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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Systematic Review of the Effects of Iron on Cardiovascular, Kidney, and Safety Outcomes in Patients With CKD
Bernard Chan1,2, Amanda Varghese3, Sunil V Badve4,5
1Department of Cardiology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Insights
Iron supplementation may lower the risk of heart failure hospitalization and cardiovascular death in patients with chronic kidney disease (CKD). This finding holds true for both dialysis and non-dialysis CKD patients, suggesting a beneficial role for iron therapy.
Area of Science:
- Nephrology
- Cardiology
- Hematology
Background:
- Heart failure and chronic kidney disease (CKD) frequently coexist.
- Iron deficiency is common in patients with heart failure and CKD.
- Current guidelines offer conflicting recommendations on iron use in these populations.
Purpose of the Study:
- To evaluate the clinical outcomes of iron therapy versus usual care or placebo in patients with CKD.
- To assess the impact of iron on heart failure hospitalization and cardiovascular death.
- To analyze the effects of iron in both dialysis-dependent and non-dialysis-dependent CKD patients.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials.
- Searched Medline, Embase, and Cochrane Register up to February 1, 2024.
- Assessed certainty of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
Main Results:
- Iron therapy reduced the risk of the composite endpoint (heart failure hospitalization or cardiovascular death) by 16% (RR: 0.84, 95% CI: 0.75-0.94; moderate certainty).
- This benefit was observed consistently in both dialysis and non-dialysis CKD populations.
- Serious adverse events were less frequent with iron therapy (RR: 0.90, 95% CI: 0.82-0.98; moderate certainty).
Conclusions:
- Iron therapy may decrease the risk of heart failure and cardiovascular death in CKD patients.
- Further randomized trials are warranted, particularly for non-dialysis CKD patients, with or without anemia.
Introduction:
Heart failure and chronic kidney disease (CKD) are closely associated, and iron deficiency is highly prevalent in both conditions. However, major cardiovascular and nephrology guidelines offer contrasting recommendations for iron use. We evaluated the effects of iron versus usual care or placebo on the clinical outcomes in patients with CKD.
Methods:
We conducted a systematic review and meta-analysis of randomized trials on i.v. or oral iron in patients with CKD (PROSPERO CRD42023453468). We searched Medline, Embase, and the Cochrane Register from database inception until February 1, 2024 to identify eligible trials. We determined the overall results and stratified them by dialysis- and nondialysis-requiring CKD using random effects models, with certainty of evidence assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. The primary composite endpoint was hospitalization for heart failure or cardiovascular death.
Results:
We identified 45 trials that met the inclusion criteria. Compared with usual care or placebo, iron reduced the risk of the primary composite endpoint (1659 events; risk ratio [RR]: 0.84, 95% confidence interval [CI]: 0.75-0.94; moderate certainty), an effect consistent across dialysis and nondialysis requiring CKD (P-heterogeneity = 0.70). The effect on the primary endpoint appeared driven by both components of hospitalization for heart failure (RR: 0.77; 95% CI: 0.61-0.96; moderate certainty) and cardiovascular death (RR: 0.81; 95% CI: 0.65-1.02; low certainty). The incidence of serious adverse events was lower for iron compared with usual care or placebo (RR: 0.90, 95% CI: 0.82-0.98; moderate certainty; P-heterogeneity = 0.09).
Conclusion:
Iron therapy may reduce the risk of heart failure and cardiovascular death in patients with CKD. Randomized trials evaluating the effects of iron on clinical outcomes are needed, especially in nondialysis patients with CKD with or without anemia.
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