The online version of this article (https://doi.org/10.1186/s12882-018-1021-3) contains supplementary material, which is available to authorized users.
Iron deficiency is highly prevalent in chronic kidney disease (CKD) patients. In clinical practice, iron deficiency is defined based on a combination of two commonly used markers, ferritin and transferrin saturation (TSAT). However, no consensus has been reached which cutoffs of these parameters should be applied to define iron deficiency. Hence, we aimed to assess prospectively which cutoffs of ferritin and TSAT performed optimally for outcomes in CKD patients.
We meticulously analyzed 975 CKD community dwelling patients of the Prevention of Renal and Vascular Endstage Disease prospective study based on an estimated glomerular filtration rate < 60 ml/min/1.73m2, albuminuria > 30 mg/24 h, or albumin-to-creatinine ratio ≥ 30 mg/g. Cox proportional hazard regression analyses using different sets and combinations of cutoffs of ferritin and TSAT were performed to assess prospective associations with all-cause mortality, cardiovascular mortality, and development of anemia.
Of the included 975 CKD patients (62 ± 12 years, 64% male with an estimated glomerular filtration rate of 77 ± 23 ml/min/1.73m2), 173 CKD patients died during a median follow-up of 8.0 (interquartile range 7.5–8.7) years of which 70 from a cardiovascular cause. Furthermore, 164 CKD patients developed anemia. The highest risk for all-cause mortality (hazard ratio, 2.83; 95% confidence interval, 1.53–5.24), cardiovascular mortality (4.15; 1.78–9.66), and developing anemia (3.07; 1.69–5.57) was uniformly observed for a TSAT< 10%, independent of serum ferritin level.
In this study, we have shown that of the traditionally used markers of iron status, reduced TSAT, especially TSAT< 10%, is most strongly associated with the risk of adverse outcomes in CKD patients irrespective of serum ferritin level, suggesting that clinicians should focus more on TSAT rather than ferritin in this patient setting. Specific attention to iron levels below this cutoff seems warranted in CKD patients.
Additional file 1: Table S1. Different cutoff values of ferritin and TSAT, adjusted for age and sex, with respect to risk of all-cause mortality in 975 CKD patients (based on eGFR< 60 ml/min/1.73m2 or albuminuria > 30 mg/24 h or albumin-to-creatinine ratio ≥ 30 mg/g). (DOCX 16 kb)12882_2018_1021_MOESM1_ESM.docx
Additional file 2: Table S2. Association of different cutoff values of ferritin and TSAT, adjusted for age and sex, with respect to risk of cardiovascular mortality in CKD patients (based on eGFR< 60 ml/min/1.73m2 or albuminuria > 30 mg/24 h or albumin-to-creatinine ratio ≥ 30 mg/g). (PDF 229 kb)12882_2018_1021_MOESM2_ESM.pdf
Additional file 3: Table S3. Association of different cutoff values of ferritin and TSAT, adjusted for age and sex, with respect to risk of anemia in CKD patients (based on eGFR< 60 ml/min/1.73m2 or albuminuria > 30 mg/24 h or albumin-to-creatinine ratio ≥ 30 mg/g). (PDF 226 kb)12882_2018_1021_MOESM3_ESM.pdf
Additional file 4: Table S4, Table S5, and Table S6. Showing the association of different cutoff values of ferritin and TSAT, adjusted for age and sex, in CKD patients with eGFR< 60 ml/min/1.73m2 with respect to risk of all-cause mortality, cardiovascular mortality, and anemia, respectively. (PDF 195 kb)12882_2018_1021_MOESM4_ESM.pdf
Additional file 5: Table S7, Table S8, and Table S9. Showing the association of different cutoff values of ferritin and TSAT, adjusted for age, sex, hs-CRP, and albumin, in 717 CKD patients (based on eGFR< 60 ml/min/1.73m2 or albuminuria > 30 mg/24 h or albumin-to-creatinine ratio ≥ 30 mg/g) with respect to risk of all-cause mortality, cardiovascular mortality, and anemia, respectively. (PDF 255 kb)12882_2018_1021_MOESM5_ESM.pdf
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- Association of different iron deficiency cutoffs with adverse outcomes in chronic kidney disease
Michele F. Eisenga
Ilja M. Nolte
Peter van der Meer
Stephan J. L. Bakker
Carlo A. J. M. Gaillard
- BioMed Central
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