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Renal Development and Dysfunction
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DOUGLAS J STEWART and STEPHEN D MARKS
Topics covered
2
Renal physiology in the fetus and neonate
Renal impairment in infancy, childhood and
adolescence
RENAL PHYSIOLOGY IN THE
FETUS AND NEONATE
Introduction
Nephron formation (nephrogenesis) commences
during the h week of gestation. Recognisable
glomerular structures are present from the ninth
week and glomerular development (glomerulogenesis) is complete by 32–34 weeks. Over 80%
of nephrogenesis occurs in the third trimester.
Kidney growth continues aer 34 weeks’ gestation but this is due to maturation of existing
nephrons (tubular and vascular growth) rather
than formation of new glomeruli or nephrons.
In preterm infants, the process of nephrogenesis may continue aer birth but the immature
kidneys are vulnerable to potential insults during this period. e total number of nephrons
in the two kidneys at the time of birth is highly
variable, ranging from 200,000 to 2.7 million.
Because damaged nephrons are incapable of
repair or regeneration anything which impairs
Complications of chronic kidney disease
Renal replacement therapy
nephrogenesis (such as intrauterine urinary tract
obstruction), may result in a reduced number of
nephrons at birth. is increases the subsequent
risk of chronic kidney disease (CKD) and related
complications.
e presence of urine in the fetal bladder can
be visualised on ultrasound at 9 weeks gestation.
Fetal urine is the major constituent of amniotic
uid and the volume of amniotic uid increases
with gest ational age. Amniot ic u id is swallowed,
absorbed in the gastrointestinal tract and ‘recycled’ into the amniotic cavity via the kidneys. By
20 weeks gestation, fetal urine constitutes 80%
of liquor volume (approximately 800 mL/day).
Fetal urine ow rate increases progressively
throughout pregnancy to 15–30 mL/hour from
31 weeks onwards. Reduced or absent urinary
output (e.g. due to severe outow obstruction,
bilateral cystic disease or bilateral renal agenesis) leads to oligohydramnios-reduced amniotic
uid volume.
Aer birth, the glomerular ltration rate
(GFR) correlates with gestational age, total
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kidney volume and mean arterial pressure.
GFR is approximately 3.5–6 mL/min/1.73 m2 in
premature infants depending on birth weight,
and 13 mL/min/1.73 m2 in infants born at term
(40 weeks). Postnatally there is a sharp increase
in GFR, which doubles by 2 weeks of age and triples by 4 weeks of age. However, it takes approximately 1–2 years for adjusted GFR values to reach
adult levels. is increase in GFR is a consequence of greater glomerular surface area as well
as renal maturation and growth. At birth, the
kidneys only receive a small percentage (2.5–4%)
of cardiac output. is increases over the rst few
weeks of life to 15–18% of cardiac output. For
comparison, renal perfusion accounts for 20–25%
of cardiac output in adults.
Serum creatinine is an unreliable marker
of renal function in neonates because it freely
crosses the placental barrier and maternal creatinine is present in the neonate’s circulation.
Furthermore, there is a variable degree of proximal tubular reabsorption of creatinine in the
immature kidneys.
e low GFR in neonates is of considerable
relevance to clinical management, especially
when interpreting laboratory results and calculating uid requirements and drug dosages.
is is particularly important in sick premature
infants. Although the neonatal kidney can cope
with many physiological demands, its functional
reserve is limited and may be overwhelmed by
some of the stresses commonly encountered in
the neonatal period.
Fluid and Water Homeostasis
In early fetal life, water constitutes approximately
90% of body weight, and the extracellular uid
(ECF) represents 60% of body weight. During
fetal development there is contraction of the ECF
volume so that by term, 75% of body weight is
composed of water and the ECF volume constitutes 40% of body weight. Preterm infants have
much higher body water composition than those
born at term.
Following delivery, there may be an early
phase of oliguria but aer 24–48 hours this
is followed by an acute isotonic volume
contraction leading to weight loss. A loss of 10%
of birth weight is not uncommon. is phenomenon, which is part of the normal physiological
adaptation to extrauterine life, is most pronounced and prolonged in premature infants.
Most babies regain their birth weight between 7
and 10 days of age. e reduction in pulmonary
vascular resistance and increase in pulmonary
venous return aer birth stimulates release of
atrial natriuretic peptide (ANP), thus contributing to diuresis and contraction of the ECF
volume. Early and excessive administration of
sodium and water before this period of diuresis/natriuresis has occurred may contribute to
hypervolaemic (dilutional) hyponatraemia.
is poses an increased risk of morbidity and
mortality in neonates compared with regimens
where water and sodium intake is restricted in
the rst few days of life.
Due to tubular immaturity, the maximal urine
concentrating ability of the kidney in new born
infants is impaired (up to 600–800 mOsmo/
kg). Neonates therefore produce large volumes
of dilute urine, typically at a rate of 2–3 mL/kg/
hour. e concentrating ability of the kidneys
increases rapidly over the rst 2 months and
continues to increase at a slower rate thereaer.
e limited concentrating ability of the kidney
reects a reduced responsiveness of the kidneys
to antidiuretic hormone (vasopressin) and an
inability to maintain a corticomedullary osmotic
gradient (partially because the tubules themselves are small). Neonates can usually respond
to a hypotonic uid load by initially producing a
greater volume of dilute urine but have diculty
in producing more concentrated urine thereafter. Neonates are therefore easily predisposed to
dehydration.
Sodium Homeostasis
Total body sodium content is higher in neonates, infants and young children. A positive
sodium balance is essential for normal growth.
In healthy neonates the sodium requirement
is typically 2–3 mmol/kg/day in the rst week,
rising to 3–5 mmol/kg/day aer the rst week.
In preterm babies, and very low birth weight
infants, the sodium requirement can be two
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to three-fold higher as a result of reduced ability of the immature renal tubules to reabsorb
sodium combined with the additional sodium
requirements for growth. e use of diuretics may also increase sodium and potassium
excretion leading to increased requirement for
supplementation.
Potassium Homeostasis
Tubular excretion of potassium in neonates differs from infants and older children. eir renal
clearance of potassium is reduced even aer correction is made for their lower GFR. e combination of reduced renal clearance and increased
intestinal absorption of potassium puts neonates
into a net positive potassium balance. In term
infants, potassium levels usually fall rapidly in
the rst week of life whereas preterm infants
experience a gradual rise the serum potassium
which reaches a maximum around the third to
fourth weeks of life. Elevated serum potassium
levels may be a consequence of hypoxia, metabolic acidosis, catabolic stress, oliguric renal failure and inadequate excretion by the immature
distal nephron. e daily potassium requirement
in a healthy neonate is typically 1–2 mmol/kg/
day in the rst week, rising to 2–3 mmol/kg/day
thereaer.
Acid-Base Homeostasis
Due to tubular immaturity, neonates are unable
to adequately acidify their urine and their blood
is therefore relatively acidotic. is may be a
mixed respiratory and metabolic acidosis, and is
usually accompanied by cardiopulmonary compensation. e renal threshold for bicarbonate
reabsorption is lower in neonates (18–20 mmol/L)
but this rises to 24–26 mmol/L by 1 year of age
as the renal acidication mechanism develops.
Because excessive administration of sodium
chloride can contribute to a hyperchloraemic
metabolic acidosis the sodium content of total
parenteral nutrition (TPN) is therefore oen
given in the form of sodium acetate, a base,
rather than sodium chloride. Prolonged acidosis in the neonate and infant (e.g. secondary to
CKD) should be avoided as this can lead to poor
feeding and growth impairment. Bicarbonate
supplementation may therefore be required with
the aim of maintaining serum bicarbonate level
above 17 mmol/L.
RENAL IMPAIRMENT IN
INFANCY, CHILDHOOD
AND ADOLESCENCE
Introduction and Denitions
Renal impairment may be congenital or acquired,
and is classied as either acute kidney injury
(AKI) or chronic kidney disease (CKD).
Acute kidney injury (AKI)
AKI has now superseded the term acute renal
failure (ARF). It is characterised by a sudden,
potentially reversible reduction in kidney function which is typically accompanied by a rise in
serum creatinine. AKI is usually associated with
a decrease in urine output but polyuria may also
occur. Dierent classication systems exist for
AKI including the Kidney Disease Improving
Global Outcomes (KDIGO) 2012 (Table 2.1) and
pRIFLE (Table 2.2) classication systems. e
pRIFLE system is used to identify children with
AKI and those at risk of renal impairment. e
dierent categories have been found to correlate
Table 2.1 KDIGO 2012 AKI classication
Measured serum
AKI stage
1 >1.5–1.9 times
2 2–2.9 times
3 ≥3 times baseline
creatinine
baseline
creatinine
baseline
creatinine
creatinine
Urine ouput
(mL/kg/hour)
<0.5 for 6–12
hours
<0.5 for ≥12
hours
<0.3 for
≥24 hours
or anuric for
12 hours
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Table 2.2 pRIFLE classication
Urine output
Category Estimated GFR
Risk Decrease by 25%
from baseline
Injury Decrease by
50%
Failure Decrease by 75%
or <35 mL/
min/1.73 m
Loss Renal failure for >4 weeks
End-stage Renal failure >3 months
2
(mL/kg/hour)
<0.5 for
8 hours
<0.5 for
16 hours
<0.3 for
24 hours or
anuric for
12 hours
with morbidity and mortality outcomes. e management of AKI includes: identifying and avoiding
the causative agent(s), avoiding exposure to other
potential nephrotoxic agents and careful uid
management with supportive measures to correct electrolyte disturbance. In severe cases, renal
replacement therapy may be required to facilitate
clearance of waste products and uid removal.
Chronic kidney disease (CKD)
e Kidney Disease Improving Global Outcomes
(KDIGO) guidelines dene CKD as the presence
of kidney damage, either functional or structural,
exceeding 3 months duration. Table 2.3 lists the
dierent CKD stages.
Table 2.3 CKD staging
GFR (mL/min/
Stage
1 >90 Kidney damage but
2 60–89 Kidney damage with
3a 45–59 Mild to moderate loss
3b 30–44 Moderate to severe
4 15–29 Severe loss of renal
5 <15 End-stage kidney
1.73 m
2
) Description
normal renal
function
mild loss of renal
function
of renal function
loss of renal function
function
disease
of the kidney and urinary tract account for
around 30% of all congenital anomalies and
are more common in certain ethnicities, particularly in African Americans and Australian
aboriginals.
Some patients with CKD may have stable
renal function for several years and there may
even be some improvement in their GFR, particularly over the first 4 years of life. However,
they typically experience a decline in GFR with
puberty.
Epidemiology of CKD
e true incidence of CKD in childhood is
unknown. Figures of 2 to 16 per million of agerelated population (pmarp) per year are quoted
depending on dierent national registry data.
However, this is probably an underestimate
because the early stages of CKD are usually
asymptomatic. Many patients with CKD may not
present until later in childhood or adolescence –
or until they reach adulthood.
The incidence and prevalence of CKD are
higher in males because they have a higher
incidence of congenital anomalies of the kidney
and urinary tract (CAKUT) – which is the commonest cause of CKD. Congenital anomalies
Aetiology of CKD
Primary causes of CKD dier signicantly in
children compared with adults. e main aetiologies are:
●
Congenital anomalies of the kidney and urinary tract (CAKUT) (49.1%)
●
Steroid-resistant nephrotic syndrome (10.4%)
●
Chronic glomerulonephritis – e.g. in lupus
nephritis, Henoch–Schönlein nephritis, and
Alport syndrome (8.1%)
●
Renal ciliopathies such as nephronophthisis
(5. 3%)
Rarer causes of CKD include haemolytic uraemic
syndrome (HUS) and malignancy such as Wilms
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tumour. Prematurity is being increasingly recognised as a risk factor for CKD and rising rates
of childhood obesity are associated with early
type 2 diabetes mellitus and consequent diabetic
nephropathy.
Renal replacement therapy is usually
required once stage 5 CKD (end-stage kidney
disease [ESKD]) is reached. Pre-emptive living
donor (LD) kidney transplantation is considered the gold standard of treatment for ESKD.
Ideally patients should undergo transplantation before they reach the point of requiring
dialysis. However, this is challenging and many
patients experience deterioration in renal function before a donor can be found. Alternatively,
they may present acutely with ESKD which
necessitates the need for acute dialysis. e GFR
in early childhood is a predictor of the likely
requirement for renal replacement therapy by 20
years of age.
●
GFR 51–75 mL/min/1.73 m2 – 37% likelihood
of renal replacement therapy
●
GFR 25–50 mL/min/1.73 m2 – 70% likelihood
of renal replacement therapy
●
GFR <20 mL/min/1.73 m2 – 97% likelihood of
renal replacement therapy
Assessment of Renal Function
in Children
Although measurement of serum creatinine is
widely used to assess renal function it has several limitations. Creatinine is a breakdown
product of creatinine phosphate in muscle
and is produced at a rate of 10–25 mg/kg/day
(90 –210 µmol/kg/day). Serum creatinine values rise with growth and increasing muscle
mass. Aer the neonatal period, creatinine is
freely secreted via the renal tubules with only
minimal reabsorption. When renal function is
impaired, however, the ability of the tubules to
secrete creatinine is reduced and serum values
rise. Saturation of tubular secretion of creatinine
may not occur until GFR has fallen by 50% with
the result that reliance on creatinine values may
result in an overestimate of GFR. Furthermore,
creatinine can only be used to estimate GFR
when it is in steady state and rapid uctuations
in serum creatinine may make it an unreliable
way of estimating GFR.
Children with low muscle mass may have low
serum creatinine values which are not an accurate reection of their true GFR.
e gold standard measurement of GFR is by
inulin clearance. is requires injection of an
intravenous bolus of inulin followed by a continuous infusion with subsequent measurement
of serum and urine inulin levels. is test is
impractical in the clinical setting, particularly for
children who are not toilet trained and for those
with voiding diculties. Clearance of radioactive isotopes, such as 51Cr[EDTA], can be used to
measure GFR but this requires serial serum samples to be taken and exposure to radioisotopes –
which is undesirable. e use of iohexol serum
clearance is a promising alternative to inulin and
radioisotopes for GFR determination but remains
expensive and is not in widespread use.
Cystatin C measurement may be of use in
children with low muscle bulk in whom calculations based on serum creatinine are unreliable.
Cystatin C is a small protein produced from
all nucleated cells and is readily ltered via the
glomeruli. As such, it is not aected by muscle
mass.
e modied Schwartz formula is frequently
used as a creatinine-clearance estimate of GFR
in paediatrics, although the aforementioned
considerations need to be taken into account.
However, the formula lacks validation the range
2
of GFR values of 15–75 mL/min/1.73m
. e formulae, adapted for dierent units of creatinine,
are listed below:
●
eGFR (mL/min/1.73 m2) = 0.413 × height
(cm)/serum creatinine (mg/dL)
●
eGFR (mL/min/1.73 m2) = 36.5 × height (cm)/
serum creatinine (µmol/L)
Outcomes for Patients with CKD
CKD is associated with reduced life expectancy, with cardiovascular risk being increased
even for patients in the early stages of CKD.
Cardiovascular disease is the main cause of
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death for patients with ESKD. Survival rates
for children and young people on dialysis, and
post-transplant, continue to increase, albeit at a
relatively slow rate. e lifespan of patients on
chronic dialysis is reduced by 40–60 years and by
20–30 years for renal transplant recipients.
COMPLICATIONS OF CHRONIC
KIDNEY DISEASE
Chronic Kidney Disease-Mineral
and Bone Disorder (CKD-MBD)
CKD-MBD (previously referred to as ‘renal
osteodystrophy’) is a systemic disorder which
results from impaired vitamin D metabolism
and secondary hyperparathyroidism. In CKD,
the kidneys produce less 1-alpha hydroxylase,
the enzyme required to convert 25-hydroxyvitamin D (calcidiol) to its active form, 1,25 dihydroxyvitamin D3 (calcitriol). Low calcitriol
levels result in reduced calcium absorption from
the gut and reduced renal calcium reabsorption.
Coupled with hyperphosphataemia (resulting
from reduced renal excretion of phosphate) this
stimulates increased secretion of parathyroid
hormone (PTH) from the parathyroid glands.
Secondary hyperparathyroidism results in
increased bone resorption and impaired osteoid mineralisation. Bones are weakened and
there may be radiological evidence of rickets.
If untreated, secondary hyperparathyroidism
can cause bone pain and an increased risk of
fractures and slipped epiphyses. Measurement
of intact PTH levels serves as a marker of
active bone disease and can be used to monitor
response to treatment. e aims of treatment are
to normalise bone metabolism, improve bone
strength and growth, reduce the risk of bony
deformity, and also reduce the risk of vascular
calcication (by maintaining serum calcium
levels within a normal range).
Management of CKD-MBD (renal osteodys-
trophy) includes:
1. Correction of acidosis using medications
such as sodium bicarbonate.
2. Dietary phosphate restriction and the use of
phosphate binding medications, e.g. calcium
acetate, calcium carbonate and Sevelamer.
ese need to be taken at mealtimes to promote intestinal excretion of phosphate.
3. Supplementation with alfacalcidol (a vitamin
D analogue) or calcitriol to suppress PTH
if control cannot be achieved by dietary
restriction alone.
4. e use of cinacalcet (a calcimimetic agent
that mimics the action of calcium on tissues
via activation of the calcium-sensing receptors) for patients with refractory secondary
hyperparathyroidism and those at risk of
tertiary hyperparathyroidism.
Anaemia
Anaemia is common in children with CKD and
it may aect their neurocognitive ability, exercise tolerance and cardiovascular status (e.g.
increased risk of le ventricular hypertrophy). e
ideal haemoglobin level for children with CKD
is debated but evidence suggests that outcomes
are not improved above a haemoglobin level of
13 g/dL. e reported prevalence of anaemia is
73% for stage 3 CKD, 87% for stage 4 and >93%
for stage 5. Anaemia in CKD is caused predominantly by decreased renal erythropoietin production and impaired physiological regulation of iron.
Recombinant human erythropoietin (rHuEPO)
is almost invariably required in the latter stages
of CKD, and can be used safely in children on
dialysis. It can be administered either subcutaneously or intravenously. Younger children typically require higher doses of rHuEPO than adults.
Iron supplementation, either administered orally
or intravenously, is also required and iron stores
should be monitored closely to avoid iron overload.
Growth, Nutrition and
Development
Growth impairment is a common and visible
complication of CKD. In a study of 5000 children
with CKD it was found that 35% had a height
which was lower than the third percentile (or
below a median height standard deviation score
[HtSDS] of –1.88). Factors limiting the growth of
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children with CKD include disorders of mineral
and bone metabolism, polyuria, metabolic acidosis, poor nutritional intake, anaemia and uid
and electrolyte disorders. Uraemia may cause
anorexia and vomiting with a consequent reduction in nutritional intake. For this reason nasogastric or gastrostomy feeding may be required in
order to maximise caloric intake. Protein intake
should be maintained above the recommended
reference nutrient intake to ensure adequate
growth. However, protein intake should be no
higher than 120% of daily recommended intake
in children with stage 4–5 CKD or 100% of daily
recommended intake for children on dialysis.
Recombinant human growth hormone (rhGH)
should be considered if the child’s height and/
or growth velocity remain signicantly reduced
despite optimal nutritional and dialysis status,
correction of metabolic acidosis and reduction of
steroid therapy to a minimum.
Standard childhood vitamin supplements
should not routinely be prescribed for CKD patients
because of adverse eects related to increased
intake of Vitamin A. Special multivitamin supplements are available for patients on dialysis.
Hyperkalaemia occurs when GFR has declined
to less than 10% of normal. is is mainly related
to dietary intake but other contributory factors
include: reduced caloric intake, acidosis, and the
use of certain antihypertensives (e.g. ACE inhibitors) and potassium-sparing drugs (e.g. spironolactone, amiloride). Hyperkalaemia can oen be
managed with dietary restriction but treatment
with agents such as calcium resonium or sodium
resonium may also be required.
RENAL REPLACEMENT
THERAPY
Peritoneal Dialysis
Peritoneal dialysis (PD) is usually the best form of
renal replacement therapy for children on chronic
dialysis. e major benet of PD is that it can be
performed at home. PD relies on the principles of
diusion and osmosis. Sterile dialysate is instilled
into the peritoneal cavity. Solutes move along
a concentration gradient across the peritoneal
membrane via diusion, and the transfer of water
occurs by osmosis. In addition, the ‘ultraltration’ of water across the peritoneal membrane is
accompanied by ‘solvent drag’ which results in the
transfer of solutes across the peritoneal membrane
even when a concentration gradient is not present.
Commercial dialysate solutions are typically
available with dextrose concentrations of 1.5%,
2.5% and 4.25%. By increasing the osmotic gradient across the peritoneal membrane, higher dextrose concentrations usually have a greater ability
to remove uid. However, the long-term use of
hypertonic dialysate solutions results can result
in peritoneal brosis and impaired function due
to chronic exposure of the peritoneal membrane
to glucose degradation products (GDPs).
e main PD regimens are:
●
Continuous ambulatory peritoneal dialysis
(CA PD). Fluid is manually instilled into the
peritoneal cavity and then drained from it –
typically up to four times per day. Fluid is
also instilled overnight and drained in the
morning. In practice, CAPD is rarely used in
children
●
Automated peritoneal dialysis (APD) (Figure 2.1)
An automated PD cycler machine is used to
deliver a personalised programme of dialysis over
a certain number of cycles and hours. Children
receiving this form of dialysis are either managed
by nocturnal intermittent PD (NIPD) or continuous cycling PD (CCPD).
●
NIPD: is consists of an overnight regimen,
with PD being performed while the young
patient is asleep. e peritoneal cavity is le
empty during the day.
●
CCPD: is involves a combination of overnight PD and day time lling.
●
Adapted APD (AAPD): Some machines oer
more exible control of dwell times and ll volumes overnight to promote sodium removal.
●
Tidal PD: In this variant only a proportion of
the ll volume (usually 50–80%) is drained with
each cycle during the overnight PD regimen.
is may be indicated in children who experience discomfort/pain with drainage of PD.
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Figure 2.1 Compact peritoneal dialysis machine for automated overnight home dialysis.
e eciency of PD is dependent on the integrity
of the peritoneal membrane and the ease with
which the PD catheter allows the instillation and
drainage of uid in and out of the peritoneal cavity.
Infection
If peritonitis is suspected, a PD uid sample
should be collected as soon as possible and be
sent for cell count and bacterial/fungal culture.
Treatment with intraperitoneal and/or intravenous antibiotics is commenced it there is an elevated white cell count (>100 WBC × 106/L) in the
PD euent or the presence of peritonitis is conrmed on positive culture. Appropriate antifungal coverage (usually with oral anti-fungal agent)
may also be indicated.
Indications for removal of a PD catheter include:
●
Recurrent bacterial peritonitis with the same
organism within 4 weeks of stopping therapy
(particularly Pseudomonas infection as this is
dicult to eradicate)
●
Refractory catheter infections
●
Exit-site and PD catheter tunnel infections
with an organism which is also responsible
for concurrent peritonitis, or which then leads
to peritonitis
●
Fungal peritonitis
●
Severe peritonitis leading to septic shock
Haemodialysis
Haemodialysis (HD) is more ecient for solute
clearance and can be used in the acute setting
to rapidly remove large volumes of uid (e.g. in
patients with pulmonary oedema). HD works on
the principles of both diusion and convection.
Removal of water is due mainly to hydrostatic
pressure across the dialyser membrane (ultraltration) while waste products are mostly removed
from the circulation by via diusion. Convection
relies on the principle of solvent drag. It is independent of the concentration gradient across the
dialysis membrane but is dependent on both the
dialyser and the rate of ultraltration.
Patients requiring acute in-centre HD usually attend 3–4 times a week for sessions lasting
between 3 and 4 hours. Some centres oer nocturnal in-centre dialysis whereby the dialysis time can
be maximised whilst the patient is asleep. e use
of home HD is increasing and has been demonstrated to have many benets including increased
opportunities to attend school, improved cardiovascular outcomes, improved blood pressure control and reduced requirement for antihypertensive
medications. It also oers improved growth and
energy levels, and improved quality of life.
New HD machines have been designed for
small infants requiring intermittent HD. One such
machine can be used in infants weighing between
2.5 and 10 kg whilst another machine is suitable
for use in infants weighing as little as 800g.
Vascular access for acute HD ty pically requires
the insertion of a temporary double lumen catheter (e.g. Vascath) (Figure 2.2). Chronic HD is
performed via a tunnelled double lumen catheter (e.g. Permcath) or an arteriovenous stula. Fistulas are oen preferable because of the
lower risk of catheter-related infection. However,
the disadvantages of stulas include the delay
of around 6 weeks before they can be used and
the requirement for the child to co-operate with
repeated needle punctures.
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comprises steroids, and either basiliximab (an
anti-CD25 monoclonal antibody) or antithymocyte globulin. Following renal transplantation the immunosuppressive regimen usually
includes a calcineurin inhibitor (e.g. tacrolimus)
and an antiproliferative agent (e.g. mycophenolate mofetil) with or without corticosteroids.
e complications and potential adverse longterm eects of transplantation include:
Figure 2.2 Haemodialysis via subclavian vascu-
lar access catheter.
Haemodialtration (HDF) is a modality which
provides more eective removal of middle-sized
molecular weight molecules and has been proven
to improve long-term cardiovascular outcomes.
However, there are a number of limitations to its
use and HDF is only provided by a few paediatric
nephrology centres at present.
Continuous renal replacement therapy (CRRT)
involves an extracorporeal circuit similar to intermittent HD and is typically used in t he intensive care
setting. CRRT is the modality of choice for patients
who are haemodynamically unstable as it generally
avoids causing rapid uid shis which may precipitate drops in blood pressure or cardiac output.
Kidney Transplantation
Kidney transplantation remains the gold standard for renal replacement therapy. Compared
with both PD and HD, renal transplantation provides a better quality of life, improved growth
potential and a lower risk of signicant complications. Young children receiving a renal transplant have the best long-term outcomes of any age
group. e freedom from dietary and uid volume restrictions, as well as the ability to attend
school and live a life independent of a dialysis
machine benets both the child and their family.
A living donor (LD) kidney is preferable
because gra survival rates are superior to those
obtained with deceased donor (DD) kidneys.
To increase the rates of living donation, several
countries have introduced living kidney sharing
schemes to promote paired donation of kidneys.
An induction regimen of immunosuppression is given at the time of transplantation. is
●
Infection. Immunosuppression may allow
proliferation of Epstein–Barr virus (EBV),
cytomegalovirus (CMV) and BK virus (BKV).
Screening for EBV should be performed prior
to transplantation. Proliferation of EBV may
increase the risk of post-transplant lymphoproliferative disorder (PTLD) – which may
range in severity from benign enlargement of
tissues or an organ to classical Hodgkin lymphoma-type PTLD. Patients are particularly
at risk of Pneumocystis jirovecii pneumonia
in the rst 6 months post-transplant and cotrimoxazole prophylaxis is oen prescribed
during this time period.
●
Immunisation risks. Any immunisations
with live vaccines should be given prior to
transplantation. ereaer, children with a
renal transplant should only be immunised
with inactivated vaccines because of the risk
of vaccine-induced disease secondary to
immunosuppression.
●
Acute rejection. is is an important cause
of early gra dysfunction and may be due to
either T-cell mediated rejection or antibodymediated rejection. e diagnosis is made by
renal biopsy and identifying donor specic
antibodies (DSA) in the recipient’s blood.
●
Increased cancer risk. In addition to posttransplant lymphoproliferative disorder,
transplant recipients are known to be at an
increased long-term risk of developing skin
cancer (particularly squamous cell carcinoma) and Kaposi sarcoma.
●
Recurrent disease. Certain conditions, such
as focal and segmental glomerulosclerosis
(FSGS) have a high risk of recurring in the
transplant kidney. Other conditions carrying
a risk of recurrence include: atypical HUS, C3
glomerulopathy and dense deposit disease.
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