Associations between plasma osteopontin, sex, and 2-year global and cardiorenal outcomes in older outpatients screened for CKD: a secondary analysis of the SCOPE study
Authors: Soraci Luca , Ärnlöv Johan , Carlsson Axel C , Feldreich Tobias Rudholm , Larsson Anders , Roller-Wirnsberger Regina , Wirnsberger Gerhard , Mattace-Raso Francesco , Tap Lisanne , Formiga Francesc , Moreno-González Rafael , Soltysik Bartlomiej , Kostka Joanna , Artzi-Medvedik Rada , Melzer Itshak , Weingart Christian , Sieber Cornel , Marcozzi Serena , Muglia Lucia , Lattanzio Fabrizia ,   the Screening for CKD among Older People across Europe (SCOPE) study investigators, Lattanzio Fabrizia , Corsonello Andrea , Bustacchini Silvia , Bolognini Silvia , D'Ascoli Paola , Moresi Raffaella , Di Stefano Giuseppina , Giammarchi Cinzia , Bonfigli Anna Rita , Galeazzi Roberta , Lenci Federica , Bella Stefano Della , Bordoni Enrico , Provinciali Mauro , Giacconi Robertina , Giuli Cinzia , Postacchini Demetrio , Garasto Sabrina , Firmani Romano , Nacciariti Moreno , Di Rosa Mirko , Fabbietti Paolo , Wirnsberger Gerhard Hubert , Roller-Wirnsberger Regina Elisabeth , Herzog Carolin , Lindner Sonja , Mattace-Raso Francesco , Tap Lisanne , Ziere Gijsbertus , Goudzwaard Jeannette , Polinder-Bos Harmke , Kostka Tomasz , Guligowska Agnieszka , Kroc Łukasz , Sołtysik Bartłomiej K , Pigłowska Małgorzata , Gutowska Agnieszka , Chrza˛stek Zuzanna , Sosowska Natalia , Antoszczyk Anna , Kostka Joanna , Fife Elizaveta , Smyj Katarzyna , Zel Kinga , Artzi-Medvedik Rada , Melzer Yehudit , Clarfield Mark , Melzer Itshak , Artzi-Medvedik Rada , Yehoshua Ilan , Melzer Yehudit , Formiga Francesc , Moreno-González Rafael , Corbella Xavier , Martínez Yurema , Polo Carolina , Cruzado Josep Maria , Gregorio Pedro Gil , Martínez Sara Laínez , Alonso Mónica González , Calvo Jose A Herrero , Molina Fernando Tornero , Fuentes Lara Guardado , García Pamela Carrillo , Pérez María Mombiedro , Renz Alexandra , Muck Susanne , Theobaldy Stephan , Bekmann Andreas , Kaltsa Revekka , Britting Sabine , Kob Robert , Weingart Christian , Freiberger Ellen , Sieber Cornel , Ärnlöv Johan , Carlsson Axel , Feldreich Tobias 
Published: November 2024

ABSTRACT

Background
Plasma osteopontin (pOPN) is a promising aging-related biomarker among individuals with and without kidney disease. The interaction between sex, pOPN levels, and global and cardiorenal outcomes among older individuals was not previously evaluated.

Methods
In this study we investigated the association of pOPN with 24-month global mortality, major cardiovascular events (MACEs), MACEs + cardiovascular (CV) mortality, and renal decline among older individuals; we also evaluated whether sex modified observed associations. pOPN levels were measured in a cohort of 2013 outpatients (908 men and 1105 women) aged 75 years or more enrolled in the context of a multicenter prospective cohort study in Europe. Multivariable linear regression, Cox and Fine Gray models, and linear mixed regression models were fitted to evaluate whether sex modified the associations between biomarkers and study outcomes.

Results
In total, 2013 older participants with a median age of 79 years, 54.9% of whom women, were included in the study; increased pOPN levels were associated with all-cause mortality specifically among women [reduced fully adjusted model resulting from backward selection, hazard ratio, 95% confidence interval (CI): 1.84, 1.20–2.89]. Addition of pOPN to models containing age, eGFR, and albumin-to-creatinine ratio (ACR) improved the time-dependent area under the curve (AUC) at 6, 12, and 24 months, among women only. No significant association was found between the biomarker levels, MACE, and MACE + CV mortality. Conversely, increased baseline pOPN was associated with eGFR decline in all patients (−0.45, 95%CI: −0.68 to −0.22 ml/min/1.73 m2 year) but with slightly steeper declines in women compared to men (−0.57, −0.99 to −0.15 vs −0.47, −0.88 to −0.07).

Conclusions
pOPN levels were significantly lower in women than in men but associated with all-cause mortality in women only; increase in serum pOPN was associated with eGFR decline over time in all patients, but with stronger associations among women. Assessment of pOPN may help identifying older female participants at risk of poor outcomes.