Sex differences in the development of CKD complications

Abstract Background and hypothesis 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. Methods We performed a retrospective study within the CRIC cohort, including adults with baseline 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 hyperkalemia, systolic blood pressure (SBP) for hypertension, serum phosphate (P) for hyperphosphatemia, 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. Results A total of 3 683 individuals (24 075 measurements) were included. Men had higher prevalence of anaemia, acidosis, hyperkalemia, and hyperparathyroidism, while women showed more hyperphosphatemia. 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 to 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 Conclusions 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.