Skip to content

Advertisement

  • Research note
  • Open Access

Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients

BMC Research Notes201811:363

https://doi.org/10.1186/s13104-018-3483-6

©  The Author(s) 2018

  • Received: 30 March 2018
  • Accepted: 5 June 2018
  • Published:

Abstract

Objective

Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients.

Results

Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients.

Keywords

  • CKD-MBD
  • Dialysis
  • FGF23
  • Iron-based phosphate binder
  • Renal anemia

Introduction

In patients with chronic kidney disease- mineral and bone disorder (CKD-MBD), hyperphosphatemia is reported to increase the risk of cardiovascular events resulting from vascular calcification and death [1–3], and to affect bone lesions. It has been shown that phosphate binders are able to improve hyperphosphatemia and reduce the risk of cardiovascular events and overall mortality [4, 5]. Moreover, levels of fibroblast growth factor 23 (FGF23), an endocrine hormone playing an important role in phosphorus metabolism [6], increase as CKD progresses. FGF23 is an early marker of phosphorus load [7] that has been attracting attention as an independent risk factor for cardiovascular events and mortality rate [8–10], similar to serum phosphorus levels.

Sucroferric oxyhydroxide is a novel, non-calcium-based phosphate binder with a unique complex structure consisting of polynuclear iron(III) oxyhydroxide and carbohydrate. The efficacy and safety of long-term administration have been shown in clinical studies [11–14]. Notably, sucroferric oxyhydroxide contains approximately 20% iron and has also been reported to positively affect renal anemia [15, 16]. Furthermore, in an animal study, FGF23 levels after sucroferric oxyhydroxide was administered were lower than those after lanthanum carbonate or sevelamer hydrochloride was administered [17]. However, clinical data on sucroferric oxyhydroxide in patient populations with various demographic characteristics are limited and no clinical data are available for the effects of this agent on FGF23.

Therefore, we conducted an exploratory evaluation of the clinical efficacy and safety of sucroferric oxyhydroxide given over a 16-week period in hemodialysis (HD) patients, and evaluated the effect on serum phosphorus levels, FGF23 levels and renal anemia treatment when HD patients receiving existing hyperphosphatemia drugs with insufficient benefit were switched to sucroferric oxyhydroxide.

Main text

Study design

This study is a prospective, one-arm, open-label study in HD patients with hyperphosphatemia. Subjects were HD (hemodialysis and hemodiafiltration) patients who visited a specialized dialysis facility in Japan (Kawashima Dialysis Clinic, Tokushima), who planned to continue their current hemodialysis regimen (≥ 3 times/week) during the study period, and who had experienced insufficient benefits, or a serum phosphorus level of > 6.0 mg/dL, while on their existing hyperphosphatemia treatment for ≥ 4 weeks before the start of this study. After the start of this study, the patient’s current hyperphosphatemia drugs, with the exception of calcium carbonate, were switched to chewable sucroferric oxyhydroxide tablets, administered orally three times a day before meals. Dose was adjusted to achieve a target serum phosphorus level of ≥ 3.5 and ≤ 6.0 mg/dL [18]. Doses of erythropoiesis-stimulating agents (ESAs) and intravenous iron (IV-iron) were also adjusted to achieve a target hemoglobin (Hb) level of ≥ 10 and < 12 g/dL [19]. For more details, please refer to the Additional file 1.

Outcomes and assessments

CKD-MBD-related tests, Hb and iron-related tests were conducted in Weeks 0, 8, and 16 after the start of study drug administration. FGF23 and high-sensitivity C-reactive protein (hs-CRP) were measured in Weeks 0 and 16 after the start of study drug administration. The cumulative doses of ESAs and IV-iron were recorded in Week 0, 4, 8, 12, and 16.

Statistical analysis

All data were expressed as the mean ± standard deviation (SD). Statistical analyses were performed with paired t test using SAS 9.4 software (SAS Institute Inc., Cary, NC, USA). p < 0.05 was considered to be statistically significant. Subgroup analyses were performed in two groups (switching to sucroferric oxyhydroxide and adding sucroferric oxyhydroxide to calcium carbonate monotherapy). For more details, please refer to the Additional file 1.

Results

Subjects

All 54 enrolled patients received sucroferric oxyhydroxide, of whom 40 patients completed 8 weeks’ treatment, and 33 patients (61.1%) completed 16 weeks’ treatment. In 21 patients, the study was discontinued due to adverse events, etc. (Additional file 2: Fig. S1). Table 1 shows patient backgrounds. Hyperphosphatemia drugs used prior to sucroferric oxyhydroxide treatment were calcium carbonate in 26 patients (65.0%) and lanthanum carbonate hydrate in 18 patients (45.0%; some patients received both agents); the mean dose of lanthanum carbonate at baseline was 1500.0 ± 500.0 mg. ESAs were used in 38 patients (95.0%), and IV-iron in 5 patients (12.5%). Six patients were newly administered calcium carbonate after the start of the study. Ten patients were administered sucroferric oxyhydroxide in addition to calcium carbonate monotherapy (Adding group). Therefore, 24 patients were switched from existing hyperphosphatemia agents to sucroferric oxyhydroxide (Switching group) (Additional file 2: Fig. S1). Characteristics of the patients in the Switching group are shown in Additional file 3: Table S1.
Table 1

Patient demographics and clinical characteristics

Variable

n/mean

Percentage/SD

Sex

  

 Male

27

67.5

Age, year

61.5

12.9

Age

  

 < 65 years

18

45.0

 ≥ 65 years

22

55.0

Dialysis method

  

 Hemodialysis

15

38.5

 Hemodiafiltration

24

61.5

Dialysis history

  

 < 1 year

3

7.5

 ≥ 1 and < 3 years

7

17.5

 ≥ 3 years

30

75.0

Primary disease of dialysis

  

 Chronic glomerulonephritisa

16

40.0

 Diabetic nephropathy

13

32.5

 Nephrosclerosis

7

17.5

 Polycystic kidney

1

2.5

 Unknown

3

7.5

Complication

  

 Hypertension

33

82.5

 Diabetes mellitus

16

40.0

 Dyslipidaemia

12

30.0

Prior hyperphosphatemia drug

  

 Calcium carbonate

10

25.0

 Calcium carbonate + lanthanum carbonate hydrate

7

17.5

 Calcium carbonate + sevelamer hydrochloride

3

7.5

 Calcium carbonate + bixalomer

3

7.5

 Calcium carbonate + iron(III) citrate hydrate

2

5.0

 Calcium carbonate + lanthanum carbonate hydrate + iron(III) citrate hydrate

1

2.5

 Lanthanum carbonate hydrate

9

22.5

 Lanthanum carbonate hydrate + iron(III) citrate hydrate

1

2.5

 Bixalomer

4

10.0

Daily dose of lanthanum carbonate hydrate, mg

1500.0

500.0

ESAsb administration

38

95.0

Cumulative dose of ESAs, IUc

25,315.8

18,207.7

Intravenous iron administration

5

12.5

Cumulative dose of intravenous iron, mg

160.0

0.0

The values are mean (standard deviation) or n (%). Data for the 4 weeks before the start of the study shown for ESAs and intravenous iron

aIncluding IgA nephropathy

bErythropoiesis-stimulating agents

cInternational unit

Efficacy outcomes

Serum phosphorus level had declined significantly by Week 8 (− 1.5 ± 1.6 mg/dL, p < 0.0001) and remained low until Week 16 (− 1.4 ± 1.8 mg/dL, p < 0.0001) (Table 2). Additional file 4: Fig. S2 shows the time point at which target serum phosphorus levels were achieved for the first time. The majority of patients had achieved the target for the first time by 8 weeks (70%). No significant changes were observed in adjusted calcium levels or intact- parathyroid hormone (PTH) levels (Table 2). Calcium phosphate product had decreased by Week 8 (− 13.1 ± 13.0 mg2/dL2, p < 0.0001) and remained low at Week 16 (− 11.7 ± 16.4 mg2/dL2, p = 0.0003). FGF23 had significantly decreased at Week 16 (− 4487.8 ± 12,122.0 pg/mL, p = 0.0412). Hb had significantly increased by Week 8 (+ 1.5 ± 1.5 g/dL, p < 0.0001) and remained increased at Week 16 (+ 1.7 ± 1.8 g/dL, p < 0.0001). The cumulative dose of ESAs had significantly decreased by Week 12 (− 8493.6 ± 14,897.5 IU, p = 0.0010) and was still low at Week 16 (− 9544.1 ± 20,983.4 IU, p = 0.0122). The cumulative dose of IV-iron had decreased by Week 12 (− 20.5 ± 54.2 mg, p = 0.0233) (Table 2).
Table 2

Efficacy parameters

 

Actual value

Changes

n

mean

SD

n

mean

SD

p-valuem

Serum phosphorus, mg/dL

       

 Baseline

40

7.0

0.7

–

–

–

–

 Week 8

39

5.5

1.3

39

− 1.5

1.6

< 0.0001

 Week 16

33

5.6

1.5

33

− 1.4

1.8

< 0.0001

Corrected serum calcium, mg/dL

       

 Baseline

40

8.6

0.9

–

–

–

–

 Week 8

39

8.6

0.8

39

0.0

1.0

0.8459

 Week 16

33

8.7

0.7

33

0.2

0.9

0.3332

Calcium-phosphorus products, mg2/dL2

       

 Baseline

40

59.8

8.4

–

–

–

–

 Week 8

39

46.8

9.8

39

− 13.1

13.0

< 0.0001

 Week 16

33

48.6

12.4

33

− 11.7

16.4

0.0003

Serum intact-PTHa, pg/mL

       

 Baseline

25

262.3

191.5

–

–

–

–

 Week 8

19

243.6

193.9

19

− 24.0

108.5

0.3477

 Week 16

22

336.1

589.3

17

− 50.4

137.7

0.1511

FGF23b, pg/mL

       

 Baseline

40

15,282.3

13,548.6

–

–

–

–

 Week 16

33

10,999.7

10,594.0

33

− 4487.8

12,122.0

0.0412

Hbc, g/dL

       

 Baseline

40

11.1

1.1

    

 Week 8

39

12.6

1.1

39

1.5

1.5

< 0.0001

 Week 16

33

12.7

1.2

33

1.7

1.8

< 0.0001

RBCd, × 10−4/μL

       

 Baseline

40

393.6

40.2

–

–

–

–

 Week 8

39

419.1

45.7

39

25.5

36.2

< 0.0001

 Week 16

33

410.5

53.0

33

18.8

53.1

0.0500

Hte, %

       

 Baseline

40

34.9

3.1

–

–

–

–

 Week 8

39

39.3

3.7

39

4.3

4.4

< 0.0001

 Week 16

33

38.8

4.0

33

4.3

5.4

< 0.0001

Cumulative dose of ESAsf, IU

       

 Baselineh

40

24,050.0

18,594.1

–

–

–

–

 Week 4i

38

24,236.8

20,653.1

38

− 526.3

12,019.1

0.7887

 Week 8j

37

26,533.8

21,679.5

37

1533.8

9123.4

0.3133

 Week 12k

39

15,762.8

15,613.6

39

− 8493.6

14,897.5

0.0010

 Week 16 l

34

14,985.3

15,135.9

34

− 9544.1

20,983.4

0.0122

Cumulative dose of IV-irong, mg

       

 Baselineh

40

20.0

53.6

–

–

–

–

 Week 4i

38

14.7

38.8

38

− 6.3

41.1

0.3496

 Week 8j

37

3.2

19.7

37

− 18.4

60.1

0.0709

 Week 12k

39

0.0

0.0

39

− 20.5

54.2

0.0233

 Week 16 l

34

10.6

61.7

34

− 8.2

83.4

0.5688

Daily dose of calcium carbonate, g

       

 Baseline

40

1.3

1.2

–

–

–

–

 Week 4

38

1.3

1.2

38

0.0

0.4

0.5706

 Week 8

39

1.5

1.2

39

0.2

0.6

0.0577

 Week 12

40

1.4

1.2

40

0.1

0.8

0.6348

 Week 16

33

1.4

1.2

33

0.1

0.9

0.3786

Daily dose of sucroferric oxyhydroxide, mg

       

 Baseline

40

1000.0

477.0

–

–

–

–

 Week 4

38

1256.6

613.7

38

243.4

549.8

0.0097

 Week 8

39

1282.1

626.1

39

269.2

591.6

0.0072

 Week 12

40

1250.0

718.3

40

250.0

662.6

0.0220

 Week 16

34

1323.5

727.0

34

294.1

672.7

0.0156

Cumulative doses of ESAs and intravenous iron were regarded as 0 when they were not administered

aParathyroid hormone

bFibroblast growth factor 23

cHemoglobin

dred blood cell count

eHematocrit

fErythropoiesis-stimulating agents

gIntravenous iron

hWeeks − 4 to 0

iWeeks 0–4

jWeeks 4–8

kWeeks 8–12

lWeeks 12–16

mPaired t-test (vs. baseline)

Efficacy outcomes of the Switching group and the Adding group are shown in Additional files 5, 6, 7, 8: Tables S2–S4 and Fig. S3. In the Switching group, serum phosphorus level and calcium phosphate product had declined significantly by Week 8 and remained declined at Week 16 (− 1.4 ± 1.7 mg/dL, p = 0.0017; − 12.2 ± 17.9 mg2/dL2, p = 0.0084). Hb and Ht had significantly increased by Week 8 and remained increased at Week 16 (1.4 ± 1.5 g/dL, p = 0.0005; 3.6 ± 4.1%, p = 0.0013). The cumulative dose of ESAs had significantly decreased by Week 12 and remained decreased at Week 16 (− 12,075.0 ± 23,438.6 IU, p = 0.0327). The cumulative dose of IV-iron had decreased from Week 4 to Week 16 (− 32.0 ± 65.7 mg, p = 0.0421). No significant changes were observed in the adjusted calcium levels, intact-PTH, and FGF23 levels.

Safety outcomes

As shown in Table 3, serum iron, serum ferritin, and transferrin saturation (TSAT) levels increased from baseline at Week 8, and serum ferritin level continued to rise through to Week 16 (90.6 ± 79.5 ng/mL). Hs-CRP levels increased from baseline at Week 16. Adverse reactions occurred in 18 of 54 patients (33.3%); the most frequent event was diarrhea, which was observed in 9 of 54 patients (16.7%) (Additional file 9: Table S5). Serious adverse events were observed in 8 of 54 patients (14.8%), none of which were found to have a causal relationship with sucroferric oxyhydroxide. In terms of the safety parameters and adverse reactions of the Switching group and the Adding group, please refer to the Additional files 10, 11: Tables S6, S7.
Table 3

Safety parameters

 

Actual value

n

Mean

SD

Serum iron, μg/dL

Week 0

54

60.1

33.5

Week 8

33

82.1

23.5

Week 16

33

80.2

29.0

Serum ferritin, ng/mL

Week 0

54

29.7

22.8

Week 8

33

51.4

44.0

Week 16

33

90.6

79.5

TSATa, %

Week 0

54

19.2

11.7

Week 8

33

29.3

9.5

Week 16

33

30.7

11.3

hs-CRPb, ng/mL

Week 0

54

2801.6

4134.1

Week 16

32

5980.6

16,191.3

aTransferrin saturations

bHigh-sensitivity C-reactive protein

Discussion and conclusion

In this study, hyperphosphatemia treatment with sucroferric oxyhydroxide (monotherapy or concomitant therapy with calcium carbonate) was found to successfully control serum phosphorus levels, even in HD patients who had received insufficient benefits from other phosphate-binders. In addition, target levels were achieved by Week 8 in 70% of patients, suggesting that this drug may have an early effect in terms of improvement in serum phosphorus levels. This result may reflect the fact that the equivalent dose of a sucroferric oxyhydroxide tablet is the highest of the commercially available phosphate-binders [20]. Calcium phosphate product is a possible factor affecting vascular calcification [21] and is recommended to be ≤ 55 mg2/dL2 [22]. In this study, calcium phosphate product levels decreased to within the target range in and after Week 8, which suggested that hyperphosphatemia treatment with sucroferric oxyhydroxide suppresses vascular calcification.

FGF23 may be more important than serum phosphorus, serum calcium, and PTH levels in the treatment of CKD-MBD [7]. Transcription of FGF23 has been reported to be enhanced by iron deficiency but not directly by serum phosphorus, serum calcium, or intact-PTH [23, 24], and an animal study reported that sucroferric oxyhydroxide, which contains iron, decreased FGF23 to a significantly greater extent than either lanthanum carbonate or sevelamer hydrochloride [17]. To the best of our knowledge, this study is the first clinical report indicating that the improvement in iron deficiency associated with hyperphosphatemia treatment with sucroferric oxyhydroxide possibly contributes directly to the decrease in FGF23 levels.

Increased Hb and decreased cumulative doses of ESAs and IV-iron were observed after administration of sucroferric oxyhydroxide, suggesting that the drug may act to improve renal anemia. These results may be attributed to the intestinal absorption of iron, a physiological metal contained in sucroferric oxyhydroxide [25]. Hb has been reported to affect vital prognosis [26], and overdoses of IV-iron have been reported to possibly increase cardiovascular risk and the risk of infection-related hospitalization [27–29]; therefore, administration of sucroferric oxyhydroxide may be expected to increase survival rate by improving renal anemia and avoiding the risks associated with IV-iron. Note that the mean of the cumulative dose of IV-iron had decreased significantly by Week 12 and had increased slightly by Week 16 in this study. This result can be attributed to the IV-iron that was administered for the comorbidity (subcutaneous hemorrhage) of pneumonia (1 patient), and no patient received IV-iron for renal anemia in Week 16.

Iron-based phosphorus binders are associated with a risk of iron overdose [30]. In this study, an increase in serum ferritin and TSAT level was observed, and the serum ferritin level continued to increase until Week 16. Although the means of these parameters were below 100 ng/mL, and were considered to remain at levels below those associated with safety concerns in Week 16, it may be necessary to monitor iron-related parameters during administration of sucroferric oxyhydroxide.

The most common adverse reaction in this study was diarrhea. Based on the results, sucroferric oxyhydroxide can be regarded as a drug that can safely control serum phosphorus levels when given as a 16-week treatment course. Non-compliance in HD patients affects overall mortality [31]. Although the benefits of sucroferric oxyhydroxide can be obtained with a smaller number of tablets than for sevelamer hydrochloride [11, 13], the tablets are relatively large, and in this study, administration was discontinued in four patients due to discomfort associated with study drug ingestion. To continue intake of sucroferric oxyhydroxide, a more sophisticated drug formulation are considered important.

The results of this study may be obtained not only by sucroferric oxyhydroxides but also through hyperphosphatemia treatment with sucroferric oxyhydroxide. There was also concern about the possibility that our results might be influenced by those patients who had been newly administered calcium carbonate after the start of the study (n = 6) and administered sucroferric oxyhydroxide in addition to calcium carbonate monotherapy (Adding group, n = 10). Therefore, we performed additional subgroup analyses on patients switched to sucroferric oxyhydroxide (Switching group, n = 24). As a result, the Switching group showed the same trends as full analysis set (n = 40). The findings from this study suggest that sucroferric oxyhydroxides reduce the disadvantages of existing hyperphosphatemia drugs and are useful therapeutic options for treating hyperphosphatemia in HD patients. Further studies involving more patients are needed.

In conclusion, the results of this study suggest that hyperphosphatemia treatment with sucroferric oxyhydroxide improves renal anemia and various factors affecting the vital prognosis of HD patients (such as FGF23, serum phosphorus, calcium phosphate product, and Hb levels and the use of IV-iron), and further investigation is expected.

Limitations

This study is biased due to its design: a one-arm, open-label, before-and-after study. Intact-PTH was evaluated in only a few patients because it was measured only in patients who received cinacalcet hydrochloride tablets.

Abbreviations

CKD-MBD: 

chronic kidney disease-mineral and bone disorder

FGF23: 

fibroblast growth factor 23

HD: 

hemodialysis

ESAs: 

erythropoiesis-stimulating agents

IV-iron: 

intravenous iron

Hb: 

hemoglobin

hs-CRP: 

high-sensitivity C-reactive protein

SD: 

standard deviation

PTH: 

parathyroid hormone

TSAT: 

transferrin saturation

Declarations

Authors’ contributions

HS drafted the first manuscript. HS, KM, KO, JM, and SK performed the literature search. KM, KO, JM, and SK coordinated the data analysis and critically commented on the manuscript. KM, KO, JM, and SK helped with writing the manuscript. All authors participated in discussions, and read and approved the final manuscript.

Acknowledgements

We thank Sogo Rinsho Medefi Co., Ltd. for preparation of the protocol, execution of statistical analyses, and preparation of the publication.

Competing interests

The authors declare that they have no competing interests.

Availability of data and materials

The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.

Consent for publication

Not applicable.

Ethics approval and consent to participate

This study was approved by the Kawashima Hospital Ethics Review Committee and was conducted in accordance with “Helsinki Declaration” and “Japanese ethical guideline”. Written informed consent was obtained from every patient.

Funding

This study was funded by Kissei Pharmaceutical Co., Ltd. The company was not involved in the design of the study and collection, analysis and interpretation of data and in writing the manuscript.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Kidney Disease, Kawashima Hospital, 1-39 Kitasakoichiban-cho, Tokushima 770-0011, Japan
(2)
Department of Internal Medicine, Kawashima Hospital, 1-39 Kitasakoichiban-cho, Tokushima 770-0011, Japan

References

  1. Block GA. Control of serum phosphorus: implications for coronary artery calcification and calcific uremic arteriolopathy (calciphylaxis). Curr Opin Nephrol Hypertens. 2001;10:741–7.View ArticlePubMedGoogle Scholar
  2. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004;15:2208–18.View ArticlePubMedGoogle Scholar
  3. Palmer SC, Hayen A, Macaskill P, Pellegrini F, Craig JC, Elder GJ, et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. JAMA. 2011;305:1119–27.View ArticlePubMedGoogle Scholar
  4. Isakova T, Gutiérrez OM, Chang Y, Shah A, Tamez H, Smith K, et al. Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol. 2009;20:388–96.View ArticlePubMedPubMed CentralGoogle Scholar
  5. Lopes AA, Tong L, Thumma J, Li Y, Fuller DS, Morgenstern H, et al. Phosphate binder use and mortality among hemodialysis patients in the dialysis outcomes and practice patterns study (DOPPS): evaluation of possible confounding by nutritional status. Am J Kidney Dis. 2012;60:90–101.View ArticlePubMedPubMed CentralGoogle Scholar
  6. Fukumoto S, Yamashita T. FGF23 is a hormone-regulating phosphate metabolism—unique biological characteristics of FGF23. Bone. 2007;40:1190–5.View ArticlePubMedGoogle Scholar
  7. Oliveira RB, Cancela AL, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, et al. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol. 2010;5:286–91.View ArticlePubMedPubMed CentralGoogle Scholar
  8. Nasrallah MM, El-Shehaby AR, Salem MM, Osman NA, El Sheikh E, Sharaf El Din UA. Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients. Nephrol Dial Transplant. 2010;25:2679–85.View ArticlePubMedGoogle Scholar
  9. Jean G, Bresson E, Terrat JC, Vanel T, Hurot JM, Lorriaux C, et al. Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant. 2009;24:948–55.View ArticlePubMedGoogle Scholar
  10. Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359:584–92.View ArticlePubMedPubMed CentralGoogle Scholar
  11. Koiwa F, Yokoyama K, Fukagawa M, Terao A, Akizawa T. Efficacy and safety of sucroferric oxyhydroxide compared with sevelamer hydrochloride in Japanese haemodialysis patients with hyperphosphataemia: a randomized, open-label, multicentre, 12-week phase III study. Nephrology. 2017;22:293–300.View ArticlePubMedPubMed CentralGoogle Scholar
  12. Koiwa F, Yokoyama K, Fukagawa M, Akizawa T. Long-term assessment of the safety and efficacy of PA21 (sucroferric oxyhydroxide) in Japanese hemodialysis patients with hyperphosphatemia: an open-label, multicenter, phase III study. J Ren Nutr. 2017;27:346–54.View ArticlePubMedGoogle Scholar
  13. Floege J, Covic AC, Ketteler M, Rastogi A, Chong EM, Gaillard S, et al. A phase III study of the efficacy and safety of a novel iron-based phosphate binder in dialysis patients. Kidney Int. 2014;86:638–47.View ArticlePubMedPubMed CentralGoogle Scholar
  14. Floege J, Covic AC, Ketteler M, Mann JF, Rastogi A, Spinowitz B, et al. Long-term effects of the iron-based phosphate binder, sucroferric oxyhydroxide, in dialysis patients. Nephrol Dial Transplant. 2015;30:1037–46.View ArticlePubMedPubMed CentralGoogle Scholar
  15. Coyne DW, Ficociello LH, Parameswaran V, Anderson L, Vemula S, Ofsthun NJ, et al. Real-world effectiveness of sucroferric oxyhydroxide in patients on chronic hemodialysis: a retrospective analysis of pharmacy data. Clin Nephrol. 2017;88:59–67.View ArticlePubMedPubMed CentralGoogle Scholar
  16. Covic AC, Floege J, Ketteler M, Sprague SM, Lisk L, Rakov V, et al. Iron-related parameters in dialysis patients treated with sucroferric oxyhydroxide. Nephrol Dial Transplant. 2017;32:1330–8.PubMedGoogle Scholar
  17. Phan O, Maillard M, Malluche HH, Stehle JC, Funk F, Burnier M. Effects of sucroferric oxyhydroxide compared to lanthanum carbonate and sevelamer carbonate on phosphate homeostasis and vascular calcifications in a rat model of chronic kidney failure. Biomed Res Int. 2015;2015:515606.PubMedPubMed CentralGoogle Scholar
  18. Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, et al. Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial. 2013;17:247–88.View ArticlePubMedGoogle Scholar
  19. Yamamoto H, Nishi S, Tomo T, Masakane I, Saito K, Nangaku M, et al. 2015 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease. Renal Replace Ther. 2017;3:36.View ArticleGoogle Scholar
  20. Peter WLS, Wazny LD, Weinhandl E, Cardone KE, Hudson JQ. A review of phosphate binders in chronic kidney disease: incremental Progress or just higher costs? Drugs. 2017;77:1155–86.View ArticleGoogle Scholar
  21. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342:1478–83.View ArticlePubMedGoogle Scholar
  22. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42:S1–201.Google Scholar
  23. Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013;28:1793–803.View ArticlePubMedGoogle Scholar
  24. Bhattacharyya N, Chong WH, Gafni RI, Collins MT. Fibroblast growth factor 23: state of the field and future directions. Trends Endocrinol Metab. 2012;23:610–8.View ArticlePubMedPubMed CentralGoogle Scholar
  25. Cozzolino M, Funk F, Rakov V, Phan O, Teitelbaum I. Preclinical pharmacokinetics, pharmacodynamics and safety of sucroferric oxyhydroxide. Curr Drug Metab. 2014;15:953–65.View ArticlePubMedPubMed CentralGoogle Scholar
  26. Akizawa T, Saito A, Gejyo F, Suzuki M, Nishizawa Y, Tomino Y, et al. Low hemoglobin levels and hypo-responsiveness to erythropoiesis-stimulating agent associated with poor survival in incident Japanese hemodialysis patients. Ther Apher Dial. 2014;18:404–13.View ArticlePubMedGoogle Scholar
  27. Kuo KL, Hung SC, Lin YP, Tang CF, Lee TS, Lin CP, et al. Intravenous ferric chloride hexahydrate supplementation induced endothelial dysfunction and increased cardiovascular risk among hemodialysis patients. PLoS ONE. 2012;7:e50295.View ArticlePubMedPubMed CentralGoogle Scholar
  28. Brookhart MA, Freburger JK, Ellis AR, Wang L, Winkelmayer WC, Kshirsagar AV. Infection risk with bolus versus maintenance iron supplementation in hemodialysis patients. J Am Soc Nephrol. 2013;24:1151–8.View ArticlePubMedPubMed CentralGoogle Scholar
  29. Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ. 2013;347:f4822.View ArticlePubMedPubMed CentralGoogle Scholar
  30. Umanath K, Jalal DI, Greco BA, Umeukeje EM, Reisin E, Manley J, et al. Ferric citrate reduces intravenous iron and erythropoiesis-stimulating agent use in ESRD. J Am Soc Nephrol. 2015;26:2578–87.View ArticlePubMedPubMed CentralGoogle Scholar
  31. Yusuf AA, Weinhandl ED, St Peter WL. Comparative effectiveness of calcium acetate and sevelamer on clinical outcomes in elderly hemodialysis patients enrolled in medicare part D. Am J Kidney Dis. 2014;64:95–103.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s) 2018

Advertisement

BMC Research Notes

ISSN: 1756-0500

Contact us