Sex differences in the development of CKD complications

Evidence on sex-related differences in chronic kidney disease (CKD)-related complications is limited and often based on cross-sectional studies. This study longitudinally examines clinical and biochemical parameters of CKD complications, focusing on differences between men and women.

We performed a retrospective study within the Chronic Renal Insufficiency Cohort (CRIC) Study cohort, including adults with baseline estimated glomerular filtration rate (eGFR) 20-70 mL/min/1.73 m² and at least one serum creatinine measurement. Demographic, clinical, laboratory and therapeutic data were collected, with a 10-year follow-up. The main clinical and laboratory parameters related to CKD complications [haemoglobin (Hb) for anaemia, total CO2 (tCO₂) for acidosis, serum potassium (K+) for hyperkalaemia, systolic blood pressure (SBP) for hypertension, serum phosphorus for hyperphosphataemia and intact parathyroid hormone (iPTH) for hyperparathyroidism] were evaluated for their longitudinal association in relation to eGFR, with the aim of describing their trajectories, and for their association with mortality. Trajectories were estimated using mixed-effects linear regression, including sex-based comparisons. Associations with mortality were evaluated through time-dependent Cox regression models, with interaction tests to explore sex effects. Sensitivity analyses were conducted restricting the population to post-menopausal women.

A total of 3683 individuals (24 075 measurements) were included. Men had higher prevalence of anaemia, acidosis, hyperkalaemia and hyperparathyroidism, while women showed more hyperphosphataemia. Longitudinally, Hb, tCO₂ and SBP declined with worsening eGFR, whereas K⁺, phosphate and iPTH increased. Sex-stratified analyses revealed steeper declines in Hb and tCO₂ and more pronounced rise in iPTH among men compared with women. Mortality analyses showed higher all-cause mortality in men. In sex-stratified analyses, no differences in mortality risk were observed between men and women.

The study found sex-specific differences in CKD complications: men experienced a faster decline in Hb and tCO₂ and a greater increase in iPTH with worsening eGFR. These sex-specific progression patterns did not translate into differences in mortality risk for the complications explored.