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Pediatr Nephrol (2016) 31:819–826

DOI 10.1007/s00467-015-3284-2

ORIGINAL ARTICLE

Comparison of reticulocyte hemoglobin equivalent


with traditional markers of iron and erythropoiesis
in pediatric dialysis
Sarka Davidkova 1 & Timothy D. Prestidge 2 & Peter W. Reed 3 &
Tonya Kara 4 & William Wong 4 & Chanel Prestidge 4

Received: 17 May 2015 / Revised: 19 November 2015 / Accepted: 19 November 2015 / Published online: 14 December 2015
# IPNA 2015

Abstract Conclusions Ret-He is a more relevant marker of iron status


Background Anemia is a major complication for patients on than ferritin and TSAT. This supports prospectively testing
chronic dialysis. Erythropoietin is effective if iron is available, Ret-He to distinguish between iron deficiency and suboptimal
however unnecessary iron supplementation results in iron erythropoietin dosing as competing causes for anemia. Ferritin
overload. Reticulocyte hemoglobin equivalent (Ret-He) may is an unhelpful biomarker of iron deficiency in this setting.
be useful for assessing iron status.
Methods A national retrospective cohort study including all Keywords Anemia . End-stage kidney disease .
children on chronic dialysis in New Zealand between 2007 Iron deficiency . Reticulocyte hemoglobin equivalent .
and 2013, pairing Ret-He with demographic information, ane- Ferritin . TSAT . children
mia indices, and markers of iron status.
Results In 606 observations, we found a modest relationship
between Ret-He and transferrin saturation (TSAT) (r=0.34, Introduction
p<0.001) and a poor correlation between Ret-He and ferritin
(r=0.09, p=0.04). There was a negative correlation between Despite the use of recombinant human erythropoietin
ferritin and hemoglobin (r=−0.14, p=0.002), a weak positive (rHuEPO) and iron supplementation, anemia remains a major
correlation between TSAT and hemoglobin (r= 0.12, p= complication in children with chronic kidney disease (CKD),
0.007), and a modest positive correlation between Ret-He especially for those on chronic dialysis [1–3]. Anemia in turn
and hemoglobin (r=0.22, p<0.001). The diagnostic perfor- is associated with increased morbidity and mortality and re-
mance of Ret-He to detect absolute iron deficiency (cut-off duced quality of life in children and young people with CKD
value 28.9 pg, sensitivity 90 %, specificity 75 %, AUC 0.87) [1, 4–6].
was good. Other than erythropoietin insufficiency and a shortened red
blood cell life span, iron deficiency is the most common cause
of anemia in this population [3, 7–9]. Dialysis patients are
particularly at risk of absolute iron deficiency due to blood
* Chanel Prestidge loss from blood testing, the extra-corporeal circuit and for
chanelp@adhb.govt.nz
some, vascular access surgeries. Dietary restrictions and re-
duced appetite can lead to poor iron intake, and medications
1
Department of Pediatrics, Starship Children’s Hospital, such as gastric acid inhibitors and phosphate binders further
Auckland, New Zealand reduce iron absorption and thus available iron. In addition,
2
Blood and Cancer Centre, Starship Children’s Hospital, inflammation, which commonly coexists with or complicates
Auckland, New Zealand dialysis, results in elevated hepcidin. Hepcidin reduces iron
3
Children’s Research Centre, Starship Children’s Hospital, absorption further and inhibits the release of existing iron from
Auckland, New Zealand reticuloendothelial stores, limiting iron available for erythro-
4
Department of Nephrology, Starship Children’s Hospital, Park Road, poiesis [10, 11]. Furthermore, patients with CKD who receive
Private Bag 92024, Auckland 1142, New Zealand rHuEPO treatment have increased iron requirements due to
820 Pediatr Nephrol (2016) 31:819–826

supra physiological erythropoiesis. Therefore, the risk of func- aimed to investigate the relationship between Ret-He and the
tional iron deficiency, defined as insufficient iron availability currently used traditional markers of iron and erythropoiesis in
to meet the demands of stimulated erythropoiesis, even though pediatric patients on chronic dialysis. We hypothesized that
the total body iron stores may not be depleted, is high [12]. Ret-He is a clinically useful tool for the evaluation of iron
Both absolute and functional iron deficiency ultimately status in this population.
limit the effectiveness of rHuEPO therapy, resulting in high
dosing and costs [13, 14]. As in adults, the appropriate iron
supplementation in the pediatric population on dialysis can Materials and methods
improve the erythropoietic response to rHuEPO [15–17]. On
the other hand, unnecessary iron treatment, especially in the Study design and settings
parenteral form, can be associated with serious immediate and
long-term side effects. Therefore, evaluation of iron status is This was a national retrospective cohort study of children with
an essential part of assessment and management of anemia in end-stage kidney disease (ESKD) on chronic dialysis under
CKD [7, 18, 19]. the care of the pediatric national renal service at Starship Chil-
The traditional biomarkers for iron availability, serum fer- dren’s Hospital in New Zealand.
ritin and transferrin saturation (TSAT), are recognized as sub-
optimal measures of iron status in patients with CKD. Serum Participants
ferritin reflects total body iron stores but is also an acute phase
reactant, making its level difficult to interpret in patients with All patients under 18 years of age on dialysis for a min-
CKD [20, 21]. In fact, rather than diagnosing an iron-limited imum of 3 months between July 1, 2007 and June 30,
anemic state, serum ferritin has been found to have an inverse 2013 were eligible. The study period commenced from
relationship with hemoglobin (Hb) in both children on dialysis the time Ret-He was routinely included in our dialysis
and with non-dialysis CKD [1, 22]. The TSAT (serum iron database. Each patient’s diagnosis history was screened
divided by total iron binding capacity) is also used as a marker for alternative causes of anemia, and any patient with
of iron availability for erythropoiesis [7]. However, TSAT such diagnoses was excluded. Participant data was cen-
levels display diurnal fluctuation [23] and can be falsely ele- sored if they received a renal transplant, died, or were
vated when transferrin synthesis is reduced in the setting of transferred to adult services. Participants were managed
malnutrition or chronic disease [20]. Despite the evidence, with rHuEPO and iron therapy according to local proto-
serum ferritin and TSAT continue to be commonly used as col, aiming to maintain Hb between 100 and 120 g/l for
the primary tools in assessment of iron status in renal anemia, children under 6 months and between 110 and 130 g/l for
partly due to a lack of accepted and available alternative those over 6 months of age. Parenteral and/or oral iron
measures. replacement was provided to target a TSAT above 0.2 and
A number of other biomarkers have been evaluated to as- serum ferritin between 200 and 500 mg/l.
sess iron availability for erythropoiesis and predict response to
iron therapy in the CKD population. These markers may not Data collection
all be widely available and their diagnostic performance is
variable [7, 18, 19, 24]. One marker, reticulocyte hemoglobin Data were collected from the department database and the
content, reflects iron availability for incorporation into reticu- hospital and laboratory electronic record systems. The da-
locytes in real time, over the preceding 2–4 days [25]. It is tabase contains clinical and laboratory data of all pediatric
measured by flow cytometry on ADVIA120 and 2120 ana- dialysis patients from inpatient and outpatient encounters.
lyzers (called CHr) and on the widely used XE-2100 Sysmex Data obtained from the database were verified for accura-
analyzer (called Ret-He) [26–28]. Ret-He has been found to cy with the hospital and laboratory electronic systems and
be a marker of iron availability for erythropoiesis in adults on were entered into an Excel data spreadsheet in de-
hemodialysis, although the cut-off values, specificity, and sen- identified form. The data included demographic variables,
sitivity vary [27, 29, 30]. While reticulocyte hemoglobin con- type of renal disease (as defined by the European Renal
tent can be a reliable screening tool for iron deficiency in Association-European Dialysis Transplant Association
otherwise healthy infants and children [31, 32], evidence re- (ERA-EDTA) [33]), anthropometric data, the mode, dura-
garding the utility of Ret-He to assess iron availability in chil- tion, and outcome of dialysis and episodes of peritonitis.
dren on chronic dialysis is not available. Anemia and iron status indices included paired data of
The Ret-He parameter has been available in our laboratory Ret-He with Hb, reticulocyte count, serum iron, ferritin,
since 2005. The national pediatric renal service at Starship total iron binding capacity, TSAT, and dose of rHuEPO at
Children’s Hospital has been monitoring this parameter in all multiple observations from each patient. The observations
children on chronic dialysis since July 2007. In this study, we were determined by Ret-He data. Missing height data at
Pediatr Nephrol (2016) 31:819–826 821

observations were determined by extrapolation using the Table 1 Demographic and clinical characteristics of study population
most recent preceding and succeeding height percentile Characteristic n (%)
from WHO growth charts.
Female patients 24 (53 %)
Statistical analysis Previous renal transplant 4 (9 %)
Primary renal diagnosis
Statistical analysis was conducted with the use of statistical Congenital 16 (36 %)
software JMP 10.0 (SAS Inc). Descriptive statistical analysis Glomerulopathy 15 (33 %)
was performed and normally distributed data were reported as Vasculitis 4 (9 %)
mean and standard deviation. Skewed data were reported as Metabolic 1 (2 %)
median and interquartile range (IQR). To allow for the non- Ischemia 5 (11 %)
independence of the repeated observations from each patient, Other 4 (9 %)
Bland–Altman multiple linear regression was used to deter- Native kidneys in situ at study enrolment 41 (91 %)
mine the within-patient correlation between Ret-He and tradi- Dialysis modality during study
tional markers of iron deficiency (ferritin and TSAT), Hb, and PD only 26 (58 %)
reticulocyte count within each patient [34]. Receiver operating HD only 4 (9 %)
characteristic (ROC) analysis was utilized to determine the PD and HD 15 (33 %)
performance of Ret-He in diagnosing absolute iron deficiency Age (years) at start of dialysis in years 6.7 [1.6–12.6]
anemia. The presence of absolute iron deficiency anemia was (median [IQR])
defined as Hb less than 100 g/l in children younger than <1 year 6 (13 %)
6 months or less than 110 g/l in children over 6 months, with 1–<5 years 12 (27 %)
ferritin less than 100 mcg/l, and TSAT less than 0.2. Addition- 5–<12 years 15 (33 %)
ally, we analyzed those with apparent “functional iron defi- 12–18 years 12 (27 %)
ciency” anemia, defined by Hb less than 100 g/l under Age (years) at study enrolment (median [IQR]) 7.6 [1.8–12.7]
6 months of age or 110 g/l older than 6 months of age with <1 year 5 (11 %)
TSAT of less than 0.2 and ferritin >200 mcg/l. The Ret-He cut- 1–<5 years 11 (24 %)
off was established based on the optimal combination of sen- 5–<12 years 18 (40 %)
sitivity and specificity. 12–18 years 11 (24 %)
Outcome of dialysis
Renal transplant 26 (58 %)
Results Death 4 (9 %)
Transfer to adult service on ongoing dialysis 8 (18 %)
Patient characteristics Ongoing dialysis under pediatric care 7 (16 %)
Duration of dialysis in months 15.5 [10.9–38.6]
Forty-five patients satisfied inclusion criteria. Patient charac- (median [IQR])
teristics are summarized in Table 1. Patients were followed up <6 months 5 (11 %)
for a median of 14.8 months (IQR 10.9–29.6 months). 6–<12 months 9 (20 %)
Follow-up was discontinued during the study period in 38 12 mo–<24 months 14 (31 %)
patients (84 %) due to renal transplant, death, or transfer to 24 mo–<48 months 10 (22 %)
the adult services. Fifty-eight percent of patients were on peri- >48 months 7 (16 %)
toneal dialysis, however only a third of patients required at Duration of follow-up in months (median [IQR]) 14.8 [10.9–29.6]
least one change of dialysis modality. rHuEPO was used con- Peritonitis during study 27 (60 %)
tinuously throughout the observation period in 25 patients Episodes of peritonitis per patient (median [IQR]) 1 [0–3]
(56 %), intermittently in 18 patients (40 %), and not at all in ACE inhibitor treatment 22 (49 %)
two patients (4 %). rHuEPO treatment 43 (96 %)

IQR interquartile range, HD hemodialysis, PD peritoneal dialysis,


Anemia and iron status characteristics rHuEPO human recombinant erythropoietin, ACE angiotensin-
converting enzyme
The final data set contained 606 observations of paired Ret-He
data with anemia and iron status indices. The median number
of observations per patient was seven (IQR 4–20). The serum observations. The weekly rHuEPO dose could not be accu-
ferritin was missing in 60 observations, TSAT in 62 observa- rately calculated in 210 observations due to missing weight
tions, Hb in seven observations, and reticulocytes in three data.
822 Pediatr Nephrol (2016) 31:819–826

Table 2 Anemia and iron status


characteristics Characteristics Number of observations

Ret-He (pg) (median [IQR]) 606 31.2 [28.6–32.9]


Hemoglobin (g/l) 599
<6 months of age (mean (SD)) 6 108 (10.6)
<100 g/l 1 17 %
100–130 g/l 5 83 %
≥6 months of age (mean (SD)) 593 111 (19.7)
<110 g/l 269 45 %
110–130 g/l 231 39 %
>130 g/l 93 16 %
Reticulocyte count (median [IQR]) 603 52 [36–71]
Ferritin (mcg/l) (median [IQR]) 546 282.5 [168–507.5]
<100 mcg/l 68 12 %
100–500 mcg/l 341 63 %
>500 mcg/l 137 25 %
TSAT (median [IQR]) 544 26 [19–36]
<0.2 154 28 %
≥0.2 390 72 %
rHuEpo treatment 606 569 (94 %)
rHuEpo dose (weekly IU/m2 BSA) (median [IQR]) 372 6365.2 [4643.1–9084.50]
Dialysis modality at observation 606
PD 381 63 %
HD 225 37 %

IQR interquartile range, Ret-He reticulocyte hemoglobin content, HD hemodialysis, PD peritoneal dialysis,
rHuEPO recombinant human erythropoietin, TSAT transferrin saturation, BSA body surface area

Anemia and iron status characteristics are given in Table 2. episode of peritonitis, minimizing the confounding effect of
The median Ret-He was 31.2 pg (IQR 28.6–32.9). The mean acute inflammation on ferritin and transferrin.
Hb in patients under 6 months of age was 108 g/l, and 17 % of
patients in this age group were classified as anemic. In chil- Association of Ret-He with anemia and traditional
dren over 6 months of age, the mean Hb was 111 g/l; the markers of iron status
proportion of anemia in this group was 45 %. The majority
of observations were measured while receiving rHuEPO. The In the multiple linear regression analysis, there was a modest
median weekly dose of rHuEPO, where the body surface area relationship between Ret-He and TSAT in 544 observations
(BSA) could be calculated, was 6365 IU/m2. The majority of on 45 patients (r=0.34, p<0.001). The correlation between
observations (94 %) were obtained at least 1 month after an Ret-He and TSAT was stronger in patients on hemodialysis

Fig. 1 a Correlation between serum ferritin and hemoglobin (r=−0.14, The average regression lines for each individual are shown (observations
p value=0.002). The average regression lines for each individual are = 538, individuals = 45). c Correlation between Ret-He and hemoglobin
shown (observations = 539, individuals = 45). b Correlation between (r = 0.22, p value <0.001). The average regression lines for each
transferrin saturation (TSAT) and hemoglobin (r=0.12, p value=0.007). individual are shown (observations = 599, individuals = 45)
Pediatr Nephrol (2016) 31:819–826 823

Table 3 Combined iron parameter results categorized by hemoglobin

Iron parameter Low Hb Target Hb

Ferritin <100 TSAT <0.2 Ret-He <28.9 7 (59 %) 5 (41 %)


Ret-He ≥28.9 1 (5 %) 20 (95 %)
TSAT ≥0.2 Ret-He <28.9 3 (30 %) 7 (70 %)
Ret-He ≥28.9 3 (15 %) 17 (85 %)
Ferritin 100–500 TSAT <0.2 Ret-He <28.9 24 (67 %) 12 (33 %)
Ret-He ≥28.9 21 (31 %) 47 (69 %)
TSAT ≥0.2 Ret-He <28.9 19 (51 %) 18 (49 %)
Ret-He ≥28.9 67 (39 %) 104 (61 %)
Ferritin >500 TSAT <0.2 Ret-He <28.9 13 (100 %) 0 (0 %)
Ret-He ≥28.9 3 (43 %) 4 (57 %)
TSAT ≥0.2 Ret-He <28.9 18 (75 %) 6 (25 %)
Fig. 2 ROC curve of reticulocyte hemoglobin equivalent (Ret-He) to Ret-He ≥28.9 41 (44 %) 52 (56 %)
detect absolute iron deficiency anemia (observations = 536)
TSAT transferrin saturation, Ret-He reticulocyte hemoglobin equivalent,
(r=0.47, p value <0.001) than on peritoneal dialysis (r=0.22, Low Hb Hemoglobin <100 g/l if<6 months old and<110 g/l if>6 months
old, Target Hb >100 g/l if <6 months old and>110 g/l if>6 months old
p<0.001). Poor correlation between Ret-He and serum ferritin
was noted (r=0.09, p=0.04). When segregating patients by
dialysis modality, the correlation was present in those on he- The goal was to determine the diagnostic performance
modialysis (r=0.27, p=0.001), but lost in patients on perito- of Ret-He against traditional diagnostic markers of iron
neal dialysis (r=−0.03, p=0.63). There was a weak negative deficiency anemia. The ROC analysis demonstrated that a
correlation between hemoglobin and serum ferritin (r=−0.14, cut-off Ret-He value of 28.9 pg is able to detect absolute
p=0.002) (Fig. 1a). There was no correlation in patients on iron deficiency anemia with the best combination of 90 %
hemodialysis (r=−0.06, p=0.42) in comparison to those on sensitivity and 75 % specificity. The area under the curve
peritoneal dialysis (r=−0.21, p=0.0004). A weak positive cor- (AUC) was 0.87 (Fig. 2). When using ROC analysis to
relation was found between TSAT and hemoglobin (r=0.12, evaluate the diagnostic performance of Ret-He to detect
p=0.007) (Fig. 1b). As was seen with Ret-He, this relationship “functional iron deficiency anemia” as defined by a low
was lost in patients on peritoneal dialysis (r=0.05, p=0.37) in TSAT but normal to high ferritin, a Ret-He value of
comparison to those on hemodialysis (r=0.15, p=0.03). As 27.7 pg detected this with 55 % sensitivity and 83 % spec-
shown in Fig. 1c, modest correlation was noted between Ret- ificity. The AUC was 0.721 (Fig. 3). Finally, given the
He and hemoglobin (r=0.22, p<0.001). There was no associ- limitations of ferritin, we additionally performed ROC
ation between Ret-He and reticulocyte count (r=−0.03, p= analysis defining iron deficiency anemia with the same
0.48). Ret-He and rHuEPO weekly dose were modestly neg- Hb values and a TSAT <0.2 but with no inclusion of ferri-
atively correlated (r=−0.26, p<0.001). tin. In this setting, the best cut-off value for Ret-He was
28.8 pg with 63 % sensitivity and 79.5 % specificity, AUC
0.73 (figures not shown).
Using the Ret-He cut-off of 28.9, the data based on all
three iron parameters for patients with low hemoglobin
versus target hemoglobin are presented in Table 3. Using
Ret-He, 38 % of patients with low hemoglobin would be
predicted to have iron-limited erythropoiesis contributing
to their anemia. Similarly, using low ferritin and/or low
TSAT, 34 % are identified as iron limited. However,
44 % of those with low Ret-He are not identified by the
ferritin/TSAT criteria, and 37 % of those with low ferritin
and/or TSAT are not identified as iron limited by the Ret-
He method. For patients with hemoglobin in the target
range, 16 % are identified as potentially iron-limited de-
spite normal hemoglobin levels when using Ret-He,
Fig. 3 ROC curve of reticulocyte hemoglobin equivalent (Ret-He) to whereas 38 % of patients with normal hemoglobin have a
detect functional iron deficiency anemia (observations = 536) low ferritin or TSAT.
824 Pediatr Nephrol (2016) 31:819–826

Discussion correlation further supports the utility of Ret-He. Taken togeth-


er, prospectively testing whether patients with adequate Ret-He
Anemia remains a major clinical challenge when managing who remain anemic may benefit more from increasing
patients with CKD. While anemia is associated with increased rHuEPO than iron supplementation warrants consideration.
morbidity and mortality, both iron overload and high doses of The diagnostic performance of Ret-He to detect absolute
rHuEPO are also associated with poor outcomes [13, 14]. iron deficiency anemia is superior to currently used parame-
Therefore, when correcting anemia, accurate measurement ters and fits within the range of results demonstrated in previ-
of iron status is required to avoid unnecessary iron supplemen- ous adult studies. These have demonstrated an AUC between
tation yet recognize when use of rHuEPO alone will be insuf- 0.657 and 0.913, sensitivities between 40 and 100 %, and
ficient. The currently accepted markers of iron status in CKD, specificities between 65 and 95 % [26, 27, 30, 35]. The vari-
TSAT and serum ferritin, are already known to have limited ability in reported Ret-He cut-off values reflects in part the
reliability in assessing iron availability in patients on dialysis lack of an easily reproducible gold standard test. Iron bone
[7, 10]. While newer and more sensitive and specific methods, marrow staining, as the adult gold standard for absolute iron
including the Ret-He parameter, have become available, the deficiency, is impractical, invasive, has high inter-observer
specificity, sensitivity, and cut-off Ret-He values vary in pub- variability, and is poorly validated in children. Using a func-
lished studies and have not been reported in the pediatric pop- tional definition, such as a response to intravenous iron with
ulation to date [26, 29, 30, 35]. an increase in hemoglobin or decrease in rHuEPO require-
Our results, in agreement with other reports [1, 22, 27], ment [29, 30], may be a more valid method to diagnose func-
confirm the poor correlation between Hb and ferritin (r= tional iron deficiency, although this has the disadvantage of
−0.14) and highlight the limitations of ferritin as a reliable being retrospective.
marker of iron availability in patients on dialysis. Even Our study has several weaknesses inherent in retrospec-
allowing for difficulties that exist in determining iron status tive cohort study design, including incomplete data for
in this population, employing a poorly or negatively correlated some variables. Additionally, in the absence of a uniformly
variable to guide therapy is questionable and the widespread accepted definition of functional iron deficiency or the
incorporation of ferritin into decision-making algorithms for ability to assess erythropoietic response to iron supplemen-
iron management in dialysis lacks evidence. Ferritin levels, tation in our study, for this analysis we have used a defini-
rather than revealing useful information on iron metabolism, tion including TSAT and ferritin, which as discussed likely
more likely reflect the degree of chronic inflammation over has inherent error.
time, which explains the negative correlation with Hb. In con- The lack of a reliable and practical gold standard assess-
trast, Ret-He was positively correlated with Hb in our study ment for iron status engenders difficulty when examining the
(r=0.22), and demonstrated stronger correlation than TSAT utility of newer biomarkers. However, future research would
with Hb (r=0.12) and therefore may be a more helpful bio- be improved by a prospective design that captures the change
marker. Though an individual Ret-He value only reflects iron in Ret-He, markers of erythropoiesis and rHuEPO require-
availability in the preceding few days, it is not an acute phase ment following iron administration.
reactant and is more specific to erythropoietic activity than
ferritin. While Hb takes several months to generate, patients
with satisfactory Ret-He at one time point likely had iron Conclusions
available during the recent past, explaining the positive corre-
lation with Hb. Similarly, the poor association between Ret- In summary, Ret-He demonstrated superiority over ferritin
He and reticulocyte count may be expected due to the timing and TSAT in the evaluation of iron status in anemic children
of observations. During erythropoiesis Ret-He increases ear- on chronic dialysis. Ret-He values of 28.9 and 27.7 pg pro-
lier than reticulocyte count by a few days, with the reticulocyte duced the best sensitivity and specificity for the diagnosis of
count subsequently returning to normal once Hb has been absolute iron deficiency anemia and functional iron deficiency
corrected. Therefore, a concurrent Ret-He and reticulocyte anemia, respectively, and were within the range reported in
count will not show a correlation unless the improved iron adult studies. The Ret-He correlations with Hb, rHuEPO, and
status has only recently occurred. TSAT support prospectively testing the hypothesis that Ret-He
The modest correlation between Ret-He and TSAT in our can be used to distinguish between iron deficiency and sub-
study (r=+0.34) is in keeping with the study by Miwa et al. optimal rHuEPO dosing as competing causes for anemia in
[27], and strengthens the hypothesis that this combination of this population. However, until such data is available, the rou-
biomarkers warrants further exploration independent of ferritin. tine incorporation of this parameter in monitoring and treat-
Our study demonstrated a weaker negative correlation between ment algorithms will represent an improvement on ferritin,
Ret-He and the dose of rHuEPO (r=−0.26) than demonstrated which should be abandoned as a measure of iron status in this
in an adult population [36]. Nevertheless, the direction of the population.
Pediatr Nephrol (2016) 31:819–826 825

Acknowledgments We would like to acknowledge Jane Ronaldson, during r-huEPO therapy—a consensus report. Nephrol Dial
renal nurse specialist at Starship Hospital for her continued data collection Transplant 11:246–250
efforts and exemplary care provided to our children needing dialysis. 15. Ruiz-Jaramillo M, Guízar-Mendoza JM, Gutiérrez-Navarro MJ,
Dubey-Ortega LA, Amador-Licona N (2004) Intermittent versus
Study approval Institutional ethical approval was obtained from the maintenance iron therapy in children on hemodialysis: a random-
Auckland District Health Board research review office with a waiver of ized study. Pediatr Nephrol 19:77–81
patient informed consent requirement due to the retrospective nature of 16. Warady BA, Kausz A, Lerner G, Brewer ED, Chadha V, Brugnara
the study. C, Dahl NV, Watkins SL (2004) Iron therapy in the pediatric hemo-
dialysis population. Pediatr Nephrol 19:655–661
Compliance with ethical standards 17. Warady BA, Zobrist RH, Wu J, Finan E (2005) Sodium ferric glu-
conate complex therapy in anemic children on hemodialysis.
Conflict of interest No funding source was required for the preparation Pediatr Nephrol 20:1320–1327
of this work. 18. Locatelli F, Aljama P, Bárány P, Canaud B, Carrera F, Eckardt KU,
The authors have no financial or ethical conflicts of interest as relate to Hörl WH, Macdougal IC, Macleod A, Wiecek A, Cameron S,
this manuscript. European Best Practice Guidelines Working Group (2004)
Revised European best practice guidelines for the management of
anemia in patients with chronic renal failure. Nephrol Dial
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19. Padhi S, Glen J, Pordes BA (2015) Management of anaemia in
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