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1. Kidney failure prediction models

Author

Ramspek, Chava L, Evans, Marie, Wanner, Christoph, Drechsler, Christiane, Chesnaye, Nicholas C, Szymczak, Maciej, Krajewska, Magdalena, Torino, Claudia, Porto, Gaetana, Hayward, Samantha, Caskey, Fergus, Dekker, Friedo W, Jager, Kitty J, van Diepen, Merel, EQUAL Study Investigators: Adamasco Cupisti, Adelia Sagliocca, Alberto Ferraro, Aleksandra Musiała, Alessandra Mele, Alessandro Naticchia, Alex Còsaro, Alistair Woodman, Andrea Ranghino, Andrea Stucchi, Andreas Jonsson, Andreas Schneider, Angelo Pignataro, Anita Schrander, Anke Torp, Anna McKeever, Anna Szymczak, Anna-Lena Blom, Antonella De Blasio, Antonello Pani, Aris Tsalouichos, Asad Ullah, Barbara McLaren, Bastiaan van Dam, Beate Iwig, Bellasi Antonio, Biagio Raffaele Di Iorio, Björn Rogland, Boris Perras, Butti Alessandra, Camille Harron, Carin Wallquist, Carl Siegert, Carla Barrett, Carlo Gaillard, Carlo Garofalo, Cataldo Abaterusso, Charles Beerenhout, Charlotte O'Toole, Chiara Somma, Christian Marx, Christina Summersgill, Christof Blaser, Claudia D'alessandro, Claudia Emde, Claudia Zullo, Claudio Pozzi, Colin Geddes, Cornelis Verburgh, Daniela Bergamo, Daniele Ciurlino, Daria Motta, Deborah Glowski, Deborah McGlynn, Denes Vargas, Detlef Krieter, Domenico Russo, Dunja Fuchs, Dympna Sands, Ellen Hoogeveen, Ellen Irmler, Emöke Dimény, Enrico Favaro, Eva Platen, Ewelina Olczyk, Ewout Hoorn, Federica Vigotti, Ferruccio Ansali, Ferruccio Conte, Francesca Cianciotta, Francesca Giacchino, Francesco Cappellaio, Francesco Pizzarelli, Fredrik Sundelin, Fredrik Uhlin, Gaetano Greco, Geena Roy, Gaetana Porto, Giada Bigatti, Giancarlo Marinangeli, Gianfranca Cabiddu, Gillian Hirst, Giordano Fumagalli, Giorgia Caloro, Giorgina Piccoli, Giovanbattista Capasso, Giovanni Gambaro, Giuliana Tognarelli, Giuseppe Bonforte, Giuseppe Conte, Giuseppe Toscano, Goffredo Del Rosso, Gunilla Welander, Hanna Augustyniak-Bartosik, Hans Boots, Hans Schmidt-Gürtler, Hayley King, Helen McNally, Hendrik Schlee, Henk Boom, Holger Naujoks, Houda Masri-Senghor, Hugh Murtagh, Hugh Rayner, Ilona Miśkowiec-Wiśniewska, Ines Schlee, Irene Capizzi, Isabel Bascaran Hernandez, Ivano Baragetti, Jacek Manitius, Jane Turner, Jan-Willem Eijgenraam, Jeroen Kooman, Joachim Beige, Joanna Pondel, Joanne Wilcox, Jocelyn Berdeprado, Jochen Röthele, Jonathan Wong, Joris Rotmans, Joyce Banda, Justyna Mazur, Kai Hahn, Kamila Jędrzejak, Katarzyna Nowańska, Katja Blouin, Katrin Neumeier, Kirsteen Jones, Kirsten Anding-Rost, Knut-Christian Gröntoft, Lamberto Oldrizzi, Lesley Haydock, Liffert Vogt, Lily Wilkinson, Loreto Gesualdo, Lothar Schramm, Luigi Biancone, Łukasz Nowak, Maarten Raasveld, Magdalena Durlik, Manuela Magnano, Marc Vervloet, Marco Ricardi, Margaret Carmody, Maria Di Bari, Maria Laudato, Maria Luisa Sirico, Maria Stendahl, Maria Svensson, Maria Weetman, Marjolijn van Buren, Martin Joinson, Martina Ferraresi, Mary Dutton, Merel van Diepen, Michael Matthews, Michele Provenzano, Monika Hopf, Moreno Malaguti, Nadja Wuttke, Neal Morgan, Nicola Palmieri, Nikolaus Frischmuth, Nina Bleakley, Paola Murrone, Paul Cockwell, Paul Leurs, Paul Roderick, Pauline Voskamp, Pavlos Kashioulis, Pawlos Ichtiaris, Peter Blankestijn, Petra Kirste, Petra Schulz, Phil Mason, Philip Kalra, Pietro Cirillo, Pietro Dattolo, Pina Acampora, Rincy Sajith, Rita Nigro, Roberto Boero, Roberto Scarpioni, Rosa Sicoli, Rosella Malandra, Sabine Aign, Sabine Cäsar, Sadie van Esch, Sally Chapman, Sandra Biribauer, Santee Navjee, Sarah Crosbie, Sharon Brown, Sheila Tickle, Sherin Manan, Silke Röser, Silvana Savoldi, Silvio Bertoli, Silvio Borrelli, Siska Boorsma, Stefan Heidenreich, Stefan Melander, Stefania Maxia, Stefano Maffei, Stefano Mangano, Stephanie Palm, Stijn Konings, Suresh Mathavakkannan, Susanne Schwedler, Sylke Delrieux, Sylvia Renker, Sylvia Schättel, Szyszkowska Dorota, Teresa Cicchetti, Teresa Nieszporek, Theresa Stephan, Thomas Schmiedeke, Thomas Weinreich, Til Leimbach, Tiziana Rappa, Tora Almquist, Torsten Stövesand, Udo Bahner, Ulrika Jensen, Valentina Palazzo, Walter De Simone, Wolfgang Seeger, Ying Kuan, Zbigniew Heleniak, Zeynep Aydin, Internal Medicine, Chava L, Ramspek, Marie, Evan, Christoph, Wanner, Christiane, Drechsler, Nicholas C, Chesnaye, Maciej, Szymczak, Magdalena, Krajewska, Claudia, Torino, Gaetana, Porto, Samantha, Hayward, Fergus, Caskey, Friedo W, Dekker, Kitty J, Jager, Merel, van Diepen, Study Investigators: Adamasco Cupisti, Equal, Sagliocca, Adelia, Ferraro, Alberto, Musiała, Aleksandra, Mele, Alessandra, Naticchia, Alessandro, Còsaro, Alex, Woodman, Alistair, Ranghino, Andrea, Stucchi, Andrea, Jonsson, Andrea, Schneider, Andrea, Pignataro, Angelo, Schrander, Anita, Torp, Anke, Mckeever, Anna, Szymczak, Anna, Blom, Anna-Lena, De Blasio, Antonella, Pani, Antonello, Tsalouichos, Ari, Ullah, Asad, Mclaren, Barbara, van Dam, Bastiaan, Iwig, Beate, Antonio, Bellasi, Raffaele Di Iorio, Biagio, Rogland, Björn, Perras, Bori, Alessandra, Butti, Harron, Camille, Wallquist, Carin, Siegert, Carl, Barrett, Carla, Gaillard, Carlo, Garofalo, Carlo, Abaterusso, Cataldo, Beerenhout, Charle, O'Toole, Charlotte, Somma, Chiara, Marx, Christian, Summersgill, Christina, Blaser, Christof, D'Alessandro, Claudia, Emde, Claudia, Zullo, Claudia, Pozzi, Claudio, Geddes, Colin, Verburgh, Corneli, Bergamo, Daniela, Ciurlino, Daniele, Motta, Daria, Glowski, Deborah, Mcglynn, Deborah, Vargas, Dene, Krieter, Detlef, Russo, Domenico, Fuchs, Dunja, Sands, Dympna, Hoogeveen, Ellen, Irmler, Ellen, Dimény, Emöke, Favaro, Enrico, Platen, Eva, Olczyk, Ewelina, Hoorn, Ewout, Vigotti, Federica, Ansali, Ferruccio, Conte, Ferruccio, Cianciotta, Francesca, Giacchino, Francesca, Cappellaio, Francesco, Pizzarelli, Francesco, Sundelin, Fredrik, Uhlin, Fredrik, Greco, Gaetano, Roy, Geena, Porto, Gaetana, Bigatti, Giada, Marinangeli, Giancarlo, Cabiddu, Gianfranca, Hirst, Gillian, Fumagalli, Giordano, Caloro, Giorgia, Piccoli, Giorgina, Capasso, Giovanbattista, Gambaro, Giovanni, Tognarelli, Giuliana, Bonforte, Giuseppe, Conte, Giuseppe, Toscano, Giuseppe, Del Rosso, Goffredo, Welander, Gunilla, Augustyniak-Bartosik, Hanna, Boots, Han, Schmidt-Gürtler, Han, King, Hayley, Mcnally, Helen, Schlee, Hendrik, Boom, Henk, Naujoks, Holger, Masri-Senghor, Houda, Murtagh, Hugh, Rayner, Hugh, Miśkowiec-Wiśniewska, Ilona, Schlee, Ine, Capizzi, Irene, Bascaran Hernandez, Isabel, Baragetti, Ivano, Manitius, Jacek, Turner, Jane, Eijgenraam, Jan-Willem, Kooman, Jeroen, Beige, Joachim, Pondel, Joanna, Wilcox, Joanne, Berdeprado, Jocelyn, Röthele, Jochen, Wong, Jonathan, Rotmans, Jori, Banda, Joyce, Mazur, Justyna, Hahn, Kai, Jędrzejak, Kamila, Nowańska, Katarzyna, Blouin, Katja, Neumeier, Katrin, Jones, Kirsteen, Anding-Rost, Kirsten, Gröntoft, Knut-Christian, Oldrizzi, Lamberto, Haydock, Lesley, Vogt, Liffert, Wilkinson, Lily, Gesualdo, Loreto, Schramm, Lothar, Biancone, Luigi, Nowak, Łukasz, Raasveld, Maarten, Durlik, Magdalena, Magnano, Manuela, Vervloet, Marc, Ricardi, Marco, Carmody, Margaret, Di Bari, Maria, Laudato, Maria, Luisa Sirico, Maria, Stendahl, Maria, Svensson, Maria, Weetman, Maria, van Buren, Marjolijn, Joinson, Martin, Ferraresi, Martina, Dutton, Mary, van Diepen, Merel, Matthews, Michael, Provenzano, Michele, Hopf, Monika, Malaguti, Moreno, Wuttke, Nadja, Morgan, Neal, Palmieri, Nicola, Frischmuth, Nikolau, Bleakley, Nina, Murrone, Paola, Cockwell, Paul, Leurs, Paul, Roderick, Paul, Voskamp, Pauline, Kashioulis, Pavlo, Ichtiaris, Pawlo, Blankestijn, Peter, Kirste, Petra, Schulz, Petra, Mason, Phil, Kalra, Philip, Cirillo, Pietro, Dattolo, Pietro, Acampora, Pina, Sajith, Rincy, Nigro, Rita, Boero, Roberto, Scarpioni, Roberto, Sicoli, Rosa, Malandra, Rosella, Aign, Sabine, Cäsar, Sabine, van Esch, Sadie, Chapman, Sally, Biribauer, Sandra, Navjee, Santee, Crosbie, Sarah, Brown, Sharon, Tickle, Sheila, Manan, Sherin, Röser, Silke, Savoldi, Silvana, Bertoli, Silvio, Borrelli, Silvio, Boorsma, Siska, Heidenreich, Stefan, Melander, Stefan, Maxia, Stefania, Maffei, Stefano, Mangano, Stefano, Palm, Stephanie, Konings, Stijn, Mathavakkannan, Suresh, Schwedler, Susanne, Delrieux, Sylke, Renker, Sylvia, Schättel, Sylvia, Dorota, Szyszkowska, Cicchetti, Teresa, Nieszporek, Teresa, Stephan, Theresa, Schmiedeke, Thoma, Weinreich, Thoma, Leimbach, Til, Rappa, Tiziana, Almquist, Tora, Stövesand, Torsten, Bahner, Udo, Jensen, Ulrika, Palazzo, Valentina, De Simone, Walter, Seeger, Wolfgang, Kuan, Ying, Heleniak, Zbigniew, Aydin, Zeynep, Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Quality of Care, and APH - Global Health

Subjects
Male, progression of chronic renal failure, medicine.medical_specialty, Time Factors, epidemiology and outcome, 030232 urology & nephrology, Risk Assessment, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Older patients, external validation, Predictive Value of Tests, medicine, Humans, Failure risk, Clinical Epidemiology, In patient, comprehensive external validation, 030212 general & internal medicine, Statistic, Aged, Aged, 80 and over, Kidney, Models, Statistical, business.industry, External validation, General Medicine, prediction, kidney failure, Europe, prediction model, medicine.anatomical_structure, chronic kidney disease, epidemiology and outcomes, prognosis, Nephrology, Emergency medicine, Disease Progression, Kidney Failure, Chronic, Female, business, prognostic, Predictive modelling, prognosi, Cohort study
Abstract

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Published
2021
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2. CKD NUTRITION, INFLAMMATION AND OXIDATIVE STRESS

Author

Abdelouahed Khalil, Anteo Di Napoli, Stephen Zewinger, Mariusz Flisiński, Domenico Trimboli, Maurizio Bossola, Marina Biagioli, Odile Azoulay, Michele Buemi, Piergiorgio Bolasco, Andreea Ilyes, Ángeles Álvarez, Valeria Cernaro, Polichronis Alivanis, Gabriel Stefan, Mehmet Haberal, Marcelo Costa Batista, Jerzy Chudek, Mujdat Batur Canoz, Branka Mitic, Abdul Rashid Qureshi, Anna Stefańska, Christiaan L. Meuwese, Anna Kamińska, Vera Jankowski, Yeon Soon Jung, Luisa Sereni, Rafał Donderski, Ho Sik Shin, Ciprian Stoica, Peter Stenvinkel, Insa E. Emrich, Rosanna Coppo, Boris Zingerman, Rachid Saile, Sonja Radenkovic, Yener Koc, Ilona Miśkowiec-Wiśniewska, Tatjana Cvetkovic, Danilo Fliser, Grigore Dogaru, Simonetta Palleschi, Milica Bozic, Urszula Spiechowicz-Zatoń, Kevin J. Woollard, Serpil Nebioğlu, Erik W. Holy, Hark Rim, Mahmut Gok, Adriana Arena, Iryna Dudar, Goran Paunovic, Elvira Fernández, Maria Inês Barreto-Silva, Jacek Manitius, Naohito Isoyama, Demet Yavuz, Michael Böhm, Jose M. Valdivielso, Paolo Maria Ghezzi, Silvia Regina Manfredi, Paweł Stróżecki, Yusuf Oguz, Maria L Lusini, Miomir Stojanovic, Gabriel Mircescu, Mikio Sugano, Paula Maria Gliga, Zeynep Bal, Mirela Liana Gliga, Elisa Loiacono, Hilmi Umut Ünal, Viktoria Alekseeva, Sun Chul Kim, Hyun Yul Rhew, José Tarcísio Giffoni de Carvalho, Foteini Lamprianou, Ekrem Kara, Sang-Kyung Jo, Barbara E. Stähli, Abdulkadir Unsal, Francesco Franco, Murat Karaman, Shunsuke Goto, Sumie Goto, Richard J. Johnson, Tamer Sakaci, Christophe Dubois, Roman Junik, Nikolaos Karvouniaris, Nikitas Moschos, Timo Speer, Kathleen Claes, Maria Teresa Ingegneri, Gunnar H. Heine, Pieter Evenepoel, Zahava Gamzo, Juan Jesus Carrero, Keiji Kono, Bertrand Gondouin, Sylwia Rotkegel, Mehmet Kanbay, Sebahattin Sari, Roxanne Darbousset, Shinichi Nishi, Andrzej Brymora, Bahar Gurlek Demirci, Vincenzo Bellizzi, Joanna Siódmiak, Domenico Di Lallo, Ye Na Kim, Latife Atasoy Karakas, Adam M. Zawada, Alexander Akhmedov, Mustafa Sevinc, Tuncay Sahutoglu, Hrvoje Cvija, Giovanni G. Camici, Ayse C Akbasli, Mahmut I Yilmaz, Christos Paliouras, Karolina Paunovic, Bulent Erbay, Carla Cavalheiro da Silva Lemos, Frances Costa-Silva, Marina Davoli, Liesbeth Viaene, Fatma Nurhan Ozdemir, Mehtap Erkmen Uyar, Kentaro Nakai, Adrian Covic, Danijela Tasic, Jarosław Ciepał, Mauro Atti, Gunnar Heine, Stéphane Burtey, Domenico Santoro, Benaya Rozen-Zvi, Simone Vargas, Lucia Rohrer, Gaetano Montalto, Hakki Cetinkaya, Turan Colak, Bert Bammens, Alessandro Amore, Tayfun Eyileten, Paul Leurs, Liliana Viasu, Theodoros Haviatsos, Yalcin Solak, Antonino Sidoti, Carmen de Pablo, Tayfun EyIeten, Vincenzo Savica, Maria Dolores Sanchez-Niño, Yasemin Gulcan Kurt, Gordana Kocic, Joachim Jankowski, Andrea Pisacane, Katarzyna Wyskida, Kenan Keven, Sunna Snaedal, Zorica Dimitrijevic, Nikolaos Papagiannis, Abdülgaffar Vural, Taner Basturk, Mutlu Saglam, Björn Anderstam, Hilmi Umut Unal, Serena Chicca, Aline Trevisan Peres, Maria Eugênia Fernandes Canziani, Alberto Ortiz, Mahmut Ilker Yilmaz, Bengt Lindholm, Stéphane Poitevin, Kiryong Park, Paolo M. Ghezzi, Antonio Pisani, Marialuisa Caiazzo, Noreddine Ghalim, Viktor Krot, Silvia Lucisano, Maria Aparecida Dalboni, Eleonora Riccio, Sarah Seiler, Giorgos Ntetskas, Oskar Svedberg, Carmela Aloisi, Sangeon Gwoo, Peter Bárány, Maria Bożentowicz-Wikarek, Alpaslan Altunoglu, O.M. Loboda, Elbis Ahbap, Dariusz Klein, Tuncer Cayci, Siren Sezer, Rosaria Lupica, Giuseppe Vita, Ruben Poesen, Björn Meijers, Nagba Yendoubé Gbandjaba, Magdalena Olszanecka-Glinianowicz, Burak Sayin, Won Yong Cho, Beata Marie Redublo Quinto, J. J. Carrero, Yuriko Yonekura, Felix C. Tanner, Miguel Cendoroglo, Olof Heimbürger, Cuneyt Akgol, Paola Michelozzi, Sarah Triem, Yoshiharu Ito, Emanouil Anastasakis, GrażYna Odrowa˛ż-Sypniewska, Caren Cristina Grabulosa, Aniceta Brzozowska, Hyung Kyu Kim, Marek Kretowicz, Maria Inês Barreto Silva, Thereza Christina Barja-Fidalgo, Yusuke Yamashita, Hideki Fujii, Simona Stancu, Luigi Tazza, Giuseppe Palladino, Nilufer Bayraktar, Rachel Bregman, Rahman Yavuz, Cengizhan Acikel, Barbara Rossi, Cristina Capusa, Massimo Sabbatini, Myung Gyu Kim, Guido Bellinghieri, Renata de Souza Mendes, Dorin Tarta, Radmila Veličković-Radovanović, Kyrill S. Rogacev, Kostantinos Roufas, and Thomas F. Lüscher

Subjects
Transplantation, medicine.medical_specialty, Framingham Risk Score, Cardiovascular History, business.industry, Hazard ratio, Renal function, medicine.disease, Gastroenterology, Endocrinology, Nephrology, Diabetes mellitus, Internal medicine, medicine, Myocardial infarction, Prospective cohort study, business, Kidney disease
Abstract

Introduction and Aims: Serum p-cresyl sulfate associates with cardiovascular disease in patients at different stages of chronic kidney disease. p-Cresyl sulfate concentrations are determined by intestinal uptake of p-cresol, human metabolism to p-cresyl sulfate and renal clearance. Whether intestinal uptake of p-cresol itself is associated with cardiovascular disease in patients with renal disease has not been studied to date. Methods: We performed a prospective study in patients with chronic kidney disease stage 1-5 (clinicaltrials.gov NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24h urinary excretion of p-cresyl sulfate. Primary endpoint was time to first cardiovascular event, i.e. cardiac death, myocardial infarction/ischemia, ventricular arythmia, cardiovascular surgery, cerebrovascular accident or symptomatic peripheral arterial disease. Statistical analysis was done using Kaplan Meier estimates and Cox proportional hazard analyses. Results: In a cohort of 200 patients, median 24h urinary excretion of p-cresyl sulfate was 457.47 µmol (IQR 252.68-697.17). After a median follow-up of 52 months, 25 patients reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.0368, see figure). Higher urinary excretion of p-cresyl sulfate was related with cardiovascular events (univariate hazard ratio per 100 µmol increase: 1.112, P 0.0015). In multivariate analysis, urinary excretion of p-cresyl sulfate remained a predictor of cardiovascular events, independent of markers of renal function (Hazard ratio 1.120, P 0.0022) and in different models with other cardiovascular risk factors (Framingham risk factors, cardiovascular history, diabetes mellitus and biochemical parameters). The independent association between urinary excretion of p-cresyl sulfate and outcome persisted after correction for serum p-cresyl sulfate. Conclusions: Intestinal uptake of p-cresol associates with cardiovascular disease independent of renal function. Insights into mechanisms governing intestinal generation and absorption of p-cresol may lead to identification of novel therapeutic targets to reduce cardiovascular disease risk in patients with chronic kidney disease.

Published
2014
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3. The AGE–RAGE Pathway and Its Relation to Cardiovascular Disease in Patients with Chronic Kidney Disease

Author

Paul Leurs and Bengt Lindholm

Subjects
Glycation End Products, Advanced, Oncology, medicine.medical_specialty, business.industry, Receptor for Advanced Glycation End Products, General Medicine, Disease, medicine.disease, Pathophysiology, RAGE (receptor), Endocrinology, Cardiovascular Diseases, Risk Factors, Glycation, Internal medicine, medicine, Humans, In patient, cardiovascular diseases, Morbidity, Receptors, Immunologic, Renal Insufficiency, Chronic, business, Signal Transduction, Kidney disease
Abstract

Chronic kidney disease (CKD) carries an unequivocal high risk for cardiovascular disease (CVD) contributing to high morbimortality; however, the underlying reasons are not fully known. Among mechanisms involved in the pathophysiology of CVD, chronic overstimulation of the advanced glycation end-products (AGE)–receptor for AGE (RAGE) pathway is likely a major contributor in patients with CKD. This review describes briefly some of the components of this pathway, highlighting especially differences between circulating AGE and tissue AGE and how activation of the AGE–RAGE pathway may promote CVD in CKD.

Published
2013
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4. Effects of Hemodiafiltration on Uremic Inflammation

Author

Bengt Lindholm, Paul Leurs, and Peter Stenvinkel

Subjects
Inflammation, medicine.medical_specialty, Inflammation biomarkers, business.industry, medicine.medical_treatment, Hemodiafiltration, Hematology, General Medicine, Disease, Systemic inflammation, High morbidity, Treatment Outcome, Risk Factors, Nephrology, medicine, Humans, Kidney Failure, Chronic, In patient, Hemodialysis, medicine.symptom, Intensive care medicine, business, Prospective cohort study
Abstract

Chronic inflammation is highly prevalent among end-stage renal disease patients and is linked to, and thought to contribute to, the high morbidity and mortality in this patient population. Hemodiafiltration (HDF) may potentially reduce inflammatory stimuli induced by the bioincompatibility of conventional hemodialysis (HD) systems. In addition, HDF may more efficiently remove inflammatory mediators. This brief review shows that the circulating levels of various markers of systemic inflammation in general are somewhat reduced in patients treated by HDF as compared to HD. On the other hand, according to the current literature, this favorable small impact on inflammation biomarkers does not seem to translate into better clinical outcomes. It is possible that this is due to inadequate design, inadequate number of investigated patients and too short duration of previous studies. The results of larger, better-designed ongoing prospective studies may hopefully clarify this.

Published
2013
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5. Plasma Pentosidine and Its Association with Mortality in Patients with Chronic Kidney Disease

Author

Naohito Isoyama, Olof Heimbürger, Abdul Rashid Qureshi, Peter Stenvinkel, Peter Bárány, Paul Leurs, Björn Anderstam, Anna Machowska, Bengt Lindholm, and Jia Sun

Subjects
Male, Physiology, medicine.medical_treatment, 030232 urology & nephrology, lcsh:Medicine, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Gastroenterology, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Chronic Kidney Disease, Medicine and Health Sciences, Longitudinal Studies, lcsh:Science, 2. Zero hunger, Aged, 80 and over, Multidisciplinary, Hematology, Middle Aged, 3. Good health, Body Fluids, Blood, Nephrology, Cardiovascular Diseases, Regression Analysis, Female, Hemodialysis, Anatomy, Research Article, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Endocrine Disorders, Renal function, Nutritional Status, Arginine, Blood Plasma, Peritoneal dialysis, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Albumins, Medical Dialysis, medicine, Diabetes Mellitus, Humans, Pentosidine, Renal Insufficiency, Chronic, Aged, Inflammation, Renal Physiology, business.industry, Lysine, lcsh:R, Biology and Life Sciences, Proteins, Cell Biology, medicine.disease, Oxidative Stress, chemistry, Relative risk, Metabolic Disorders, lcsh:Q, business, Body mass index, Biomarkers, Kidney disease
Abstract

Background Circulating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD). Here we evaluated factors linked to increased plasma pentosidine and its association with mortality in patients with different stages of CKD and undergoing different treatments. Methods Plasma pentosidine, biomarkers of inflammation, oxidative stress and nutritional status were investigated in CKD 1–2 (n = 37), CKD 3–4 (n = 54), CKD 5 non-dialyzed (CKD5-ND; n = 386), peritoneal dialysis (PD; n = 74) and hemodialysis (HD; n = 195) patients. Factors predicting plasma pentosidine were analysed by multivariate regression analysis and mortality risk was assessed by GENMOD procedure. Results Plasma pentosidine levels, which were higher in CKD5-ND, PD and HD groups than in CKD 1–2 group, were significantly lower in PD than in HD patients, and not different between PD patients and CKD5-ND patients. Pentosidine associated inversely with glomerular filtration rate (GFR), and additionally in PD with 8-hydroxy-2‘-deoxyguanosine (8-OHdG), and interleukin 6 (IL-6); in HD with age, IL-6 and body mass index (BMI); in CKD5-ND with age, 8-OHdG, IL-6, high-sensitive C-reactive protein (hsCRP), and soluble vascular cell adhesion protein-1 (sVCAM-1); in CKD 3–4 with 8-OHdG and sVCAM-1; and in CKD 1–2 with age and sVCAM-1. In multivariate analysis, age (one standard deviation, 1-SD higher), malnutrition (subjective global assessment, SGA), oxidative stress (8-OHdG, 1-SD higher), and belonging to CKD5-ND, HD and PD cohorts associated with 1-SD higher pentosidine. In GENMOD, 1-SD higher pentosidine independently predicted all-cause mortality (relative risk, RR = 1.04; 95% confidence interval, CI, 1.01–1.08, p = 0.01) and CVD mortality (RR = 1.03; 95% CI, 1.01–1.06, p = 0.03) after adjusting for all confounders. Conclusions Plasma pentosidine is markedly elevated in CKD and associates with low GFR, oxidative stress and inflammation, and is an independent predictor of mortality in CKD patients.

Published
2016

6. Timing of dialysis initiation: when to start? Which treatment?

Author

Bengt Lindholm, Anna Machowska, and Paul Leurs

Subjects
medicine.medical_specialty, Time Factors, medicine.medical_treatment, Hemodialysis Catheter, Medicine (miscellaneous), Renal function, Peritoneal dialysis, Renal Dialysis, Risk Factors, medicine, Humans, Intensive care medicine, Wasting, Dialysis, Nutrition and Dietetics, business.industry, medicine.disease, Comorbidity, Uremia, Nephrology, Practice Guidelines as Topic, Kidney Failure, Chronic, Hemodialysis, medicine.symptom, business, Glomerular Filtration Rate
Abstract

During the late 1990s early initiation of dialysis was introduced on a large scale and between 1996 and 2008, the percentage of patients with an estimated glomerular filtration rate (eGFR) above 10 mL/minute starting dialysis rose from 25% to 54% in the United States. However, several subsequent studies showed no survival benefit for patients commencing dialysis earlier. One possible explanation for the negative results could be that eGFR may be a flawed index; s-creatinine is lower in patients with muscle wasting or fluid overload and these vulnerable patients with high comorbidity burden often start "early", i.e., at higher eGFR. Another explanation could be that dialysis is in fact harmful; dialysis initiation with conventional thrice weekly in-center hemodialysis clearly associates with increased initial mortality risk especially when using temporary dialysis catheters. Interestingly, patients starting on peritoneal dialysis (PD) appear to have better initial outcomes. More attention should be given to finding new objective mortality-predictive markers of uremia, reducing the use of temporary hemodialysis catheters, and increasing the use of PD as initial dialysis modality. PD may not only provide better initial dialysis outcomes but may also preserve renal function and vessels for vascular access for the benefit of better long-term outcomes.

Published
2014

7. Plasma S100A12 and soluble receptor of advanced glycation end product levels and mortality in chronic kidney disease Stage 5 patients

Author

Peter Bárány, Björn Anderstam, Bengt Lindholm, Paul Leurs, Olof Heimbürger, Annette Bruchfeld, Naohito Isoyama, Abdul Rashid Qureshi, and Peter Stenvinkel

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Receptor for Advanced Glycation End Products, Renal function, urologic and male genital diseases, Gastroenterology, End stage renal disease, Peritoneal dialysis, Renal Dialysis, Internal medicine, medicine, Humans, Receptors, Immunologic, Renal Insufficiency, Chronic, Survival rate, Dialysis, Aged, Inflammation, Transplantation, biology, business.industry, C-reactive protein, Hazard ratio, S100 Proteins, S100A12 Protein, Middle Aged, medicine.disease, Prognosis, Survival Rate, Endocrinology, C-Reactive Protein, Nephrology, biology.protein, Female, business, Peritoneal Dialysis, Biomarkers, Kidney disease, Glomerular Filtration Rate
Abstract

Background. Alterations in the advanced glycation end-products (AGE)—receptor of AGE (RAGE) system are linkedto several chronic diseases, which may result from vasculardamage. A high circulating level of the pro-inflammatoryRAGE-ligand S100A12, also known as EN-RAGE, is thoughtto promote while a high level of soluble RAGE (sRAGE) isthought to protect against development of atherosclerotic car-diovascular disease (CVD). We evaluated circulating S100A12and sRAGE in relation to clinical characteristics, nutritionalstatus, inflammation and mortality risk in chronic kidneydisease (CKD) Stage 5 patients starting on dialysis.Methods. Plasma S100A12 and sRAGE, biomarkers of inflam-mation and nutritional status, and comorbidities were investi-gated in 200 CKD Stage 5 patients [median age of 56 years,62% men and median glomerular filtration rate (GFR) of6.2 mL/min/1.73 m 2 ] in conjunction with initiation of dialysistherapy. Associations between mortality risk and S100A12 orsRAGE were assessed after a median follow-up period of23 months. In addition, for comparative analyses, S100A12and sRAGE levels were assessed also in 58 haemodialysis and78 peritoneal dialysis patients after 1 year of dialysis, 56 CKDStages 3–4 patients and 50 community-based control subjects.Results. The median level of S100A12 was 4-fold higher, mediansRAGE 2.4 higher and median ratio S100A12/sRAGE 2.27 timeshigher in CKD 5 patients than in controls. Similar alterationswere observed in CKD 3–4 patients; however, CKD 5 patientshad a higher median level of sRAGE than the CKD 3 –4patients.In the CKD 5 patients, S100A12 levels were higher in those withdiabetes or CVD than in those without these comorbidities. Fur-thermore, S100A12 correlated with high-sensitivity C-reactiveprotein (hsCRP) levels (ρ=0.53; P

Published
2014

8. SP429CIRCULATING PLASMA PENTOSIDINE IN PRE-DIALYSIS, PRE-TRANSPLANT, PERITONEAL DIALYSIS (PD) AND HEMODIALYSIS (HD) PATIENTS (PTS)

Author

Abdul Rashid Qureshi, Peter Stenvinkel, Peter Bárány, Bengt Lindholm, Olof Heimbürger, Anna Machowska, Paul Leurs, Björn Anderstam, and Naohito Isoyama

Subjects
Transplantation, medicine.medical_specialty, business.industry, medicine.medical_treatment, Pre-dialysis, Urology, Peritoneal dialysis, chemistry.chemical_compound, chemistry, Nephrology, medicine, Pentosidine, business, Hemodialysis hd
Published
2015
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9. Tissue factor pathway inhibitor and other endothelium-dependent hemostatic factors in elderly individuals with normal or impaired glucose tolerance and type 2 diabetes

Author

Bruce H. R. Wolffenbuttel, Diederick E. Grobbee, Karly Hamulyák, R. van Oerle, Ronald P. Stolk, Paul Leurs, Interne Geneeskunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
VONWILLEBRAND-FACTOR, Blood Glucose, Male, medicine.medical_specialty, VON-WILLEBRAND-FACTOR, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Lipoproteins, Thrombomodulin, Type 2 diabetes, PLASMINOGEN-ACTIVATOR INHIBITOR-1, Impaired glucose tolerance, chemistry.chemical_compound, Insulin resistance, Tissue factor pathway inhibitor, NIDDM, Internal medicine, Diabetes mellitus, von Willebrand Factor, Internal Medicine, medicine, Humans, HUMAN-PLASMA, ALBUMIN EXCRETION, Aged, Advanced and Specialized Nursing, Hemostasis, business.industry, Insulin, Glucose Tolerance Test, Middle Aged, medicine.disease, INSULIN, Endocrinology, chemistry, Diabetes Mellitus, Type 2, CARDIOVASCULAR-DISEASE, Plasminogen activator inhibitor-1, Tissue Plasminogen Activator, cardiovascular system, RISK-FACTORS, Female, Endothelium, Vascular, Insulin Resistance, business, Biomarkers, FIBRINOLYTIC-ACTIVITY
Abstract

OBJECTIVE—Impaired glucose tolerance (IGT) is believed to be a prediabetic phase that precedes the development of type 2 diabetes. In elderly subjects, IGT and diabetes are both independently associated with the occurrence of cardiovascular disease. Endothelial damage precedes atherosclerotic changes of the vascular wall. Therefore, several markers of endothelial dysfunction were examined in elderly subjects with IGT and elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), and thrombomodulin were studied as markers of endothelial dysfunction in a population-based study of elderly subjects with normal glucose tolerance (NGT) or IGT and type 2 diabetes. In addition to these endothelium-dependent factors, we also investigated tissue factor pathway inhibitor (TFPI) activity in relation to metabolic parameters and cardiovascular risk factors. RESULTS—All data were adjusted for age. Increased levels of vWF antigen, t-PA antigen, and PAI-1 activity were seen in the IGT and diabetic group compared with the NGT group. TFPI activity and thrombomodulin levels were increased in all elderly subjects, and no differences were seen between the groups. There was a positive association between HbA1c and TFPI activity and vWF antigen. Fasting blood glucose levels correlated with vWF antigen, t-PA antigen, and PAI-1 activity, whereas urine albumin excretion correlated with TFPI activity, vWF antigen, and PAI-1 activity. Serum insulin levels correlated strongly not only with vWF antigen and t-PA antigen but also with PAI-1 activity. This correlation did not change after further adjustment for serum glucose and HbA1c, which may suggest that in the elderly subjects, impaired fibrinolysis is probably associated with insulin resistance. There were no associations between the endothelium-dependent hemostatic factors and lipids, except for a negative correlation between HDL cholesterol and thrombomodulin. CONCLUSIONS—In elderly subjects with IGT, several endothelium-dependent hemostatic factors are already consistently increased, indicating endothelial damage in this stage.

Published
2002

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