Ferritin Elevation and Improved Responsiveness to Erythropoiesis-Stimulating Agents in Patients on Ferric Citrate Hydrate

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Introduction

In hemodialysis patients on ferric citrate hydrate, the increase in ferritin level is mainly due to the administration of the compound. We investigated possible other factors associated with ferritin level and how erythropoietin resistance index and erythropoiesis in those patients were affected. We looked at ferritin-elevating factors using data from a Japanese phase III long-term clinical trial of ferric citrate hydrate.

Methods

The factors with a strong association with ferritin levels at week 28 were selected by the process of variable selection. In addition, selected factors were analyzed by Mixed Model for Repeated Measurement. Subjects were divided into 3 groups by quantiles (<Q1, Q1–Q3, Q3<) of the most strongly correlated factors. Then the least-squares means of change of ferritin at each time point for each group were calculated. Finally, the differences of the least-squares means were examined. Changes of both erythropoiesis-stimulating agent dose and erythropoietin resistance index for each group were investigated. The differences in mean erythropoietin resistance index between groups at baseline, week 28, and week 52 were analyzed using t tests.

Results

Dose of ferric citrate hydrate showed the strongest correlation with change of ferritin and the second strongest was the reduction of erythropoiesis-stimulating agents. The mean erythropoietin resistance index was lowered in group <Q1. Group <Q1 showed significantly lower levels of ferritin at baseline.

Discussion

It is suggested that not only iron load but also the erythropoiesis-stimulating agent dose reduction may be involved in ferritin elevation during ferric citrate hydrate treatment, resulting in a decrease of erythropoietin resistance index.

Related collections

Most cited references 16

Record: found
Abstract: found
Article: found

Chronic Kidney Disease Causes Disruption of Gastric and Small Intestinal Epithelial Tight Junction

Nosratola D. Vaziri, Jun Yuan, Sohrab Nazertehrani … (2013)

Background: Integrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility. Methods: Sprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins. Results: The CKD rats showed marked azotemia, systemic oxidative stress, and marked depletion of the key protein constituents of the epithelial TJ (claudin-1, occludin, and ZO1) in the stomach, jejunum, and ileum. Conclusions: The present study extends the earlier finding of uremia-induced disruption of colonic epithelial TJ by documenting the involvement of the stomach, jejunum, and ileum as well.

0 comments Cited 67 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Ferric citrate controls phosphorus and delivers iron in patients on dialysis.

Julia Lewis, Mohammed Sika, Mark Koury … (2015)

Patients on dialysis require phosphorus binders to prevent hyperphosphatemia and are iron deficient. We studied ferric citrate as a phosphorus binder and iron source. In this sequential, randomized trial, 441 subjects on dialysis were randomized to ferric citrate or active control in a 52-week active control period followed by a 4-week placebo control period, in which subjects on ferric citrate who completed the active control period were rerandomized to ferric citrate or placebo. The primary analysis compared the mean change in phosphorus between ferric citrate and placebo during the placebo control period. A sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, transferrin saturation, and intravenous iron and erythropoietin-stimulating agent usage as prespecified secondary outcomes in the active control period. Ferric citrate controlled phosphorus compared with placebo, with a mean treatment difference of -2.2±0.2 mg/dl (mean±SEM) (P<0.001). Active control period phosphorus was similar between ferric citrate and active control, with comparable safety profiles. Subjects on ferric citrate achieved higher mean iron parameters (ferritin=899±488 ng/ml [mean±SD]; transferrin saturation=39%±17%) versus subjects on active control (ferritin=628±367 ng/ml [mean±SD]; transferrin saturation=30%±12%; P<0.001 for both). Subjects on ferric citrate received less intravenous elemental iron (median=12.95 mg/wk ferric citrate; 26.88 mg/wk active control; P<0.001) and less erythropoietin-stimulating agent (median epoetin-equivalent units per week: 5306 units/wk ferric citrate; 6951 units/wk active control; P=0.04). Hemoglobin levels were statistically higher on ferric citrate. Thus, ferric citrate is an efficacious and safe phosphate binder that increases iron stores and reduces intravenous iron and erythropoietin-stimulating agent use while maintaining hemoglobin.

0 comments Cited 49 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients

Jürgen Floege, Adrian C. Covic, Markus Ketteler … (2015)

Background Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of sevelamer carbonate (sevelamer) in an open-label Phase III extension study. Methods In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day (2−6 tablets/day; n = 710) or sevelamer 2.4−14.4 g/day (3−18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Results Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n = 260 sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02 ± 0.52 mmol/L with sucroferric oxyhydroxide and 0.09 ± 0.58 mmol/L with sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13–1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for sucroferric oxyhydroxide (4.0 ± 1.5) versus sevelamer (10.1 ± 6.6). Patient adherence was 86.2% with sucroferric oxyhydroxide versus 76.9% with sevelamer. Mean serum ferritin concentrations increased over the extension study in both treatment groups, but transferrin saturation (TSAT), iron and hemoglobin concentrations were generally stable. Gastrointestinal-related adverse events were similar and occurred early with both treatments, but decreased over time. Conclusions The serum phosphorus-lowering effect of sucroferric oxyhydroxide was maintained over 1 year and associated with a lower pill burden, compared with sevelamer. Sucroferric oxyhydroxide was generally well tolerated long-term and there was no evidence of iron accumulation.

0 comments Cited 47 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Keitaro Yokoyama

Journal

Journal ID (nlm-ta): Kidney Int Rep

Journal ID (iso-abbrev): Kidney Int Rep

Title: Kidney International Reports

Publisher: Elsevier

ISSN (Electronic): 2468-0249

Publication date PMC-release: 05 January 2017

Publication date Collection: May 2017

Publication date (Electronic): 05 January 2017

Volume: 2

Issue: 3

Pages: 359-365

Affiliations

[1 ]Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

[2 ]Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Kanagawa, Japan

[3 ]Sekikawa Hospital, Tokyo, Japan

[4 ]Department of Nephrology, Hypertension, Fukushima Medical University School of Medicine, Fukushima, Japan

[5 ]Biostatistics Team, Clinical Development, Pharmaceutical Division, Japan Tobacco Inc., Tokyo, Japan

[6 ]Medical Affairs, R&D, Torii Pharmaceutical Co., Ltd., Tokyo, Japan

[7 ]Division of Kidney Diseases and Hypertension, Department of Medicine, Northwell Health System, Hofstra Northwell School of Medicine, Great Neck, New York, USA

[8 ]Fukuoka Renal Clinic, Fukuoka, Japan

Author notes

[∗ ] Correspondence: Keitaro Yokoyama, Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minao-ku, Tokyo 1058471, Japan.Division of Nephrology and HypertensionDepartment of Internal MedicineJikei University School of Medicine3-25-8 Nishi-ShinbashiMinao-kuTokyo 1058471Japan Keitaro@ 123456jikei.ac.jp

Article

Publisher ID: S2468-0249(16)30192-9

DOI: 10.1016/j.ekir.2016.12.005

PMC ID: 5678664

SO-VID: 86c78dc7-9c75-481d-abe8-d930595e6397

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 11 September 2016

Date revision received : 29 November 2016

Date accepted : 21 December 2016

Comments

Comment on this article

scite_

Cited by 5

See all cited by

Most referenced authors 237

See all reference authors

Ferritin Elevation and Improved Responsiveness to Erythropoiesis-Stimulating Agents in Patients on Ferric Citrate Hydrate

Read this article at

Abstract

Introduction

Methods

Results

Discussion

Related collections

Open source discrete and agent-based modeling frameworks for biology

Most cited references 16

Chronic Kidney Disease Causes Disruption of Gastric and Small Intestinal Epithelial Tight Junction

Ferric citrate controls phosphorus and delivers iron in patients on dialysis.

Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 179

Cited by 5

Most referenced authors 237