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1. The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease

Author

Massy Z. A., Chesnaye N. C., Larabi I. A., Dekker F. W., Evans M., Caskey F. J., Torino C., Porto G., Szymczak M., Drechsler C., Wanner C., Jager K. J., Alvarez J. C., Schneider A., Torp A., Iwig B., Perras B., Marx C., Blaser C., Emde C., Krieter D., Fuchs D., Irmler E., Platen E., Schmidt-Gurtler H., Schlee H., Naujoks H., Schlee I., Casar S., Beige J., Rothele J., Mazur J., Hahn K., Blouin K., Neumeier K., Anding-Rost K., Schramm L., Hopf M., Wuttke N., Frischmuth N., Ichtiaris P., Kirste P., Schulz P., Aign S., Biribauer S., Manan S., Roser S., Heidenreich S., Palm S., Schwedler S., Delrieux S., Renker S., Schattel S., Stephan T., Schmiedeke T., Weinreich T., Leimbach T., Stovesand T., Bahner U., Seeger W., Cupisti A., Sagliocca A., Ferraro A., Mele A., Naticchia A., Cosaro A., Ranghino A., Stucchi A., Pignataro A., De Blasio A., Pani A., Tsalouichos A., Bellasi A., Raffaele Di Iorio B., Butti A., Abaterusso C., Somma C., D'Alessandro C., Zullo C., Pozzi C., Bergamo D., Ciurlino D., Motta D., Russo D., Favaro E., Vigotti F., Ansali F., Conte F., Cianciotta F., Giacchino F., Cappellaio F., Pizzarelli F., Greco G., Bigatti G., Marinangeli G., Cabiddu G., Fumagalli G., Caloro G., Piccoli G., Capasso G., Gambaro G., Tognarelli G., Bonforte G., Conte G., Toscano G., Del Rosso G., Capizzi I., Baragetti I., Oldrizzi L., Gesualdo L., Biancone L., Magnano M., Ricardi M., Di Bari M., Laudato M., Luisa Sirico M., Ferraresi M., Provenzano M., Malaguti M., Palmieri N., Murrone P., Cirillo P., Dattolo P., Acampora P., Nigro R., Boero R., Scarpioni R., Sicoli R., Malandra R., Savoldi S., Bertoli S., Borrelli S., Maxia S., Maffei S., Mangano S., Cicchetti T., Rappa T., Palazzo V., De Simone W., Schrander A., Van Dam B., Siegert C., Gaillard C., Beerenhout C., Verburgh C., Janmaat C., Hoogeveen E., Hoorn E., Boots J., Boom H., Eijgenraam J. -W., Kooman J., Rotmans J., Vogt L., Raasveld M., Vervloet M., Van Buren M., Van Diepen M., Leurs P., Voskamp P., Blankestijn P., Van Esch S., Boorsma S., Berger S., Konings C., Aydin Z., Musiala A., Szymczak A., Olczyk E., Augustyniak-Bartosik H., Miskowiec-Wisniewska I., Manitius J., Pondel J., Jedrzejak K., Nowanska K., Nowak L., Durlik M., Dorota S., Nieszporek T., Heleniak Z., Jonsson A., Blom A. -L., Rogland B., Wallquist C., Vargas D., Dimeny E., Sundelin F., Uhlin F., Welander G., Bascaran Hernandez I., Grontoft K. -C., Stendahl M., Svensson M., Heimburger O., Kashioulis P., Melander S., Almquist T., Jensen U., Woodman A., McKeever A., Ullah A., McLaren B., Harron C., Barrett C., O'Toole C., Summersgill C., Geddes C., Glowski D., McGlynn D., Sands D., Roy G., Hirst G., King H., McNally H., Masri-Senghor H., Murtagh H., Rayner H., Turner J., Wilcox J., Berdeprado J., Wong J., Banda J., Jones K., Haydock L., Wilkinson L., Carmody M., Weetman M., Joinson M., Dutton M., Matthews M., Morgan N., Bleakley N., Cockwell P., Roderick P., Mason P., Kalra P., Sajith R., Chapman S., Navjee S., Crosbie S., Brown S., Tickle S., Mathavakkannan S., Kuan Y., Massy, Z. A., Chesnaye, N. C., Larabi, I. A., Dekker, F. W., Evans, M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Drechsler, C., Wanner, C., Jager, K. J., Alvarez, J. C., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Bellasi, A., Raffaele Di Iorio, B., Butti, A., Abaterusso, C., Somma, C., D'Alessandro, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Heimburger, O., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., Kuan, Y., Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, APH - Quality of Care, APH - Global Health, APH - Health Behaviors & Chronic Diseases, and ACS - Pulmonary hypertension & thrombosis

Subjects
Transplantation, Nephrology, uremic toxins, CKD, symptoms, symptom, elderly
Abstract

Background Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD. Methods The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden and the UK were included in the present study (n = 795). Data and symptom self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and 10 uremic toxins were quantified. We tested the association between uremic toxins and symptoms and adjusted P-values for multiple testing. Results Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine N-oxide (TMAO; positive association with fatigue), p-cresyl sulfate (PCS) with constipation and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analyses. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although it only reached statistical significance in the full population. In contrast, TMAO (fatigue) and PCS and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women. Conclusion Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia-related factors or psychosocial factors not yet explored might contribute to symptom burden.

Published
2022
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2. Association of longitudinal high-sensitivity troponin T with Mortality in patients with chronic kidney disease

Author

Chesnaye, N.C., Al-Sodany, E., Szummer, K., Barany, P., Heimburger, O., Almquist, T., Melander, S., Uhlin, F., Dekker, F., Wanner, C., Jager, K.J., Evans, M., Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Methodology, APH - Quality of Care, APH - Global Health, and APH - Health Behaviors & Chronic Diseases

Subjects
Aged, 80 and over, Male, troponin T, Age Factors, survival, Europe, Survival Rate, Risk Factors, Humans, Female, Longitudinal Studies, Prospective Studies, Renal Insufficiency, Chronic, Cardiology and Cardiovascular Medicine, chronic kidney disease, Aged, joint model
Abstract

BACKGROUND Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed. OBJECTIVES This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD. METHODS The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged $65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival. RESULTS There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.06.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure. CONCLUSIONS Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk. (J Am Coll Cardiol 2022;79:327-336) (c) 2022 by the American College of Cardiology Foundation.

Published
2022

4. Health related quality of life and life-style factors are associated with decline in nutritional status in older adults with chronic kidney disease; the equal study

Author

Windahl, K., primary, Faxén Irving, G., additional, Korkeila Lidén, M., additional, Almquist, T., additional, Stenvinkel, P., additional, Chesnaye, N., additional, Gaetana Porto, T., additional, Torino, C., additional, Klinger, M., additional, Szymczak, M., additional, Janmaat, C., additional, Postorini, M., additional, Drechsler, C., additional, Hole, B., additional, Caskey, F., additional, Wanner, C., additional, Dekker, F., additional, Jager, K., additional, and Evans, M., additional

Published
2018
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5. Lipid-lowering treatment and inflammatory mediators in diabetes and chronic kidney disease

Author

Almquist, T., Jacobson, S. H., Mobarrez, F., Näsman, Per, Hjemdahl, P., Almquist, T., Jacobson, S. H., Mobarrez, F., Näsman, Per, and Hjemdahl, P.

Abstract

Background: Inflammation may contribute to the high cardiovascular risk in diabetes mellitus (DM) and chronic kidney disease (CKD). Monocyte chemoattractant protein-1 (MCP-1) facilitates the recruitment of monocytes into atherosclerotic lesions and is involved in diabetic nephropathy. Interferon gamma (IFNγ) is important in atherosclerosis and increases the synthesis of chemokines including MCP-1. Lipid-lowering treatment (LLT) with statins may have anti-inflammatory effects, and ezetimibe cotreatment provides additional cholesterol lowering. Methods: After a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S+E) were compared in a randomized, double-blind, cross-over study on inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1·73 m2 (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR > 75 mL/min (DM only) were included. Results: At baseline, monocyte chemoattractant protein 1 (MCP-1) (P = 0·03), IFNγ (P = 0·02), tumour necrosis factor-α (TNFα) (P < 0·01) and soluble vascular adhesion molecule (sVCAM) (P = 0·001) levels were elevated in DM-CKD compared with DM-only patients. LLT with S and S+E reduced MCP-1 levels (P < 0·01 by anova) and IFNγ levels (P < 0·01) in DM-CKD patients but not in DM-only patients. Reductions were most pronounced with the combination treatment. Conclusions: DM patients with CKD stages 3-4 had increased inflammatory activity compared with DM patients with normal GFR. Lipid-lowering treatment decreased the levels of MCP-1 and IFNγ in DM patients with concomitant CKD, which may be beneficial with regard to the progression of both atherosclerosis and diabetic nephropathy., QC 20140228

Published
2014
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8. Nitrous Oxide-Oxygen Sedation: USAF Dental Guidelines.

Author

SCHOOL OF AEROSPACE MEDICINE BROOKS AFB TX, Schade,C M, Almquist,T C, Jerman,A C, Young,J M, SCHOOL OF AEROSPACE MEDICINE BROOKS AFB TX, Schade,C M, Almquist,T C, Jerman,A C, and Young,J M

Abstract

These guidelines are to be used in teaching the dental applications of nitrous oxide-oxygen sedation. The guidelines will be the basic document for a course designed to certify participating dental officers in the use of nitrous oxide-oxygen sedation in the dental treatment room. (Author)

Published
1981

10. Predicting Kidney Failure, Cardiovascular Disease and Death in Advanced CKD Patients

Author

Chava L. Ramspek, Rosemarijn Boekee, Marie Evans, Olof Heimburger, Charlotte M. Snead, Fergus J. Caskey, Claudia Torino, Gaetana Porto, Maciej Szymczak, Magdalena Krajewska, Christiane Drechsler, Christoph Wanner, Nicholas C. Chesnaye, Kitty J. Jager, Friedo W. Dekker, Maarten G.J. Snoeijs, Joris I. Rotmans, Merel van Diepen, 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, 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, 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, Vascular Surgery, MUMC+: MA Med Staf Spec Vaatchirurgie (9), RS: Carim - V03 Regenerative and reconstructive medicine vascular disease, Ramspek, C. L., Boekee, R., Evans, M., Heimburger, O., Snead, C. M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Krajewska, M., Drechsler, C., Wanner, C., Chesnaye, N. C., Jager, K. J., Dekker, F. W., Snoeijs, M. G. J., Rotmans, J. I., van Diepen, M., Cupisti, A., Sagliocca, A., Ferraro, A., Musiala, A., Mele, A., Naticchia, A., Cosaro, A., Woodman, A., Ranghino, A., Stucchi, A., Jonsson, A., Schneider, A., Pignataro, A., Schrander, A., Torp, A., Mckeever, A., Szymczak, A., Blom, A. -L., De Blasio, A., Pani, A., Tsalouichos, A., Ullah, A., Mclaren, B., van Dam, B., Iwig, B., Antonio, B., Di Iorio, B. R., Rogland, B., Perras, B., Alessandra, B., Harron, C., Wallquist, C., Siegert, C., Barrett, C., Gaillard, C., Garofalo, C., Abaterusso, C., Beerenhout, C., O'Toole, C., Somma, C., Marx, C., Summersgill, C., Blaser, C., D'Alessandro, C., Emde, C., Zullo, C., Pozzi, C., Geddes, C., Verburgh, C., Bergamo, D., Ciurlino, D., Motta, D., Glowski, D., Mcglynn, D., Vargas, D., Krieter, D., Russo, D., Fuchs, D., Sands, D., Hoogeveen, E., Irmler, E., Dimeny, E., Favaro, E., Platen, E., Olczyk, E., Hoorn, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Sundelin, F., Uhlin, F., Greco, G., Roy, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Hirst, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Welander, G., Augustyniak-Bartosik, H., Boots, H., Schmidt-Gurtler, H., King, H., Mcnally, H., Schlee, H., Boom, H., Naujoks, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Miskowiec-Wisniewska, I., Schlee, I., Capizzi, I., Hernandez, I. B., Baragetti, I., Manitius, J., Turner, J., Eijgenraam, J. -W., Kooman, J., Beige, J., Pondel, J., Wilcox, J., Berdeprado, J., Rothele, J., Wong, J., Rotmans, J., Banda, J., Mazur, J., Hahn, K., Jedrzejak, K., Nowanska, K., Blouin, K., Neumeier, K., Jones, K., Anding-Rost, K., Grontoft, K. -C., Oldrizzi, L., Haydock, L., Vogt, L., Wilkinson, L., Gesualdo, L., Schramm, L., Biancone, L., Nowak, L., Raasveld, M., Durlik, M., Magnano, M., Vervloet, M., Ricardi, M., Carmody, M., Di Bari, M., Laudato, M., Sirico, M. L., Stendahl, M., Svensson, M., Weetman, M., van Buren, M., Joinson, M., Ferraresi, M., Dutton, M., Matthews, M., Provenzano, M., Hopf, M., Malaguti, M., Wuttke, N., Morgan, N., Palmieri, N., Frischmuth, N., Bleakley, N., Murrone, P., Cockwell, P., Leurs, P., Roderick, P., Voskamp, P., Kashioulis, P., Ichtiaris, P., Blankestijn, P., Kirste, P., Schulz, P., Mason, P., Kalra, P., Cirillo, P., Dattolo, P., Acampora, P., Sajith, R., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Aign, S., Casar, S., van Esch, S., Chapman, S., Biribauer, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Manan, S., Roser, S., Savoldi, S., Bertoli, S., Borrelli, S., Boorsma, S., Heidenreich, S., Melander, S., Maxia, S., Maffei, S., Mangano, S., Palm, S., Konings, S., Mathavakkannan, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Dorota, S., Cicchetti, T., Nieszporek, T., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Rappa, T., Almquist, T., Stovesand, T., Bahner, U., Jensen, U., Palazzo, V., De Simone, W., Seeger, W., Kuan, Y., Heleniak, Z., Aydin, Z., Medical Informatics, APH - Aging & Later Life, APH - Methodology, APH - Quality of Care, Nephrology, ACS - Microcirculation, APH - Health Behaviors & Chronic Diseases, APH - Global Health, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, and Internal Medicine

Subjects
SDG 3 - Good Health and Well-being, external validation, Nephrology, cardiovascular disease, death, CKD, kidney failure, prognostic model
Abstract

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries.

Published
2022
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11. Associations between depressive symptoms and disease progression in older patients with chronic kidney disease

Author

Eveleens Maarse, Boukje C., Chesnaye, Nicholas C., Robbert, Schouten, Michels, Wieneke M., Bos, Willem Jan W., Maciej, Szymczak, Magdalena, Krajewska, Marie Evans, Olof Heimburger, Caskey, Fergus J., Christoph, Wanner, Jager, Kitty J., Dekker, Friedo W., Yvette, Meuleman, Andreas, Schneider, Anke, Torp, Beate, Iwig, Boris, Perras, Christian, Marx, Christiane, Drechsler, Christof, Blaser, Claudia, Emde, Detlef, Krieter, Dunja, Fuchs, Ellen, Irmler, Eva, Platen, Hans, Schmidt-Gürtler, Hendrik, Schlee, Holger, Naujoks, Ines, Schlee, Sabine, Cäsar, Joachim, Beige, Jochen, Röthele, Justyna, Mazur, Kai, Hahn, Katja, Blouin, Katrin, Neumeier, Kirsten, Anding-Rost, Lothar, Schramm, Monika, Hopf, Nadja, Wuttke, Nikolaus, Frischmuth, Pawlos, Ichtiaris, Petra, Kirste, Petra, Schulz, Sabine, Aign, Sandra, Biribauer, Sherin, Manan, Silke, Röser, Stefan, Heidenreich, Stephanie, Palm, Susanne, Schwedler, Sylke, Delrieux, Sylvia, Renker, Sylvia, Schättel, Theresa, Stephan, Thomas, Schmiedeke, Thomas, Weinreich, Til, Leimbach, Torsten, Stövesand, Udo, Bahner, Wolfgang, Seeger, Cupisti, Adamasco, Adelia, Sagliocca, Alberto, Ferraro, Alessandra, Mele, Alessandro, Naticchia, Alex, Còsaro, Andrea, Ranghino, Andrea, Stucchi, Angelo, Pignataro, Antonella De Blasio, Antonello, Pani, Aris, Tsalouichos, Bellasi, Antonio, Biagio Raffaele Di Iorio, Butti, Alessandra, Cataldo, Abaterusso, Chiara, Somma, Claudia, D'Alessandro, Claudia, Torino, Claudia, Zullo, Claudio, Pozzi, Daniela, Bergamo, Daniele, Ciurlino, Daria, Motta, Domenico, Russo, Enrico, Favaro, Federica, Vigotti, Ferruccio, Ansali, Ferruccio, Conte, Francesca, Cianciotta, Francesca, Giacchino, Francesco, Cappellaio, Francesco, Pizzarelli, Gaetano, Greco, Gaetana, Porto, Giada, Bigatti, Giancarlo, Marinangeli, Gianfranca, Cabiddu, Giordano, Fumagalli, Giorgia, Caloro, Giorgina, Piccoli, Giovanbattista, Capasso, Giovanni, Gambaro, Giuliana, Tognarelli, Giuseppe, Bonforte, Giuseppe, Conte, Giuseppe, Toscano, Goffredo Del Rosso, Irene, Capizzi, Ivano, Baragetti, Lamberto, Oldrizzi, Loreto, Gesualdo, Luigi, Biancone, Manuela, Magnano, Marco, Ricardi, Maria Di Bari, Maria, Laudato, Maria Luisa Sirico, Martina, Ferraresi, Maurizio, Postorino, Michele, Provenzano, Moreno, Malaguti, Nicola, Palmieri, Paola, Murrone, Pietro, Cirillo, Pietro, Dattolo, Pina, Acampora, Rita, Nigro, Roberto, Boero, Roberto, Scarpioni, Rosa, Sicoli, Rosella, Malandra, Silvana, Savoldi, Silvio, Bertoli, Silvio, Borrelli, Stefania, Maxia, Stefano, Maffei, Stefano, Mangano, Teresa, Cicchetti, Tiziana, Rappa, Valentina, Palazzo, Walter De Simone, Anita, Schrander, Bastiaan van Dam, Carl, Siegert, Carlo, Gaillard, Charles, Beerenhout, Cornelis, Verburgh, Cynthia, Janmaat, Ellen, Hoogeveen, Ewout, Hoorn, Friedo, Dekker, Johannes, Boots, Henk, Boom, Jan-Willem, Eijgenraam, Jeroen, Kooman, Joris, Rotmans, Kitty, Jager, Liffert, Vogt, Maarten, Raasveld, Marc, Vervloet, Marjolijn van Buren, Merel van Diepen, Nicholas, Chesnaye, Paul, Leurs, Pauline, Voskamp, Peter, Blankestijn, Sadie van Esch, Siska, Boorsma, Stefan, Berger, Constantijn, Konings, Zeynep, Aydin, Aleksandra, Musiała, Anna, Szymczak, Ewelina, Olczyk, Hanna, Augustyniak-Bartosik, Ilona, Miśkowiec-Wiśniewska, Jacek, Manitius, Joanna, Pondel, Kamila, Jędrzejak, Katarzyna, Nowańska, Łukasz, Nowak, Magdalena, Durlik, Szyszkowska, Dorota, Teresa, Nieszporek, Zbigniew, Heleniak, Andreas, Jonsson, Anna-Lena, Blom, Björn, Rogland, Carin, Wallquist, Denes, Vargas, Emöke, Dimény, Fredrik, Sundelin, Fredrik, Uhlin, Gunilla, Welander, Isabel Bascaran Hernandez, Knut-Christian, Gröntoft, Maria, Stendahl, Maria, Svensson, Marie, Evans, Olof, Heimburger, Pavlos, Kashioulis, Stefan, Melander, Tora, Almquist, Ulrika, Jensen, Alistair, Woodman, Anna, Mckeever, Asad, Ullah, Barbara, Mclaren, Camille, Harron, Carla, Barrett, Charlotte, O'Toole, Christina, Summersgill, Colin, Geddes, Deborah, Glowski, Deborah, Mcglynn, Dympna, Sands, Fergus, Caskey, Geena, Roy, Gillian, Hirst, Hayley, King, Helen, Mcnally, Houda, Masri-Senghor, Hugh, Murtagh, Hugh, Rayner, Jane, Turner, Joanne, Wilcox, Jocelyn, Berdeprado, Jonathan, Wong, Joyce, Banda, Kirsteen, Jones, Lesley, Haydock, Lily, Wilkinson, Margaret, Carmody, Maria, Weetman, Martin, Joinson, Mary, Dutton, Michael, Matthews, Neal, Morgan, Nina, Bleakley, Paul, Cockwell, Paul, Roderick, Phil, Mason, Philip, Kalra, Rincy, Sajith, Sally, Chapman, Santee, Navjee, Sarah, Crosbie, Sharon, Brown, Sheila, Tickle, Suresh, Mathavakkannan, Ying, Kuan, Internal medicine, Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, Graduate School, APH - Quality of Care, ACS - Microcirculation, APH - Health Behaviors & Chronic Diseases, APH - Global Health, ACS - Pulmonary hypertension & thrombosis, Eveleens Maarse, B. C., Chesnaye, N. C., Schouten, R., Michels, W. M., Bos, W. J. W., Szymczak, M., Krajewska, M., Evans, M., Heimburger, O., Caskey, F. J., Wanner, C., Jager, K. J., Dekker, F. W., Meuleman, Y., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Drechsler, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Antonio, B., Raffaele Di Iorio, B., Alessandra, B., Abaterusso, C., Somma, C., D'Alessandro, C., Torino, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Porto, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Postorino, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., and Kuan, Y.

Subjects
Transplantation, prospective cohort study, depressive symptoms, nephrology care, Nephrology, clinical outcome, chronic kidney disease, clinical trial, epidemiology, joint model, survival analysis, depressive symptom
Abstract

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0–100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was –0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03–1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men.

Published
2022
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12. The safety of a low-protein diet in older adults with advanced chronic kidney disease.

Author

Windahl K, Chesnaye NC, Irving GF, Stenvinkel P, Almquist T, Lidén MK, Drechsler C, Szymczak M, Krajewska M, de Rooij E, Torino C, Porto G, Caskey FJ, Wanner C, Jager KJ, Dekker FW, and Evans M

Subjects
Humans, Aged, Male, Female, Prospective Studies, Follow-Up Studies, Aged, 80 and over, Prognosis, Europe, Survival Rate, Renal Insufficiency, Chronic mortality, Diet, Protein-Restricted methods, Diet, Protein-Restricted adverse effects, Glomerular Filtration Rate, Nutritional Status
Abstract

Background: A low-protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD., Methods: The EQUAL study is a prospective, observational study including patients ≥65 years of age with an incident estimated glomerular filtration rate <20 ml/min/1.73 m2 in six European countries with follow-up through 6 years. Nutritional status was assessed by a 7-point subjective global assessment (SGA) every 3-6 months. Prescribed diet (g protein/kg of bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease of ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights., Results: Of 1738 adults (631 prescribed LPD at any point during follow-up), there were 1319 with repeated SGA measurements, of which 267 (20%) decreased in SGA ≥2 points and 565 (32.5%) who died. There was no difference in survival or decrease in nutritional status for patients prescribed a LPD ≤0.8 g/kg ideal bodyweight {odds ratio [OR] for mortality 1.15 [95% confidence interval (CI) 0.86-1.55)] and OR for decrease in SGA 1.11 [95% CI 0.74-1.66]} in the adjusted models. In patients prescribed a LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and older age >75 years, lower SGA and higher comorbidity burden for both mortality and nutritional status decline., Conclusions: In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Published
2024
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13. Patient-Reported Measures and Lifestyle Are Associated With Deterioration in Nutritional Status in CKD Stage 4-5: The EQUAL Cohort Study.

Author

Windahl K, Irving GF, Almquist T, Lidén MK, Stenvinkel P, Chesnaye NC, Drechsler C, Szymczak M, Krajewska M, Fu EL, Torino C, Porto G, Roderick P, Caskey FJ, Wanner C, Dekker FW, Jager KJ, and Evans M

Subjects
Aged, Cohort Studies, Female, Humans, Life Style, Male, Nutritional Status, Patient Reported Outcome Measures, Prospective Studies, Kidney Failure, Chronic therapy, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic epidemiology
Abstract

Objective: The aim of this study was to explore the changes in nutritional status before dialysis initiation and to identify modifiable risk factors of nutritional status decline in older adults with advanced renal disease., Design and Methods: The European Quality Study on treatment in advanced chronic kidney disease (EQUAL) is a prospective, observational cohort study involving six European countries. We included 1,103 adults >65 years with incident estimated glomerular filtration rate <20 mL/min/1.73 m 2 not on dialysis, attending nephrology care. Nutritional status was assessed with the 7-point Subjective Global Assessment tool (7-p SGA), patient-reported outcomes with RAND-36 and the Dialysis Symptom Index. Logistic regression was used to estimate the associations between potential risk factors and SGA decline., Results: The majority of the patients had a normal nutritional status at baseline, 28% were moderately malnourished (SGA ≤5). Overall, mean SGA decreased by -0.18 points/year, (95% confidence interval -0.21; -0.14). More than one-third of the study participants (34.9%) deteriorated in nutritional status (1 point decline in SGA) and 10.9% had a severe decline in SGA (≥2 points). The proportion of patients with low SGA (≤5) increased every 6 months. Those who dropped in SGA also declined in estimated glomerular filtration rate and mental health score. Every 10 points decrease in physical function score increased the odds of decline in SGA by 23%. Lower physical function score at baseline, gastrointestinal symptoms, and smoking were risk factors for impaired nutritional status. There was an interaction between diabetes and physical function on SGA decline., Conclusions: Nutritional status deteriorated in more than one-third of the study participants during the first year of follow-up. Lower patient-reported physical function, more gastrointestinal symptoms, and current smoking were associated with decline in nutritional status., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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14. Association of Longitudinal High-Sensitivity Troponin T With Mortality in Patients With Chronic Kidney Disease.

Author

Chesnaye NC, Al-Sodany E, Szummer K, Barany P, Heimbürger O, Almquist T, Melander S, Uhlin F, Dekker F, Wanner C, Jager KJ, and Evans M

Subjects
Age Factors, Aged, Aged, 80 and over, Europe, Female, Humans, Longitudinal Studies, Male, Prospective Studies, Renal Insufficiency, Chronic complications, Risk Factors, Survival Rate, Renal Insufficiency, Chronic blood, Renal Insufficiency, Chronic mortality, Troponin T blood
Abstract

Background: Cardiac troponin T (cTnT) is associated with mortality in chronic kidney disease (CKD). However, the association between longitudinal cTnT measurements and survival has not previously been assessed., Objectives: This study determined whether various parameterizations of longitudinal cTnT measurements were associated with patient survival in the older population with advanced CKD., Methods: The EQUAL (European QUALity) study is an observational prospective cohort study that includes subjects with stage 4-5 CKD aged ≥65 years and not on dialysis. The study includes 176 participants in Sweden, where longitudinal information of cTnT was collected. The study uses joint models for longitudinal and time-to-event data to assess the longitudinal association between cTnT and survival., Results: There were 927 cTnT measurements (median 6 per patient) collected over a median follow-up of 2.4 years. The overall 5-year survival was 57% (95% CI: 46%-69%). Longitudinally measured cTnT was associated with mortality risk, with every SD increase in cTnT, at any time point, associated with a 3.3-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). The slope of the cTnT trajectory was also associated with increased mortality risk (HR: 3.2; 95% CI: 2.0-6.0), as was the area under the cTnT trajectory (HR: 4.2; 95% CI: 2.6-7.2), which reflected the cumulative cTnT exposure., Conclusions: Longitudinally measured cTnT is independently associated with mortality risk in older patients with stage 4 and 5 CKD, which suggests that monitoring patients with cTnT could be a valuable tool for the identification of subjects with a high mortality risk., Competing Interests: Funding Support and Author Disclosures Main funding was received from the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA). Contributions came from the Swedish Medical Association (SLS), the Stockholm County Council ALF Medicine and Center for Innovative research (CIMED), the Italian Society of Nephrology (SIN-Reni), the Dutch Kidney Foundation (SB 142), the Young Investigators grant in Germany, and the National Institute for Health Research (NIHR) in the United Kingdom. Dr Wanner has received honoraria for consultancy and lecturing from Amicus, AstraZeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Sanofi-Genzyme, and Takeda. Dr Evans has received payment for advisory boards and lectures by Astellas Pharma, Vifor Pharma, and AstraZeneca; and has received institutional grants from AstraZeneca and Astellas Pharma, outside of this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Published
2022
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15. Association Between Renal Function and Troponin T Over Time in Stable Chronic Kidney Disease Patients.

Author

Chesnaye NC, Szummer K, Bárány P, Heimbürger O, Magin H, Almquist T, Uhlin F, Dekker FW, Wanner C, Jager KJ, and Evans M

Subjects
Aged, Cardiovascular Diseases epidemiology, Cohort Studies, Diabetes Mellitus epidemiology, Europe epidemiology, Female, Humans, Longitudinal Studies, Male, Renal Insufficiency, Chronic classification, Sex Factors, Biomarkers blood, Glomerular Filtration Rate, Renal Insufficiency, Chronic epidemiology, Troponin T blood
Abstract

Background People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis. Methods and Results The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged ≥65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m²). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (≤14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19; P <0.0001). Each 15 mL/min/1.73 m 2 lower mean estimated GFR was associated with a 23% (95% CI, 14-31; P <0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%; P <0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%). Conclusions In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m 2 lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors.

Published
2019
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16. Acute effects of haemodialysis on circulating microparticles.

Author

de Laval P, Mobarrez F, Almquist T, Vassil L, Fellström B, and Soveri I

Abstract

Background: Microparticles (MPs) are small cell membrane-derived vesicles regarded as both biomarkers and mediators of biological effects. Elevated levels of MPs have previously been associated with endothelial dysfunction and predict cardiovascular death in patients with end-stage renal disease. The objective of this study was to measure change in MP concentrations in contemporary haemodialysis (HD)., Methods: Blood was sampled from 20 consecutive HD patients before and 1 h into the HD session. MPs were measured by flow cytometry and phenotyped based on surface markers., Results: Concentrations of platelet (CD41 + ) (P = 0.039), endothelial (CD62E + ) (P = 0.004) and monocyte-derived MPs (CD14 + ) (P < 0.001) significantly increased during HD. Similarly, endothelial- (P = 0.007) and monocyte-derived MPs (P = 0.001) expressing tissue factor (TF) significantly increased as well as MPs expressing Klotho (P = 0.003) and receptor for advanced glycation end products (RAGE) (P = 0.009). Furthermore, MPs expressing platelet activation markers P-selectin (P = 0.009) and CD40L (P = 0.045) also significantly increased. The increase of endothelial (P = 0.034), monocyte (P = 0.014) and RAGE + MPs (P = 0.032) as well as TF + platelet-derived MPs (P = 0.043) was significantly higher in patients treated with low-flux compared with high-flux dialysers., Conclusion: Dialysis triggers release of MPs of various origins with marked differences between high-flux and low-flux dialysers. The MPs carry surface molecules that could possibly influence coagulation, inflammation, oxidative stress and endothelial dysfunction. The clinical impact of these findings remains to be established in future studies.

Published
2018
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17. Prevalence and Risk of Protein-Energy Wasting Assessed by Subjective Global Assessment in Older Adults With Advanced Chronic Kidney Disease: Results From the EQUAL Study.

Author

Windahl K, Faxén Irving G, Almquist T, Lidén MK, van de Luijtgaarden M, Chesnaye NC, Voskamp P, Stenvinkel P, Klinger M, Szymczak M, Torino C, Postorini M, Drechsler C, Caskey FJ, Wanner C, Dekker FW, Jager KJ, and Evans M

Subjects
Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Europe epidemiology, Female, Glomerular Filtration Rate, Humans, Male, Muscular Atrophy epidemiology, Nutrition Assessment, Obesity complications, Obesity epidemiology, Obesity, Abdominal complications, Obesity, Abdominal epidemiology, Prospective Studies, Renal Insufficiency, Chronic complications, Risk Factors, Protein-Energy Malnutrition epidemiology, Renal Insufficiency, Chronic physiopathology, Wasting Syndrome epidemiology
Abstract

Objectives: Prevalence and risk factors for protein-energy wasting (PEW) are poorly studied in the nondialysis, older population with advanced chronic kidney disease (CKD). Our aim was to evaluate the prevalence of PEW in advanced stage CKD patients aged greater than 65 years. Furthermore, we aimed to describe risk factors for PEW in the overall study population and among obese individuals., Design: Prospective observational cohort study., Methods: The EQUAL study, a European Quality Study on treatment in advanced chronic kidney disease, is a multicenter prospective observational cohort study in six European countries. We included patients aged ≥65 years with incident glomerular filtration rate <20mL/min/1.73m 2 not on dialysis attending nephrology care. PEW was assessed by 7-point Subjective Global Assessment (7-p SGA)., Results: In general, the study cohort (n = 1,334) was overweight (mean body mass index [BMI] 28.4 kg/m 2 ). The majority of the patients had a normal nutritional status (SGA 6-7), 26% had moderate PEW (SGA 3-5), and less than 1% had severe PEW (SGA 1-2). Muscle wasting and loss of fat tissue were the most frequent alterations according to the SGA subscales, especially in those aged >80 years. The prevalence of PEW was higher among women, increased with age, and was higher in those with depression/dementia. PEW was the most common in those with underweight (BMI <22 kg/m 2 ), 55% or normal weight (BMI 22-25 kg/m 2 ), 40%. In obese individuals (BMI >30 kg/m 2 ), 25% were diagnosed with protein wasting. Risk factors for SGA ≤5 in obese people were similar to those for the overall study population., Conclusion: This European multicenter study shows that the prevalence of PEW is high in patients with advanced CKD aged >65 years. The risk of PEW increases substantially with age and is commonly characterized by muscle wasting. Our study suggests that focus on nutrition should start early in the follow-up of older adults with CKD., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Published
2018
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19. Effects of lipid-lowering treatment on circulating microparticles in patients with diabetes mellitus and chronic kidney disease.

Author

Almquist T, Mobarrez F, Jacobson SH, Wallén H, and Hjemdahl P

Subjects
Aged, Anticholesteremic Agents therapeutic use, Cardiovascular Diseases blood, Cardiovascular Diseases etiology, Cross-Over Studies, Double-Blind Method, Drug Therapy, Combination, Female, Flow Cytometry, Humans, Male, Middle Aged, P-Selectin, Renal Insufficiency, Chronic complications, Risk Factors, Biomarkers blood, Cardiovascular Diseases drug therapy, Cell-Derived Microparticles metabolism, Diabetes Mellitus blood, Ezetimibe therapeutic use, Renal Insufficiency, Chronic blood, Simvastatin therapeutic use
Abstract

Background: Elevated levels of circulating microparticles (MPs) may contribute to the high cardiovascular risk in diabetes mellitus (DM) and chronic kidney disease (CKD). Therefore, we investigated the effects of lipid-lowering treatment (LLT) with simvastatin alone (S) or with ezetimibe (S+E) on MPs in DM patients with or without CKD., Methods: After a placebo run-in period, 18 DM patients with an estimated glomerular filtration rate (eGFR) of 15-59 mL/min (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR >75 mL/min (DM-only) were treated with S and S+E in a randomized, double-blind, crossover study. MPs from platelets, monocytes and endothelial cells (PMPs, MMPs and EMPs), and their expression of phosphatidylserine (PS), P-selectin, CD40 ligand (CD40L) and tissue factor (TF) were measured by flow cytometry., Results: At baseline, all types of MPs, except TF-positive MMPs, were elevated in DM-CKD compared with DM-only patients. All MPs, regardless of origin and phenotype, were inversely correlated with eGFR. S reduced the expression of P-selectin, TF and CD40L on PMPs and of TF on MMPs in both patient groups. S+E had no further effect. S also reduced total PS-positive procoagulant MPs, PMPs and MMPs in DM-CKD but not in DM-only patients., Conclusions: DM patients with CKD stages 3-4 had elevated PMPs, EMPs and MMPs compared with DM patients with normal GFR. Simvastatin reduced procoagulant MPs, MMPs and PMPs in DM-CKD patients, suggesting a beneficial reduction of hypercoagulability in this high-risk patient group. Differences between DM-CKD and DM-only patients were counteracted by LLT., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Published
2016
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20. Lipid-lowering treatment and inflammatory mediators in diabetes and chronic kidney disease.

Author

Almquist T, Jacobson SH, Mobarrez F, Näsman P, and Hjemdahl P

Subjects
Aged, Case-Control Studies, Chemokine CCL2 immunology, Cross-Over Studies, Diabetes Mellitus immunology, Diabetic Nephropathies immunology, Double-Blind Method, Drug Therapy, Combination, Ezetimibe, Female, Humans, Inflammation immunology, Inflammation Mediators immunology, Interferon-gamma immunology, Male, Middle Aged, Renal Insufficiency, Chronic immunology, Tumor Necrosis Factor-alpha immunology, Vascular Cell Adhesion Molecule-1 immunology, Anticholesteremic Agents therapeutic use, Azetidines therapeutic use, Diabetes Mellitus drug therapy, Diabetic Nephropathies drug therapy, Renal Insufficiency, Chronic drug therapy, Simvastatin therapeutic use
Abstract

Background: Inflammation may contribute to the high cardiovascular risk in diabetes mellitus (DM) and chronic kidney disease (CKD). Monocyte chemoattractant protein-1 (MCP-1) facilitates the recruitment of monocytes into atherosclerotic lesions and is involved in diabetic nephropathy. Interferon gamma (IFNγ) is important in atherosclerosis and increases the synthesis of chemokines including MCP-1. Lipid-lowering treatment (LLT) with statins may have anti-inflammatory effects, and ezetimibe cotreatment provides additional cholesterol lowering., Methods: After a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S+E) were compared in a randomized, double-blind, cross-over study on inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1·73 m(2) (CKD stages 3-4) (DM-CKD) and 21 DM patients with eGFR > 75 mL/min (DM only) were included., Results: At baseline, monocyte chemoattractant protein 1 (MCP-1) (P = 0·03), IFNγ (P = 0·02), tumour necrosis factor-α (TNFα) (P < 0·01) and soluble vascular adhesion molecule (sVCAM) (P = 0·001) levels were elevated in DM-CKD compared with DM-only patients. LLT with S and S+E reduced MCP-1 levels (P < 0·01 by anova) and IFNγ levels (P < 0·01) in DM-CKD patients but not in DM-only patients. Reductions were most pronounced with the combination treatment., Conclusions: DM patients with CKD stages 3-4 had increased inflammatory activity compared with DM patients with normal GFR. Lipid-lowering treatment decreased the levels of MCP-1 and IFNγ in DM patients with concomitant CKD, which may be beneficial with regard to the progression of both atherosclerosis and diabetic nephropathy., (© 2013 Stichting European Society for Clinical Investigation Journal Foundation.)

Published
2014
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21. Iatrogenic hypocalcemic tetany.

Author

Edmondson S and Almquist TD

Subjects
Calcium Gluconate therapeutic use, Child, Preschool, Emergencies, Humans, Hypocalcemia chemically induced, Hypocalcemia drug therapy, Male, Tetany drug therapy, Tetany physiopathology, Water-Electrolyte Imbalance blood, Water-Electrolyte Imbalance drug therapy, Enema adverse effects, Hypocalcemia complications, Phosphates adverse effects, Tetany etiology
Abstract

The treatment of a patient with hypocalcemic tetany secondary to sodium phosphate enemas is reported. The patient presented with a serum calcium level of 5.2 mg/dL and a phosphate level of 17.5 mg/dL. Physical manifestations included tetanic contraction of the muscles of the legs and arms. There was rapid symptomatic resolution with IV calcium. The electrolyte imbalance normalized over the next two days with oral calcium supplementation.

Published
1990
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22. Controlled comparison of humidified inhalation and peritoneal lavage in rewarming of immersion hypothermia.

Author

White JD, Butterfield AB, Almquist TD, Holloway RR, and Schoem S

Subjects
Animals, Dogs, Peritoneal Cavity, Respiratory Therapy, Therapeutic Irrigation, Hypothermia, Induced
Abstract

Random source dogs were anesthetized and cooled by immersion in ice water to a stable core temperature of 25 degrees C and subsequently rewarmed with either normal saline peritoneal lavage (43 degrees C, 175 ml/kg/h) or warmed humidified inhalation (43 degrees C, 450 ml/kg/min ventilation). The time required for core rewarming to 30 degrees C was 192 +/- 61 minutes for lavage and 331 +/- 96 minutes for inhalation therapy (P less than 0.03). These data suggest that peritoneal lavage is superior to inhalation therapy for core rewarming of rapidly induced immersion hypothermia.

Published
1984
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23. Echocardiographic diagnosis of acute pericardial effusion in penetrating chest trauma.

Author

Whye D, Barish R, Almquist T, Groleau G, Tso E, and Browne B

Subjects
Acute Disease, Cardiac Tamponade etiology, Emergencies, Humans, Male, Middle Aged, Pericardial Effusion therapy, Wounds, Stab surgery, Aorta injuries, Cardiac Tamponade diagnosis, Echocardiography, Pericardial Effusion diagnosis, Wounds, Stab diagnosis
Abstract

Pericardial tamponade persists as a diagnostic challenge to the clinician. The immediate diagnosis is particularly difficult when the patient is well compensated hemodynamically. In contrast to the deceptively stable appearance, the patient is at increased risk due to delayed onset, recognition, and therapy. A case of penetrating thoracic trauma is presented in which the concern about pericardial tamponade was considerable. However, the elements of clinical assessment were inconclusive. Two-dimensional echocardiography was employed in the emergency department to detect a pericardial effusion and thus avoid delayed management. Pericardial tamponade and associated vascular injuries were confirmed at surgery.

Published
1988
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