++
The complications that should be anticipated in children with
chronic kidney disease (CKD) are listed in Table
477-2. Including stage 1 CKD, an overall complication rate
of 70% hypertension, 37% anemia, 17% metabolic
bone disease, and 12% growth failure has been observed.5 The
frequency and severity of these complications of CKD increase as
the stage of CKD increases. Consensus management recommendations
for the complications of CKD have been provided by the Kidney Disease Outcomes
Quality Initiative (KDOQI) guidelines and by groups of European
expert panels, as summarized in this section.
++
+++
Nutritional
Disorders
++
Malnutrition in children with chronic kidney disease (CKD) is
often accompanied by protein-energy wasting, which is characterized
by decreased body stores of protein and energy fuels (fat mass).6 In
CKD, additional factors that contribute to development of protein-energy
wasting may include nonspecific inflammation, transient infections,
chronic acidemia, resistance to insulin, growth hormone resistance,
increased glucagon levels, hyperparathyroidism, and blood loss through
dialysis or from frequent phlebotomy.6 Although the underlying
cause of malnutrition in children with CKD is often multifactorial,
it is extremely important that it be recognized and treated promptly. Nutritional
assessment should include measurement of height, weight, body mass
index (BMI; weight/height2), head circumference
in infants, skinfold thickness, mid-arm circumference, serum albumin,
cholesterol, and C-reactive protein (as a marker of nonspecific
inflammation). No single one of these measures will define malnutrition,
but in a child with CKD, where two or more are abnormal, attention should
focus on his or her nutritional state (see Chapter 28). Nutritional support from a specialized dietitian is necessary
to optimize caloric intake, which is the overriding goal of treatment for
malnutrition in children with CKD.
++
Achieving adequate caloric intake may be difficult. Children
with CKD often have an impaired appetite, possibly associated with
impaired taste and sometimes with nausea and vomiting. They may also
require the restriction of specific dietary components, especially
potassium and phosphate, and of the renal solute load. Polyuria may
also inhibit intake of other calorically dense liquids in children with
congenital renal disease that require increased water intake due to
the inability of the kidney to concentrate urine. Thus, administration
of a formula with a low renal solute load (low protein, sodium,
and potassium) is often necessary. Breast milk can be used, but
specialized infant formulas designed for children with CKD are often
required. These have lower sodium, potassium, and phosphorus, as
well as a lower renal solute load, than other infant and pediatric
formulas. In North America, these include PM 60/40 and
Good Start.
++
If additional caloric density is required, it is preferable to
add modular commercial components rather than to simply concentrate the
formula because concentration increases electrolyte and mineral content.
These include a variety of protein powder (Beneprotein powder, Resource),
carbohydrate (Polycose, Benecalorie), and fat (vegetable oil, Microlipid)
products. Specific adult “renal formulas” that
are high calorie with low electrolytes and phosphorus are not recommended
for use in children younger than 2 years due to their high osmolality
and inappropriate mineral content, especially higher magnesium content.
Due to the child’s poor appetite, and sometimes unpalatable
formula and fluid requirements, it can be unrealistic to expect
an infant or child to achieve adequate nutrient intake by mouth.
In these circumstances, it may be necessary to provide enteral nutrition
(nasogastric or gastrostomy) or parenteral nutrition. Approaches
to the administration of enteral and enteral nutrition are discussed
in Chapter 28. Percutaneous gastrostomy placement
is contraindicated if peritoneal dialysis is likely.
++
Consultation with a specialized dietitian with expertise in the
management of children with CKD is often necessary. Psychologic
consultation may also be necessary to assure continued dietary compliance
in older children where difficulty in compliance with the required
restricted diet is common.
++
Impaired growth is a common complication of chronic kidney disease
(CKD); it can have a profound psychologic impact on a child and
adversely affect his or her quality of life. Population studies
show increased mortality in children with CKD and severe growth
delay.7 Children with CKD are approximately 1.5 standard
deviations below normal for height, and this height deficit is greatest
in the youngest children, despite improved efforts to sustain growth.2 About
one third of all children with CKD and about one fifth of those
with glomerular filtration rate > 50 mL/min/1.73
m2 have a height below the third percentile for age. The
maximal deterioration in height seems to occur in the first several
months of life or prior to referral to a pediatric nephrologist;
once appropriate treatment of their undernutrition and renal osteodystrophy
ensues, a normal growth pattern is usually established until at
least stage 5 CKD (dialysis) is reached. However, growth lost in
these first months of life may be very difficult to restore.
++
The causes of growth delay in children with chronic kidney disease are
numerous, and include malnutrition/protein-energy wasting, chronic
acidosis, severe renal osteodystrophy, sodium depletion, and growth
hormone (GH) resistance. Where possible, treatment should be directed
to correction of these metabolic disturbances prior to introduction
of GH.
++
GH is not deficient in children with chronic kidney disease,
and in fact, plasma GH levels may be elevated. However, a number
of abnormalities have been demonstrated in the steps required for
activation for GH. These abnormal steps in the GH metabolic pathway include
abnormal actions of GH directly on bone, defective conversion of
GH to insulinlike growth factor 1 (IgF-1) in the liver, and accumulation
of IGF-binding proteins in the serum, some of which interfere with
the action or IgF-1 on the bone.
++
Randomized controlled trials show that growth hormone (GH) treatment
can promote short-term growth in children with chronic kidney disease
(CKD). Previous concerns about the potential adverse effects of
GH therapy and the possibility of a diminishing effect with prolonged
usage have not been substantiated by long-term usage studies.8 Occasional
complications of GH use include pseudotumor cerebri, worsening renal
osteodystrophy, and slipped capital femoral epiphysis, but the incidence
of these is probably no different than children with CKD who are
not treated with GH.9 Therefore, current consensus recommendations
are that children with growth impairment and CKD, for whom no other
cause is apparent, be treated with GH. Despite this recommendation,
only about one in five children with a height less than the fifth
percentile are prescribed GH.2
+++
Metabolic Bone
Disease
++
Metabolic bone disease affects many children with chronic kidney
disease (CKD). In its severe form, metabolic bone disease deformities
associated with rickets will impair growth. The exact cause of the
bone abnormalities seen in children with CKD is not clear, but two
pathogenetic mechanisms are recognized: (1) insufficiency of vitamin
D from deficient activation of cholecalciferol to the active form
of 1,25-dihydrocholecalciferol in the kidney or due to low cholecalciferol
levels as a result of dietary insufficiency; and (2) retention of
phosphate as renal function declines. Elevation of phosphate levels in
plasma produces a reciprocal fall in plasma calcium values, which
in turn stimulates parathyroid hormone (PTH) secretion; PTH then
increases phosphate excretion by suppression of tubular phosphate
reabsorption, thereby returning phosphate values to normal, but
at the expense of persisting elevation of PTH values. These mechanisms
are illustrated in Figure 477-1.
++
++
Over the past two decades, renal bone disease has been classified
according to the findings on histomorphometry of tetracycline-labeled
bone tissue. Hyperparathyroidism produces a state of high bone turnover
with osteitis fibrosa and thickened irregularly shaped trabeculae
with initially increased, but later reduced, bone volume; increased
resorption of cortical bone also produces decrease in cortical bone volume.10 More
recently, low turnover (adynamic) bone disease has been reported
in almost one third of children, and may result from attempts to
treat hyperparathyroidism with activated vitamin D compounds and
calcium-containing phosphate binders.10
++
The effects of metabolic bone disease on the epiphysis are unique
to children with chronic kidney disease, and may include growth
failure, slipped epiphysis, and, as mentioned previously, rickets.
The effects of low turnover bone disease, which leads to increased fractures
in adults, are less clear in children but may adversely affect growth.
As shown in Figure 477-2, both low and high turnover
bone disease may impair mineralization of bone and contribute to
calcification of vessels.
++
++
Because expertise is not available to evaluate bone histomorphometry
in most pediatric hospitals, recognition of metabolic bone disease
in chronic kidney disease relies on a number of surrogate markers,
and imaging techniques. Historically, x-rays of the knees, wrist/hand,
and hips have been used, and may demonstrate changes of rickets,
or subperiosteal resorption due to hyperparathyroidism, but the
sensitivity for detection of mild disease is poor. Also, radiologic techniques
will not distinguish high turnover from low turnover states. Dual-energy
x-ray absorptiometry (DXA) is of limited value to evaluate renal
osteodystrophy because (1) it measures bone mineral density as total
bone mass in a given area and may not detect structural alterations in
trabecular and cortical bone density and architecture, (2) DXA does
not distinguish the effects of PTH on cortical and trabecular bone,
and (3) interpretation of results is confounded by impaired growth,
and whether comparison should be with height or chronologic age
as well as pubertal stage. Therefore, great reliance is placed on
surrogate biochemical markers to detect and treat renal osteodystrophy.10
++
Two major expert panels have proposed guidelines for prevention
and management of renal osteodystrophy in children with chronic
kidney disease: one in the United States11 and one in Europe.12 The
plasma levels for calcium, phosphate, calcium × phosphate
product, and parathyroid hormone (PTH) values that they recommend
are outlined in Table 477-3. Whereas there
is a great deal of symmetry in these recommendations, there is divergence
concerning the appropriate range to maintain PTH values, with a
higher range recommended by the Kidney Disease Outcomes Quality Initiative
(KDOQI) panel, based on a fear of developing low turnover bone disease
with lower PTH values. Despite this disagreement,
it is reasonable to suggest that for children with chronic kidney
disease stages 2 and 3, PTH values should approximate or slightly
exceed the upper limit of normal, and that this suggested level
should increase somewhat as renal function worsens.
++
++
There are four groups of therapeutic agents that are used to
prevent and treat renal bone disease. (1) The first agent is vitamin
D3 (cholecalciferol). If plasma levels of 25-OH vitamin D are subnormal,
supplementation with vitamin D3 400 to 800 U/day
should be provided. (2) If metabolic acidosis is present, this should
be corrected with either oral sodium bicarbonate or sodium citrate
supplements. (3) Activated vitamin D analogs should be prescribed
if the calcium level is low and the PTH exceeds the recommended
limits. The most commonly used analog in North America is calcitriol
(Rocaltrol), but alfacalcidol, doxercalciferol, and paricalcitol
may work equally well. (4) In the presence of elevated plasma phosphate
values, if dietary phosphate restriction is ineffective, phosphate
binders such as calcium carbonate, calcium acetate, or sevelamer
should be prescribed. Calcium-containing compounds are available
in liquid formulations and, therefore, are most easily used in young
children. However, excessive total calcium ingestion may lead to
hypercalcemia and increased calcium phosphate product, which in turn
has been associated with vascular calcification. Therefore, the total
(dietary and pharmacologic) intake of calcium daily should not exceed
two times the daily recommended intake for calcium based on age
or 2500 mg/day.
+++
Developmental
Delay and Quality of Life
++
Children with chronic kidney disease (CKD) are at risk for developmental
delay. This has been attributed to a variety of causes, including aluminum
intoxication associated with the use of aluminum-containing phosphate
binders and malnutrition. Improved nutritional management and discontinuation
of aluminum-containing medications has reduced the severity of developmental
delay, although with more precise testing it also became apparent
that developmental problems of some degree occur in many children
with CKD, including those not receiving dialysis.
++
Developmental issues are most evident when renal failure occurs
in infancy, where developmental problems occur in as many as 25%,
and severity correlates with the severity of renal dysfunction.13-17 Cognitive
deficits are also noted in older children, and the overall IQ of
school-age children with CKD is lower than the normal population.
These delays often persist over time, and some cross-sectional studies
have shown little difference between children on dialysis or after
transplantation. However, some longitudinal studies have demonstrated
improvement in specific developmental deficits following renal transplant.
++
Specific deficits in language abilities have been observed, and
in such cases, it is important to ensure that hearing is not impaired.
Similarly, visual-motor constructive or perceptive abilities, impaired
memory, and attention deficits have been reported in isolation,
as combined disorders in children with CKD, and following transplantation;
some children demonstrate improvement after, as compared to prior
to, transplantation, but this is inconsistent. The factors causing
these developmental or school problems for children with CKD are
unclear. Chronic hospitalization may contribute. In some, coexistent
extrarenal morbid conditions may impact cognitive and motor abilities.
These morbidities may be due to congenital abnormalities, but may
also result from acquired complications of their renal disease such
as severe renal osteodystrophy, adverse medication effects (particularly
steroids), and marked growth impairment. Irrespective of the underlying
cause, only half of children starting hemodialysis and three fourths
of those beginning home peritoneal dialysis attend school full time.2 It
is therefore hardly surprising that these children have difficulty achieving
normal educational standards and are at risk of social isolation
from their peers. This combination of factors has an impact on their
quality of life. In addition to growth impairment and the other
issues outlined previously, anemia of a relatively mild nature has
been reported to adversely affect quality of life scores.
++
Multiple studies have evaluated quality of life and social behavior
in children with CKD, and despite shortcomings in design, the studies
indicate that children with CKD prior to dialysis have a better
quality of life than those on dialysis. Following renal transplant,
quality of life improves compared to dialysis but does not achieve pretransplant
quality. This is not surprising because transplant patients are
a heterogeneous group, whose quality of life may be substantially influenced
by medication side effects and their level of renal dysfunction.
Despite the documentation that quality of life may be reduced in
children with CKD, children’s perception of the quality
of life is considerably better than their parents’ perception
of their quality of life.
++
The lower limit of acceptable hemoglobin (Hb) in children with
chronic kidney disease (CKD) has been defined by the KDOQI workgroup
as < 11 g/dL, suggesting that a level below that threshold
be considered anemia.14 This rather arbitrary definition
includes a caveat that consideration should be given to the normal
variation of Hb levels at different ages. Using a cut-off value
of 12 g/dL, it has been reported that anemia is present
in 36% of all children with CKD, and the prevalence increases
to 93% in stages 4 and 5 CKD.5 Using the KDOQI
value of 11 g/dL as the lower limit of acceptable Hb, 54% of
children on hemodialysis and 70% on peritoneal dialysis
were anemic, despite treatment with erythropoietin (EPO).15 However,
improved hematocrit (Hct) counts have been noted more recently with
the increased use of EPO.2
++
The most common cause of anemia with CKD is a deficiency of EPO.
EPO is normally produced in the peritubular interstitial cells of
the kidneys, and regulates bone marrow erythroid cell proliferation,
differentiation, and survival. However, EPO deficiency in CKD is
often aggravated by a number of other causes of anemia. These include
chronic inflammation associated with “anemia of chronic
disease”—possibly due to increased hepcidin production
with inflammation, which prevents release of iron from macrophages
and may inhibit intestinal iron absorption—iron deficiency
that may be due to a reduction in transferring (the iron carrier
protein) in CKD, increased blood loss associated with surgical procedures,
and frequent phlebotomy. Less common contributing factors include
carnitine, folate, and vitamin B12 deficiencies; severe
hyperparathyroidism; and aluminum toxicity.
++
Investigation of anemia in children with CKD should routinely
include measurement of serum iron, transferrin, ferritin, reticulocyte
count, and, where available, red blood cell (RBC) transferrin receptor.
Less frequently, or when treatment with EPO and iron is ineffective,
haptoglobin, lactic dehydrogenase (LDH), folate, vitamin B12, carnitine,
and aluminum values should be checked. Also, severe hyperparathyroidism
(parathyroid hormone [PTH] values), inflammation
(C-reactive protein [CRP] values), and stool blood
loss should be considered. However, in the usual circumstance, investigation
is focused on distinction between iron deficiency and inadequate
EPO dosing. In isolation, no single one of the previous tests will
identify iron deficiency. Transferrin saturation is the most helpful,
but it may be falsely increased in CKD patients with proteinuria,
in which case this test is not useful. The evaluation of anemia
is further discussed in Chapter 430. A low
reticulocyte count may indicate insufficient EPO effect, iron, folate,
or vitamin B12 deficiency, or bone marrow unresponsiveness, whereas
a high value may indicate an appropriately responsive bone marrow
or the presence of covert hemolysis.
++
Consequences of anemia for children with chronic kidney disease
(CKD) are not as well studied as in adults with CKD. It would be
impractical and unethical to compare outcomes for children with
hemoglobin values in the normal range versus very low hemoglobin
values. Nonetheless, a number of studies have demonstrated some
adverse affects of anemia. The health-related quality of life of
children with CKD appears to be lessened by anemia. Growth impairment
may also be due to anemia because administration of EPO to children
with CKD appears to promote catch-up growth prior to dialysis; as
hemoglobin values increase,16 analysis of a large cohort
of children in the North American Pediatric Renal Transplant Cooperative
Study (NAPRTCS) database demonstrated that a hematocrit less than
33% is an independent risk factor for short stature in
children with CKD.17 Regardless of whether anemia is related
to reduced cognitive abilities in children with CKD is unclear,
and it will be difficult to clarify this relationship in the future
because of the widespread use of EPO-stimulating agents (ESAs).
++
The most serious potential complication of anemia in children
with CKD is the enhanced risk of cardiovascular disease. In a 2-year
prospective study of children with CKD prior to dialysis, 19% had
left ventricular hypertrophy (LVH) when first evaluated, but this
increased to 39% during the 2-year follow-up period. A lower
hemoglobin value was associated with LVH at baseline and also independently
predicted interval increase in left ventricular mass index.18 These
same investigators confirmed an association between the presence
of anemia and increased left ventricular mass index in children
with CKD stages 2 to 4.
++
ESAs are the cornerstone of treatment for anemia in pediatric
chronic kidney disease patients. EPO can be administered either
subcutaneously or intravenously (although the latter may require
increased dosing). Whereas dosing was originally prescribed thrice
weekly, for most children hemoglobin is maintained in the normal
range with EPO 150 U/kg/week administered once
or twice weekly. Although there is some disagreement as to the dose
required for treatment of younger children, observational data from
the NAPRTCS database show that younger children receive higher doses,
and in infants, the recommended dose is 200 to 300 U/kg/week.
An alternative ESA, darbepoetin, has a slightly altered molecule
compared to EPO. A weekly starting dose of approximately 0.5 μg/kg
is suggested. Although it is administered less frequently, some report
increased pain at the injection site compared to EPO. Either EPO
or darbepoetin can be used to successfully treat anemia in the vast
majority of children with chronic kidney disease.
++
Iron therapy is required for almost all children with chronic
kidney disease to prevent and treat anemia. KDOQI guidelines suggest
that oral iron can be administered at a dose of up to 6 mg/kg/day
of elemental iron in two to three divided doses. The problem with
oral iron in this patient population is that the majority of these
patients take phosphate-binding agents, which cannot be given at
the same time, thereby increasing the complexity of administering
multiple medications each day. Also, because hydrochloric acid is
required for absorption of oral iron, the concomitant use of proton
pump inhibitors may interfere with its efficacy.
++
Intravenous iron in the form of iron sucrose or sodium ferric
gluconate is associated with a greatly reduced incidence of anaphylactic reactions
compared to the previously recommended iron dextran. Weekly maintenance
therapy with a dose of 2 mg/kg to a maximum of 100 mg is
effective, or intermittent administration to patients with documented
iron deficiency, with a dose of 7 mg/kg (maximum dose 200
mg), is effective. Obviously, the use of intravenous (IV) iron on a
regular basis is not suited for the majority of chronic kidney disease patients
unless they have some form of vascular access; IV iron is also considerably
more expensive than the oral variety.
+++
Cardiovascular
Disease and Hypertension
++
Two studies have shown dramatically increased risk for cardiovascular
disease in children with chronic kidney disease (CKD). One reported
that from 1990 to 1996 almost one fourth of the deaths of US children
with end-stage renal disease requiring dialysis was due to cardiac
causes, with a cardiovascular mortality rate 100 times higher than
the general population in the 25- to 34-year-old age group.19 Analysis
of data from Australia and New Zealand on children requiring renal
replacement therapy showed a 20-year survival rate of 66%,
being 30 times higher than those with end-stage renal disease, with
45% of deaths due to cardiovascular disease.20
++
Contributing factors likely include chronic hypertension, hyperlipidemia,
and arterial calcification. Hyperlipidemia is discussed in the next
section. Hypertension, defined as blood pressure greater than or
equal to age-, sex-, and height-specific 95thpercentiles,
has been reported in more than three fourths of children starting
dialysis, with it being poorly controlled in half.21Another
study confirmed these prevalence rates for hypertension in children
with CKD of all stages, and of particular concern was an incidence
of 63%, even with stage 1 CKD.5 The prevalence
of hypertension was less in children with congenital or obstructive
uropathy than in those in whom renal disease was acquired from or
related to an immunologic cause.21
++
Excessive coronary artery calcification has been shown in young
adults with end-stage renal disease using electron-beam computerized
tomography screening of the coronary arteries.22 Arterial
calcification is now known to infer substantial risk for cardiovascular
disease in CKD, likely contributed to by chronic hyperphosphatemia,
hypercalcemia, and an increased calcium-phosphate product. This
concern has led to the KDOQI guidelines for normalization phosphate,
calcium, and calcium-phosphate product, and to the use of calcium-containing
phosphate binders when possible, so that calcium intake will not
exceed a total of 2500 mg daily, including dietary calcium.11
++
The KDOQI guidelines for management and prevention of dyslipidemias,
states that patients ages 18 to 20 years should be considered at
increased risk of atherosclerotic cardiovascular disease similarly
to all adults with chronic kidney disease (CKD).23 Pubertal
children younger than 18 years are also included in the KDOQI guidelines,
whereas prepubertal children should follow the guidelines of the
National Cholesterol Education Program (NCEP) Expert Panel on Children. The
recommendations from and differences between the NCEP and KDOQI
are outlined in Table 477-3.23 It
is important to include patients with persistent
nephrotic syndrome, which is not responsive to steroid therapy,
among those with CKD who should be considered for lipid-lowering
treatment, despite apparently normal renal function.
++
Statins are the primary drug class recommended for treatment
of increased cholesterol values. However, neither NCEP nor KDOQI guidelines
are of much value to assist with management of hypertriglyceridemia
in children, which is equally common as elevation of low-density
lipoprotein (LDL) cholesterol, but which is poorly responsive to
treatment with statins. The fibrate class of drugs has been recommended
for adults, but there is little experience with these drugs in children
with CKD. Use of omega-3 fatty acids 3 to 8 g/d provided
as fish oil supplements may reduce serum triglyceride levels in
children on dialysis and might be considered as a safer alternative
to fibrates. The problem is that many fish oil supplement products
are unregulated; therefore, the omega-3 content may be unreliable.
++
+++
Metabolic Acidosis
and Electrolyte Imbalance
++
A number of electrolyte derangements may be seen in children
with chronic kidney disease (CKD). Metabolic acidosis may occur
as a result of primary renal tubular damage in which case a normal
serum anion gap will be present, or as a result of increasing uremia
when retention of phosphate or sulphate as acids may lead to an
increased anion gap metabolic acidosis. The cardinal feature of
metabolic acidosis is a reduction of bicarbonate on blood gases
or tCO2 on serum electrolytes. Treatment consists primarily
of supplemental bicarbonate or citrate solutions.
++
Hyponatremia may occur as a reflection of urinary sodium wasting,
which is common with congenital high-output causes of CKD, and treatment
may require salt supplementation. Caution must be exercised to ensure
that the child is not volume overloaded with dilutional hyponatremia.
Hyperkalemia commonly results from impaired potassium excretion
and may be aggravated by metabolic acidosis. Treatment may require
potassium restriction in the diet. Chronic treatment with potassium-binding
resins may also be required (eg, Kayexalate or calcium resonium).
In association to disorders causing CKD as a result of proximal
tubular defects (Fanconi syndrome), hypophosphatemia may be noted
and may require supplemental phosphate. However, for most children
with CKD, phosphate retention is more common and should be treated
with phosphate binders.
+++
Preventing Progression
+++
Dietary Protein
Intake
++
In adults, intake of a reduced protein intake may reduce proteinuria
and slow the decline of kidney function. This has been corroborated
in studies of rats following subtotal nephrectomy. However, concern
exists about implementation of a low protein diet in children, for
whom growth is essential. A 2-year prospective study randomized children
to receive a restricted protein diet (125% World Health
Organization [WHO]-recommended protein intake)
or a controlled diet (181% WHO-recommended protein intake).
The lower protein intake did not provide any benefit as measured
by the rate of decline in creatinine clearance over a 2-year period,
and growth occurred independent of protein intake.24 Therefore,
it is not recommended to restrict protein intake in patients with
chronic kidney disease (CKD) unless evaluation of an individual’s
diet or laboratory values suggests that their protein intake is clearly
excessive.
++
Improved blood pressure control is associated with a slowing
in the rate of deterioration of chronic kidney disease (CKD) in
adults, leading to recommendations that in adults with CKD blood
pressure optimally be less than 120/80 mm Hg and that any
blood pressure greater than 130/80 mm Hg should be treated.
The translation of these data to children implies that blood pressures
should be maintained around the 75th percentile for age, which is
clearly much more rigorous than generally applied in current clinical
practice. This is best achieved by use of angiotensin-converting
enzyme (ACE) inhibitors or angiotensin receptor blocking (ARB) agents, either
alone or in combination. These have the added benefit of reducing
proteinuria, and because the severity of proteinuria is a concomitant risk
factor for progression of CKD, it makes sense to improve blood pressure
control and reduce proteinuria with the same medication whenever
possible. To maximize the antiproteinuric effect of these agents,
large doses may be required. Side effects from these medications in
children with CKD include hyperkalemia and volume depletion. Therefore,
electrolytes should be monitored within a week of starting treatment,
and children should be advised about the risk of acute dizziness
or syncope with vigorous exercise or activities such as roller coaster
rides. Teenage girls who are sexually active should also be advised
to practice contraception or to notify their doctor in the event
of a suspected pregnancy. The efficacy of ACE inhibitors for blood
pressure and proteinuria control in children has been demonstrated
in the ESCAPE trial, which studied 400 children with CKD in Europe.25 Calcium
channel blockers are also widely used for blood pressure control
in children, but the most commonly used dihydropyridine group of
calcium channel blockers, specifically, amlodipine and nifedipine,
do not effectively reduce proteinuria.
+++
Nonspecific
Therapies
++
Therapies aimed at prevention or treatment of renal bone disease
and cardiovascular disease associated with chronic kidney disease
(CKD) may also indirectly impact the rate of progression of CKD.
For example, although phosphate control is important and commonly
requires the use of calcium-containing phosphate binders, caution
must be employed to ensure that hypercalcemia and/or an
elevated calcium phosphate product, which might produce vascular
and/or renal interstitial calcification, do not result.
Similarly, whereas statin agents are recommended for control of
LDL cholesterol, they may also have an indirect beneficial effect
to produce some slight reduction in proteinuria.
++
For children with obstructive uropathies, particularly those
with incomplete control of bladder emptying or those who require
intermittent catheterization, increasing hydronephrosis, which may
indicate partial lower tract obstruction, should be dealt with promptly
by a urologist. Similarly, for those with repeated urinary tract
infections, efforts should be focused on prevention either by assuring
appropriate bladder drainage or by using prophylactic antibiotics.
++
Finally, although malnutrition is clearly a feature that is commonly
seen in children with CKD, development of obesity must also be prevented. This
is particularly important for the teenage patients, where participation
in normal social and sporting activities must be encouraged.