Abstract: TH-PO1192
Tumor Necrosis Factor-alpha Is Independently Associated with Anemia in Pediatric Patients with CKD
Session Information
- Pediatric Nephrology: CV Health, CKD, AKI, Dialysis, Transplantation, and Health Services Research
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Munera, Ana Maria, Weill Cornell Medicine, New York, New York, United States
- Zhu, Yuan-Shan, Weill Cornell Medicine, New York, New York, United States
- Liu, Diane, Weill Cornell Medicine, New York, New York, United States
- Akchurin, Oleh M., Weill Cornell Medicine, New York, New York, United States
Background
Anemia is a common complication of chronic kidney disease (CKD) involving impaired erythropoiesis and disordered iron handling, both linked to inflammation via effects on both erythropoietin responsiveness and iron availability. While interleukin (IL)-6 contributes via hepcidin-mediated iron restriction, other potentially targetable pathways remains incompletely understood. TNF-α is of interest given available anti-TNF therapies and evidence of effects on erythropoiesis in non-CKD inflammatory anemia, but its independent role in pediatric CKD has not been established.
Methods
We performed a cross-sectional analysis of a pediatric CKD cohort at Weill Cornell Medicine (CKD stages I-V non-dialysis). The exposure was log-transformed TNF-α (pg/mL); the outcome was hemoglobin (Hb, g/dL). Participants were grouped by TNF-α tertiles. Sequential multivariable linear regression evaluated the TNF-α-Hb association adjusting for: (M1) unadjusted; (M2) age, sex; (M3) + eGFR; (M4a-c) + serum iron, transferrin saturation (TSAT), or ferritin; (M5a-b) + log IL-6 or log IFN- γ. Mediation analysis used the Baron & Kenny approach with Sobel test.
Results
The cohort (N=98) had median age 11.4 years (60% male, 22% Black; mean Hb 12.3 g/dL). Across TNF-α tertiles (T1/T2/T3), Hb (12.9/ 12.8/ 11.1 g/dL, p<0.001) and serum iron (78.6/ 83.7/ 59.5 μg/dL, p=0.007) declined, ferritin increased nonsignificantly (p=0.27), suggesting functional iron deficiency. TNF-α correlated inversely with Hb (r=-0.38, p<0.001) and serum iron (r=-0.27, p=0.025) and positively with IFN- γ (r=0.56, p<0.01) and IL-6 (r=0.32, p=0.002). Log TNF-α remained associated with lower Hb through models M1-M3 (all p<0.001) and after adjustment for log-IL-6 (M5a, p=0.01), indicating non-redundant cytokine effects. Adjustment for serum iron (M4a, p=0.011) and TSAT (M4b, p=0.5) attenuated the association. Serum iron mediated 23% of the TNF-α effect on Hb (B=-19.3, p=0.02; Sobel p=0.04). Ferritin was not a mediator (p=0.55). Adjustment for IFN-γ further attenuated the association (M5b, p=0.07), supporting a shared inflammatory axis.
Conclusion
TNF-α is associated with anemia in pediatric CKD independent of kidney function, age and IL-6. Iron partly mediates this effect, implicating TNF-α-driven iron restriction, potentially alongside IFN-γ. TNF-α may represent a novel therapeutic target to correct anemia in children with CKD and inflammation.
Funding
- NIDDK Support