Table 2.
Summary of observational studies of IV iron in patients with non-dialysis-dependent and dialysis-dependent CKD (2013−present)
| Reference | Study population | n | Study design | Study conclusions |
|---|---|---|---|---|
| Brookhart et al. 2016 [49] | Medicare ICHD patients (2004–05) | 66 207 | Comparison of short-term safety of IV sodium ferric gluconate versus iron sucrose; 1-month exposure period; outcomes (all-cause mortality, infection-related and CV hospitalization and mortality) assessed over 3-month follow-up period | No difference in mortality outcomes |
| Among CVC patients, slightly reduced risk of infection-related events in ferric gluconate patients | ||||
| Bolus dosing associated with increased infection-related events in both groups | ||||
| Freburger et al. 2016 [50] | ICHD patients of large US dialysis organization (2008–10) | 13 039 | Iron and ESA dosing assessed during 1-month and 2-week exposure periods; HRQOL measured over 3-month outcome period | In patients with low-baseline Hb, higher ESA dosing and bolus iron dosing associated with higher HRQOL scores |
| Airy et al. 2015 [51] | USRDS, incident HD patients (2009–11) | 14 206 | Comparison of HD facilities switching from iron sucrose or ferric gluconate to ferumoxytol with facilities that did not switch; incident patients at these facilities were followed until censoring, facility switch to different iron formulation or end of study (31 Dec 2011); outcomes assessed were all-cause mortality, CV hospitalization/mortality, infectious hospitalization/mortality | No difference in outcomes between facilities that switched to ferumoxytol and those that did not |
| Bailie et al. 2015 [52] | DOPPS facility HD patients (2009–11) | 32 435 | Assessed association between total prescribed IV iron dose over first 4 months in study with clinical outcomes (mortality, cause-specific mortality) | Increased risk of mortality for patients receiving 300–399 (13%) or 400+ mg/month (18%) compared with 100–199 mg/month; associations with cause-specific mortality and hospitalization similar |
| Ishida et al. 2015 [53] | USRDS ICHD patients (2010) | 22 820 | Comparison of outcomes for patients receiving versus not receiving IV iron while in hospital for bacterial infection | Receipt of IV iron not associated with higher 30-day mortality or readmission for infection |
| Karaboyas et al. 2015 [54] | DOPPS facility patients (2009–13) | 9735 | Trends in mean ferritin, haemoglobin, IV iron dose and ESA dose from 2009 to 2013 assessed among patients at 91 DOPPS facilities | IV iron increased from 220 mg/month in 2009/10 to 280 mg/month in 2011 then declined back to 200 mg/month in 2012–13; mean ferritin increased from 601 ng/mL in Q3 2009 to 887 ng/mL in Q1 2012; increase in ferritin not solely due to iron dosing practices |
| Kuo et al. 2015 [55] | Taiwan National Health Insurance Research Database, CKD-ND patients (2000–09) | 31 971 | Prospective cohort study of patients with creatinine >6 mg/dL, haematocrit <28%, treated with ESA; patients receiving versus not receiving IV iron within 90 days of starting ESA compared; outcomes assessed: death before dialysis initiation, hospitalization | Iron supplementation associated with 15% reduction in mortality and reduction in risk of hospitalization but higher risk of faster progression to ESRD |
| Tangri et al. 2015 [56] | HD patients of Dialysis Clinic Inc. (2003-08) | 9544 | Iron exposure assessed over 1-, 3- and 6-month time windows; incident hospitalizations assessed during 30-day outcome window | Higher cumulative dose of IV iron not associated with increased risk of hospitalization |
| Freburger et al. 2014 [57] | Medicare HD patients of small US dialysis provider | 6505 | Iron dosing patterns (bolus, maintenance, no iron) assessed during 1-month exposure windows; outcomes assessed over 3-month follow-up period | Bolus iron dosing associated with increased risk of infection-related hospitalization and use of IV antibiotics; no association between dosing practice and CV outcomes |
| Miskulin et al. 2014 [58] | Incident HD patients of Dialysis Clinic Inc. (2003–08) | 14 078 | Iron exposure assessed over 1-, 3- and 6-month time windows; all-cause, CV and infection-related mortality assessed during 30-day outcome window | Receipt of ≤1050 mg iron in 3 months or ≤ 2100 mg in 6 months not associated with all-cause, CV or infection-related mortality |
| Receipt of >1050 mg iron in 3 months or >2100 mg in 6 months possibly associated with infection-related mortality (non-statistically significant) | ||||
| Schiller et al. 2014 [59] | Patients of three US dialysis chains | 8666 | Patients treated with ferumoxytol at any time in 12-month period assessed; efficacy and safety outcomes considered | Ferumoxytol effective in increasing and maintaining Hb with AE profile similar to that reported in clinical trials |
| Bailie et al. 2013 [60] | DOPPS facility patients (1999–2011) | 32 192 | Trends in iron use and associations of IV iron dose with ferritin and TSAT assessed | IV iron use varied by country and increased over 2009–11 in most countries; increases in ferritin but not TSAT also observed |
| Brookhart et al. 2013 [61] | HD patients of large dialysis provider (2004–08) | 117 050 | Iron dosing patterns (bolus versus maintenance) assessed over 1-month exposure periods; mortality and infection-related hospitalization assessed n subsequent 3 months | Bolus iron dosing associated with increased risk of infection-related hospitalization and mortality; maintenance iron dosing not associated with increased risk for adverse outcomes compared with no iron |
| Kshirsagar et al. 2013 [62] | HD patients of large dialysis provider (2004–08) | 117 050 | Compared bolus versus maintenance and high versus low iron dose during 1-month exposure period and 3-month follow-up period; outcomes assessed: MI, stroke and CV mortality | Large doses of IV iron were not associated with increased risk of short-term CV morbidity and mortality |
| Kshirsagar et al. 2013 [63] | HD patients of large dialysis provider (2004–08) | 117 050 | Compared bolus versus maintenance and high versus low iron dose during 1-month exposure period and 6-week follow-up period; outcomes assessed: Hb, ESA dose, TSAT, serum ferritin | Large doses of IV iron associated with improved measures of anaemia management |
| Miskulin et al. 2013 [64] | HD patients from medium-sized US dialysis provider (2004–10) | Indicators of anaemia management assessed in HD patients over 2004–07, 2007–09 and 2010 | Median proportion of patients with Hb >12 g/dL and median weekly ESA doses declined sharply in 2010; iron doses, serum ferritin and TSAT increased over time |
DOPPS, Dialysis Practice Patterns and Outcomes Study; Hb, haemoglobin; HD, haemodialysis; HRQOL, health-related quality of life; ICHD, in-centre haemodialysis.