The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease
Ziad A. Massy, Nicholas C Chesnaye, Islam Amine Larabi, Friedo W. Dekker, Marie Evans, Fergus Caskey, Claudia Torino, Gaetana Porto, Maciej Szymczak, Christiane Drechsler, Christoph Wanner, Kitty J. Jager, Jean‐Claude Alvarez, EQUAL study investigators, Andreas Schneider, Anke Torp, Beate Iwig, Boris Perras, Christian Marx, Christiane Drechsler, Christof Blaser, Christoph Wanner, Claudia Emde, Detlef H. 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, Adamasco Cupisti, Adelia Sagliocca, Alberto Ferraro, Alessandra Mele, Alessandro Naticchia, Alex Còsaro, Andrea Ranghino, Andrea Stucchi, Angelo Pignataro, Antonella De Blasio, Antonello Pani, Aris Tsalouichos, Antonio Bellasi, Biagio 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 Neve Vigotti, Ferruccio Ansali, Ferruccio Conte, Francesca Cianciotta, Francesca Giacchino, Francesco Cappellaio, Francesco Pizzarelli, Gaetano Greco, Gaetana Porto, Giada Bigatti, Giancarlo Marinangeli
Abstract
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.