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

Introduction: 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. Methods: 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. Results: 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 (22.85%) 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. Conclusion: 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.