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

Abstract

Background: 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 estimated glomerular filtration rate (eGFR) levels. We analyzed National Health and Nutrition Examination Survey (NHANES) data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 mL/min/1.73 m2. The outcomes were CKD-related complications [hypertension, anaemia, cardiovascular (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 and hazard ratios 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 a 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; NHANES; eGFR; mortality; sex.