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1. Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis

Author

Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Trotman ML, Wheeler DC, Parfrey PS., Evolve Team, Chertow G, Parfrey P, Block G, Drüeke T, Goodman W, Herzog C, London G, Mahaffey K, Moe S, Wheeler D, Hennekens C, Baigent C, Brown W, O'Brien P, Anderson S, Hoel J, Szczech L, Patel U, Wampole J, Pun P, Felker M, Inrig J, Shah S, Hernandez A, Patel C, Brennan M, Albizem M, Capper E, Cauchi L, Cheng S, Dehmel B, Dhami K, Durham C, Francioni M, Gadd S, Goodman B, Guimaraes L, Grey N, Hamlin R, Harris C, Harris E, Heavey S, Heiges T, Heiser D, Jaeger P, James M, James P, Karimi S, Kewalramani R, Kraszewski A, Liang J, Maguire J, McCormick K, McFarlane K, Mix C, Modafferi D, Prathikanti R, Ryan C, Santiago N, Schumacher J, Seder C, Shahinfar S, Soares B, Stolman D, Tisher C, Trotman M, Tseng S, Ulias G, Unger P, Vyshenskaya A, Walsh L, White C, Wilde K, Santos J, Zarazaga C, Marin I, Garrote N, Cusumano A, Penalba N, Del Valle E, Juncos L, Saye J, Lef L, Altobelli V, Petraglia G, Rosa-Diez G, Douthat W, Lobo J, Gallart C, Lafalla A, Diez G, Linares B, Lopez N, Ramirez N, Gonzalez R, Valtuille R, Beresan H, Hermida O, Rudolf G, Marchetta N, Rano M, Ramirez M, Garcia N, Gillies A, Jones B, Pedagogos E, Walker R, Talaulikar G, Bannister K, Suranyi M, Kark A, Roger S, Kerr P, Disney A, Mount P, Fraenkel M, Mathew M, Fassett R, Jose M, Hawley C, Lonergan M, Mackie J, Ferrari P, Menahem S, Sabto J, Hutchison B, Langham R, Pollock C, Holzer H, Oberbauer R, Arias I, Graf H, Mayer G, Lhotta K, Neyer U, Klauser-Braun R, Hoerl W, Horn S, Kovarik J, Kramar R, Eigner M, Dhaene M, Billiouw J, De Meester J, Warling X, Cambier-Dwelschauwers P, Evenepoel P, Daelemans R, Dratwa M, Maes B, Stolear J, Dejagere T, Vanwalleghem J, Bouman K, Jadoul M, Peeters J, Vanholder R, Tielemans C, Donck J, Almeida F, de Oliveira J, Burdmann E, Garcia V, Thome F, Deboni L, Bregman R, Lugon J, Araújo S, Ferreira Filho S, Daher Ede F, Baptista M, Carvalho A, d'Avila D, Moyses Neto M, Yu L, Bastos M, Lacativa P, Jorgetti V, Romão Ede A, da Costa JC, Pecoits Filho R, Gordan P, Salgado N, Araújo M, Coelho S, Oliveira I, Moysés R, Vasconcellos L, Batista P, Gross J, Pedrosa A, Cournoyer S, LeBlanc M, Chow S, Karunakaran S, Wong G, Tobe S, Desmeules S, Zimmerman D, Murphy S, Montambault P, Donnelly S, MacRae J, Culleton B, Soroka S, Rabbat C, Jindal K, Vasilevsky M, Michaud M, Wijeyesinghe E, Zacharias J, Lok C, Muirhead N, Verrelli M, Da Roza G, Sapir D, Olgaard K, Daugaard H, Brandi L, Jensen P, Boulechfar H, Ang K, Simon P, Rieu P, Brunet P, Touchard G, Torres P, Combe C, Durrbach A, Ortiz J, Hannedouche T, Vela C, Lionet A, Ryckelynck P, Zaoui P, Choukroun G, Fessi H, Lang P, Stroumza P, Joly D, Mousson C, Laville M, Dellanna F, Erley C, Braun J, Rambausek M, Riegel W, Klingberg M, Schwertfeger E, Wizemann V, Eckardt K, Reichel H, Passauer J, Hübel E, Frischmuth N, Liebl R, Fiedler R, Schwenger V, Voßkühler A, Kunzendorf U, Renders L, Rattensberger D, Rump L, Ketteler M, Neumayer H, Zantvoort F, Stahl R, Ladanyi E, Braun B, Kulcsar I, Mezei I, Csiky B, Rikker C, Arkossy O, Berta K, Szegedi J, Major L, Ferenczi S, Fekete A, Szabo T, Zakar G, Wagner G, Erdelyine S, Borbas B, Eustace J, Reddan D, Capasso G, Locatelli F, Villa G, Cozzolino M, Brancaccio D, Messa P, Bolasco P, Ricciardi B, Malberti F, Moriero E, Cannella G, Ortalda V, Stefoni S, Frascà G, Cappelli G, Albertazzi A, Zoccali C, Farina M, Elli A, Avella F, Ondei P, Mingardi G, Errico R, Losito A, Di Giulio S, Pertosa G, Schena F, Grandaliano G, Gesualdo L, Auricchio M, Bochicchio-Ricardelli T, Correa-Rotter J, Verástegui F, Peña J, Wong A, Cruz-Valdez J, Zamora M, Solis M, Diaz M, Flores M, Sandoval E, van den Dorpel M, Brink H, Van Kuijk W, Vermeij C, Gregoor P, Hagen E, van der Sande F, Klinger M, Nowicki M, Muszytowski M, Bidas K, Bentkowski W, Wiecek A, Ksiazek A, Marczewski K, Ostrowski M, Switalski M, Sulowicz W, Matuszkiewicz-Rowinska J, Mysliwiec M, Durlik M, Rutkowski B, Macario F, Carvalho B, Frazao J, Machado D, Weigert A, Andrusev A, Khrustalev O, Zemtchenkov A, Gurevich K, Staroselsky K, Khadikova N, Rozhinskaya L, Timokhovskaya G, Strokov A, Balkarova O, Ermolenko V, Kolmakova E, Komandenko M, Timofeev M, Shilo V, Shostka G, Smirnov A, Anashkin V, Volgina G, Domashenko O, Gurevich A, Perlin D, García J, Ribes E, Piera E, Lucas M, Galicia M, Prados M, González M, Romero R, de Francisco ÁM, Montenegro J, Santiago C, García F, de La Ossa J, Arrieta J, Pons J, Martín-Malo A, Amigó J, Cases A, Sterner G, Jensen G, Wikström B, Jacobson S, Lund U, Weiss L, Ståhl A, von Albertini B, Burnier M, Meier P, Martin P, Uehlinger D, Dickenmann M, Yaqoob M, Zehnder D, Kalra P, Padmanabhan N, Roe S, Eadington D, Pritchard N, Hutchison A, Davies S, Wilkie M, Davies M, Pai P, Swift P, Kwan J, Goldsmith D, Tomson C, Stratton J, Dasgupta I, Sarkar S, Moustafa M, Gandhi K, Jamal A, Galindo-Ramos E, Tuazon J, Batlle D, Tucker K, Schiller-Moran B, Assefi A, Martinez C, Samuels L, Goldman J, Cangiano-Rivera J, Darwish R, Lee M, Topf J, Kapatkin K, Baer H, Kopelman R, Acharya M, Tharpe D, Bernardo M, Nader P, Guzman-Rivera J, Pergola P, Sekkarie M, Alas E, Zager P, Liss K, Navarro J, Roppolo M, Denu-Ciocca C, Kshirsagar A, El Khatib M, Kant K, Scott D, Murthyr B, Finkelstein F, Keightley G, McCrary R, Pitone J, Cavalieri T, Tsang A, Pellegrino B, Schmidt R, Ahmad S, Brown C, Friedman E, Mittman N, Fadem S, Shapiro W, Reddy M, Goldberger S, Woredekal Y, Agarwal A, Anger M, Haque M, Chidester P, Kohli R, Rubinstein S, Newman G, Gladish R, Ayodeji O, Soman S, Sprague S, Hunt N, Gehr T, Rizk D, Warnock D, Polack D, Pahl M, Fischer D, Dreyer P, James G, Husserl F, Rogers T, Raff A, Sedor J, Silver M, Smith M, Steinberg S, DelGiorno T, Jones E, Cunha P, Cheng J, Pogue V, Blumenthal S, Brown E, Charytan C, Buerkert J, Cook M, Felsenfeld A, Tareen N, Gupta A, Herman T, Diamond S, Hura C, Laski M, MacLaurin J, Plumb T, Brosnahan G, Kumar J, Henriquez M, Poole C, Osanloo E, Matalon A, Sholer C, Arfeen S, Azer M, Belledonne M, Gross M, Dunnigan E, McConnell K, Becker B, Rigolosi R, Spiegel D, Stegman M, Patak R, Streja D, Ranjit U, Youell T, Wooldridge T, Stafford C, Cottiero R, Weinberg M, Schonefeld M, Shahmir E, Hazzan A, Ashfaq A, Bhandari K, Cleveland W, Culpepper M, Golden J, Lai L, Lien Y, Lorica V, Robertson J, Malireddi K, Morse S, Thakur V, Israelit A, Raguram P, Alfred H, Weise W, Al-Saghir F, El Shahawy M, Rastogi A, Nissenson A, Kopyt N, Lynn R, Lea J, McClellan W, Teredesai P, Ong S, Tolkan S, Sugihara J, Minga T, Mehrotra R, Minasian R, Bhatia D, Specter R, Capelli J, Sidhu P, Dalal S, Dykes P, Khan M, Rahim F, Saklayen M, Thomas A, Michael B, Torres M, Al-Bander H, Murray B, Abukurah A, Gupta B, Nosrati S, Raja R, Zeig S, Braun M, Amatya A, Endsley J, Sharon Z, Dolson G, Dumler F, Ntoso K, Rosansky S, Kumar N, Gura V, Thompson N, Goldfarb D, Halligan R, Middleton J, Widerhorn A, Arbeit L, Arruda J, Crouch T, Friedman L, Khokhar S, Mittleman J, Light P, Taparia B, West C, Cotton J, Dhingra R, Kleinman L, Arif F, Lew S, Nammour T, Sterrett J, Williams M, Ramirez J, Rubin J, McCarthy J, Noble S, Chaffin M, Rekhi A., Chertow, Gm, Block, Ga, Correa-Rotter, R, Drüeke, Tb, Floege, J, Goodman, Wg, Herzog, Ca, Kubo, Y, London, Gm, Mahaffey, Kw, Mix, Tc, Moe, Sm, Trotman, Ml, Wheeler, Dc, Parfrey, Ps., Evolve, Team, Chertow, G, Parfrey, P, Block, G, Drüeke, T, Goodman, W, Herzog, C, London, G, Mahaffey, K, Moe, S, Wheeler, D, Hennekens, C, Baigent, C, Brown, W, O'Brien, P, Anderson, S, Hoel, J, Szczech, L, Patel, U, Wampole, J, Pun, P, Felker, M, Inrig, J, Shah, S, Hernandez, A, Patel, C, Brennan, M, Albizem, M, Capper, E, Cauchi, L, Cheng, S, Dehmel, B, Dhami, K, Durham, C, Francioni, M, Gadd, S, Goodman, B, Guimaraes, L, Grey, N, Hamlin, R, Harris, C, Harris, E, Heavey, S, Heiges, T, Heiser, D, Jaeger, P, James, M, James, P, Karimi, S, Kewalramani, R, Kraszewski, A, Liang, J, Maguire, J, Mccormick, K, Mcfarlane, K, Mix, C, Modafferi, D, Prathikanti, R, Ryan, C, Santiago, N, Schumacher, J, Seder, C, Shahinfar, S, Soares, B, Stolman, D, Tisher, C, Trotman, M, Tseng, S, Ulias, G, Unger, P, Vyshenskaya, A, Walsh, L, White, C, Wilde, K, Santos, J, Zarazaga, C, Marin, I, Garrote, N, Cusumano, A, Penalba, N, Del Valle, E, Juncos, L, Saye, J, Lef, L, Altobelli, V, Petraglia, G, Rosa-Diez, G, Douthat, W, Lobo, J, Gallart, C, Lafalla, A, Diez, G, Linares, B, Lopez, N, Ramirez, N, Gonzalez, R, Valtuille, R, Beresan, H, Hermida, O, Rudolf, G, Marchetta, N, Rano, M, Ramirez, M, Garcia, N, Gillies, A, Jones, B, Pedagogos, E, Walker, R, Talaulikar, G, Bannister, K, Suranyi, M, Kark, A, Roger, S, Kerr, P, Disney, A, Mount, P, Fraenkel, M, Mathew, M, Fassett, R, Jose, M, Hawley, C, Lonergan, M, Mackie, J, Ferrari, P, Menahem, S, Sabto, J, Hutchison, B, Langham, R, Pollock, C, Holzer, H, Oberbauer, R, Arias, I, Graf, H, Mayer, G, Lhotta, K, Neyer, U, Klauser-Braun, R, Hoerl, W, Horn, S, Kovarik, J, Kramar, R, Eigner, M, Dhaene, M, Billiouw, J, De Meester, J, Warling, X, Cambier-Dwelschauwers, P, Evenepoel, P, Daelemans, R, Dratwa, M, Maes, B, Stolear, J, Dejagere, T, Vanwalleghem, J, Bouman, K, Jadoul, M, Peeters, J, Vanholder, R, Tielemans, C, Donck, J, Almeida, F, de Oliveira, J, Burdmann, E, Garcia, V, Thome, F, Deboni, L, Bregman, R, Lugon, J, Araújo, S, Ferreira Filho, S, Daher Ede, F, Baptista, M, Carvalho, A, D'Avila, D, Moyses Neto, M, Yu, L, Bastos, M, Lacativa, P, Jorgetti, V, Romão Ede, A, da Costa, Jc, Pecoits Filho, R, Gordan, P, Salgado, N, Araújo, M, Coelho, S, Oliveira, I, Moysés, R, Vasconcellos, L, Batista, P, Gross, J, Pedrosa, A, Cournoyer, S, Leblanc, M, Chow, S, Karunakaran, S, Wong, G, Tobe, S, Desmeules, S, Zimmerman, D, Murphy, S, Montambault, P, Donnelly, S, Macrae, J, Culleton, B, Soroka, S, Rabbat, C, Jindal, K, Vasilevsky, M, Michaud, M, Wijeyesinghe, E, Zacharias, J, Lok, C, Muirhead, N, Verrelli, M, Da Roza, G, Sapir, D, Olgaard, K, Daugaard, H, Brandi, L, Jensen, P, Boulechfar, H, Ang, K, Simon, P, Rieu, P, Brunet, P, Touchard, G, Torres, P, Combe, C, Durrbach, A, Ortiz, J, Hannedouche, T, Vela, C, Lionet, A, Ryckelynck, P, Zaoui, P, Choukroun, G, Fessi, H, Lang, P, Stroumza, P, Joly, D, Mousson, C, Laville, M, Dellanna, F, Erley, C, Braun, J, Rambausek, M, Riegel, W, Klingberg, M, Schwertfeger, E, Wizemann, V, Eckardt, K, Reichel, H, Passauer, J, Hübel, E, Frischmuth, N, Liebl, R, Fiedler, R, Schwenger, V, Voßkühler, A, Kunzendorf, U, Renders, L, Rattensberger, D, Rump, L, Ketteler, M, Neumayer, H, Zantvoort, F, Stahl, R, Ladanyi, E, Braun, B, Kulcsar, I, Mezei, I, Csiky, B, Rikker, C, Arkossy, O, Berta, K, Szegedi, J, Major, L, Ferenczi, S, Fekete, A, Szabo, T, Zakar, G, Wagner, G, Erdelyine, S, Borbas, B, Eustace, J, Reddan, D, Capasso, G, Locatelli, F, Villa, G, Cozzolino, M, Brancaccio, D, Messa, P, Bolasco, P, Ricciardi, B, Malberti, F, Moriero, E, Cannella, G, Ortalda, V, Stefoni, S, Frascà, G, Cappelli, G, Albertazzi, A, Zoccali, C, Farina, M, Elli, A, Avella, F, Ondei, P, Mingardi, G, Errico, R, Losito, A, Di Giulio, S, Pertosa, G, Schena, F, Grandaliano, G, Gesualdo, L, Auricchio, M, Bochicchio-Ricardelli, T, Correa-Rotter, J, Verástegui, F, Peña, J, Wong, A, Cruz-Valdez, J, Zamora, M, Solis, M, Diaz, M, Flores, M, Sandoval, E, van den Dorpel, M, Brink, H, Van Kuijk, W, Vermeij, C, Gregoor, P, Hagen, E, van der Sande, F, Klinger, M, Nowicki, M, Muszytowski, M, Bidas, K, Bentkowski, W, Wiecek, A, Ksiazek, A, Marczewski, K, Ostrowski, M, Switalski, M, Sulowicz, W, Matuszkiewicz-Rowinska, J, Mysliwiec, M, Durlik, M, Rutkowski, B, Macario, F, Carvalho, B, Frazao, J, Machado, D, Weigert, A, Andrusev, A, Khrustalev, O, Zemtchenkov, A, Gurevich, K, Staroselsky, K, Khadikova, N, Rozhinskaya, L, Timokhovskaya, G, Strokov, A, Balkarova, O, Ermolenko, V, Kolmakova, E, Komandenko, M, Timofeev, M, Shilo, V, Shostka, G, Smirnov, A, Anashkin, V, Volgina, G, Domashenko, O, Gurevich, A, Perlin, D, García, J, Ribes, E, Piera, E, Lucas, M, Galicia, M, Prados, M, González, M, Romero, R, de Francisco, Ám, Montenegro, J, Santiago, C, García, F, de La Ossa, J, Arrieta, J, Pons, J, Martín-Malo, A, Amigó, J, Cases, A, Sterner, G, Jensen, G, Wikström, B, Jacobson, S, Lund, U, Weiss, L, Ståhl, A, von Albertini, B, Burnier, M, Meier, P, Martin, P, Uehlinger, D, Dickenmann, M, Yaqoob, M, Zehnder, D, Kalra, P, Padmanabhan, N, Roe, S, Eadington, D, Pritchard, N, Hutchison, A, Davies, S, Wilkie, M, Davies, M, Pai, P, Swift, P, Kwan, J, Goldsmith, D, Tomson, C, Stratton, J, Dasgupta, I, Sarkar, S, Moustafa, M, Gandhi, K, Jamal, A, Galindo-Ramos, E, Tuazon, J, Batlle, D, Tucker, K, Schiller-Moran, B, Assefi, A, Martinez, C, Samuels, L, Goldman, J, Cangiano-Rivera, J, Darwish, R, Lee, M, Topf, J, Kapatkin, K, Baer, H, Kopelman, R, Acharya, M, Tharpe, D, Bernardo, M, Nader, P, Guzman-Rivera, J, Pergola, P, Sekkarie, M, Alas, E, Zager, P, Liss, K, Navarro, J, Roppolo, M, Denu-Ciocca, C, Kshirsagar, A, El Khatib, M, Kant, K, Scott, D, Murthyr, B, Finkelstein, F, Keightley, G, Mccrary, R, Pitone, J, Cavalieri, T, Tsang, A, Pellegrino, B, Schmidt, R, Ahmad, S, Brown, C, Friedman, E, Mittman, N, Fadem, S, Shapiro, W, Reddy, M, Goldberger, S, Woredekal, Y, Agarwal, A, Anger, M, Haque, M, Chidester, P, Kohli, R, Rubinstein, S, Newman, G, Gladish, R, Ayodeji, O, Soman, S, Sprague, S, Hunt, N, Gehr, T, Rizk, D, Warnock, D, Polack, D, Pahl, M, Fischer, D, Dreyer, P, James, G, Husserl, F, Rogers, T, Raff, A, Sedor, J, Silver, M, Smith, M, Steinberg, S, Delgiorno, T, Jones, E, Cunha, P, Cheng, J, Pogue, V, Blumenthal, S, Brown, E, Charytan, C, Buerkert, J, Cook, M, Felsenfeld, A, Tareen, N, Gupta, A, Herman, T, Diamond, S, Hura, C, Laski, M, Maclaurin, J, Plumb, T, Brosnahan, G, Kumar, J, Henriquez, M, Poole, C, Osanloo, E, Matalon, A, Sholer, C, Arfeen, S, Azer, M, Belledonne, M, Gross, M, Dunnigan, E, Mcconnell, K, Becker, B, Rigolosi, R, Spiegel, D, Stegman, M, Patak, R, Streja, D, Ranjit, U, Youell, T, Wooldridge, T, Stafford, C, Cottiero, R, Weinberg, M, Schonefeld, M, Shahmir, E, Hazzan, A, Ashfaq, A, Bhandari, K, Cleveland, W, Culpepper, M, Golden, J, Lai, L, Lien, Y, Lorica, V, Robertson, J, Malireddi, K, Morse, S, Thakur, V, Israelit, A, Raguram, P, Alfred, H, Weise, W, Al-Saghir, F, El Shahawy, M, Rastogi, A, Nissenson, A, Kopyt, N, Lynn, R, Lea, J, Mcclellan, W, Teredesai, P, Ong, S, Tolkan, S, Sugihara, J, Minga, T, Mehrotra, R, Minasian, R, Bhatia, D, Specter, R, Capelli, J, Sidhu, P, Dalal, S, Dykes, P, Khan, M, Rahim, F, Saklayen, M, Thomas, A, Michael, B, Torres, M, Al-Bander, H, Murray, B, Abukurah, A, Gupta, B, Nosrati, S, Raja, R, Zeig, S, Braun, M, Amatya, A, Endsley, J, Sharon, Z, Dolson, G, Dumler, F, Ntoso, K, Rosansky, S, Kumar, N, Gura, V, Thompson, N, Goldfarb, D, Halligan, R, Middleton, J, Widerhorn, A, Arbeit, L, Arruda, J, Crouch, T, Friedman, L, Khokhar, S, Mittleman, J, Light, P, Taparia, B, West, C, Cotton, J, Dhingra, R, Kleinman, L, Arif, F, Lew, S, Nammour, T, Sterrett, J, Williams, M, Ramirez, J, Rubin, J, Mccarthy, J, Noble, S, Chaffin, M, and Rekhi, A.

Subjects
Adult, Male, Dialysis, Cinacalcet, Cardiovascular Disease, medicine.medical_specialty, Calcimimetic, medicine.medical_treatment, Naphthalenes, Coronary artery disease, Renal Dialysis, Internal medicine, Odds Ratio, medicine, Humans, Intensive care medicine, Aged, Etelcalcetide, Hyperparathyroidism, Hypocalcemia, business.industry, General Medicine, Middle Aged, medicine.disease, Intention to Treat Analysis, Cardiovascular Diseases, Parathyroid Hormone, Cinacalcet Hydrochloride, Kidney Failure, Chronic, Female, Hyperparathyroidism, Secondary, Secondary hyperparathyroidism, business, medicine.drug
Abstract

Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

Published
2012
Full Text
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3. [The IL-6 soluble receptors in hemodialyzed patients]

Author

MEMOLI, BRUNO, Grandaliano G, Soccio M, Procino A, Pertosa G., Memoli, Bruno, Grandaliano, G, Soccio, M, Procino, A, and Pertosa, G.

Subjects
Membrane Glycoproteins, Antigens, CD, Renal Dialysis, Cytokine Receptor gp130, Leukocytes, Mononuclear, Humans, Receptors, Interleukin-6
Abstract

Pro-inflammatory cytokines, in addition to their role in host defence, can be considered a disease mediator; therefore, a reduction in cytokine synthesis or its effects is becoming a target of many diseases. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that could play a role in several clinical problems related to dialysis treatment. Biological activities of IL-6 could be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R can enhance the inflammatory effects of IL-6 and; therefore, is an "agonistically" acting molecule. On the contrary, sgp130 efficiently binds the IL-6/sIL-6R complex with "antagonistic" effects. In this study we evaluated sgp130 release by peripheral blood mononuclear cells (PBMC) harvested from 10 healthy controls (CON) and 11 end-stage renal disease (ESRD) patients undergoing renal dialysis therapy RDT) with cellulosic hemophan membrane (HD). We also evaluated gp130 gene expression by reverse transcriptase polymerase chain reaction (RT-PCR). gp130 is the membrane bound receptor of IL-6 that could be proteolytically cleaved to generate soluble sgp130. Our results demonstrated that HD. at basal conditions, showed a higher release of sgp130 as compared with CON. We also demonstrated by RT-PCR at basal conditions a higher gene expression of gp130 in HD, as compared with CON. These results took place in the absence of any mitogenic stimulation and suggest that in HD patients an inflammatory subclinical status increases sgp130 release. The results obtained after lipopolysaccharide (LPS) stimulation confirm the role of inflammation on the increased release of sgp130 in HD patients.

Published
2005

4. 'In vivo' modulation of solubile antagonistic IL-6 receptor and release in ESRD

Author

Memoli B., Grandaliano G., Soccio M., Guida B., Bisesti V., Esposito P., Procino A., Marrone D., Michael A., Andreucci M., Schena F. P., Pertosa G., POSTIGLIONE, LOREDANA, Memoli, B., Grandaliano, G., Soccio, M., Postiglione, Loredana, Guida, B., Bisesti, V., Esposito, P., Procino, A., Marrone, D., Michael, A., Andreucci, M., Schena, F. P., and Pertosa, G.

Abstract

Soluble gp130 (sgp130) is a soluble circulating receptor of IL-6 with "antagonistic" biologic activity. It is generated independently by either shedding of the extracellular domain of membrane gp130 or alternative mRNA splicing. This study was addressed to clarify the mechanisms underlying sgp130 synthesis and release in patients who undergo regular dialysis treatment (RDT) using dialytic membranes with different biocompatibility. Two groups of RDT patients were enrolled: 11 patients who were treated with cellulosic membranes (C) and 10 patients who were treated with synthetic membranes (S). Ten healthy subjects constituted the control group. Serum samples and peripheral blood mononuclear cells (PBMC) were harvested in all groups (before dialysis in RDT patients). PBMC were cultured for 24 h in the absence or presence of LPS. The serum levels of sgp130 were significantly higher in C group than in control and S patients (C, 603.1 +/- 89.9; control, 396 +/- 49.5; S, 423.4 +/- 27.7 ng/ml; P < 0.01). PBMC from C patients, in the absence of any mitogenic stimulation, released a significantly greater amount of sgp130 as compared with S and control groups (C, 532.6 +/- 161.2; S, 332.4 +/- 148.6; control, 341.4 +/- 125.4 pg/ml; P < 0.01). The sgp130 release was positively correlated with the release of both IL-6 (r = 0.336, P < 0.05) and sIL-6R receptor (r = 0.324, P < 0.05). A significantly higher gp130 gene expression was also observed in unstimulated PBMC from C patients when compared with control and S groups. It is interesting that the expression of the 85-bp exon characteristic of the alternative splicing mRNA for sgp130 was low in all groups. Finally, confocal microscopy analysis showed an increased expression of gp130 on cell surface in unstimulated PBMC from C patients as compared with control and S groups. Our results demonstrate that in patients on RDT with C membranes, the synthesis and release of sgp130 "antagonistic" receptor is significantly increased. This release is seemingly due to a shedding of membrane-bound gp130 receptor. The increased sgp130 release may partially counteract the inflammatory effects caused by IL-6.

Published
2005

5. [Double renal transplant. Retrospective analysis of data on the patient population with double kidney transplantation in the setting of the AIRT]

Author

Infante, B., Stallone, G., Schena, A., Grandaliano, G., DI PAOLO, S., Battaglia, M., Ditonno, P., Feliciangeli, G., Stefoni, S., Messina, M., Segoloni, Giuseppe, and Schena, Fp

Subjects
Graft Survival, Humans, Middle Aged, Kidney Transplantation, Aged, Retrospective Studies
Abstract

The number of patients on the waiting list for renal transplantation has progressively increased in the last decade, while the number of potential donors have remained the same. The expansion of the donor pool using marginal donors may represent a possible, although partial solution to this problem. Thus, the aim of the present analysis was to evaluate the graft survival of double renal transplant from marginal donors performed within the Associazione InterRegionale Trapianti (AIRT) and to assess whether this procedure is characterized by an increase in surgical complications.79 double renal transplants were performed from January 1st 1999 to December 31st 2002 in three AIRT transplant centers (Bari, Bologna, Torino). Immunosuppressive therapy for all patients included anti-IL-2 receptor antibodies, corticosteroids, tacrolimus and mofetil micophenolate.Graft survival was 90% at 36 months. Acute rejection incidence was 6.4%, while the incidence of surgical complications was 16.6%.The present study opens new perspectives to overcome the actual shortage of donor kidneys. Indeed, the use of marginal organs for double renal transplantation not suitable for single transplantation may create an additional pool of potential donors and significantly increase the number of kidney transplants.

Published
2004

10. Increased placental expression of tissue factor is associated with abnormal uterine and umbilical Doppler waveforms in severe preeclampsia with fetal growth restriction

Author

Di Paolo, S., Volpe, P., Grandaliano, G., Stallone, G., Schena, A., Greco, P., Resta, L., Selvaggi, L., RAFFAELE IVAN CINCIONE, Schena, F. P., and Gesualdo, L.

Subjects
Adult, Fetal Growth Retardation, Endothelin-1, Staining and Labeling, Histocytochemistry, Placenta, Uterus, NADPH Dehydrogenase, Gene Expression, Ultrasonography, Doppler, Kidney Transplantation, NO, Thromboplastin, Umbilical Cord, Pre-Eclampsia, Pregnancy, Humans, Female, RNA, Messenger, Nitric Oxide Synthase, Blood Flow Velocity, In Situ Hybridization
Abstract

This study investigated whether modifications of placental expression of endothelin-1 (ET-1), nitric oxide synthase (NOS) and tissue factor (TF) are associated with abnormal Doppler waveforms.Fourteen pre-term severe preeclamptic (PE) women with fetal growth restriction (FGR) and 14 normal preg nant women underwent serial Doppler examination of the uterine and umbilical arteries (UA). Placental ET-1 and T expression was evaluated by in situ hybridization, NOS by NADPH-diaforase staining and in situ hybridization Doppler evaluation was extended to 11 female kidney transplant recipients (Tx), without FGR and/or PE, in wh we previously demonstrated a strong modification of placental ET-1/NOS vasoactive balance.PE women showed a marked reduction of endothelial constitutive NOS (ecNOS) expression in the syncy tiotrophoblast layer of all villi, whereas ET-1 expression was unchanged. All cases showed abnormal uterine artery blood flow velocimetry, 13 out of 14 PE women showed abnormal UA Doppler waveforms. In contrast, all Tx women showed normal UA blood velocimetry, all but one woman displayed a normal uterine artery waveform pattern. The Doppler velocimetry abnormalities were significantly associated with only TF expression, which was markedly increased, exclusively, in the endothelial cells within the basal decidua of PE women.The modification of ET-1/NOS vasoactive balance, per se, did not lead to Doppler impedance modifica tions in the UA and uterine arteries, observed in pre-term PE women with FGR. Instead, Doppler velocimetry modi fications appeared to correlate with endothelial cell activation, as revealed by increased TF expression.

13. De Novo Malignancies after Organ Transplantation: Focus on Viral Infections

Author

Piselli, P1, Busnach, G, Fratino, L, Citterio, F, Ettorre, Gm, De Paoli, P, Serraino, D, Dal Maso, L, Di Maso, M, Zucchetto, A, Agresta, A, Cimaglia, C, Puro, V, Ippolito, G, Miglioresi, L, Vennarecci, G, Santoro, R, Famulari, A, Delreno, F, Grandaliano, G, Fiorentino, M, Stefoni, S, Todeschini, P, Panicali, L, Valentini, C, Valerio, F, Bossini, N, Setti, G, Michittu, Mb, Murgia, Mg, Onano, B, Veroux, Pierfrancesco, Giuffrida, G, Giaquinta, A, Zerbo, D, Di Leo, L, Perrino, Ml, Colombo, V, Sghirlanzoni, Mc, Leoni, A, Buscemi, B, Lazzarin, M, Zanini, S, Spagnoletti, G, Salerno, Mp, Favi, E, De Luca, L, Lavacca, A, Cascone, C, Virgilio, B, Dossi, F, Fontanella, A, Ambrosini, A, Di Cicco, M., Piselli P, Busnach G, Fratino L, Citterio F, Ettorre GM, De Paoli P, Serraino D, Todeschini P, and Immunosuppression and Cancer Study Group

Subjects
SOLID ORGAN TRANSPLANT, Herpesvirus 4, Human, medicine.medical_specialty, Skin Neoplasms, Settore MED/18 - CHIRURGIA GENERALE, medicine.medical_treatment, Lymphoproliferative disorders, cancer risk, medicine.disease_cause, Biochemistry, Organ transplantation, Virus, medicine, Humans, Sarcoma, Kaposi, Molecular Biology, solid organ transplantation, Immunosuppression Therapy, business.industry, ORGAN, Cancer, Kaposi sarcoma, Immunosuppression, KAPOSI'S SARCOMA, General Medicine, renal transplantation, medicine.disease, iatrogenic immunosuppression, Kidney Transplantation, neoplasia, VIRAL INFECTIONS, Herpesvirus 8, Human, Immunology, Molecular Medicine, POST-TRANSPLANT MALIGNANCY, Sarcoma, viral infection, Carcinogenesis, business, Oncovirus
Abstract

Organ transplantation is an increasingly used medical procedure for treating otherwise fatal end stage organ diseases with 107,000 transplants performed worldwide in 2010. Newly developed anti-rejection drugs greatly helped to prolong long-term survival of both the individual and the transplanted organ, and they facilitate the diffusion of organ transplantation. Presently, 5-year patient survival rates are around 90% after kidney transplant and 70% after liver transplant. However, the prolonged chronic use of immunosuppressive drugs is well known to increase the risks of opportunistic diseases, particularly infections and virus-related malignancies. Although transplant recipients experience a nearly 2-fold elevated risk for all types of de-novo cancers, persistent infections with oncogenic viruses - such as Kaposi sarcoma herpes virus, high-risk human papillomaviruses, and Epstein-Barr virus - are associated with up to 100-fold increased cancer risks. This review, focusing on kidney and liver transplants, highlights updated evidences linking iatrogenic immunosuppression, persistent infections with oncogenic viruses and cancer risk. The implicit capacity of oncogenic viruses to immortalise infected cells by disrupting the cell-cycle control can lead, in a setting of induced lowered immune surveillance, to tumorigenesis and this ability is thought to closely correlate with cumulative exposure to immunosuppressive drugs. Mechanisms underlying the relationship between viral infections, immunosuppressive drugs and the risk of skin cancers, post-transplant lymphoproliferative disorders, Kaposi sarcoma, cervical and other ano-genital cancers are reviewed in details.

20. Relation of C. pneumoniae antibodies to inflammation and atherosclerosclerosis in dialysis patients

Author

Monno, R., Pertosa, G., Grandaliano, G., Fumarola, L., Gianluigi Giannelli, and Simone, S.

Subjects
Adult, Adolescent, Fluorescent Antibody Technique, Enzyme-Linked Immunosorbent Assay, Complement Membrane Attack Complex, Risk Assessment, Young Adult, Nephelometry and Turbidimetry, Renal Dialysis, Risk Factors, Humans, Cellulose, Aged, Inflammation, Chi-Square Distribution, Membranes, Artificial, Equipment Design, Chlamydophila pneumoniae, Middle Aged, Atherosclerosis, Antibodies, Bacterial, Echocardiography, Doppler, Color, Femoral Artery, C-Reactive Protein, Carotid Arteries, Logistic Models, Italy, Case-Control Studies, Kidney Failure, Chronic, Inflammation Mediators
Abstract

the aim of this study was to investigate the association between the presence of antibodies to C. pneumoniae, some markers of inflammation and the presence of preclinical atherosclerotic lesions in hemodyalisis (HD) patients treated with different dialytic membranes.C. pneumoniae antibodies were measured by microimmunofluorescence in blood samples of 68 chronic HD patients and in 120 healthy blood donors. Intima-media thickness (IMT) of carotid and of femoral arteries, eco-color doppler of sovraortic trunk and lower limb vessels were evaluated. Plasma levels of C-reactive protein (CRP) and terminal complement (C) complex, C5b-9, were measured.HD patients treated by cellulosic membranes have significantly higher plasma levels of C5b-9 and of CRP compared to those treated by synthetic membranes. A significantly higher prevalence of IgG antibodies to C. pneumoniae and also at higher titre was observed in HD patients in comparison to the controls (66% vs. 28%). The carotid artery mean wall thickness was significantly lower in C. pneumoniae seronegative patients than C. pneumoniae seropositive patients. Similar results were obtained for limb arteries. The use of cellulosic membranes, but not synthetic membranes, was associated with higher carotid IMT and this was independent of the C. pneumoniae serology status.in addition to known risk factors, the type of dialytic membrane used may contribute to the progression of atherosclerosis lesions in HD patients. Our data strengthen the evidences that C. pneumoniae infection under high inflammatory status might be a further risk factor for progression of atherosclerosis in HD patients, particularly in those treated with cellulosic membranes.

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

Author

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

Subjects
Settore MED/14 - Nefrologia, CDK, Diabetes, ESKD, SGLT2i, Diabete, Kidney, Diabetes Mellitus, Type 2, Nephrology, Albuminuria, Humans, Renal Insufficiency, Chronic, Sodium-Glucose Transporter 2 Inhibitors
Abstract

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

Published
2022

23. Rapamycin for treatment of type I autosomal dominant polycystic kidney disease (RAPYD-study): a randomized, controlled study

Author

Eustacchio Montemurno, Loreto Gesualdo, T. Tataranni, Barbara Infante, Francesca Bruno, Daniela Mezzopane, Giuseppe Grandaliano, Christos Bristogiannis, Massimo Sabbatini, Luca Macarini, Annalisa Schirinzi, Giovanni Stallone, Francesco Paolo Schena, Antonio Pisani, Stallone, G, Infante, B, Grandaliano, G, Bristogiannis, C, Macarini, L, Mezzopane, D, Bruno, F, Montemurno, E, Schirinzi, A, Sabbatini, Massimo, Pisani, Antonio, Tataranni, T, Schena, Fp, Gesualdo, L., G., Stallone, B., Infante, G., Grandaliano, C., Bristogianni, L., Macarini, D., Mezzopane, F., Bruno, E., Montemurno, A., Schirinzi, T., Tataranni, F. P., Schena, and L., Gesualdo

Subjects
Ramipril, Adult, Male, medicine.medical_specialty, Adolescent, Autosomal dominant polycystic kidney disease, Urology, Renal function, Kidney Volume, Cystic kidney disease, Young Adult, Internal medicine, medicine, Humans, Cyst, Prospective Studies, Phosphorylation, Antihypertensive Agents, Aged, Sirolimus, Transplantation, Kidney, business.industry, Ribosomal Protein S6 Kinases, 70-kDa, Kidney Diseases, Cystic, Middle Aged, medicine.disease, Polycystic Kidney, Autosomal Dominant, Prognosis, medicine.anatomical_structure, Endocrinology, Nephrology, Disease Progression, Trough level, Drug Therapy, Combination, Female, business, Immunosuppressive Agents, medicine.drug, Follow-Up Studies, Glomerular Filtration Rate
Abstract

Background. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of cystic kidney disease. An inappropriate stimulation of mammalian target of rapamycin may represent the converging point in the molecular pathways leading to renal cyst growth. Methods. The primary objectives of this prospective, open-label, randomized clinical trial were to assess whether rapamycin may reduce the progressive increase in single cyst and total kidney volume in type I ADPKD and the decline in renal function and to identify the optimal rapamycin dose. Fifty-five patients with type I ADPKD were enrolled and randomized to receive ramipril (Group A), ramipril + high-dose rapamycin (Group B, trough level 6–8 ng/mL) and ramipril + low-dose rapamycin (Group C, trough levels 2–4 ng/mL). Rapamycin efficacy was monitored measuring p70 phosphorylation in peripheral blood mononuclear cells. Results. Both rapamycin doses significantly reduced p70 phosphorylation. Nevertheless, total kidney volume increased in all groups after 24 months, although only in Groups A and B, was the final volume significantly higher compared with the baseline. Single cyst final volume was not significantly different in the three groups, although it was increased in Group A compared with the baseline, whereas in Groups B and C, it was significantly reduced. We did not observe any difference in renal function at 24 months among the three study groups. Group A presented a significant worsening of renal function that remained stable in both Groups B and C. Conclusions. Our study would suggest that rapamycin does not influence the progression of type I ADPKD, although the higher drug dose tested prevented both the increase in kidney volume and the worsening of renal function (RAPYD-study, EUDRACT No. 2007006557-25).

Published
2012

24. Inflammation may modulate IL-6 and C-reactive protein gene expression in the adipose tissue: the role of IL-6 cell membrane receptor

Author

Marco Del Prete, Alfredo Procino, Giovanni Pertosa, Annamaria Colao, Bruno Memoli, Giuseppe Paolo Ferulano, Pasquale Esposito, Michele Andreucci, Brunella Guida, Paolo Calabrò, Silvia Savastano, Clemente Cillo, Giuseppe Grandaliano, Saverio Di Lillo, Memoli, Bruno, Procino, A, Calabrò, P, Esposito, P, Grandaliano, G, Pertosa, G, Del Prete, M, Andreucci, Michele, Di Lillo, S, Ferulano, GIUSEPPE PAOLO, Cillo, Clemente, Savastano, Silvia, Colao, Annamaria, and Guida, Bruna

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Stromal cell, Physiology, Endocrinology, Diabetes and Metabolism, Adipose tissue macrophages, Adipose tissue, Inflammation, Physiology (medical), Internal medicine, Gene expression, medicine, Body Fat Distribution, Humans, Interleukin 6, PRDM16, Regulation of gene expression, biology, Interleukin-6, Middle Aged, Receptors, Interleukin-6, Endocrinology, C-Reactive Protein, Adipose Tissue, Gene Expression Regulation, Organ Specificity, biology.protein, Female, medicine.symptom, Stromal Cells
Abstract

Only few studies have been addressed to the presence and regulation of C-reactive protein (CRP) gene expression in different districts of adipose tissue, and no study has investigated the role of adipose tissue in presence of inflammation. Therefore, the aim of this study was to investigate the inflammatory involvement of either adipose tissue or adipose cells (adipocytes and stromal cells, respectively) in patients with chronic inflammatory disease, focusing on regional adipose tissue CRP gene expression. Eighteen patients with inflammatory disease and 14 healthy controls were enrolled. All subjects underwent specific surgical procedures. Inflamed and noninflamed patients provided samples of subcutaneous and/or omental adipose tissue. All samples were analyzed by RT-PCR and real-time PCR for specific gene expression. In addition, both adipocytes and stromal cells were studied by real-time PCR and immunoprecipitation to evaluate either gene or protein expression of CRP. Our results (real-time PCR) demonstrated a higher gene expression of CRP, IL-6, and both IL-6 membrane receptors in subcutaneous samples of inflamed patients than in healthy controls. Furthermore, in omental fragments of inflamed patients, an enhanced mRNA abundance of the same genes, compared with subcutaneous, was observed. The results obtained at cellular level did not provide evidence of any difference between adipocytes and stromal cell CRP gene expression, whereas immunoprecipitation demonstrated the presence of CRP in inflamed subjects. These results provide first-time evidence of the involvement of adipose tissue in the course of chronic inflammatory diseases, with a different degree of participation of the different adipose tissue districts.

Published
2007

25. Local activation of interleukin 6 signaling is associated with arteriovenous fistula stenosis in hemodialysis patients

Author

Antonella Loverre, Simona Simone, Bruno Memoli, Francesco Paolo Schena, Giuseppe Grandaliano, Giovanni Pertosa, Carmen Capobianco, Mario Cifarelli, Daniela Marrone, Marrone, D, Pertosa, G, Simone, S, Loverre, A, Capobianco, C, Cifarelli, M, Memoli, Bruno, Schena, Fp, and Grandaliano, G.

Subjects
Adult, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, medicine.medical_treatment, Arteriovenous fistula, Constriction, Pathologic, Proinflammatory cytokine, Renal Dialysis, medicine, Cytokine Receptor gp130, Humans, cardiovascular diseases, Prospective Studies, STAT3, Interleukin 6, Aged, biology, Vascular disease, business.industry, Interleukin-6, Middle Aged, medicine.disease, Glycoprotein 130, Receptors, Interleukin-6, Nephrology, Arteriovenous Fistula, biology.protein, Hemodialysis, Janus kinase, business, Signal Transduction
Abstract

Background Vascular access failure is the main cause of morbidity in hemodialysis patients. Stenosis of the arteriovenous fistula (AVF) is similar histologically to atherosclerosis. Recent studies showed that interleukin 6 (IL-6) has a key role in the pathogenesis of atherosclerosis by binding 2 specific receptors, gp80 and gp130. When activated, gp130 interacts with a tyrosine kinase, Janus kinase (JAK2), which then activates a transcription factor, signal transducers and activators of transcription (STAT3), directly turning on several proinflammatory genes. The aim of this study is to evaluate gp130 expression and JAK2/STAT3 activation within stenotic AVFs. Methods 44 patients undergoing surgery for AVF creation were enrolled; 10 of them had AVF failure with histologically proven AVF stenosis (wall-lumen ratio > 1). A venous fragment of the AVFs was collected during creation and revision of the vascular access. gp130 and gp80 expression, as well as JAK/STAT activation, were evaluated by means of confocal microscopy. Peripheral-blood mononuclear cells were isolated at the time of AVF creation and revision. Results gp130 protein expression, barely detectable in native AVFs, was strikingly increased within the venous branch of stenotic AVFs. The signaling subunit of the IL-6 receptor broadly colocalized with gp80, the IL-6–binding subunit. gp130-expressing cells were mainly CD34 + , suggesting that this receptor is expressed primarily by neovasculature endothelial cells. At the same time, a significant increase in phosphorylation of JAK2/STAT3 was observed in endothelial cells of stenotic AVFs. Interestingly, peripheral-blood mononuclear cells isolated at the time of AVF failure presented strikingly greater IL-6 expression compared with dialysis age-matched controls. Conclusion IL-6 receptor activation may have a role in the pathogenesis of AVF failure in hemodialysis patients and may represent a potential therapeutic target in this setting.

Published
2007

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