Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Gianmarco Lombardi; Pietro Manuel Ferraro; Elisa De Tomi; Matteo Bargagli; Andrea Spasiano; Giovanni Gambaro

doi:10.1093/ndt/gfae087

Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Nephrol Dial Transplant. 2024 Apr 17:gfae087. doi: 10.1093/ndt/gfae087. Online ahead of print.

Authors

Gianmarco Lombardi¹, Pietro Manuel Ferraro¹, Elisa De Tomi¹, Matteo Bargagli², Andrea Spasiano³, Giovanni Gambaro¹

Affiliations

¹ U.O.C. Nefrologia, Department of Medicine, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Piazzale Aristide Stefani, 1, Verona, Italy.
² Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³ Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.

PMID: 38632041
DOI: 10.1093/ndt/gfae087

Abstract

Background and hypothesis: Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented.

Methods: We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73m². The outcomes were CKD-related complications (hypertension, anaemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance.

Results: The study included 49 558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women).

Conclusions: Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier, women show steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Keywords: ckd; egfr; mortality; nhanes; sex.