Đề ôn thi thử môn hóa (97)

32  Management of Anemia in Children Receiving Chronic Dialysis
55. Levin A, et al. Left ventricular mass index increase in
early renal disease: impact of decline in hemoglobin.
Am J Kidney Dis. 1999;34(1):125–34.
56. Levin A, et al. Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular
mass growth in patients with CKD. Am J Kidney Dis.
2005;46(5):799–811.
57.

Chavers BM, Li S, Collins AJ, Herzog
CA. Cardiovascular disease in pediatric chronic dialysis patients. Kidney Int. 2002;62(2):648–53.
58.Matteucci MC, et  al. Left ventricular geometry in
children with mild to moderate chronic renal insufficiency. J Am Soc Nephrol. 2005;17(1):218–26.
59.

El-Husseini AA, Sheashaa HA, Hassan NA,
El-Demerdash
FM,
Sobh
MA,
Ghoneim
MA. Echocardiographic changes and risk factors for
left ventricular hypertrophy in children and adolescents after renal transplantation. Pediatr Transplant.
2004;8(3):249–54.
60.

Morris KP, Skinner JR, Hunter S, Coulthard
MG.  Short term correction of anaemia with recombinant human erythropoietin and reduction of cardiac
output in end stage renal failure. Arch Dis Child.
1993;68(5):644–8.
61.Mitsnefes MM, Daniels SR, Schwartz SM, Meyer

RA, Khoury P, Strife CF.  Severe left ventricular
hypertrophy in pediatric dialysis: prevalence and predictors. Pediatr Nephrol. 2000;14(10–11):898–902.
62.Mitsnefes MM, et  al. Impaired left ventricular diastolic function in children with chronic renal failure.
Kidney Int. 2004;65(4):1461–6.
63.Kupferman JC, et al. BP control and left ventricular
hypertrophy regression in children with CKD. J Am
Soc Nephrol. 2014;25(1):167–74.
64.Yorgin P, Zaritsky JJ.  Management of renal anemia
in children with chronic kidney disease in pediatric
dialysis. 2nd ed. New York: Springer; 2012.
65.Foulks CJ, Mills GM, Wright LF.  Parathyroid hormone and anaemia – an erythrocyte osmotic fragility
study in primary and secondary hyperparathyroidism.
Postgrad Med J. 1989;65(761):136–9.
66.Atkinson MA, Furth SL.  Anemia in children with
chronic kidney disease. Nat Rev Nephrol. Nov.
2011;7(11):635–41.
67.Bamgbola OF, Kaskel F.  Role of folate deficiency
on erythropoietin resistance in pediatric and adolescent patients on chronic dialysis. Pediatr Nephrol.
2005;20(11):1622–9.
68.Calò LA, Vertolli U, Davis PA, Savica V.  L car
nitine in hemodialysis patients. Hemodial Int.
2012;16(3):428–34.
69.Raimann JG, Levin NW, Craig RG, Sirover W,

Kotanko P, Handelman G. Is vitamin C intake too low
in Dialysis patients? Semin Dial. 2013;26(1):1–5.
70.Nasr SH, Kashtanova Y, Levchuk V, Markowitz

GS.  Secondary oxalosis due to excess vitamin C
intake. Kidney Int. 2006;70(10):1672.

629

71.Lazarchick J.  Update on anemia and neutrope
nia in copper deficiency. Curr Opin Hematol.
2012;19(1):58–60.
72.Nangaku M, Eckardt KU. Pathogenesis of renal anemia. Semin Nephrol. 2006;26(4):261–8.
73.Geerlings W, et  al. Factors influencing anaemia in
dialysis patients. A special survey by the edta-era registry. Nephrol Dial Transplant. 1993;8(7):585.
74.Djuric P, Dimkovic N, Djuric Z, Popovic J, Tosic
J, Jankovic A.  Influence of hemodialysis duration per week on parameters of dialysis adequacy
and cardiovascular morbidity. Med Pregl Rev.
2014;10(6):388–95.
75.Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116(23):4754–61.
76.Babitt JL, Lin HY. Mechanisms of anemia in CKD. J
Am Soc Nephrol. 2012;23(10):1631–4.
77.Atkinson MA, et  al. Association between com
mon iron store markers and hemoglobin in children with chronic kidney disease. Pediatr Nephrol.
2012;27(12):2275–83.
78.Davidkova S, Prestidge TD, Reed PW, Kara T, Wong
W, Prestidge C. Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and
erythropoiesis in pediatric dialysis. Pediatr Nephrol.
2016;31(5):819–26.
79.Ratcliffe LEK, et  al. Diagnosis and management of
iron deficiency in CKD: a summary of the NICE
guideline recommendations and their rationale. Am J
Kidney Dis. 2016;67(4):548–58.
80.Urrechaga E, Borque L, Escanero JF.  Biomarkers

of hypochromia: The contemporary assessment

of iron status and erythropoiesis. BioMed Res Int.
2013;2013:603786.
81. KDOQI. KDOQI clinical practice guideline and clinical practice recommendations for anemia in chronic
kidney disease: 2007 update of hemoglobin target.
Am J Kidney Dis. 2007;50(3):471–530.
82.

“Chronic kidney disease: managing anaemia |
Guidance and guidelines | NICE.”
83.Eschbach JW, Egrie JC, Downing MR, Browne JK,
Adamson JW. Correction of the anemia of end-stage
renal disease with recombinant human erythropoietin.
Results of a combined phase I and II clinical trial. N
Engl J Med. 1987;316(2):73–8.
84.Elliott S, Pham E, Macdougall IC.  Erythropoietins:
a common mechanism of action. Exp Hematol.
2008;36(12):1573–84.
85.Elliott S, et  al. Enhancement of therapeutic protein
in  vivo activities through glycoengineering. Nat
Biotechnol. 2003;21(4):414.
86.Wish JB, et  al. Introduction of biosimilar therapeutics into nephrology practice in the United States:
report of a scientific workshop sponsored by the
National Kidney Foundation. Am J Kidney Dis.
2016;68(6):843–52.


630

87.
Hörl WH.  Differentiating factors between

erythropoiesis-­
stimulating agents: an update to
selection for anaemia of chronic kidney disease.
Drugs. 2013;73(2):117–30.
88.Warady BA, Arar MY, Lerner G, Nakanishi AM,
Stehman-Breen C. Darbepoetin alfa for the treatment
of anemia in pediatric patients with chronic kidney
disease. Pediatr Nephrol. 2006;21(8):1144–52.
89.Schaefer F, et  al. Safety and usage of darbepoetin alfa in children with chronic kidney disease:
prospective registry study. Pediatr Nephrol. Mar.
2016;31(3):443–53.
90.Schmitt CP, Nau B, Brummer C, Rosenkranz J,
Schaefer F. Increased injection pain with darbepoetin-α
compared to epoetin-β in paediatric dialysis patients.
Nephrol Dial Transplant. 2006;21(12):3520–4.
91.Macdougall IC, Eckardt KU.  Novel strategies for
stimulating erythropoiesis and potential new treatments for anaemia. Lancet. 2006;368(9539):947–53.
92.Jelkmann W.  Recombinant EPO production  –
points the nephrologist should know. Nephrol Dial
Transplant. 2007;22(10):2749–53.
93.Cano F, et  al. Continuous EPO receptor activator
therapy of anemia in children under peritoneal dialysis. Pediatr Nephrol. 2011;24(4):665–76.
94.Fischbach M, Wühl E, Reigner SCM, Morgan
Z, Schaefer F.  Efficacy and long-term safety of
C.E.R.A. maintenance in Pediatric Hemodialysis
patients with Anemia of CKD.  Clin J Am Soc
Nephrol. 2018;13(1):81–90.
95. Fishbane S, Berns JS. Hemoglobin cycling in hemodialysis patients treated with recombinant human
erythropoietin. Kidney Int. 2005;68(3):1337–43.
96.

Koshy SM, Geary DF.  Anemia in children
with chronic kidney disease. Pediatr Nephrol.
2008;23(2):209–19.
97.Port RE, Kiepe D, Van Guilder M, Jelliffe RW,
Mehls O.  Recombinant human erythropoietin for
the treatment of renal anaemia in children  – no
justification for bodyweight-adjusted dosage. Clin
Pharmacokinet. 2004;46(5):461–6.
98. Bamgbola OF, Kaskel FJ, Coco M. Analyses of age,
gender and other risk factors of erythropoietin resistance in pediatric and adult dialysis cohorts. Pediatr
Nephrol. 2009;24(3):571–9.
99.Port RE, Mehls O.  Erythropoietin dosing in children with chronic kidney disease: based on body
size or on hemoglobin deficit? Pediatr Nephrol.
2009;24(3):435–7.
100.McGowan T, Vaccaro NM, Beaver JS, Massarella
J, Wolfson M.  Pharmacokinetic and pharmacodynamic profiles of extended dosing of epoetin alfa
in anemic patients who have chronic kidney disease
and are not on dialysis. Clin J Am Soc Nephrol.
2008;4(11):1731–40.
101. Pergola PE, Gartenberg G, Fu M, Sun S, Wolfson M,
Bowers P.  A randomized controlled study comparing once-weekly to every-2-week and every-4-week
dosing of epoetin alfa in CKD patients with anemia.
Clin J Am Soc Nephrol. 2010;5(4):598–606.

M. A. Atkinson and B. A. Warady
102. Pfeffer MA, et al. A trial of darbepoetin alfa in type 2
diabetes and chronic kidney disease. N Engl J Med.
2009;361(21):2019–32.
103.Kliger AS, et  al. KDOQI US Commentary on the
2012 KDIGO Clinical Practice Guideline for Anemia

in CKD. Am J Kidney Dis. 2013;62(5):849–59.
104.Lestz RM, Fivush BA, Atkinson MA.  Association
of higher erythropoiesis stimulating agent dose and
mortality in children on dialysis. Pediatr Nephrol.
2014;29(10):2021–8.
105. Badve SV, Hawley CM, Johnson DW. Is the problem
with the vehicle or the destination? Does high-dose
ESA or high haemoglobin contribute to poor outcomes in CKD? Nephrology. 2011;16(2):144–53.

106.Goodkin DA, et  al. Naturally occurring higher
hemoglobin concentration does not increase mortality among hemodialysis patients. J Am Soc Nephrol.
2011;22(2):358–65.

107.Unger EF, Thompson AM, Blank MJ, Temple
R.  Erythropoiesis-stimulating agents–time for a
reevaluation. N Engl J Med. 2010;362(3):189–92.
108.Besarab A, et al. The effects of normal as compared
with low hematocrit values in patients with cardiac
disease who are receiving hemodialysis and epoetin.
N Engl J Med. 2002;339(9):584–90.
109.Brigandi RA, et al. A novel hypoxia-inducible factor−prolyl hydroxylase inhibitor (GSK1278863) for
anemia in CKD: a 28-day, phase 2A randomized
trial. Am J Kidney Dis. 2016;67(6):861–71.
110.Besarab A, et  al. Randomized placebo-­
controlled
dose-ranging and pharmacodynamics study
of roxadustat (FG-4592) to treat anemia in
nondialysis-­
dependent chronic kidney disease
(NDD-CKD) patients. Nephrol Dial Transplant.

2015;30(10):1665–73.
111. Schmid H, Jelkmann W. Investigational therapies for
renal disease-induced anemia. Expert Opin Investig
Drugs. 2016;25(8):901–16.
112.Cooke KS, et al. A fully human anti-hepcidin antibody modulates iron metabolism in both mice and
nonhuman primates. Blood. 2013;122(17):3054–61.
113.Gilbertson DT, Peng Y, Arneson TJ, Dunning S,
Collins AJ. Comparison of methodologies to define
hemodialysis patients hyporesponsive to epoetin and
impact on counts and characteristics. BMC Nephrol.
2013;14:44.
114.Chutia H, Ruram A, Bhattacharyya H, Boruah P,
Nath C. Association of secondary hyperparathyroidism with hemoglobin level in patients with chronic
kidney disease. J Lab Physicians. 2013;5(1):51–4.
115.Rao DS, Shih M, Mohini R.  Effect of serum parathyroid hormone and bone marrow fibrosis on the
response to erythropoietin in Uremia. N Engl J Med.
2002;328(3):171–5.
116.Fulton B, Jeffery EH.  Heme oxygenase induction.
Biol Trace Elem Res. 2008;81(6):1661–5.
117. Losekann A, et al. Aluminium intoxication in the rat
induces partial resistance to the effect of recombinant human erythropoietin. Nephrol Dial Transplant.
1990;5(4):258–63.


32  Management of Anemia in Children Receiving Chronic Dialysis
118.Pollack AH, Oron AP, Flynn JT, Munshi R.  Using
dynamic treatment regimes to understand
erythropoietin-­
stimulating agent hyporesponsiveness. Pediatr Nephrol. 2018;33(8):1411–7.
119. Bennett CL, et al. Linking drugs to obscure illnesses:

lessons from pure red cell aplasia, nephrogenic systemic fibrosis, and Reye’s syndrome. a report from the
Southern Network on Adverse Reactions (SONAR).
J Gen Intern Med. 2012;27(12):1697–703.
120.Yabu JM, et  al. Sensitization from transfusion in
patients awaiting primary kidney transplant. Nephrol
Dial Transplant. 2013;28(11):2908–18.
121. Obrador GT, Macdougall IC. Effect of red cell transfusions on future kidney transplantation. CJASN.
2013;8(5):852–60.
122.Kalantar-Zadeh K, Kalantar-Zadeh K, Lee GH. The
fascinating but deceptive ferritin: to measure it or
not to measure it in chronic kidney disease? CJASN.
2006;1(Suppl 1):S9–18.
123.Charytan DM, et al. Considerations and challenges
in defining optimal iron utilization in hemodialysis.
J Am Soc Nephrol. 2015;26(6):1238–47.
124.Anirban G, Kohli HS, Jha V, Gupta KL, Sakhuja
V.  The comparative safety of various intravenous
iron preparations in chronic kidney disease patients.
Ren Fail. 2008;30(6):629–38.
125.Pai AB.  Iron oxide nanoparticle formulations for
supplementation. Met Ions Life Sci. 2019;19 https://
doi.org/10.1515/9783110527872-­012.
126.Pai AB, et  al. In vitro and in  vivo DFO-chelatable
labile iron release profiles among commercially
available intravenous iron nanoparticle formulations. Regul Toxicol. Pharmacol. 2018;97:17–23.
127.Gillespie RS, Wolf FM.  Intravenous iron therapy
in pediatric hemodialysis patients: a meta-analysis.
Pediatr Nephrol. 2004;19(6):662–6.

128.Warady BA, et  al. Iron therapy in the pediatric hemodialysis population. Pediatr Nephrol.

2004;19(6):655–61.
129.Warady BA, et al. Sodium ferric gluconate complex
maintenance therapy in children on hemodialysis.
Pediatr Nephrol. 2006;21(4):553–60.
130.Warady BA, et al. Sodium ferric gluconate complex
therapy in anemic children on hemodialysis. Pediatr
Nephrol. 2005;20(9):1320–7.
131.Warady BA, Seligman PA, Dahl NV. Single-dosage
pharmacokinetics of sodium ferric gluconate
complex in iron-deficient pediatric hemodialysis
patients. Clin J Am Soc Nephrol. 2007;2(6):1140–6.
132.Coyne DW, Kapoian T, Suki W, Singh AK, Moran
JE, Dahl NV, Rizkala AR. Ferric gluconate is highly

631

efficacious in anemic hemodialysis patients with
high serum ferritin and low transferrin saturation:
results of the Dialysis Patients’ Response to IV Iron
with Elevated Ferritin (DRIVE) Study. J Am Soc
Nephrol. 2007;18(3):975–84.
133.Ishida JH, et  al. Receipt of intravenous iron and
clinical outcomes among hemodialysis patients
hospitalized for infection. Clin J Am Soc Nephrol.
2015;10(10):1799–805.
134. Goldstein SL, Morris D, Warady BA. Comparison of
the safety and efficacy of 3 iron sucrose iron maintenance regimens in children, adolescents, and young
adults with CKD: a randomized controlled trial. Am
J Kidney Dis. 2013;61(4):588–97.

135.Liakopoulos V, Roumeliotis S, Zarogiannis S,
Eleftheriadis T, Mertens PR.  Oxidative stress in
hemodialysis: causative mechanisms, clinical implications, and possible therapeutic interventions.
Semin Dial. 2019;32(1):58–71.

136.Kato A, Odamaki M, Takita T, Furuhashi M,
Maruyama Y, Hishida A.  C-reactive protein is a
predictor of short-term mortality in hemodialysis
patients. Am J Nephrol. 2001;21(2):176–8.
137.Goldstein SL, Currier H, Watters L, Hempe JM,
Sheth RD, Silverstein D. Acute and chronic inflammation in Pediatric patients receiving hemodialysis.
J Pediatr. 2003;143(5):653–7.
138.Weiss G, Meusburger E, Radacher G, Garimorth
K, Neyer U, Mayer G.  Effect of iron treatment on
circulating cytokine levels in ESRD patients receiving recombinant human erythropoietin. Kidney Int.
2003;64(2):572–8.

139.C. for D.  E. and Research, “Approval Package
for Application Number 208551Orig1s000,”
2016
[Online].
Available:
https://www.
accessdata.fda.gov/drugsatfda_docs/
nda/2016/208551Orig1s000Approv.pdf

140.Rooyakkers TM, et  al. Ferric saccharate induces
oxygen radical stress and endothelial dysfunction
in vivo. Eur J Clin Invest. 2003;32(Suppl 1):9–16.

141.
Pratt RD, Grimberg S, Zaritsky JJ, Warady
BA.  Pharmacokinetics of ferric pyrophosphate
citrate administered via dialysate and intravenously
to pediatric patients on chronic hemodialysis. Pediatr
Nephrol. 2018;33(11):2151–9.

142.Yagil Y, et  al. Managing hyperphosphatemia in
patients with chronic kidney disease on dialysis with
ferric citrate: latest evidence and clinical usefulness.
Ther Adv Chronic Dis. 2015;6(5):252–63.


Immune Function
and Immunizations in Dialyzed
Children

33

Annabelle N. Chua and Sevcan A. Bakkaloğlu

Introduction
Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are associated with significant alterations in immune function. On the one
hand, CKD is associated with a state of chronic
inflammation, which in turn has been associated
with increased muscle catabolism, vascular calcification, insulin resistance, and malnutrition [1].
However, patients with CKD and ESKD also have
immunodeficiency, as manifested by an increased
risk for infection and sepsis and impaired response
to vaccinations [1]. Infection is a leading reported

cause of death in children with ESKD [2, 3].
Peritoneal dialysis (PD) continues to be plagued
with the infectious complication of peritonitis,
and hemodialysis (HD) is complicated by the
development of catheter-­
related bacteremia.
Excluding transplantation, infection is reported to
be the most common reason for dialysis modality
termination in children [2]. The treatment and the
prevention of infections are therefore important

A. N. Chua
Department of Pediatrics, Duke Children’s Hospital,
Durham, NC, USA
S. A. Bakkaloğlu (*)
Department of Pediatric Nephrology, Gazi University
School of Medicine, Ankara, Turkey
e-mail:

elements in the care of pediatric dialysis patients,
both for reduction of mortality and morbidity, and
in the setting of PD, for preservation of the peritoneal membrane function. This chapter will provide a brief review of currently available
information regarding the immune dysfunction
associated with CKD and ESKD.  In addition,
because delivery of routine childhood and supplemental vaccinations remains a cornerstone of
infection prevention, data regarding response to
immunizations in children with CKD and alterations to the routine immunization schedule for
healthy children required for children with CKD
will be presented.

Immune Dysfunction
Information regarding immune function in children with CKD or ESKD is sparse. The incidence
of peritonitis and catheter-related infections in
children is higher than that found in adults, and
infants and children up to 6 years of age develop
peritonitis more frequently than older children.
Immaturity of the immune system also contributes to the immune system dysfunction in children with CKD and ESKD. Therefore, the results
obtained from adults cannot be directly extrapolated to children. A complete review of innate
and acquired immunity in CKD is beyond the
scope of this chapter; however, the following provides a brief overview of this complex topic.

© Springer Nature Switzerland AG 2021
B. A. Warady et al. (eds.), Pediatric Dialysis, />
633


634

 hite Blood Cell Differentiation
W
and Function
Lymphopenia has been noted in adult dialysis
patients; however, the percentages of B-cells,
T-cells, and T-cell subsets are usually normal
[4–11]. Several studies evaluating lymphocyte
number and the percentages of B-cells, T-cells,
T-cell subsets, and NK cells in the peripheral
blood of children with CKD or ESKD have produced conflicting results [12–18]. Children with
pre-dialytic CKD have been reported to have
alterations in memory T-cell subsets, and

reduced numbers of memory B-cells have been
reported in children on dialysis [19, 20].
Possible explanations for the reduced numbers
of memory B-cells are a general suppression,
suboptimal T helper activity, or disturbances in
the B-cell migration process caused by uremia
or dialysis treatment. Irrespective of the mechanism of memory B-cell reduction, the consequence might be a lower capacity to mount a
secondary immune response, resulting in a
decreased response to vaccination and predisposition to increased infection rates [20, 21].
In addition to alterations in the number or percentage of T-cells, abnormalities of T-cell-­
mediated immune responses have been
demonstrated in CKD [7, 22–25]. T-cells from
dialysis-treated patients show a combination of
reduced proliferation and signs of activation [26–
28]. The abnormal T-cell proliferation of uremic
patients might be due to a defect within the T-cell
population itself, to circulating inhibiting factors
in uremic serum, or to the function of accessory
cells such as monocytes [25, 29–39]. In children,
data on this subject are scarce and conflicting.
Two studies could not establish a difference in
lymphocyte proliferation between children with
CKD, dialyzed or not, and healthy children [12,
13]. George et al. performed an analysis of T-cell
populations in children with CKD and demonstrated significant skewing toward advanced differentiation phenotypes in both the CD8 and
CD4 subsets, which may represent features of
advanced immune exhaustion and senescence
[40]. Various alterations in cytokine production,
particularly IFN-γ (gamma), have been reported

A. N. Chua and S. A. Bakkaloğlu

in children with CKD, with one study demonstrating normalization of these abnormalities
with HD [17, 41, 42].

Phagocytic Cells and Receptors
Reduced chemotaxis, adhesion, migration, and
phagocytosis characterize the dysfunction of
neutrophils and monocytes demonstrated in
patients on dialysis [27, 43–46]. Data on the
characteristics and function of phagocytes in
children with CKD are limited [47, 48].
Interestingly, one study demonstrated that treatment with recombinant human growth hormone
enhanced the oxidative burst activity of neutrophils in uremic children [47]. Wasik and colleagues concluded that PD improves phagocytosis
and intracellular killing of bacteria by peritoneal
macrophages but not by peripheral blood neutrophils in ESKD patients [48]. In another study of
pediatric patients with ESKD, marked dysregulation in inflammatory cell chemokine receptor
expression and responsiveness was noted and
was more pronounced in the subgroup of patients
who had multiple serious bacterial infections in
the preceding year [49].
Limited information is available on the impact
of CKD on IgG receptor (Fcγ(gamma)R) and
complement receptor (CR) expression or function [50–54]. These receptors are important components in the interaction between humoral and
cellular immunity and facilitate the phagocytic
process. Some authors described an increased
CD16 (Fcγ(gamma)RIII)-positive monocyte
population in adult PD and HD patients when
compared to healthy controls, a phenotype that
has been linked to tissue macrophages in the context of the state of maturation [50, 51]. In children with pre-dialytic CKD and ESKD, studies

have demonstrated a lower expression of
Fcγ(gamma)RII (CD32) on peripheral blood
monocytes and neutrophils compared to healthy
children [41, 55–58]. Furthermore, reduced CR
type 1 (CR1) expression, which is important for
inducing phagocytosis of complement-coated
bacteria, on lymphocytes and increased expression of Fcγ(gamma)R and CR on peritoneal


33  Immune Function and Immunizations in Dialyzed Children

­ acrophages and neutrophils have been shown in
m
pediatric CKD patients [41, 55–58].

Immunoglobulins
Low levels of IgG and/or subclasses have been
described in patients on PD, attributed to peritoneal loss in most of the studies [59–70]. However,
two studies in children reported that the immunoglobulin deficiency was already present before
dialysis started, which suggests inhibition of synthesis by the uremic state [63, 64]. In one study, a
deficiency of one or more IgG subclasses was
present in 40% of children with CKD, with IgG2
being the major subclass affected [64]. Children
receiving PD had the lowest serum Ig levels [64].
The role of serum IgG or subclass deficiency
in the pathogenesis of PD-associated peritonitis
is unclear. Studies in adults could not establish a
relationship between the peritonitis incidence
and IgG or subclass deficiency [65, 70]. In children, a study by Kuizon et al. found a significant
relationship between IgG and the incidence of

peritonitis [71]. In another study, although not all
children with IgG deficiency had a high incidence of peritonitis, all of the children with a
high number of peritonitis episodes were in the
IgG-deficient group [64]. On the contrary, a study
by Lalan et al. found that while hypogammaglobulinemia is a frequent complication of peritoneal
dialysis during infancy, it was not associated with
an increased risk of peritonitis, and some infants
developed peritonitis even after therapeutic IVIG
administration [72].
In summary, numerous abnormalities in
immune function have been described in CKD;
however, these deficiencies are not consistently
seen in pediatric patients. In addition, although
the uremic state is likely a major contributor to
this immune dysfunction, it seems plausible that
a variety of uremic toxins may impact the individual components of the immune reaction in
disparate ways. For the dialysis patient, it follows
that a dialysis prescription measured only in
terms of small solute clearance cannot be
expected to optimize all of the factors that influence immune function. In addition, the impact of

635

the dialysis procedure itself on immune function
and activation must be considered. Thus, specific
CKD-related treatment strategies to improve
immune function, beyond the obvious goals of
optimizing nutrition and correcting mineral bone
disorder, metabolic imbalance, and anemia,
remain elusive. It bears mentioning that despite

data demonstrating low IgG levels in children
receiving PD, there are no data at this time to support the routine use of intravenous immunoglobulin infusions for peritonitis treatment or
prevention. One treatment strategy that is available specifically to minimize risk for infection in
pediatric dialysis patients is the timely delivery
of routine and supplemental immunizations, and
the remainder of the chapter focuses on this topic.

Immunizations
Children with CKD and dialysis may have reduced
response to and/or reduced duration of antibody
after immunization and therefore may be at
increased risk for infection from vaccine-­
preventable diseases. In order to minimize this risk,
they require all the recommended childhood immunizations according to the standard schedule and
additional vaccines and booster doses [73–77].
The completion of the vaccination schedule
before renal transplantation (RTx) is of particular
importance. Due to the complexity of clinical
care of these children, immunizations can be
delayed, overlooked, or not properly recorded. In
fact, in a recent retrospective case series, only 22
out of 254 dialysis patients (9%) presented complete vaccination coverage prior to RTx. In particular, vaccination coverage against hepatitis B
and MMR was more reasonable compared to
varicella and pneumococci (89%, 83%, 59%, and
42%, respectively) [78]. The United States Renal
Data System (USRDS) 2013 report revealed that
among prevalent pediatric dialysis patients,
approximately 40% received seasonal influenza
vaccine between 2008 and 2011, and only 16%
received vaccination against Streptococcus pneumoniae [79].

Although immunization recommendations for
dialysis patients slightly vary among countries