Gender-specific risk factors and outcomes of hyperkalemia in CKD patients: smoking as a driver of hyperkalemia in men
Authors: Valdivielso Jose M , Carriazo Sol , Martin Marisa , Fernandez-Fernandez Beatriz , Bermudez-López Marcelino , Ortiz Alberto ,   NEFRONA investigators, Regidor Aladrén , Almirall Jaume , Ponz Esther , Coloma Arteaga , Rubio Bajo , Mª Auxiliadora Díaz , Belart Rodríguez Montserrat , Gascón Antonio , Sanjuan Jordi Bover , Bronsoms Artero Josep , Cabezuelo Romero Juan B , Muray Cases Salomé , Calviño Varela Jesús , Caro Acevedo Pilar , Carreras Bassa Jordi , Cases Amenós Aleix , Massó Jiménez Elisabet , Moreno López Rosario , Cigarrán Guldris Secundino , López Prieto Saray , Comas Mongay Lourdes , Comerma Isabel , Compte Jové Mª Teresa , Cuberes Izquierdo Marta , de Álvaro Fernando , Hevia Ojanguren Covadonga , de Arriba de la Fuente Gabriel , del Pino y Pino Mª Dolores , Diaz-Tejeiro Izquierdo Rafael , Dotori Marta , Duarte Verónica , Estupiñan Torres Sara , Fernández Reyes Mª José , Fernández Rodríguez Mª Loreto , Fernández Guillermina , Galán Serrano Antonio , García Cantón Cesar , García Herrera Antonio L , García Mena Mercedes , Gil Sacaluga Luis , Aguilar Maria , Górriz José Luis , Loza Emma Huarte , Lerma José Luis , Cañada Antonio Liebana , Marín Álvarez Jesús Pedro , Martín Alemany Nàdia , Martín García Jesús , Martínez Castelao Alberto , Martínez Villaescusa María , Martínez Isabel , Moina Eguren Iñigo , Moreno Los Huertos Silvia , Mouzo Mirco Ricardo , Munar Vila Antonia , Muñoz Díaz Ana Beatriz , Navarro González Juan F , Nieto Javier , Carreño Agustín , Novoa Fernández Enrique , Ortiz Alberto , Fernandez Beatriz , Paraíso Vicente , Pérez Fontán Miguel , Peris Domingo Ana , Piñera Haces Celestino , Prados Garrido Mª Dolores , Prieto Velasco Mario , Puig Marí Carmina , Rivera Gorrín Maite , Rubio Esther , Ruiz Pilar , Salgueira Lazo Mercedes , Martínez Puerto Ana Isabel , Sánchez Tomero José Antonio , Emilio Sánchez José , Sans Lorman Ramon , Saracho Ramon , Sarrias Maria , Serón Daniel , Soler María José , Barrios Clara , Sousa Fernando , Toran Daniel , Molina Fernando Tornero , Carrasco José Javier Usón , Cortes Ildefonso Valera , Vilaprinyo del Perugia Mª Merce , Virto Ruiz Rafael C 
Published: October 2023

ABSTRACT

Background
Hyperkalemia is common among patients with chronic kidney disease (CKD) but there is scarce information on differential risk factors and outcomes for men and women. For instance, smoking has been suggested to be a risk factor for hyperkalemia, but specific analysis of the sex-specific impact of smoking on hyperkalemia in CKD is lacking.

Methods
We studied serum potassium levels in 2891 participants from the NEFRONA cohort: 483 controls (47% women) and 2408 CKD patients (38% women) without prior cardiovascular disease (CVD), assessing whether smoking is a risk factor for hyperkalemia, and if hyperkalemia is associated with outcomes separately for men and women.

Results
Median potassium levels and prevalence of hypo and hyperkalemia were higher in CKD participants than in controls. Serum potassium levels were higher and hyperkalemia and severe hyperkalemia more prevalent in men than in women with non-dialysis CKD (G3–G5). The highest prevalence of hyperkalemia for each gender was found in CKD G4-G5 and hemodialysis patients for men (46%) and in hemodialysis (54%) for women. Gender-specific etiological multivariate analysis identified current smoking as a risk factor for hyperkalemia only in men. Hyperkalemia was independently associated with stopping RAASi, an outcome which was more common in women. Hyperkalemia was also associated to higher risk of cardiovascular events within 4 years in men. In conclusion, hyperkalemia is common among men and women with CKD, but the prevalence, risk factors and outcomes may differ by gender. Specifically, current smoking is a driver of hyperkalemia in men.