Iron deficiency care benefits patients with chronic kidney disease with, without anemia
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Iron deficiency was associated with all-cause mortality and major adverse cardiovascular events regardless of whether anemia was also present, results of a multinational study of patients with chronic kidney disease showed.
According to Murilo Guedes, MD, of the Arbor Research Collaborative for Health in Ann Arbor, Michigan, and colleagues, these findings point toward the potential benefits of treating iron deficiency in all patients with kidney disease (ie, those with and those without anemia).
“KDIGO guidelines of anemia management in non-dialysis CKD (ND-CKD) patients suggest screening and monitoring of iron stores, a recommendation that is restricted to patients with anemia who are being considered to start or are in maintenance therapy with erythropoiesis stimulating agents (ESA),” the researchers wrote. “The guidelines go on to state that TSAT [of no more than] 30% and ferritin [of no more than] 500 ng/mL targets should be pursued to ensure sufficient absolute and functional iron stores, enabling effective erythropoiesis with ESA doses as low as possible to achieve recommended targets. Despite these evidence-based recommendations published almost a decade ago, our recent real-world multinational study reported that ND-CKD patients with clear indications for iron replacement therapy remain considerably under-treated.”
Contending that previous studies on the matter have been limited by the exclusion of patients without anemia, Guedes and colleagues assessed outcomes related to 5,145 participants enrolled in the CKD-Outcomes and Practice Patterns Study. Iron saturation (TSAT) and ferritin levels were measured at baseline (mean of 24% and 196 ng/mL, respectively), with ESAs subsequently prescribed to 13% of the sample and iron prescribed to 21% (oral or IV).
All-cause mortality, cardiovascular events
During a median follow-up of 3 years, researchers observed an overall mortality rate (before initiation of kidney replacement therapy) of 4.7 per 100 patient-years, with patients who had TSAT levels of 15% or less and 46% or greater at highest risk (patients with TSAT levels between 36% and 45% had the lowest mortality risk).
Further findings indicated that, when compared with TSAT levels of 26% to 35%, patients with TSAT of 15% or less had the highest adjusted risks for all-cause mortality and major adverse cardiovascular events (hazard ratios of 1.44 and 1.77, respectively).
No directional associations were found between ferritin and the assessed outcomes, except for increased all-cause mortality risk with ferritin of at least 300 ng/mL, the researchers noted.
Treatment of iron deficiency, future research
“This study provides observational support to the hypothesis that iron deficiency, regardless of anemia status, may impact clinical outcomes in ND-CKD patients,” Guedes and colleagues concluded. “Long overdue in the ND-CKD setting, well-designed RCTs are needed to assess the clinical benefits of iron supplementation for patients with ID, with or without anemia, and therefore confirm the results provided in this study.
Proactive iron interventions, particularly IV iron, may lead to better tissue iron delivery and therefore better outcomes. With the shift in the paradigm in the anemia treatment provided by the approval of the novel class of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), which, among other effects, improve iron availability, an integrative approach considering both iron status and hemoglobin may yield important benefits for ND-CKD individuals.”
Study co-investigator Roberto Pecoits-Filho, MD, PhD, further commented on the findings in a related press release.
“Intervention studies addressing the impact of iron deficiency treatment beyond its erythropoietic effects are necessary to challenge the anemia-focused paradigm of iron deficiency management in CKD, potentially fostering more optimal strategies for improving patient outcomes,” he said.
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