In this study, published in the Journal of the American Society of Nephrology, the researchers studied patients at nephrology clinics in Brazil, France, the United States and Germany to assess a possible independent association of iron store anemia in patients with or without the disease and not on dialysis on risk of death and cardiovascular events.
The authors noted that patients with CKD not on dialysis with clinical factors indicating the need for iron replacement therapy are generally undertreated. In addition, studies of patients with heart failure and with a similar iron deficiency status found improved cardiovascular outcomes when iron deficiency was treated, regardless of the presence of anemia.
The study included 5145 CKDopps patients, using their first available levels of iron saturation (TSAT) and ferritin as exposure variables. Cox models were used to estimate the risk ratios for all-cause mortality (MCA) and major adverse cardiovascular events (MACE), with gradual adjustment confounding variables. Further analysis using linear spline models was used to assess exposure-outcome associations.
Patients were followed for a median of 3 years; 59% were men, with an average age of 69, and 45% had diabetes, 28% had coronary artery disease and 15% had heart failure. The cohort had an average eGFR of 28 ml / min per 1.73 m2 and an average TSAT and ferritin of 24% and 196 ng / ml, respectively. The average Hgb hemoglobin was 12.3 g / dl. Erythropoiesis stimulating agents were prescribed initially for 13% and 21% received iron.
Researchers found that low levels of TSAT were linked to an increased risk of MCA and incidence of MACE, regardless of anemia status, with 47 deaths per 1,000 patients each year and 48 major cardiovascular events. per 1000 patients.
Patients with low TSAT and high ferritin had the highest risk of adverse clinical events.
Compared with patients with 26% to 35% TSAT, those with â¤15% TSAT had the highest adjusted risks for ACM and MACE.
Further analysis revealed that patients with 40% TSAT had the lowest risk of ACM and MACE.
Patients with â¥ 46% TSAT or ferritin â¥ 300 ng / ml were at higher risk for ACD but not MACE, although the authors said the results should be “interpreted with caution” for several reasons. One hypothesis is that this subgroup has an increased risk of infectious disease, although this was not an endpoint in the study. It is also possible that TSAT levels above 45% “may indicate iron overload and iron-mediated oxidative stress, which can cause organ dysfunction and increased risk of adverse clinical events.”
The effect estimates were similar after adjusting for hemoglobin.
“Intervention studies examining the impact of iron deficiency treatment beyond its erythropoietic effects are needed to challenge the anemia-focused paradigm of iron deficiency management in CRF , potentially promoting more optimal strategies for improving patient outcomes, âsaid one of the authors, Roberto Pecoits-Filho, MD, PhD, of the Arbor Research Collaborative for Health, in Ann Arbor, Michigan, in a report. He also said that randomized controlled clinical trials are needed to establish the role of iron therapy in these patients.
Guedes M, Muenz D, Zee J, et al. Serum biomarkers of iron stores are associated with an increased risk of all-cause mortality and cardiovascular events in patients with chronic kidney disease not on dialysis, with or without anemia. J Am Soc Nephrol. Published online July 8, 2021. doi: 10.1681 / ASN.2020101531