Attribute-based cross-classification reveals sex- and age-specific prognostic impact of anemia in ADPKD

Anemia is less prevalent in autosomal dominant polycystic kidney disease (ADPKD) owing to preserved erythropoietin production. However, its impact on kidney prognosis remains unclear. Given sex-related differences in hemoglobin (Hb) levels, we hypothesized that the prognostic relevance of anemia may vary by sex and age. Therefore, we aimed to identify subgroup-specific risk patterns using an attribute-based cross-classification approach to support individualized anemia management in ADPKD.

We analyzed 552 Japanese patients with ADPKD from a single-center cohort. The primary outcome was a ≥ 30% decline in the estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Cox regression analysis was used to assess the association between Hb and kidney outcomes. Subgroup analyses were performed using cross-classification by sex and age (< 50 or ≥ 50 years). Anemia was defined using multiple Hb thresholds (< 11, < 12, and < 13 g/dL).

Lower Hb levels were independently associated with worse renal outcomes (hazard ratio [HR] per 1 g/dL increase: 0.83). Cross-classified analyses revealed distinct risk patterns. Anemia (Hb level < 13.0 g/dL) significantly increased the risk in young (HR: 2.92) and old men (HR: 3.84). In women, anemia defined as a Hb level < 12.0 g/dL was associated with adverse outcomes in both age groups (HR: 1.98 in < 50 years; HR: 2.08 in ≥ 50 years).

Anemia is a significant prognostic marker for kidney disease progression in ADPKD. Its prognostic impact differs by sex and age, suggesting the need for attribute-based, individualized hemoglobin thresholds rather than uniform cutoffs, to optimize risk stratification and clinical assessment.