ArticleJournal of the American Society of Nephrology : JASN2021
Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients, with or without Anemia.
Article in Journal of the American Society of Nephrology : JASN, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03381950 (Chronic Kidney Disease - Renal Epidemiology and Information Network), which is not on this map. Cited by 52 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Chronic Kidney Disease - Renal Epidemiology and Information Network: The CKD-REIN Cohort
Who cites it
52 citing papers in PubMed, 4 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- UK kidney association clinical practice guideline: update of anaemia of chronic kidney disease.BMC nephrology · 2025Guideline
- Interleukin-6 levels can be used to estimate cardiovascular and all-cause mortality risk in dialysis patients: A meta-analysis and a systematic review.Immunity, inflammation and disease · 2023Pooled it
- An updated meta-analysis on the efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitor treatment of anemia in nondialysis-dependent chronic kidney disease.Renal failure · 2023Pooled it
- Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT.Communications biology · 2022Pooled it
- Canagliflozin and iron metabolism in the CREDENCE trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025 · on this mapTrial
- Article
- KDIGO 2026 Clinical Practice Guideline for Anemia in Chronic Kidney Disease (CKD): a commentary from the European Renal Best Practice (ERBP).Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Article
- Relationship between iron deficiency and corrected QT-interval prolongation in Japanese patients undergoing maintenance hemodialysis.Clinical and experimental nephrology · 2026Article
- Optimal patient care in advanced chronic kidney disease progressing to kidney failure.Nature reviews. Nephrology · 2026Review
- Study on the Threshold of Serum Ferritin Required for Erythropoiesis and Iron Sufficiency in Hemodialysis Patients.International journal of molecular sciences · 2026Article
- Longitudinal associations between iron status and patient-reported outcomes in incident dialysis patients: a DOMESTICO substudy.Journal of nephrology · 2025Article
- Higher Urinary Iron Levels Are Associated with Kidney Dysfunction, Tubular Damage, and Increased Mortality in Kidney Transplant Recipients.Kidney360 · 2025Article
- Ultrafiltration rate and mortality in patients undergoing extended-hours haemodialysis.Clinical kidney journal · 2025Article
- Anemia and iron deficiency in post-kidney transplantation: an unsolved challenge.Clinical kidney journal · 2025Review
- Clinical Outcomes of Iron Supplement Therapy in Non-Anemic Female CKD Stage 3 Patients with Low Serum Ferritin Level: A Multi-Institutional TriNetX Analysis.Journal of clinical medicine · 2025Article
- Association between anemia and mortality in patients with rheumatoid arthritis: A retrospective cohort study of the National Health and nutrition examination survey (NHANES) database.Preventive medicine reports · 2025Article
- Associations between iron markers with hemoglobin and outcomes in peritoneal dialysis patients: results from the PDTAP study.Clinical kidney journal · 2025Article
- Systematic Review of the Effects of Iron on Cardiovascular, Kidney, and Safety Outcomes in Patients With CKD.Kidney international reports · 2025Article
- Anemia Management in the Cardiorenal Patient: A Nephrological Perspective.Journal of the American Heart Association · 2025Review
- Detection and Determinants ofPublic health challenges · 2025Article
Corrections and comments
- Commented on byAuthors' Reply.2022
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Authors and funding
15 authors at 8 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundApproximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks.
methodsThe study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations.
resultsCompared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml.
conclusionsIron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.