Sex Differences in Kidney Prognosis in Patients with ADPKD: Attribute-Based Medicine (ABM) Insights

Background: Recently, the importance of attribute-based medicine has been emphasized. We aimed to examine the influence of sex differences to kidney disease progression of autosomal dominant polycystic kidney disease (ADPKD). Methods: We enrolled 553 ADPKD patients who were not undergoing renal replacement therapy, with a median age of 43 years, an estimated glomerular filtration rate of 55.9 mL/min/1.73 m2, and a total kidney volume of 1335.4 mL. The renal outcome, defined as a 50% reduction in estimated glomerular filtration rate or initiation of renal replacement therapy, was assessed using Cox regression analysis. Factors influencing kidney prognosis in ADPKD patients were compared based on sex categories (men or women). Results: Over a median 9.1-year follow-up, renal outcomes were assessed in 189 patients. Multivariate Cox analysis identified several significant risk factors for kidney disease progression: female gender (HR=1.56), age (HR for 10-year increase=0.63), eGFR (HR for 10 mL/min/1.73 m2 increase=0.48), urinary protein excretion (grades 0–3) (HR=2.05), total kidney volume (HR for 100 ml increase=1.02), and hypertension (HR=1.48). Significantly, interactions were observed between gender and urinary protein excretion (grades 0–3) (P=0.0158), hypertension (P=0.0065), and higher pulse pressure (≥50mmHg) (P=0.0117) concerning kidney disease progression. Subgroup analysis by gender clarified age and eGFR's association with kidney prognosis across both sub-cohorts. Conversely, hypertension (HR=2.47), pulse pressure ≥50 mmHg (HR=2.28), and urinary protein (grades 0–3) (HR=3.11) emerged as factors associated with kidney prognosis in females, whereas hypertension (HR=0.82), pulse pressure ≥50 mmHg (HR=0.90), and urinary protein (grades 0–3) (HR=1.62) were less associated with renal outcomes in males. Conclusion: Female sex was a factor for poor renal prognosis in patients with ADPKD. Hypertension, high pulse pressure, and increased proteinuria were significantly worse factors for renal prognosis in women than in men. In recent years, treatments and research that are tailored to patient attributes have been proposed, but in the case of ADPKD patients, it is necessary to change treatment policies depending on sex attributes. Funding: Government Support – Non-U.S.