Table 3.
Iron deficiency-associated outcome in patients with chronic kidney disease (CKD)
| Study | Study population | ID definition / iron status | ID / iron status-associated outcome |
|---|---|---|---|
| Kaneko et al. (2003) [75] | ID/IDA and HD-CKD*, treated with rhEPO, iv iron | TSAT level < 20% |
• Higher CRP > 5 mg/L level; associated with inflammatory process and EPO resistance → iron marker for iron supplementation therapy |
| Kalantar-Zadeh et al. (2004) [70] | ID and MHD-CKD, treated with epoetin-alfa, iv iron | Serum iron < 45.3 μg/dL [< 8.1 μmol/L] |
• Higher risk of mortality† • Higher risk of hospitalization† |
| Pollak et al. (2009) [69] | IDA and HD-CKD, treated with epoetin-alfa, iv iron | Serum ferritin ≤ 100 μg/L + TSAT ≤ 16% | • Worst long-time survival |
| Serum ferritin > 600 μg/L + TSAT > 25% | • Best long-time survival | ||
| Koo et al. (2014) [72] | IDA and HD-CKD | TSAT ≤ 20% | • Higher risks of composite cardiovascular and all-cause mortality§ |
| Gaweda et al. (2014) [74] | IDA and HD-CKD | TSAT 34% | • Max. Hb response |
| Hamano et al. (2015) [76] | ID/IDA and HD-CKD* | Serum ferritin > 100 µg/L + TSAT < 20% |
• Higher ERIs (ESA resistance index) → iron marker for ESA response |
| Eisenga et al. (2018) [73] | ID and ND-CKD | TSAT < 10% |
• Higher risk of all-cause mortality • Higher risk of cardiovascular mortality • Higher risk for developing anemia |
| Cho et al. (2019) [66] | ID and ND-CKD with/without diabetic issues |
Abnormal iron balance: TSAT 0.4–16% or 28–99.6%, serum ferritin 0.4–55 μg/L or 205–4941 μg/L FID: TSAT 0.8–16%, serum ferritin 109–2783 μg/L |
• Higher risk of all-cause mortality** |
| Awan et al. (2019) [67] | IDA and ND-CKD | AID: serum ferritin < 100 μg/L + TSAT ≤ 20% | • Higher risk of cardiovascular hospitalization |
| FID: serum ferritin > 100–500 µg/L + TSAT ≤ 20% |
• Higher risk of mortality • Higher risk of cardiovascular hospitalization |
||
| Sato et al. (2019) [68] |
MHD-CKD* (evaluated iron profiles) |
TSAT < 20% | • Higher risk of all-cause mortality# |
| Yeh et al. (2019) [71] |
HD-CKD with/without PKD (evaluated iron profiles) |
TSAT ≤ 20% | • Higher risk of mortality‡ |
| Mehta et al. (2021) [65] | ID/iron status in CKD |
ID: serum ferritin 4.85–82.48 µg/L + TSAT 1.28–17.24% FID: serum ferritin 157.7–3769.0 µg/L + TSAT 1.28–17.24% Iron-replete: serum ferritin 82.49–284.4 µg/L + TSAT 17.25–28.018% Mixed ID: serum ferritin 82.49–157.6 µg/L + TSAT 1.28–17.24% High iron: serum ferritin 284.4–3769.0 µg/L + TSAT 28.019–87.12% Nonclassified: serum ferritin 4.85–82.48 µg/L + TSAT 17.25–87.12 or serum ferritin 82.49–284.4 µg/L + TSAT 28.019–87.12% or serum ferritin 284.4–3769.0 µg/L + TSAT 17.25–28.018% |
• ID independently associated with mortality and heart failure • Mixed ID associated with mortality and ESKD • High iron associated with mortality, heart failure and ESKD • FGF23 mediated the risks of mortality and heart failure conferred by ID |
| Guedes et al. (2021) (45) | ID and ND-dependent CKD |
AID: serum ferritin < 50 µg/L + TSAT < 20% FID: serum ferritin > 300 µg/L + TSAT < 20% |
• Worse physical HRQoL |
AID absolute iron deficiency, CKD chronic kidney disease, CRP C-reactive protein, ESA erythropoiesis-stimulating agents, ESKD end-stage kidney disease, EPO erythropoietin, FGF23 Fibroblast growth factor 23, FID functional iron deficiency, HD hemodialysis, Hb hemoglobin, HRQoL health-related quality of life, ID iron deficiency, IDA iron deficiency anemia, iv intravenous, MHD maintenance hemodialysis, ND non-dialysis, PKD autosomal-dominant polycystic kidney disease, rhEPO recombinant human erythropoietin, TSAT transferrin saturation
* Japanese population
** Outcome was similar between diabetic and non-diabetic subgroups
# Compared with the reference groups with TSAT 20–40% or TSAT > 40%
† Outcomes independent of Hb level, EPO and iron doses
‡ In non-PKD group, in comparison to the high TSAT group (≥ 50%)
§ Compared with the reference group with TSAT 20–40%