Differential Associations of Iron Deficiency with Renal Progression and Mortality in Anemic Non-Dialysis-Dependent...

Iron deficiency is prevalent in chronic kidney disease (CKD), particularly among patients with anemia. However, the prognostic value of routinely measured iron biomarkers, ferritin and transferrin saturation (TSAT), in non-dialysis-dependent (NDD) CKD remains incompletely defined.

We conducted a multicenter retrospective cohort study using data from the China Renal Data System. Eligible hospitalized adults had anemia and NDD-CKD with baseline serum ferritin or TSAT measurements. Iron deficiency was defined as ferritin ≤100 ng/mL and/or TSAT ≤20%. The primary outcomes were CKD progression and all-cause mortality. Associations were assessed using multivariable Cox proportional hazards models; Fine and Gray competing risk models and prespecified subgroup analyses evaluated robustness.

Among 40,667 patients with anemic CKD, 38,307 had ferritin measurements, and 9,210 had TSAT measurements. Of these, 11,116 (29.02%) had ferritin ≤100 ng/mL and 3,295 (35.78%) had TSAT ≤20%. During follow-up, CKD progression occurred in 8,756 (22.86%) patients in the ferritin cohort and 2,459 (26.70%) in the TSAT cohort. In multivariable analyses, ferritin ≤100 ng/mL was associated with a modestly lower risk of CKD progression than levels greater than 100 ng/mL (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90-0.99), with similar results in competing risk analyses. TSAT ≤20% was not associated with CKD progression (aHR, 1.04; 95% CI, 0.95-1.13). For all-cause mortality, ferritin ≤100 ng/mL was not independently associated with risk (aHR, 0.99; 95% CI, 0.93-1.06), whereas TSAT ≤20% was associated with higher risk (aHR, 1.19; 95% CI, 1.06-1.36). CRP-stratified analyses indicated that ferritin ≤100 ng/mL was associated with lower CKD progression risk only among patients with CRP ≤10 mg/L, suggesting that the prognostic association of ferritin varied by inflammatory status.

In Chinese adults with anemia and NDD-CKD, ferritin and TSAT showed divergent prognostic associations. TSAT ≤20% identified higher mortality risk, whereas ferritin ≤100 ng/mL was associated with a modestly lower observed risk of CKD progression in an inflammation-dependent pattern. These findings support routine, context-aware assessment of iron indices, particularly TSAT, in anemic NDD-CKD.