Beyond Anemia: Why Iron Matters in Every Stage of Chronic Kidney Disease

Announcer:
You’re listening to Clinician’s Roundtable on ReachMD. On this episode, we’ll learn about the current recommendations for iron replacement in chronic kidney disease patients with Dr. Jay Wish. Not only is he a Professor of Clinical Medicine at Indiana University School of Medicine and the Chief Medical Officer for Outpatient Dialysis at Indiana University Health, but he also spoke about this exact topic at the American Society of Nephrology’s 2025 Kidney Week conference. Here’s Dr. Wish now.

Dr. Wish:
We just didn’t think about iron in our CKD patients unless the patient was anemic. Previous KDOQI and KDIGO anemia guidelines provided an algorithm for the evaluation of anemia in CKD patients where iron was not assessed unless the patient was anemic. Then iron deficiency was pursued as a cause in treatment of anemia but not as a deficiency state that may impact the patient in other ways. Our recognition of the fundamental role of iron in all cellular energy generation processes as well as the success of iron repletion in improving outcomes in patients with iron deficiency and heart failure has made the recognition and treatment of iron deficiency in patients with CKD more important.

Unfortunately, there are no specific studies of iron repletion in iron-deficient patients with CKD who are not anemic because we haven’t been testing for iron deficiency in that setting. However, the PIVOTAL study in hemodialysis patients demonstrated cardiovascular benefits of more versus less aggressive iron repletion. Patients receiving proactive iron repletion to a ceiling ferritin of 700 or a TSAT of 50 percent had a 20 percent reduction in ESA requirements compared to those receiving iron repletion when ferritin fell below 200 or a TSAT below 20 percent. This was accompanied by a 15 percent reduction in the composite primary outcome of death, MI, stroke, or heart failure hospitalization.

There are several trials that demonstrate improved outcomes in iron-deficient heart failure patients administered IV iron. The CONFIRM-HF trial demonstrated significantly improved functional status and decreased hospitalization rate. The FAIR-HF trial also demonstrated significant improvements in functional status. The IRONMAN study demonstrated a statistically significant decrease in the composite outcome of cardiovascular death and admission for heart failure. And finally, the AFFIRM-AHF trial in patients with acute heart failure demonstrated significant reductions in cardiovascular hospitalizations, cardiovascular death, and total heart failure hospitalizations. In trials where a subgroup analysis was performed, there was no difference in the benefit of IV iron in patients with and without chronic kidney disease.

The 2026 KDIGO anemia guideline, which has been released in draft form and will be published in final form in the very near future, recommends periodic assessment for anemia in patients with CKD stage 3 or greater. That assessment includes iron studies, irrespective of whether the patient has anemia. And for people with TSAT less than 20 percent and ferritin less than 30, supplemental iron is recommended even if anemia is not present.

Announcer:
That was Dr. Jay Wish discussing the current recommendations for iron replacement in patients with chronic kidney disease, which he spoke about at the 2025 Kidney Week conference. To access this and other episodes in our series, visit Clinician’s Roundtable on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!