M., additional, Morais, B. M., additional, Leite, T. T., additional, Silva, S. L., additional, Kubrusly, M., additional, Jung, Y. S., additional, Kim, Y. N., additional, Shin, H. S., additional, Rim, H., additional, Bentall, A., additional, Al-Baaj, F., additional, Williamson, S., additional, Cheshire, S., additional, Jelakovic, M., additional, Ivkovic, V., additional, Laganovic, M., additional, Karanovic, S., additional, Pecin, I., additional, Premuzic, V., additional, Vukovic Lela, I., additional, Vrdoljak, A., additional, Fucek, M., additional, Cvitkovic, A., additional, Juric, D., additional, Bozina, N., additional, Bitunjac, M., additional, Leko, N., additional, Abramovic Baric, M., additional, Matijevic, V., additional, Jelakovic, B., additional, Ullah, A., additional, Exarchou, K., additional, Archer, T., additional, Anijeet, H., additional, Brown, R., additional, Cheng, Y.-p., additional, Rocha, J. C. G., additional, Gushiken da Silva, T., additional, de Castro, P. F., additional, Kioroglo, P. S., additional, Branco Martins, J. P., additional, Tzanno-Martins, C., additional, Biesenbach, P., additional, Luf, F., additional, Fleischmann, E., additional, Grunberger, T., additional, Druml, W., additional, Gaipov, A., additional, Turkmen, K., additional, Toker, A., additional, Solak, Y., additional, Cicekler, H., additional, Ucar, R., additional, Kilicaslan, A., additional, Gormus, N., additional, Tonbul, H. Z., additional, Yeksan, M., additional, Turk, S., additional, Monteburini, T., additional, Cenerelli, S., additional, Santarelli, S., additional, Boggi, R., additional, Tazza, L., additional, Bossola, M., additional, Ferraresi, M., additional, Merlo, I., additional, Giovinazzo, G., additional, Quercia, A. D., additional, Gai, M., additional, Leonardi, G., additional, Anania, P., additional, Guarena, C., additional, Cantaluppi, V., additional, Pacitti, A., additional, Biancone, L., additional, Hissa, P. N. G., additional, Daher, E. D. F., additional, Liborio, A. B., additional, Thereza, B. M. F., additional, Mendes, C. C. P., additional, and Sousa, A. R. O., additional

Published
2013
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14. AKI - experimental models

Author

Lai, C.-F., primary, Lin, S.-L., additional, Chiang, W.-C., additional, Chen, Y.-M., additional, Kuo, M.-L., additional, Tsai, T.-J., additional, Hwang, H. S., additional, Choi, Y. A., additional, Park, K. C., additional, Yang, K. J., additional, Choi, H. S., additional, Kim, S. H., additional, Lee, S. J., additional, Chang, Y. K., additional, Kim, S. Y., additional, Yang, C. W., additional, Xiujuan, Z., additional, Yoshimura, R., additional, Matsuyama, M., additional, Chargui, J., additional, Touraine, J.-L., additional, Yoshimura, N., additional, Zulkarnaev, A. B., additional, Vasilenko, I. A., additional, Artemov, D. V., additional, Vatazin, A. V., additional, Park, S. K., additional, Kang, K. P., additional, Lee, S., additional, Kim, W., additional, Schneider, R., additional, Betz, B., additional, Moller-Ehrlich, K., additional, Wanner, C., additional, Sauvant, C., additional, Park, C. W., additional, Sohotnik, R., additional, Nativ, O., additional, Abbasi, A., additional, Awad, H., additional, Frajewicki, V., additional, Armaly, Z., additional, Heyman, S. N., additional, Abassi, Z., additional, Chen, P. Y., additional, Chen, B. L., additional, Yang, C. C., additional, Chiang, C. K., additional, Liu, S. H., additional, Abozahra, A. E., additional, Abd-Elkhabir, A. A., additional, Shokeir, A., additional, Hussein, A., additional, Awadalla, A., additional, Barakat, N., additional, Abdelaziz, A., additional, Yamaguchi, J., additional, Tanaka, T., additional, Eto, N., additional, Nangaku, M., additional, Quiros, Y., additional, Lopez-Hernandez, F. J., additional, Perez de Obanos, M. P., additional, Ruiz, J., additional, Lopez-Novoa, J. M., additional, Shin, H.-S., additional, Kim, M.-J., additional, Choi, Y.-J., additional, Ryu, E.-S., additional, Choi, H.-S., additional, Kang, D.-H., additional, Jankauskas, S. S., additional, Pevzner, I. B., additional, Zorova, L. D., additional, Babenko, V. A., additional, Morosanova, M. A., additional, Plotnikov, E. Y., additional, Zorov, D. B., additional, Huang, C.-Y., additional, Huang, T.-M., additional, Wu, V.-C., additional, Young, G.-H., additional, Chupyrkina, A. A., additional, Zorov, S. D., additional, Grande, J. P., additional, Hartono, S. P., additional, Knudsen, B. E., additional, Mederle, K., additional, Castrop, H., additional, Hocherl, K., additional, Iwakura, T., additional, Fujikura, T., additional, Ohashi, N., additional, Yasuda, H., additional, Fujigaki, Y., additional, Matsui, I., additional, Hamano, T., additional, Inoue, K., additional, Obi, Y., additional, Nakano, C., additional, Kusunoki, Y., additional, Tsubakihara, Y., additional, Rakugi, H., additional, Isaka, Y., additional, Shimomura, A., additional, Wallentin Guron, C., additional, Nguy, L., additional, Lundgren, J., additional, Grimberg, E., additional, Kashioulis, P., additional, Guron, G., additional, DiBona, G. F., additional, Nedergaard Mikkelsen, M., additional, Marcussen, N., additional, Saeed, A., additional, Edvardsson, K., additional, Lindberg, K., additional, Larsson, T., additional, Ito, K., additional, Nakashima, H., additional, Watanabe, M., additional, Abe, Y., additional, Ogahara, S., additional, Saito, T., additional, Albertoni, G., additional, Borges, F., additional, Schor, N., additional, Beresneva, O. N., additional, Parastayeva, M. M., additional, Kucher, A. G., additional, Ivanova, G. T., additional, Shved, N., additional, Rybakova, M. G., additional, Kayukov, I. G., additional, Smirnov, A. V., additional, Chen, J.-F., additional, Ni, H.-F., additional, Pan, M.-M., additional, Liu, H., additional, Xu, M., additional, Zhang, M.-H., additional, Liu, B.-C., additional, Kim, Y., additional, Choi, B. S., additional, Kim, Y. S., additional, Han, J. S., additional, Reis, L. A., additional, Christo, J. S., additional, Simoes, M. d. J., additional, Mulay, S. R., additional, Santhosh Kumar, V. R., additional, Kulkarni, O. P., additional, Darisipudi, M., additional, Lech, M., additional, Anders, H.-J., additional, Silachev, D. N., additional, Sola, A., additional, Jung, M., additional, Ventayol, M., additional, Mastora, C., additional, Buenestado, S., additional, Hotter, G., additional, Rong, S., additional, Shushakova, N., additional, Wensvoort, G., additional, Haller, H., additional, Gueler, F., additional, Morais, C., additional, Vesey, D. A., additional, Johnson, D. W., additional, Gobe, G. C., additional, Godo, M., additional, Kaucsar, T., additional, Revesz, C., additional, Hamar, P., additional, Cheng, Q., additional, Wen, J., additional, Ma, Q., additional, Zhao, J., additional, Castellano, G., additional, Stasi, A., additional, Di Palma, A. M., additional, Gigante, M., additional, Netti, G. S., additional, Curci, C., additional, Intini, A., additional, Divella, C., additional, Prattichizzo, C., additional, Fiaccadori, E., additional, Pertosa, G., additional, Grandaliano, G., additional, Gesualdo, L., additional, Wei, Q. W., additional, Jing, Q. Q., additional, Ying, N. J., additional, Dong, Q. Z., additional, Yong, G., additional, Pulkova, N. V., additional, Sukhikh, G. T., additional, Kim, S., additional, Lee, J., additional, Nam, N. J., additional, Na, K. Y., additional, Ma, S. K., additional, Joo, S. Y., additional, Kim, C. S., additional, Choi, J. S., additional, Bae, E. H., additional, Kim, S. W., additional, Cernaro, V., additional, Medici, M. A., additional, Donato, V., additional, Trimboli, D., additional, Lorenzano, G., additional, Santoro, D., additional, Montalto, G., additional, Buemi, M., additional, Longo, V., additional, Segreto, H. R. C., additional, Almeida, W., additional, Ramos, M. F., additional, Gomes, L., additional, Razvickas, C., additional, Gutberlet, M., additional, Meier, M., additional, Mengel, M., additional, Wacker, D., additional, Hueper, K., additional, Uzum, A., additional, Ersoy, R., additional, Cakalagaoglu, F., additional, Karaman, M., additional, Kolatan, E., additional, Sahin, O., additional, Yilmaz, O., additional, Cirit, M., additional, Inal, S., additional, Koc, E., additional, Okyay, G. U., additional, Pasaoglu, O., additional, Gonul, I., additional, Oyar, E., additional, Pasaoglu, H., additional, Guz, G., additional, Sabbatini, M., additional, Rossano, R., additional, Andreucci, M., additional, Pisani, A., additional, Riccio, E., additional, Choi, D. E., additional, Jeong, J. Y., additional, Kim, S. S., additional, Na, K.-R., additional, Lee, K. W., additional, Shin, Y. T., additional, Silva, A. F., additional, Teixeira, V. C., additional, Meszaros, K., additional, Koleganova-Gut, N., additional, Schaefer, F., additional, Ritz, E., additional, Walacides, D., additional, Ruskamp, N., additional, Schiffer, M., additional, Marom, O., additional, Haick, H., additional, Nakhoul, F., additional, Lv, L.-L., additional, Tang, R.-N., additional, Zhang, J.-D., additional, Ma, K.-L., additional, Chen, P.-S., additional, Ko, W.-J., additional, Misiara, G. P., additional, Coimbra, T. M., additional, Silva, G. E. B., additional, Costa, R. S., additional, Francescato, H. D. C., additional, Neto, M. M., additional, Dantas, M., additional, Olauson, H., additional, Amin, R., additional, Ponnusamy, A., additional, Goetz, R., additional, Mohammadi, M., additional, Canfield, A., additional, Kublickiene, K., additional, Rodriguez, J., additional, Reyes, E. P., additional, Cortes, P. P., additional, Fernandez, R., additional, Yoon, H. E., additional, Koh, E. S., additional, Chung, S., additional, Shin, S. J., additional, Pazzano, D., additional, Lupica, R., additional, Torre, F., additional, Costantino, G., additional, Prieto, M., additional, Gonzalez-Buitrago, J. M., additional, Lopez-Hernandez, F., additional, Morales, A. I., additional, Vicente-Vicente, L., additional, Ferreira, L., additional, Simoes, M. J., additional, Passos, C. d., additional, Schor, N. S., additional, Shimizu, M. H. M., additional, Canale, D., additional, de Braganca, A. C., additional, Andrade, L., additional, Luchi, W. M., additional, Seguro, A. C., additional, Goncalves, J., additional, Volpini, R. A., additional, Garrido, P., additional, Fernandes, J., additional, Ribeiro, S., additional, Vala, H., additional, Parada, B., additional, Alves, R., additional, Belo, L., additional, Costa, E., additional, Santos-Silva, A., additional, and Reis, F., additional

Published
2013
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16. Acute kidney injury - Experimental models

Author

Nagasaki, Y., primary, Yoshitomi, T., additional, Hirayama, A., additional, Schock-Kusch, D., additional, Xie, Q., additional, Shulhevich, Y., additional, Hesser, J., additional, Stsepankou, S., additional, Koenig, S., additional, Heinrich, R., additional, Pill, J., additional, Gretz, N., additional, Efrati, S., additional, Berman, S., additional, Abu-Hamad, R., additional, Siman-Tov, Y., additional, Weissgarten, J., additional, Kimura, T., additional, Takabatake, Y., additional, Takahashi, A., additional, Kaimori, J.-y., additional, Matsui, I., additional, Namba, T., additional, Kitamura, H., additional, Niimura, F., additional, Matsusaka, T., additional, Rakugi, H., additional, Isaka, Y., additional, Ito, K., additional, Watanabe, M., additional, Nakashima, H., additional, Abe, Y., additional, Ifuku, M., additional, Nishimura, S., additional, Saito, T., additional, Mulay, S. R., additional, Thomasova, D., additional, Ryu, M., additional, Anders, H.-J., additional, Nakayama, Y., additional, Ueda, S., additional, Yamagishi, S.-i., additional, Ando, R., additional, Kaida, Y., additional, Iwatani, R., additional, Fujimi, A., additional, Fukami, K., additional, Okuda, S., additional, Shin, Y. T., additional, Jeong, J. Y., additional, Jang, W. I., additional, Chung, S., additional, Choi, D. E., additional, Na, K. R., additional, Lee, K. W., additional, Mugitani, N., additional, Shimizu, Y., additional, Satake, K., additional, Suzuki, Y., additional, Horikoshi, S., additional, Tomino, Y., additional, Schneider, R., additional, Meusel, M., additional, Betz, B., additional, Wanner, C., additional, Koepsell, H., additional, Sauvant, C., additional, Dursun, B., additional, Abban, G., additional, Kucukatay, V., additional, Tufan, L., additional, Dodurga, Y., additional, Guclu, A., additional, Gok, D., additional, Vicente-Vicente, L., additional, Sanchez-Gonzalez, P. D., additional, Prieto, M., additional, Lopez-Novoa, J. M., additional, Lopez-Hernandez, F. J., additional, Morales, A. I., additional, Torres, A., additional, Dnyanmote, A., additional, Wu, W., additional, Nigam, S., additional, Wystrychowski, A., additional, Wystrychowski, W., additional, Kolodziejczyk, A., additional, Obuchowicz, E., additional, Wiecek, A., additional, Reis, L. A., additional, Borges, F. T., additional, Simoes, M. d. J., additional, Schor, N., additional, Mesnard, L., additional, Rafat, C., additional, Vandermeersch, S., additional, Nochy, D., additional, Garcon, L., additional, Callard, P., additional, Jouanneau, C., additional, Verpont, M.-C., additional, Hertig, A., additional, Rondeau, E., additional, Grosjean, F., additional, Torreggiani, M., additional, Esposito, V., additional, Mangione, F., additional, Serpieri, N., additional, Villa, L., additional, Sileno, G., additional, Marchi, G., additional, Fasoli, G., additional, Esposito, C., additional, Dal Canton, A., additional, Sancho-Martinez, S., additional, Striker, G., additional, Vlassara, H., additional, Zheng, F., additional, Park, D. J., additional, Kim, J. H., additional, Jung, M. H., additional, Seo, J. W., additional, Kim, H.-j., additional, Chang, S.-H., additional, Han, B.-G., additional, Yang, J.-W., additional, Yu, J.-M., additional, Choi, S.-O., additional, Christo, J. S., additional, Rusai, K., additional, Prokai, A., additional, Szebeni, B., additional, Meszaros, K., additional, Fekete, A., additional, Treszl, A., additional, Vannay, A., additional, Muller, V., additional, Reusz, G., additional, Heemann, U., additional, Tulassay, T., additional, Lutz, J., additional, Szabo, A. J., additional, Ranghino, A., additional, Bruno, S., additional, Grange, C., additional, Dolla, C., additional, Cantaluppi, V., additional, Biancone, L., additional, Tetta, C., additional, Segoloni, G. P., additional, Camussi, G., additional, Pinto, V., additional, Teixeira, V., additional, Almeida, W., additional, Fujikura, T., additional, Sun, Y., additional, Iwakura, T., additional, Yasuda, H., additional, Fujigaki, Y., additional, Simone, S., additional, Rascio, F., additional, Loverre, A., additional, Cosola, C., additional, Cariello, M., additional, Castellano, G., additional, Ditonno, P., additional, Schena, F. P., additional, Gesualdo, L., additional, Grandaliano, G., additional, Pertosa, G., additional, Choi, J.-Y., additional, Kim, J., additional, Jin, D.-C., additional, Cha, J.-H., additional, Kaynar, K., additional, Aliyazicioglu, R., additional, Ersoz, S., additional, Ulusoy, S., additional, Al, S., additional, Ozkan, G., additional, Cansiz, M., additional, Fuchs, T. C., additional, Emde, B., additional, Czasch, S., additional, von Landenberg, F., additional, Hewitt, P., additional, Abu-Salah, N., additional, Bishara, B., additional, Awad, H., additional, Ghrayeb, N., additional, Assady, S., additional, Armaly, Z., additional, Better, O., additional, and Abassi, Z., additional

Published
2011
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17. Intraglomerular basement membrane translocation of immune complex (IC) in the development of passive in situ IC nephritis of rats

Author

Fujigaki, Y., Nagase, M., and Honda, N.

Subjects
Male, Nephritis, urogenital system, Kidney Glomerulus, Fluorescent Antibody Technique, Antigen-Antibody Complex, Basement Membrane, Rats, Microscopy, Electron, Microscopy, Fluorescence, Albuminuria, Animals, Rats, Wistar, Microscopy, Immunoelectron, Research Article
Abstract

A study was performed to elucidate the mechanisms of charge-based immune complex nephritis. A chronological observation after induction of nephritis was made by immunoelectron microscopy to clarify whether antigen (Ag) remains in association with antibody (Ab) and C3 during the translocation through the glomerular basement membrane (GBM). Fifteen minutes after intrarenal perfusion with cationized ferritin (pI > 10.0) as Ag, followed by injection of rabbit anti-ferritin Ab, deposition of subendothelial Ag-Ab-C3 complexes was observed. Between 2 hours and 1 day, a large number of Ag in close association with Ab was noted in the lamina densa, but only a small amount of C3 was detectable. During this time Ag and Ab in the subendothelial region gradually decreased. However, C3 reappeared in the subepithelial region together with the Ag-Ab complex after 1 day, and the subendothelial C3 significantly decreased. At 2 hours and day 1, the distributions of Ag and Ab in the GBM were similar in immersion-fixed kidneys regardless of the preperfusion with phosphate-buffered saline. On the other hand, the passage of Ag across the lamina densa was delayed in the experimental rats as compared with the controls. Significant albuminuria also appeared on day 1. Despite the general concept that Ab binding to cationized Ag results in low avidity immune complex, cationized Ag translocated across the GBM in close association with Ab. The complement was activated biphasically in the subendothelial and in the subepithelial space. The subendothelial complement activation may have contributed to the translocation of immune complex.

Published
1993

34. Cytokines and cell cycle regulation in the fibrous progression of crescent formation in antiglomerular basement membrane nephritis of WKY rats.

Author

Fujigaki, Yoshihide, Sun, Di, Fujimoto, Taiki, Yonemura, Katsuhiko, Morioka, Tetsuo, Yaoita, Eishin, Hishida, Akira, Fujigaki, Y, Sun, D F, Fujimoto, T, Yonemura, K, Morioka, T, Yaoita, E, and Hishida, A

Abstract

Cytokines may regulate cell proliferation by cell-cycle-regulatory proteins, in which cyclin-dependent kinase inhibitors (CDKI) inhibit cell proliferation. We investigated whether CDKI p21 or p27, both of which are potentially regulated by transforming growth factor (TGF)-β, a key cytokine in fibrogenesis, are involved together with TGF-β and/or platelet-derived growth factor (PDGF) in the fibrous progression of glomerular crescent formation and examined the sequential change in the cell type and the cellular background of myofibroblasts in crescent formation. Crescentic glomerulonephritis (GN) was induced by i.v. injection of rabbit anti-rat glomerular basement membrane antiserum in WKY rats. Animals were killed 1, 2, 3 and 4 weeks after the induction of GN, and their kidneys were processed for immunohistochemical examination. After 1 week more than 85% of glomeruli showed cellular crescents, which became fibrocellular with decreased cellularity by 4 weeks. ED 1-positive macrophages were components of crescent cells in about 44% at 1–2 weeks, and this proportion declined markedly afterwards. Alpha smooth muscle actin (alpha SMA, a marker for myofibroblasts)-positive cells were found in Bowman's epithelial cells (BEP) and in some crescent cells at 1 week, becoming major components of crescent cells by 4 weeks (about 40%). It was 2 weeks before invasion of alpha SMA-positive interstitial cells into glomeruli was evident. PDGF-B and PDGF receptor β-positive cells, indicating possible targets for PDGF, were found in BEP adjoining crescent formation almost exclusively from 1 to 2 weeks. By contrast, both TGF-β receptor types I- and II-positive cells, indicating possible effectors for TGF-β, were found in BEP and crescent formation, and the percentage of these in the crescent formation did not change until 4 weeks (about 32%). Cells with positive immunostaining for proliferating cell nuclear antigen and cyclin A, markers for cell proliferation, in the crescent formation peaked in number and proportion at 1–2 weeks, then decreased. In contrast, cells with positive immunostaining for p21 and p27, CDKI, were sparse at 1 week, and then increased markedly in number and in proportion, peaking at 3 (39.6%) or 2–3 weeks (about 25–30%), respectively. The present study demonstrates that restrained expression or a transient increase in p21 and p27 may be associated with proliferation or with inhibited proliferation of crescent cells, most of which are macrophages and myofibroblasts. The action of PDGF and TGF-β may contribute to the recruitment of myofibroblasts into the crescent. The action of TGF-β on crescent cells might be linked to the expression of p21 and/or p27. [ABSTRACT FROM AUTHOR]

Published
2001
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35. Sequence of events in the glomerular capillary wall at the onset of proteinuria in passive Heymann nephritis.

Author

Fujigaki, Yoshihide, Batsford, Stephen, Yamashita, Fuyuki, Yonemura, Katsuhiko, Hishida, Akira, Kawachi, Hiroshiy, Shimizu, Fujio, Vogt, Arnold, Fujigaki, Y, Batsford, S, Yamashita, F, Yonemura, K, Hishida, A, Kawachi, H, Shimizu, F, and Vogt, A

Abstract

Proteinuria in passive Heymann nephritis (PHN) results from complement-mediated glomerular injury, since complement depletion with cobra venom factor (CVF) prevents proteinuria. However, there are no comprehensive morphological studies identifying the sites of injury leading to onset of proteinuria. To address this issue, we attempted to locate sites of injury involved in the onset of proteinuria in PHN. PHN was induced in intact Munich-Wistar rats (PHN-rats, examined at days 3, 5, and 7) and in complement-depleted rats (CVF treated, PHN-CVF-rats, examined at days 3 and 5). The distribution of endogenous albumin in the glomerular basement membrane (GBM) was studied in in situ drip-fixed glomeruli using immunogold immunocytochemistry, and glomerular anionic sites were visualized by polyethyleneimine staining. In addition, the ultrastructural localization of an epitope recognized by a proteinuria-inducing monoclonal antibody (called 5-1-6) directed against the slit diaphragm was examined. Significant proteinuria was seen in intact PHN-rats, starting at day 5. The intensity of gold labeling for endogenous albumin was significantly increased at the outermost site of the GBM (GBM interfacing foot process and the filtration slit, designated area O) at day 3 in both PHN-rats and PHN-CVF-rats in comparison to untreated controls. At day 5, labeling for albumin in area O was decreased in PHN-rats, but not in PHN-CVF-rats, where it was then higher; in PHN-rats, some areas between epithelial cells and subepithelial deposits were almost free of albumin labeling at day 7. There was no evidence of epithelial cell detachment in any group at day 5, but on day 7 limited focal detachment was seen exclusively in PHN-rats. In proteinuric rats, amorphous material that stained for albumin could be seen in the urinary space, without any exocytosis of labeling by glomerular epithelial cells. A significant reduction of intensity of staining for anionic sites was seen in parallel in both groups, but only in the regions of the lamina rara externa adjacent to subepithelial deposits. This local loss of charge might contribute to enhanced permeability to albumin in both PHN- and PHN-CVF-rats. Changes in the appearance of the filtration slits and in the density and distribution of antigen recognised by monoclonal antibody 5-1-6 were similar in PHN- and PHN-CVF-rats at day 5. Complement depletion prevented neither the reduction in anionic sites of the GBM nor the changes in the slit diaphragm observed. These data suggest that albumin leakage between the epithelial cell and the GBM (area O) could occur in PHN-rats, perhaps as a result of epithelial foot-process changes. This may be the final link in the chain of events responsible for the onset of proteinuria in PHN. [ABSTRACT FROM AUTHOR]

Published
2001
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36. Anti-DNA antibody derived from a systemic lupus erythematosus (SLE) patient forms histone-DNA-anti-DNA complexes that bind to rat glomeruli <em>in vivo</em>.

Author

Morioka, T., Fujigaki, Y., Batsford, S. R., Woitas, R., Oite, T., Shimizu, F., and Vogt, A.

Subjects
*IMMUNOGLOBULINS, *HISTONES, *ELECTRON microscopes, *DNA, *GLOMERULAR filtration rate, *KIDNEY function tests
Abstract

Histone can mediate the binding of both free DNA and DNA complexed to anti-DNA antibody to the glomerular capillary wall. We tested whether preformed histone--DNA--anti-DNA immune complexes (IC) could bind to the glomerular capillary wall. The immune complex, generated with anti-DNA antibody derived from an SLE patient and excess of 125I-DNA followed by digestion with DNase, was mixed with histones. The complex containing 4 μg DNA was injected via the aorta into the left kidney of rats. At 15 min, 1.3% of the histone-DNA--anti-DNA antibody complex bound (measured as 125I-DNA), when histone was omitted less than 0.1% of the DNA anti-DNA antibody complex bound. By immunofluorescence human immunoglobulins and histones, representing the IC, could be observed in a capillary pattern; but no complement deposition was detected. Electron microscopy revealed discrete, electron dense deposits in a subendothelial, subepithelial and mesangial localization at 15 min. These results provide direct evidence that antibodies from serum of SLE patients can form soluble histone-DNA--anti-DNA immune complexes that bind to the glomerular capillary wall in vivo. [ABSTRACT FROM AUTHOR]

Published
1996
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40. Recovery from Hemodialysis Therapy in a Patient with Renal Cholesterol Crystal Embolism

Author

Kato, A., Ohtsuji, A., Terada, T., Goto, T., Fukasawa, H., Yasuda, H., Togawa, A., Fujimoto, T., Suzuki, H., Fujigaki, Y., Yamamoto, T., Yonemura, K., and Hishida, A.

Abstract

AbstractThe prognosis of renal cholesterol crystal embolism (CCE) is poor, and many patients progressively develop to the end-stage of chronic renal failure. We herein experienced a 66-year-old male patient who recovered from hemodialysis (HD) shortly after an amputation of inflammatory toes. The patient complained of painful digital cyanosis at bilateral toes and livedo reticularis at right lower leg 4 weeks following aortic angiography. Laboratory examinations revealed eosinophilia and overt proteinuria (3.0 g/day). His serum creatinine level increased from 2.18 to 8.57 mg/dl over 6 weeks, and HD treatment was started. Treatment with simvastatin (5 mg/day) did not reverse renal failure and hypereosinophilia, but the amputation of right gangrene toes promptly increased urine output and eosinophilia completely disappeared concomitantly with a decline of C-reactive protein from 9.7 to 0.7 mg/dl. Serum creatinine level was also reduced to 3.46 mg/dl, and he eventually stopped HD totally after 32 sessions. This case suggested that the surgical amputation promptly recovered renal function. Reversal of inflammation may be more effective than lipid-lowering therapy for renal failure in our patient.Copyright © 2002 S. Karger AG, Basel

Published
2002

41. Mechanisms and Kinetics of Bowman’s Epithelial-Myofibroblast Transdifferentiation in the Formation of Glomerular Crescents

Author

Fujigaki, Y., Sun, D.F., Fujimoto, T., Suzuki, T., Goto, T., Yonemura, K., Morioka, T., Yaoita, E., and Hishida, A.

Abstract

AbstractBackground: We investigated the mechanisms and kinetics of Bowman’s epithelial-myofibroblast transdifferentiation in the formation of glomerular crescents.Methods: Crescentic glomerulonephritis was induced by i.v. injection of rabbit anti-rat glomerular basement membrane antiserum in WKY rats. Results: Cellular crescents (83.5% of glomeruli) were first observed at day 7 after disease induction. Immunostaining of alpha-smooth muscle actin (alpha-SMA), as a marker for the myofibroblast phenotype, was found in some periglomerular regions as early as day 3, when it was also seen in parietal epithelial cells (PEC) of Bowman’s capsule at day 5 and in crescent formation at day 7. Proliferation marker Ki67-positive PEC was found at day 3, and double Ki67- and alpha-SMA-positive PEC could be seen at day 5. The migratory figure of PEC with the expression of alpha-SMA was found by immunoelectron microscopy. At day 7, some crescent cells were stained positive for PEC marker, protein gene product 9.5, in association with alpha-SMA or Ki67. Expression of transforming growth factor (TGF)-β receptor types I and II, as well as platelet-derived growth factor (PDGF) receptor β and PDGF-B increased in PEC as early as day 3. At day 5 marked deposition of cellular and common fibronectin, but not other extracellular matrix components examined was found in Bowman’s spaces where ED 1-positive macrophages infiltrated. Conclusions: PEC may be stimulated to proliferate and/or transdifferentiate into myofibroblast phenotype possibly by action of TGF-β and PDGF and/or binding of fibronectin to PEC, then migrate and/or proliferate, participating in glomerular crescents.Copyright © 2002 S. Karger AG, Basel

Published
2002

42. Immunoelectron microscopic study on type I, II and III TGF-beta receptors on visceral glomerular epithelial cells in relation to glomerular basement membrane alterations in proteinuric rats.

Author

Fujigaki, Y, Watanabe, T, Ikegaya, N, Yonemura, K, Sun, D F, Hishida, A, Yamamoto, T, Kojima, K, and Nagase, M

Abstract

Transforming growth factor (TGF)-beta is a regulator of extracellular matrix accumulation. Both TGF-beta receptors, type I (TbetaRI) and type II (TbetaRII), may be required for signal transduction in the TGF-beta pathway. The aim of this study was to investigate the relationship between the TGF-beta pathways and glomerular basement membrane (GBM) accumulation in vivo.

Published
2000
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44. Hyponatremia in a patient with scleroderma renal crisis: a potential role of activated renin-angiotensin system

Author

Fukasawa Hirotaka, Furuya Ryuichi, Ishigaki Sayaka, Kinoshita Naoko, Isobe Shinsuke, and Fujigaki Yoshihide

Subjects
Hyponatremia, Renin-angiotensin system, Scleroderma renal crisis, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Scleroderma renal crisis is an important complication of scleroderma (systemic sclerosis) that is associated with significant morbidity and mortality. On the other hand, hyponatremia has never been reported in patients with scleroderma renal crisis. Case presentation A 66-year-old man with scleroderma was admitted to our hospital for an evaluation of renal dysfunction and extreme hypertension. The laboratory evaluation revealed remarkably high plasma renin activity in association with microangiopathic hemolytic anemia, and the anti-RNA polymerase III antibody assessment was positive. The patient was diagnosed with scleroderma renal crisis and was started treatment with enalapril maleate, an angiotensin-converting enzyme inhibitor. During hospitalization, the patient developed symptomatic hyponatremia three times and each laboratory analysis revealed improperly high levels of antidiuretic hormone without signs of extracellular fluid volume depletion as well as remarkably high plasma renin activities and angiotensin levels. However, hyponatremia has not been demonstrated to occur as a result of combined therapy with candesartan cilexetil, an angiotensin II receptor blocker, and aliskiren fumarate, a direct renin inhibitor. The plasma renin activities and angiotensin levels were normalized and the renal function was maintained after treatment. Conclusions To our best knowledge, this is the first documented case of scleroderma renal crisis complicated with hyponatremia. This report also suggests that the activated renin-angiotensin system may play a role in the development of hyponatremia and that hyponatremia should be taken into consideration as a rare but possible complication associated with screloderma renal crisis.

Published
2012
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46. Public participation in the setting of research and innovation agenda: virtues and challenges from a philosophical perspective

Author

Stéphanie Ruphy, République des savoirs, UAR 3608, Y. Fujigaki, S. Laugier et S. Lechevalier, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon, Fujigaki, Y., Laugier, S., and Lechevalier, S.

Subjects
0303 health sciences, 05 social sciences, Perspective (graphical), [SHS.PHIL]Humanities and Social Sciences/Philosophy, Resistance (psychoanalysis), 16. Peace & justice, 050905 science studies, Institutional support, [SHS]Humanities and Social Sciences, 03 medical and health sciences, [SHS.PHIL] Humanities and Social Sciences/Philosophy, Political science, Public participation, Citizen science, Engineering ethics, 0509 other social sciences, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

Inclusiveness in scientific research and innovation is more and more valued by many scientific institutions, as attested by the increasing visibility and displayed institutional support in favour of “citizen science”, “participatory science” and other forms of science involving in one way or another lay people. Could science benefit from being more inclusive and, in turn, could society benefit from a more inclusive science? The general aim of this chapter is to investigate how public participation may challenge and renew traditional epistemological and organisational features of scientific research, thereby providing a basis to assess the merits of public participation in this sphere. It will in particular offer epistemological arguments disqualifying common sources of resistance to public participation and discuss pending issues that need to be addressed if one wants to make a strong case in favour of public participation in science. In doing so, the chapter will (hopefully) contribute to going beyond an isolationist, decontextualised view of scientific developments and redefine the role that society is expected to play in new models of scientific research and innovation aiming at a better alignment of its outputs with society needs and interests.

Published
2019

47. Fanconi syndrome and renal tubular necrosis in patients following ingestion of potentially contaminated red yeast rice supplement: Two case reports.

Author

Yoshikawa Y, Anzai H, Odajima K, Asakawa S, Arai S, Yamazaki O, Tamura Y, Ohashi R, Shibata S, and Fujigaki Y

Subjects
Humans, Male, Middle Aged, Kidney Tubular Necrosis, Acute chemically induced, Kidney Tubular Necrosis, Acute pathology, Biological Products adverse effects, Dietary Supplements adverse effects, Food Contamination, Adult, Fanconi Syndrome chemically induced, Fanconi Syndrome pathology
Abstract

We present two cases of middle-aged men who developed Fanconi syndrome and renal dysfunction after consuming "foods with functional claims (FFC)" containing red yeast rice. In the first case, the patient had consumed an FFC for 1 year and another FFC suspected to have contained nephrotoxin for 3 weeks; kidney biopsy performed during the acute phase of renal injury showed severe acute tubular necrosis and tubular cell regeneration. He achieved near-complete recovery 40 days after the FFC was discontinued. In the second case, the patient had consumed FFC for 4 years and stopped 70 days prior to presentation; kidney biopsy revealed significant tubular recovery, persistent tubular injuries, and interstitial fibrosis. Although the manifestations of Fanconi syndrome subsided, mild renal dysfunction persisted. These cases suggest that FFC with nephrotoxins may induce Fanconi syndrome owing to acute tubular necrosis. Recovery is possible after discontinuing the FFC; while short-term ingestion of FFC allows for tubular regeneration, its long-term ingestion may cause irreversible damage and lead to chronic kidney disease. Long-term follow-up is crucial for preventing further renal deterioration., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Published
2024
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48. A Rare Case of Sporadic Medullary Cystic Kidney Disease with Rapidly Progressive Renal Dysfunction and Renal Enlargement Complicated by Idiopathic Nodular Glomerulosclerosis.

Author

Yamashiro Y, Ohashi N, Iwakura T, Isobe S, Fujikura T, Fujigaki Y, Shimizu A, and Yasuda H

Subjects
Humans, Male, Aged, 80 and over, Kidney Diseases, Cystic complications, Kidney Diseases, Cystic diagnosis, Kidney pathology, Glomerulonephritis complications, Glomerulonephritis diagnosis, Glomerulonephritis etiology, Glomerulonephritis pathology, Disease Progression
Abstract

An 81-year-old man with hypertension and a history of smoking presented with renal enlargement and progressive renal dysfunction despite no family history of kidney disease. A renal biopsy revealed diffuse tubular, dilated, and atrophic distal tubules with cystic formation and thin irregularities in the tubular basement membrane. Although no known genetic abnormalities were detected, the patient was diagnosed with medullary cystic kidney disease (MCKD). In addition, idiopathic nodular glomerulosclerosis, which is characterized by significant mesangial expansion and accentuated glomerular nodularity and is associated with hypertension and cigarette smoking, was identified as a complication of MCKD. We herein report a rare case of sporadic MCKD with idiopathic nodular glomerulosclerosis.

Published
2024
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49. Coexistence of Sjögren's Syndrome-associated Interstitial Nephritis and Hypokalemic Nephropathy in a Patient with Distal Renal Tubular Acidosis: A Case Report.

Author

Matsui R, Gojo M, Odajima K, Asakawa S, Arai S, Yamazaki O, Tamura Y, Numakura S, Oshima Y, Ohashi R, Shibata S, and Fujigaki Y

Abstract

A 42-year-old woman presented with muscle weakness and hypokalemic distal renal tubular acidosis (dRTA). Investigations revealed concurrent Sjögren's syndrome (SS) and Hashimoto's thyroiditis contributing to hypokalemic dRTA. A renal biopsy revealed focal tubulointerstitial nephritis (TIN) suggestive of SS-related renal involvement, along with distinctive ischemic glomerular changes and tubular alterations consistent with hypokalemic nephropathy. Rapid improvement in tubular injury markers and hypobicarbonemia followed potassium supplementation, suggesting that hypokalemia contributed to proximal tubular injury. This case underscores the diagnostic challenge posed by the simultaneous presence of TIN and hypokalemic nephropathy, potentially masking hypokalemic nephropathy in patients with hypokalemic dRTA secondary to SS-TIN.

Published
2024
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50. Effective Management of Hypertensive Emergencies with Aliskiren Treatment in a Patient before and after Introducing Hemodialysis Secondary to Scleroderma Renal Crisis-like Condition under Corticosteroid Treatment for Sjögren Syndrome-associated Multiple Mononeuropathy.

Author

Yamazaki O, Murakawa M, Ochiai F, Fujii W, Asakawa S, Nagura M, Arai S, Tamura Y, Ohashi R, Shibata S, and Fujigaki Y

Subjects
Humans, Female, Middle Aged, Adrenal Cortex Hormones therapeutic use, Treatment Outcome, Emergencies, Heart Failure etiology, Heart Failure drug therapy, Hypertensive Crisis, Sjogren's Syndrome complications, Sjogren's Syndrome drug therapy, Renal Dialysis, Amides therapeutic use, Fumarates therapeutic use, Hypertension drug therapy, Hypertension complications, Scleroderma, Systemic complications, Antihypertensive Agents therapeutic use
Abstract

A middle-aged woman presented with hypertensive emergency after corticosteroid treatment for Sjögren syndrome-associated multiple mononeuropathy with suspected systemic sclerosis. Hypertensive heart failure with hyperreninemia improved with antihypertensives, including aliskiren; however, she became hemodialysis-dependent. Clinical findings and biopsy-proven thrombotic microangiopathy indicated conditions resembling scleroderma renal crisis (SRC). Severe hypertension and heart failure with hyperreninemia occurred after stopping aliskiren for hypotension due to diverticular bleeding, which improved after the reintroduction of aliskiren. Aliskiren appears to be effective in managing hypertensive heart failure in patients with SRC. Nevertheless, hemodialysis remained necessary in our case, and whether or not aliskiren can restore the renal function is unclear.

Published
2024
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