Anemia and Kidney Prognosis in ADPKD: Insights from Attribute-Based Cross-Classification by Sex and Age

Background: Although anemia is less prevalent in autosomal dominant polycystic kidney disease (ADPKD) due to relatively preserved erythropoietin production, the prognostic significance of anemia in this population remains unclear. Given the sex differences in hemoglobin (Hb) levels and the increasing emphasis on attribute-based medicine (ABM), we hypothesized that the impact of anemia on kidney outcomes in ADPKD may vary by sex and age. Methods: We analyzed 553 Japanese patients with ADPKD from a multicenter cohort. The primary outcome was a 30% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Cox regression models were used to evaluate the prognostic significance of Hb levels and anemia, with subgroup analyses cross-classified by sex and age (<50 or ≥50 years). Anemia was defined using Hb thresholds of <11.0, <12.0, and <13.0 g/dL. Results: The cohort had a median age of 43 years and median eGFR of 55.9 mL/min/1.73 m2. Anemia prevalence was highest in older women and lowest in younger men. Over a mean follow-up of 6.9 years, 266 patients reached the primary endpoint. In the overall cohort, lower Hb levels were independently associated with worse renal outcomes (HR per 1 g/dL increase: 0.83; 95% CI: 0.75–0.91; P < 0.001). Cross-classified analyses revealed distinct risk patterns. Anemia (Hb <13.0 g/dL) significantly increased the risk in younger men (HR: 2.92; P = 0.028) and older men (HR: 3.84; P = 0.017). In women, anemia defined as Hb <12.0 g/dL was associated with adverse outcomes in both age groups (HR: 1.98; P = 0.035 in <50 years; HR: 2.08; P = 0.045 in ≥50 years). Additional factors such as eGFR, total kidney volume (TKV), urinary protein excretion, and hypertension also contributed to prognosis depending on sex and age. Conclusion: Anemia is an independent risk factor for kidney disease progression in patients with ADPKD, with its prognostic impact differing by sex and age. These findings highlight the importance of attribute-based approaches in anemia assessment and management in ADPKD, suggesting that individualized Hb targets may be warranted in future therapeutic strategies.