Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: Analyses from the EQUAL cohort

Lombardi, G.; Chesnaye, N. C.; Caskey, F. J.; Dekker, F. W.; Evans, M.; Heimburger, O.; Pippias, M.; Torino, C.; Szymczak, M.; Drechsler, C.; Wanner, C.; Gambaro, G.; Stel, V. S.; Jager, K. J.; Ferraro, P. M.; 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.; Antonio, B.; Di Iorio, B. R.; Alessandra, B.; 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.; Porto, G.; Bigatti, G.; Marinangeli, G.; Cabiddu, G.; Fumagalli, G.; Caloro, G.; Piccoli, G.; Capasso, 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.; Bari, M. D.; Laudato, M.; Sirico, M. L.; 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.; Dekker, F.; Boots, J.; Boom, H.; Eijgenraam, J. -W.; Kooman, J.; Rotmans, J.; Jager, K.; Vogt, L.; Raasveld, M.; Vervloet, M.; Van Buren, M.; Van Diepen, M.; Chesnaye, N.; 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.; Hernandez, I. B.; 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.; Caskey, F.; 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.

doi:10.1093/ckj/sfae254

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.