Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: analyses from the EQUAL cohort
Authors: Lombardi Gianmarco , Chesnaye Nicholas C , Caskey Fergus J , Dekker Friedo W , Evans Marie , Heimburger Olof , Pippias Maria , Torino Claudia , Szymczak Maciej , Drechsler Christiane , Wanner Christoph , Gambaro Giovanni , Stel Vianda S , Jager Kitty J , Ferraro Pietro Manuel ,   the EQUAL study investigators, Schneider Andreas , Torp Anke , Iwig Beate , Perras Boris , Marx Christian , Drechsler Christiane , Blaser Christof , Wanner Christoph , Emde Claudia , Krieter Detlef , Fuchs Dunja , Irmler Ellen , Platen Eva , Schmidt-Gürtler Hans , Schlee Hendrik , Naujoks Holger , Schlee Ines , Cäsar Sabine , Beige Joachim , Röthele Jochen , Mazur Justyna , Hahn Kai , Blouin Katja , Neumeier Katrin , Anding-Rost Kirsten , Schramm Lothar , Hopf Monika , Wuttke Nadja , Frischmuth Nikolaus , Ichtiaris Pawlos , Kirste Petra , Schulz Petra , Aign Sabine , Biribauer Sandra , Manan Sherin , Röser Silke , Heidenreich Stefan , Palm Stephanie , Schwedler Susanne , Delrieux Sylke , Renker Sylvia , Schättel Sylvia , Stephan Theresa , Schmiedeke Thomas , Weinreich Thomas , Leimbach Til , Stövesand Torsten , Bahner Udo , Seeger Wolfgang , Cupisti Adamasco , Sagliocca Adelia , Ferraro Alberto , Mele Alessandra , Naticchia Alessandro , Còsaro Alex , Ranghino Andrea , Stucchi Andrea , Pignataro Angelo , De Blasio Antonella , Pani Antonello , Tsalouichos Aris , Antonio Bellasi , Iorio Biagio Raffaele Di , Alessandra Butti , Abaterusso Cataldo , Somma Chiara , D'alessandro Claudia , Torino Claudia , Zullo Claudia , Pozzi Claudio , Bergamo Daniela , Ciurlino Daniele , Motta Daria , Russo Domenico , Favaro Enrico , Vigotti Federica , Ansali Ferruccio , Conte Ferruccio , Cianciotta Francesca , Giacchino Francesca , Cappellaio Francesco , Pizzarelli Francesco , Greco Gaetano , Porto Gaetana , Bigatti Giada , Marinangeli Giancarlo , Cabiddu Gianfranca , Fumagalli Giordano , Caloro Giorgia , Piccoli Giorgina , Capasso Giovanbattista , Gambaro Giovanni , Tognarelli Giuliana , Bonforte Giuseppe , Conte Giuseppe , Toscano Giuseppe , Del Rosso Goffredo , Capizzi Irene , Baragetti Ivano , Oldrizzi Lamberto , Gesualdo Loreto , Biancone Luigi , Magnano Manuela , Ricardi Marco , Bari Maria Di , Laudato Maria , Sirico Maria Luisa , Ferraresi Martina , Provenzano Michele , Malaguti Moreno , Palmieri Nicola , Murrone Paola , Cirillo Pietro , Dattolo Pietro , Acampora Pina , Nigro Rita , Boero Roberto , Scarpioni Roberto , Sicoli Rosa , Malandra Rosella , Savoldi Silvana , Bertoli Silvio , Borrelli Silvio , Maxia Stefania , Maffei Stefano , Mangano Stefano , Cicchetti Teresa , Rappa Tiziana , Palazzo Valentina , De Simone Walter , Schrander Anita , van Dam Bastiaan , Siegert Carl , Gaillard Carlo , Beerenhout Charles , Verburgh Cornelis , Janmaat Cynthia , Hoogeveen Ellen , Hoorn Ewout , Dekker Friedo , Boots Johannes , Boom Henk , Eijgenraam Jan-Willem , Kooman Jeroen , Rotmans Joris , Jager Kitty , Vogt Liffert , Raasveld Maarten , Vervloet Marc , van Buren Marjolijn , van Diepen Merel , Chesnaye Nicholas , Leurs Paul , Voskamp Pauline , Blankestijn Peter , van Esch Sadie , Boorsma Siska , Berger Stefan , Konings Constantijn , Aydin Zeynep , Musiała Aleksandra , Szymczak Anna , Olczyk Ewelina , Augustyniak-Bartosik Hanna , Miśkowiec-Wiśniewska Ilona , Manitius Jacek , Pondel Joanna , Jędrzejak Kamila , Nowańska Katarzyna , Nowak Łukasz , Szymczak Maciej , Durlik Magdalena , Dorota Szyszkowska , Nieszporek Teresa , Heleniak Zbigniew , Jonsson Andreas , Blom Anna-Lena , Rogland Björn , Wallquist Carin , Vargas Denes , Dimény Emöke , Sundelin Fredrik , Uhlin Fredrik , Welander Gunilla , Hernandez Isabel Bascaran , Gröntoft Knut-Christian , Stendahl Maria , Svensson Maria , Evans Marie , Heimburger Olof , Kashioulis Pavlos , Melander Stefan , Almquist Tora , Jensen Ulrika , Woodman Alistair , McKeever Anna , Ullah Asad , McLaren Barbara , Harron Camille , Barrett Carla , O'Toole Charlotte , Summersgill Christina , Geddes Colin , Glowski Deborah , McGlynn Deborah , Sands Dympna , Caskey Fergus , Roy Geena , Hirst Gillian , King Hayley , McNally Helen , Masri-Senghor Houda , Murtagh Hugh , Rayner Hugh , Turner Jane , Wilcox Joanne , Berdeprado Jocelyn , Wong Jonathan , Banda Joyce , Jones Kirsteen , Haydock Lesley , Wilkinson Lily , Carmody Margaret , Weetman Maria , Joinson Martin , Dutton Mary , Matthews Michael , Morgan Neal , Bleakley Nina , Cockwell Paul , Roderick Paul , Mason Phil , Kalra Philip , Sajith Rincy , Chapman Sally , Navjee Santee , Crosbie Sarah , Brown Sharon , Tickle Sheila , Mathavakkannan Suresh , Kuan Ying 
Published: August 2024

ABSTRACT

Background
We aimed to explore the relationship between serum bicarbonate (SBC) and mortality in advanced chronic kidney disease (CKD) during three distinct treatment periods: during the pre-kidney replacement therapy (KRT) period, during the transition phase surrounding the start of KRT (transition-CKD) and during KRT.

Methods
Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and estimated glomerular filtration rate (eGFR) ≤20 mL/min/1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. We evaluated effect modification by pre-specified variables on the relationship between SBC and mortality.

Results
We included 1485 patients with a median follow-up of 2.9 (interquartile range 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (P = .03). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (P = .01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (P = .13). We observed effect modification by subjective global assessment category (P-value for interaction = .02) and KRT (P-value for interaction = .02).

Conclusions
A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in the KRT population a trend towards an increased mortality risk was observed for low SBC levels.