AcuteComplicationsofOnlineHemodiafiltration

VersusHemodialysisinChildrenWith
ChronicKidneyDisease

ThesissubmittedforpartialfulfillmentoftheMasterDegreein
Pediatrics
By

GehanSayedIbrahim
(M.B.B.Ch.)

Supervisedby

Prof. Dr. Fatina Ibrahim Fadel

Professor of Pediatrics
Faculty of Medicine
Cairo University

Prof. Dr. Hafez Mahmoud Bazar'a

Assistant Professor of Pediatrics
Faculty of Medicine
Cairo University

Dr. Rascha Essam Eldin Abdel Aziz

Lecturer of Pediatrics
Faculty of Medicine
Cairo University

Faculty of Medicine
Cairo University
2012

) ( :

Aknowledgement

First of all, thanks are all due to ALLAH for blessing this
work until it has reached its end.

I am truly grateful to

Prof. Dr. Fatina Ibrahim Fadel,

Professor of Pediatrics, Faculty of Medicine , Cairo

University, for her close supervision, sincere help, valuable
suggestions and continuous encouragement throughout the
whole work.
I would like to express my deepest gratitude to

Prof. Dr. Hafez Mahmoud Bazar'a,

Assistant Professor of Pediatrics, Faculty of Medicine, Cairo

University,

for

his

great

support

and

continuous

encouragement throughout this whole work. It is a great honor

to work under his guidance and supervision.
My deepest appreciation and thanks are due to

Dr . Rascha Essam El din Abdalaziz

Lecturer of Pediatrics, Faculty of Medicine, Cairo University,

for her kind advice and constant help throughout this work.

Lastly, I would like to thank staff of Nephrology unit

and everyone who helped in completing this work.

Abstract

Acute complications commonly occur during routine hemodialysis

treatments, include( hypotensive episodes, cramps, nausea,). . Online haemodiafiltration (HDF) has been reported to reduce the frequency
of intradialytic acute complications. Methodes: This study included 16
children 4-16 years old CKD patients on regular hemodialysis in CPNT
(at Abou Elrish Children Hospital, Cairo University). We have followed
up the children for three consecutive months, then. The same group was
shifted to ol- HDF and was followed up for other three months. We
measured mean blood pressure, average weight gain in between dialysis
sessions and incidence rates of acute complications, HB, HCT, Ca, P and
BUN before and after sessions before and after the study.Results: There
was significant change in post-treatment mean arterial blood pressure in
the HDF group during the 3 months of the study (post-treatment(olHDF) 85.34

4.96 mm Hg vs. 93.377.69 on HD) (p value =

0.003).There was significant decrease

in the incidence of intradialytic

hypotensive episodes and its related symptoms among study group on

HDF was 3.0621.81 (range 0 to6) as compared to HD was 5.3752.96 (
range 0 to 10) (P value =0.001). Conclusion: In this study,ol- HDF
reduced the frequency of most of intradialytic acute complications
compared to HD .
Key words: OL-HDF , Hemodialysis , Acute complications ,Children.

List of Contents
Page

List of abbreviations ...... I

List of tables............... IV
List of figures............. VI
Introduction1
Aim of the work.... 3
Review of literature:
Chronic Kidney Disease. ............................................ ..4
Renal replacement therapy....... ..................................38
Hemodiafiltration.. ...................................................... 67

Patients and Methods ...................................................... 109

Results ............................................................................... 113
Discussion.......................................................................... 139
Summary........................................................................... 151
Recommendations. 153
References......................................................................... 154
Arabic summary. .............................................................

Abbreviations
ACEI.Angiotensin Converting Enzyme Inhibitor
AFB acetate-free biofiltration
ALPAlkaline phosphatase
AFB.Acetate-Free Biofiltration
AVF..Arterio-Venous Fistulae
BP.Blood Pressure
2 m

beta-2 microglobulin

BUN..Blood Urea Nitrogen

CAD.Cadaveric
CAD-RT. Cadaveric Renal Transplantation
Ca..Calcium
CAPDContinuous Ambulatory Peritoneal Dialysis
CAVH ... Continuous arteriovenous hemofiltration
CBCComplete Blood Count
CCPD...Continuous Cycler Assissted Peritoneal
Dialysis
Ccr.Creatinine Clearence rate
CFU .Colony-forming units
CHF.Congestive Heart failure
CKD.Chronic Kidney Disease
CVD.Cardiovascular Disease

CVVH ... Continuous venoovenous hemofiltration

CVVHDF ... Continuous venovenous hemodiafiltration
CAVHDF .. Continuous arteriovenous diafiltration
DBP..Diastolic Blood Pressure
DHTDihydrotachysteral
DTPADiethylThiamine Penta-Acetic acid
EPOErythropoietin
ESRDEnd Stage Renal Disease
EU Endotoxin units
GFR..Glomerular Filtration Rate
GH....Growth Hormone
GN ..Chronic glomerulonephritis
HBHaemoglobin
HCT.Hematocrit
HD...Hemodialysis
HDFHemodiafiltration
HTNHypertesion
IGF1....Insulin Like Growth Factor-1
ISH ....Intradialytic symptomatic hypotension
K/DOQI..Kidney Disease Outcome Quality Initiative
Kt/VDialyzer Urea Clearance (K) X Duration of
the Dialysis (t) / Urea Volume of distribution (V)
NAPRTCS...North American Pediatric Renal
Transplant Cooperative Study

NKFNational Kidney Foundation

Ol HDF..On-Line hemodiafiltration
OH2 D31,25 Dihydroxy Cholecalciferol
PAD..Perpheral Arterial Pulsation
PD....Peritoneal Dialysis
PTFEPolytetrafluro ethylene Teflon
PTH.Parathormone
Po4Phosphrus
PUJ..Pelvi Ureteric Junction
PUV.Posterior Urethral Valve
QUF.Ultra-filtration flow rate
RBC.Red Blood Cell
rHEPO.recombinant Human Erythropoietin
rHGH...recombinant Human Growth Hormone
RRT.Renal Replacement Therapy
RTRenal Transplantation
SBPSystolic Blood Pressure
SDStandard Deviation
SDS.Standard Deviation Scores
SEPT...Single Emission Position Tomography
TSAT.Transferrin Saturation
UFc..Ultra-Filtration coefficient
USRDSUnited State Renal Data System

List of Tables
Table

Title

Page

(1)
(2)
(3)
(4)

Stages of chronic kidney disease .

Children at risk for the development of CKD
Pathophysiology of chronic kidney disease
Factors hastening the progression of CKD
Nutritional recommendations for children with CKD on
dialysis

5
8
9
13

Modalities of dialysis
Potential pathophysiology mechanisms of intradialytic
hypertension
Anthropometric measures among study group
Descriptive statistics regarding age and duration of
hemodialysis among study group
Descriptive statistics regarding blood pressure readings
during HD session among study group

39

(5)
(6)
(7)
(8)
(9)
(10)

(11)
(12)
(13)
(14)

(16)
(17)

114
114
117

120

comparison between Incidence of intradialytic symptoms

123

52

Descriptive statistics regarding blood pressure readings

during HDF session among study group
comparison between mean blood pressure values (in
mmHg) on conventional HD & online HDF
comparison between Incidence of hypotensive episodes
among study group during HD versus HDF Sessions

comparison between Average weight gain among study

group during HD versus HDF Sessions
comparison between Incidence of pyrogenic reactions
among study group during HD versus HDF Sessions
Comparison between Incidence of convulsions among
study group during HD versus HDF Sessions

(15)

26

II

119

121

126
126
127

Table
(18)
(19)
(20)
(21)

Title
comparison between Incidence of clotting among study
group during HD versus HDF Sessions
): comparison between Incidence of excessive bleeding
from AV fistula HD versus HDF
comparison between Incidence of post session fatigue
among study group during HD versus HDF Sessions
Descriptive statistics of laboratory (Base-line) data of all
cases included in the study

Page
128
130
131
134

(22)

Descriptive statistics of laboratory ( after 3 months of HDF)

data of all cases included in the study

135

(23)

Comparison between the study group in baseline routine

laboratory investigations & after 3 months HDF

136

(24)

Descriptive statistics of laboratory (Base-line) Hemoglobin

Hamatocrit of all cases included in the study

137

(25)

Descriptive statistics of HB and HCT after 3 months of

HDF

137

(26)

Comparison between the study group in base line HB and

HCT and after 3 months of HDF

138

III

List of Figures
Figure

Title

Page

(1)
(2)

The extracorporeal circuit

The composition of a typical modern dialysis fluid in
hemodialysis.

41
44

(3)
(4)
(5)

Dilysis fluid pathway in post dilution hemodiaysis

Dilysis fluid pathway in post dilution hemodiafiltration
The typical components and function of a venovenous
haemodialysis circuit
Dialysis fluid pathway in hemodialysis
Schematic representation of high-flux hemodialysis
and on-line hemodiafiltration Dialysis fluid pathway in
haemodiafiltration

45
47
49

(9)

Circuite for hemofiltration and for hemodiafiltration

75

(10)

Flow diagrams for different forms of hemodiafiltration

77

(11)

Process steps in the preparation of fluids for dialysis

85

(12)

Water treatment system used to produce and deliver

ultrapure water to an HDF machine
sex distribution among the study group
Original renal disease distribution among study group

89

(6)
(7)

(13)
(14)
(15)

frequency of patients receiving antihypertensive drugs

(16)
(17)
(18)

113
115
116

frequency of types of antihypertensive drugs used among

study group
Mean blood pressure during HD session among study
group:

116

Mean blood pressure during HDF session among study

group

119

70
72

IV

118

Figure

Title

Page

(19)

comparison between Incidence of hypotensive episodes

among study group during HD versus HDF Sessions
comparison between Incidence of hypotensive episodes,
average weight gain and intradialytic symptoms among
study group during HD versus HDF Sessions

121

(21)
(22)

comparison between Incidence of intradialytic symptoms

comparison between Incidence of intradialytic abdominal
pain among study group
during
HD versus HDF
Sessions.

124
124

(23)

comparison between Incidence of intradialytic dizziness

among study group during HD versus HDF Sessions.

125

(24)

Comparison between Incidence of pyrogenic reactions

among study group during HD versus HDF Sessions.

127

(25)

Comparison between Incidence of convulsions

study group during HD versus HDF Sessions.

among

128

(26)

comparison between Incidence of clotting among study

group during HD versus HDF Sessions.
comparison between Incidence of bleeding among study
group during HD versus HDF Sessions.

129

(28)

comparison between Incidence of bleeding , clotting ,

pyrogenic reactions and convulsions among study group
during HD versus HDF Sessions

131

(29)

Patients' preferences of HDF versus HD modalities among

study group
Comparison between the study group in baseline HB after
3 months HDF
Comparison between the study group in baseline HCT
after 3 months HDF

133

(20)

(27)

(30)
(31)

123

130

137
138

Introduction and Aim of the Work

Introduction
Chronic kidney disease (CKD) is defined by the National Kidney
Foundation Kidney Disease and Outcome Quality Initiative (KDOQI)
group to classify any patient who has kidney damage lasting for at least 3
months with or without a decreased glomerular filtration rate( GFR) or
any patient who has a (GFR) of less than 60 mL/min per 1.73 m2 lasting
for 3 months with or without kidney damage (NKF, K/DOQI, 2008).

CKD affects

multiple systems, including the endocrine ,

hematologic, immune, and cardiovascular systems (Dilys and Richard ,

2008).
Hemodialysis is a procedure that uses extracorporeal perfusion to
clear accumulated solutes or toxins from the blood by diffusion and
convection across a semipermeable membrane (Avner et al., 2004).

Acute complications commonly occur during routine hemodialysis

treatments. They include hypotension, cramps, nausea, and vomiting,
headache, chest pain, back pain, itching, fever and chills. Less
common but serious complications include disequilibrium syndrome,
hypersensitivity reactions, arrhythmia, cardiac tamponade, intra
cranial bleeding, seizures, hemolysis and air embolism (Daugirdas et
al., 2008).
These complications are generally caused by multiple underlying
mechanisms and are poorly understood. Knowledge of their pathogenesis
is further complicated by their often simultaneous occurrence (Bregman,
1994).

-1-

Introduction and Aim of the Work

Comparing the clearance that can be obtained by the two modes of

dialysis therapy conventional haemodialysis, and hemodiafiltration
(HDF) shows that if we want significant removal of uraemic solutes in
the middle and large molecular weight range, in addition to optimizing
the small solute removal, we need to maximize the convective transport
by applying (HDF) (Leypoldt et al., 2000).

-2-

Introduction and Aim of the Work

Aim Of The Work

Comparing conventional haemodialysis to on-line haemodiafiltration
regarding limitation of acute complications of hemodialysis in children
with end stage renal disease on regular hemodialysis.

-3-

Review of Literature

Chapter 1
Chronic Kidney Disease
Introduction:
Chronic kidney disease(CKD) is characterized by a progressive
decline in the glomerular filtration rate (GFR) for a minimum of 3
months, often accompanied by albuminuria (NKF, 2002).
Chronic renal failure (CRF) is an insidious and irreversible
condition that eventually progresses to end stage renal failure
(ESRF). It is an important cause of morbidity and mortality in
children worldwide (Mouin et al ., 2003).
Chronic renal failure(CRF) is a slowly worsening loss of the
ability of the kidneys to remove wastes , concentrate urine, and
conserve electrolytes (Fogo, 2007).
The Kidney Disease Outcomes Quality Initiative of the
National Kidney Foundation(NKF: K/DOQI ) of the united stats
(2008) defines chronic kidney disease (CKD) as either kidney
damage or a decreased kidney glomerular filtration rate (GFR) of
less than 60 mL/min/1.73 m2 for 3 or more months. Whatever the
underlying etiology, the destruction of renal mass with irreversible
sclerosis and loss of nephrons leads to a progressive decline in
(GFR) (NKF: K/DOQI ,2008 ).

-4-

Review of Literature

Stages of CKD:
All individuals with a glomerular filtration rate (GFR) <60
mL/min/1.73 m2 for 3 months are classified as having chronic
kidney disease, irrespective of the presence or absence of kidney
damage & and individuals with kidney damage are classified as
having chronic kidney disease ,irrespective of the level of (GFR )
(NKF: K/DOQI ,2008 ).

Table (1) : Stages of chronic kidney disease :

(Mouin et al ., 2003).

The normal (GFR) in young adults is 120 to 130 mL/min/1.73

m2, whereas in infancy it is much lower. Even when corrected for
body surface area it increases in relationship to body size up to two
years. Kidney disease is characteristically asymptomatic and is often
not diagnosed until it is relatively advanced (Mouin et al ., 2003).

-5-

Review of Literature

Incidences and prevalence:

The prevalence of (CKD) stage II or lower in children is
reported to be approximately 18.5-58.3 per million children, annual
rate is only 1 or 2 new cases in every 100,000 children
( Atlas of End-Stage Renal Disease in the United States, 2010).

Age and Sex:

The frequency of( CKD) increases with age. Among children,
(CKD) is more common in children older than 6 years than in those
younger. The incidence and rate of progression to( ESRD) are equal
in both sexes, although obstructive uropathies are more common in
males (Ardissino et al., 2003).

Mortality/Morbidity
About 70% of children with chronic kidney disease develop
(ESRD) by age 20 years. Children with (ESRD) have a 10-year
survival rate of about 80% and an age-specific mortality rate of
about 30 times that seen in children without (ESRD). The most
common cause of death in these children is cardiovascular disease,
followed by infection. Of the deaths due to cardiovascular causes,
25% were attributed to cardiac arrest (cause uncertain), 16% to
stroke, 14% to myocardial ischemia, 12% to pulmonary edema, 11%
to hyperkalemia, and 22% to other cardiovascular causes, including
arrhythmia. Data from the Australia and New Zealand (ANZ)
-6-

Review of Literature

registry reveal that, the year in which renal replacement therapy was
initiated, the age of patients at the start of that therapy and the type
of dialysis used were associated with the risk of death (Craven et
al., 2007)

Race:
In the United States, (ESRD) rates in blacks are 2.7 times
higher than in whites. This may be due to genetic susceptibility;
other factors may include socioeconomic problems and limited
access to medical care. Such factors may result in the delivery of
excessive numbers of low birth weight (LBW) babies, partially
accounting for the observed increased incidence of (ESRD) because
chronic kidney disease is more common with increasing prematurity
and survivorship ( Choi et al.,2009).

Causes of CRF in children:

The chief causes of (CKD) in children include the following:
Obstructive uropathy.
Hypoplastic or dysplastic kidneys.
Reflux nephropathy.
Focal segmental glomerulosclerosis as a variant of childhood
nephritic syndrome.

-7-

Review of Literature

Polycystic kidney disease, both autosomal-recessive and

autosomaldominant varieties.
Idiopathic.
(Hogg et al., 2003).

Risk Factors For Chronic Renal Disease:

Table (2): Children at risk for the development of( CKD):

(Mouin et al ., 2003).

-8-