AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Chronic kidney disease (CKD) is characterized by an irreversible deterioration of renal function that gradually progresses to end-stage renal disease (ESRD). CKD has emerged as a serious public health problem. Data from the United States Renal Data System (USRDS) show that incidence of kidney failure is rising among adults and is commonly associated with poor outcomes and high cost.¹ In the past decade, the incidence of the CKD in children has steadily increased, with poor and ethnic minority children disproportionately affected.

The major health consequences of CKD include not only progression to kidney failure but also an increased risk of cardiovascular disease. Evidence-based clinical practice guidelines support early recognition and treatment of CKD-related complications to improve growth and development and, ultimately, the quality of life in children with this chronic condition. Appropriate pediatric care may reduce the prevalence of this complex and expensive condition.

The definition and classification of chronic renal disease may help identify affected individuals, possibly resulting in the early institution of effective therapy. To achieve this goal, the Kidney Disease Outcomes Quality Initiative (K/DOQI) working group of the National Kidney Foundation of the United States defined CKD as "evidence of structural or functional kidney abnormalities (abnormal urinalysis, imaging studies, or histology) that persist for at least 3 months, with or without a decreased glomerular filtration rate (GFR), as defined by a GFR of less than 60 mL/min per 1.73 m²."^{2, 3}

Pathophysiology

Despite the diverse etiologies, once CKD develops, the subsequent response of the failing kidney is similar. The kidney initially adapts to damage by increasing the filtration rate in the remaining normal nephrons, a process called adaptive hyperfiltration. As a result, patients with mild CKD often have a normal or near-normal serum creatinine concentration. Additional homeostatic mechanisms (most frequently occurring within the renal tubules) permit the serum concentrations of sodium, potassium, calcium, and phosphorous and total body water to also remain within the reference range, particularly among those with mild-to-moderate stages of CKD.

Adaptive hyperfiltration, although initially beneficial, appears to result in long-term damage to the glomeruli of the remaining nephrons, which is manifested by pathologic proteinuria and progressive kidney insufficiency. This irreversibility appears to be responsible for the development of end-stage kidney failure among persons in whom the original illness is either inactive or cured.

Although the underlying problem that initiated CKD often cannot be treated primarily, extensive studies in experimental animals and preliminary studies in humans suggest that progression in chronic renal disease may be largely due to secondary factors that are unrelated to the activity of the initial disease. These include anemia, osteodystrophy, systemic and intraglomerular hypertension, glomerular hypertrophy, proteinuria, metabolic acidosis, hyperlipidemia, tubulointerstitial disease, systemic inflammation, and altered prostanoid metabolism. This common sequence of events in diverse types of CKDs is the basis for the common management plan for children with CKD, irrespective of the etiology

Frequency

United States

Based on data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) chronic renal insufficiency (CRI) database, 5651 patients aged 2-17 years have been entered into this voluntary listing and have an estimated GFR (eGFR) of less than 75 mL/min per 1.73 m².⁴ In the past decade, the incidence of the disease has steadily increased among all ethnic groups.

International

The prevalence of CKD stage II or lower in children is reported to be approximately 18.5-58.3 per one million children. It is much lower than that in adults; in a study from India, children constituted 5.3% of all patients with CKD seen in a referral hospital.⁵ More recent data from the Italkid study report a mean incidence of 12.1 cases per year per million in the age-related population (age range, 8.8-13.9 y) and a prevalence of 74.7 per million in this population.⁶ However, underreporting due to lack of recognition may suggest an even higher prevalence in children.

Mortality/Morbidity

About 70% of children with CKD 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) 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.⁷

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 CKD is more common with increasing prematurity and survivorship. The overall incidence in US children treated for ESRD from 1995-1997 was 12 per million children per year among whites, 27 among blacks, 15 among Asian Pacific Islanders, and 17 among Native Americans. The higher overall incidence rate in blacks was primarily due to an almost 3-fold higher rate of ESRD in blacks compared with whites in the group aged 15-19 years.

Sex

The incidence and rate of progression to ESRD are equal in both sexes, although obstructive uropathies are more common in males.

Age

The frequency of CKD increases with age, and it is much more common in adults than children. Among children, CKD is more common in children older than 6 years than in those younger than 6 years. The percentages in the NAPRTCS cohort were 19%, 17%, 33%, and 31% in children aged 0-1 years, 2-5 years, 6-12 years, and older than 12 years, respectively.⁴

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Chronic kidney disease (CKD) is asymptomatic in its earliest stage (stage 1), although urinalysis findings or blood pressure may be abnormal. As CKD progresses to more advanced stages, signs and symptoms greatly increase.

• Polydipsia and nocturia (secondary to a reduced capacity to concentrate the urine) may be one of the earliest symptoms that indicate a diagnosis of CKD in an otherwise healthy-looking child who has tubulointerstitial kidney disease.
• The signs and symptoms in advanced CKD may including the following:
• • Volume overload
  • Hyperkalemia
  • Metabolic acidosis
  • Hypertension
  • Anemia
  • Bone disease (termed osteodystrophy)
  • Cardiovascular disease
  • Anorexia, nausea, vomiting
• The absolute serum levels of BUN or creatinine do not directly correlate with the development of these symptoms; however, eGFR seems to be associated with a stronger correlation.

Physical

The findings vary depending on the severity of kidney failure and can range from an absence of any physical findings to the presence of one or more of the following:

• Anemia
• Short stature
• Hypertension
• Osteodystrophy
• Cardiac abnormalities (eg, left ventricular hypertrophy [LVH], pericarditis)
• Peripheral neuropathy
• CNS abnormalities (eg, ranging from loss of concentration and lethargy to seizures, coma)

Causes

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
• Polycystic kidney disease, both autosomal-recessive and autosomal-dominant varieties

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Acute renal failure
Rapidly progressive glomerulonephritis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Initial testing must include an examination of the urine and estimation of the GFR. An important aspect of this initial evaluation is the determination of disease duration. Although the distinction between acute, subacute, and chronic kidney disease (CKD) or failure is arbitrary, the differential diagnosis can frequently be narrowed if the disease duration is known. This assessment is best performed by comparing the current urinalysis or plasma creatinine concentration (PCr) with previous results, if available.
• Urine examination is perhaps the most important test and should be considered a part of the physical examination in all children being screened or evaluated for CKD. It can be performed at the bedside or in the clinic using a fresh urine sample.
• • An initial evaluation consists of a multitest detection strip (dipstick) test, followed by urine microscopy. The dipstick is a quick method of screening and detecting proteinuria, hematuria, and pyuria and provides an estimate of the specific gravity (urine-concentrating capacity).
  • Urine microscopy is performed on a centrifuge-spun urine specimen to look for RBCs, WBCs, and casts. Most children with CKD have broad hyaline casts. Characteristic findings on microscopic examination of the urine sediment may suggest a diagnosis other than CKD. As an example, the presence of muddy-brown granular casts and epithelial cell casts is highly suggestive of acute tubular necrosis, whereas red cell casts would suggest an acute nephritic process.
  • The most appropriate, practical, and precise method for estimation of proteinuria in children is to calculate the protein-to-creatinine ratio in a spot urine specimen. Patients with a positive dipstick test finding (1+ or greater) should undergo quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio) within 3 months to confirm proteinuria. When postpubertal children with diabetes mellitus of 5 or more years' duration are screened, albumin should be measured in a spot urine sample using either albumin-specific dipstick or albumin-to-creatinine ratio testing.
• Serum chemistry provides a valuable diagnostic tool both in the initial diagnosis and in the subsequent follow-up in these children. BUN and serum creatinine assessments are the most important tests. Estimation of the serum sodium, potassium, calcium, phosphorus, bicarbonate, alkaline phosphatase, parathyroid hormone (PTH), and cholesterol and fractionated lipid levels are important in the treatment and prevention of various CKD-related complications.
• Anemia is an important clinical finding in CKD, and a CBC count is an important investigation both in the initial evaluation and the subsequent follow-up in these children. Anemia may indicate the chronic nature of the renal failure in the absence of any other obvious causes and may also be a clue to the underlying cardiovascular disease.
• The GFR is equal to the sum of the filtration rates in all of the functioning nephrons; thus, estimation of the GFR gives a rough measure of the number of functioning nephrons. A reduction in GFR implies progression of the underlying disease.
• • The current K/DOQI guidelines state that estimates of GFR are the best overall indices of the level of kidney function.⁸ The reference range of GFR in young adults is 120-130 mL/min per 1.73 m². However, the reference range of eGFR is much lower in early infancy, even when corrected for body surface area, and subsequently increases in relationship to body size for as long as 2 years. Hence, the eGFR ranges that are used to define the 5 CKD stages apply only to children aged 2 years and older. The eGFR can be estimated from the constant k, PCr (in mg/dL), and body length (L, in cm) according to the Schwartz formula, as follows:
  • • GFR = (k X L) / PCr
    • The value of k is different at different ages: k = 0.4 (preterm infants), 0.45 (full-term infants), 0.55 (aged 2-12 y)
  • Therefore, all children with CKD should have an eGFR calculated. This should be calculated from the Schwartz (or Counahan-Barratt prediction) equation in children because it is convenient, reasonably precise, and practical. The constants used in the equations differ slightly, likely related to the different assays to measure creatinine.
  • Creatinine clearance estimates are difficult and imprecise because they require 24-hour urine collections, which may be incomplete for various reasons. Remember that estimation of GFR or creatinine clearance from serum creatinine critically depends on calibration of the serum creatinine assay, specific to the expected lower levels found in children without CKD.
  • Because of the problems with changes in creatinine production and secretion, other endogenous compounds have been evaluated in an effort to provide a more accurate estimation of GFR. Perhaps the most promising is cystatin C, a low molecular weight protein that is a member of the cystatin superfamily of cysteine protease inhibitors. Cystatin C is produced by all nucleated cells, and its rate of production is relatively constant and is unaltered by inflammatory conditions or changes in diet. The plasma cystatin C concentration may correlate more closely with the GFR than with the PCr.

Imaging Studies

Imaging studies help in confirming the diagnosis of CKD and may also provide clues to its etiology. The following studies are helpful:

• Ultrasonography: This is a commonly used radiographic technique in patients who present with kidney disease because of safety, ease of use, and the information provided. Because obstruction is a readily reversible disorder, all patients who present with acute or chronic failure of unknown etiology should undergo ultrasonography, the modality of choice to assess possible obstructive disease. Although less sensitive than CT scanning in initially revealing a renal mass, ultrasonography can be useful in differentiating a simple benign cyst from a more complex cyst or a solid tumor. It is also commonly used to screen for and to diagnose types of polycystic kidney disease.
• Radionuclide studies: Early detection of renal scarring is possible with radioisotope scanning with 99m-technetium dimercaptosuccinic acid (DMSA). This is more sensitive than intravenous pyelography (IVP) in detecting renal scars and is considered the criterion standard for diagnosing reflux nephropathy, if present.
• Voiding cystourethrography: Voiding cystourethrography, which can be performed with a radionuclide tracer study, is used to detect vesicoureteral reflux.
• Retrograde or anterograde pyelography: Antegrade or retrograde pyelography may be used to better diagnose and relieve urinary tract obstruction. Their use for the diagnosis of obstruction has largely been supplanted by ultrasonography and CT scanning. However, antegrade or retrograde pyelography may be indicated when the history is highly suggestive (unexplained acute renal failure with a bland urine sediment in a patient with known pelvic malignancy) despite ultrasonography and CT scanning findings negative for hydronephrosis (because of possible ureteral encasement). Consultation with a pediatric urologist is suggested if antegrade or retrograde pyelography is considered.
• Skeletal survey: This is useful in evaluating for secondary hyperparathyroidism, a component of osteodystrophy, as well as for bone-age estimation prior to starting or in continuation of growth hormone therapy.

Procedures

• Kidney biopsy: A renal biopsy is commonly performed in patients with suspected glomerulonephritis or vasculitis and in those with otherwise unexplained CKD or acute kidney failure. If a child has small shrunken kidneys, a kidney biopsy is often unnecessary to establish a diagnosis of CKD.

Histologic Findings

In advanced stages of CKD, irrespective of the underlying etiology, the findings often consist of segmental and globally sclerosed glomeruli and tubulointerstitial atrophy, often with tubulointerstitial mononuclear infiltrates.

Staging

The following is the K/DOQI recommended classification of chronic renal disease by stage:⁹

• Stage 1 disease is defined by a normal GFR (>90 mL/min per 1.73 m²) and persistent albuminuria.
• Stage 2 disease is characterized by a GFR of 60-89 mL/min per 1.73 m² and persistent albuminuria.
• Stage 3 disease is characterized by a GFR of 30-59 mL/min per 1.73 m².
• Stage 4 disease is characterized by a GFR of 15-29 mL/min per 1.73 m².
• Stage 5 disease is characterized by a GFR of less than 15 mL/min per 1.73 m² or end-stage renal disease (ESRD).

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

According to the recommendations of the Pediatric Work Group of K/DOQI for chronic kidney disease (CKD), all children with evidence of CKD should be referred to a pediatric nephrologist for consultation and comanagement.

Patients with CKD should be evaluated to determine the following:

• Diagnosis (type of kidney disease)
• Comorbid conditions (such as hyperlipidemia)
• Severity, which based on level of kidney function
• Complications, related to level of kidney function
• Risk for loss of kidney function
• Risk for cardiovascular disease

Treatment of CKD should include the following:

• Specific therapy based on diagnosis
• Evaluation and management of reversible causes of renal dysfunction
• Prevention and treatment of complications of decreased kidney function (eg, anemia, bone disease, cardiovascular manifestations, hypertension, growth failure)
• Evaluation and management of comorbid conditions
• Slowing the loss of kidney function
• Preparation for kidney failure therapy
• Replacement of kidney function with dialysis and transplantation if signs and symptoms of uremia are present
• Evaluation of reversible causes of renal dysfunction: Every physician caring for patients with chronic kidney failure must determine the various factors or clinical states that may have aggravated or exacerbated the degree of kidney failure. Once these factors are corrected or reversed, the severity of kidney failure may improve, and kidney function may return to stable basal level of function. The common reversible causes include volume depletion, drugs (nonsteroidal anti-inflammatory drugs (NSAIDs), contrast agents), infection, and congestive heart failure.
• Retarding progression of renal disease: In adults with CKD, interventions to slow the progression of kidney disease that have been proven to be effective include strict blood pressure control and ACE inhibitor or angiotensin II receptor–blocker therapy, lipid lowering therapy, and correction of anemia. In these patients, aggressive goals are recommended for both proteinuria and blood pressure. In addition, antihypertensive therapy is used for both renal protection and cardiovascular protection because CKD is associated with a marked increase in cardiovascular risk.
• Management of complications

Anemia

The presence of anemia one month after dialysis initiation is associated with an increased risk of prolonged hospitalization and death in pediatric patients. The beneficial effects of treating anemia with erythropoietin in patients who are dialysis-dependent include the improvement of cardiac status, exercise capacity, cognitive function, and quality of life. Recombinant human erythropoietin (rHuEPO) has been used for CKD-associated anemia since 1986. Based on the K/DOQI guidelines, the recommended target hemoglobin-to-hematocrit (Hgb/Hct) ratio is 11-12 g/dL/33-36%.⁸

Iron supplementation is essential to ensure an adequate response to erythropoietin. The pediatric dose of oral iron is 2-3 mg/kg/d PO divided in 2-3 doses. Oral iron is best absorbed when ingested without food or other medications. The percent of iron absorbed orally is affected by the iron salt form (eg, ferrous sulfate, ferrous gluconate), the amount administered, the dosing regimen, and size of iron stores. Foods that enhance iron absorption include protein from meat and vitamin C. Foods that may inhibit absorption include unrefined grains, soy, coffee, cocoa, herb teas, red wine, calcium, and some proteins (eg, soy, eggs, casein).

Bone disease

Children with CKD stage 2 usually have no signs or symptoms of bone abnormalities. However, these children may have evidence of abnormalities on laboratory testing (eg, decreased serum calcitriol [1,25 dihydroxyvitamin D] and elevated serum parathyroid hormone [PTH]) [3]. This period should be used to counsel the child and family about CKD and its impact on bone metabolism. The importance of laboratory monitoring should be emphasized, and future interventions to prevent renal osteodystrophy should be discussed. Subtle signs of renal osteodystrophy begin to be observed when the GFR decreases to 50% of the reference range (stage 3 disease).

The 2 major types of bone disease commonly encountered in patients with CKD prior to maintenance dialysis include enhanced bone resorption (osteitis fibrosa) and osteomalacia/rickets. As CKD advances to end-stage renal disease (ESRD), adynamic bone disease may also be found. Mild forms of these derangements in bone metabolism may be observed in the early stages (eg, stage 2) and may become more severe as kidney function deteriorates.

Serum concentrations of calcium, phosphate, and PTH should be measured on an ongoing basis in all children with CKD, even those with mild disease who often have evidence of abnormalities in bone metabolism. For calcium and phosphorus measurements, the K/DOQI guidelines recommend monthly measurements in Stage 5 disease, whereas PTH measurements should be obtained at least every 3 months.⁹ Early detection of bone metabolic abnormalities ensures that therapeutic interventions can be initiated, thereby preventing or minimizing renal osteodystrophy.

According to the K/DOQI clinical practice guidelines for pediatric osteodystrophy, phosphate binders are recommended if phosphorus or intact PTH levels cannot be controlled within the target range despite dietary phosphorus restriction.⁹ Calcium-based phosphate binders are effective in lowering serum phosphorus levels and may be used as the initial binder therapy, but total calcium uptake should be rechecked. The serum levels of corrected total calcium should be maintained within the reference range for the laboratory used. The serum calcium-phosphorus product should be maintained at less than 55 mg²/dL in adolescents.

Serum PTH concentration is inversely correlated with renal function and is almost always elevated when the GFR falls below 60 mL/min per 1.73 m². Although the optimal serum PTH values in children with CKD are uncertain, the K/DOQI guidelines recommend targeted levels of serum intact PTH in Stage 5 disease to be 200-300 pg/mL.⁹

Patients with serum levels of intact PTH of more than 300 pg/mL may be treated with active vitamin D sterols to maintain PTH levels at about 2-4 times the reference range.

Cardiovascular manifestations

Cardiovascular disease is the major cause of mortality in both adults and children on long-term dialysis and in adults after kidney transplantation. The prevalence of coronary artery disease (CAD) and LVH, which are precursors of cardiovascular disease mortality and morbidity, is high. The prevalence of congestive heart failure (CHF), which is an independent predictor of death in chronic renal disease, is also high. Strategies should include identification and treatment of modifiable risk factors for cardiovascular disease such as smoking, obesity, hypertension, hyperlipidemia, hypertriglyceridemia, anemia, hypercalcemia, and hyperphosphatemia.

Both hypertension and anemia are associated with LVH in chronic renal disease. Treatment of each condition causes regression of LVH in chronic renal disease.

Homocysteine levels are elevated in CKD, and elevated homocysteine levels are associated with cardiovascular disease. The effect of dietary fortification with folic acid on homocysteine levels in CKD is unknown.

Elevated levels of total and low-density lipoprotein (LDL) cholesterol are associated with cardiovascular disease in chronic renal disease. The systematic treatment of dyslipidemia in children with chronic renal disease is controversial because conclusive data regarding the risks and benefits are lacking. Hepatic 3-methylglutaryl coenzyme A reductase inhibitors (statins), fibrates, plant stanols, bile acid–binding resins, and dietary manipulation are options for individualized treatment.

Hyperlipidemia

The K/DOQI guidelines on dyslipidemias recommend that all children as well as adults with CKD should be evaluated for dyslipidemia.⁹ The patients should be evaluated with a complete fasting lipid profile, including total cholesterol, LDL, high-density lipoprotein (HDL), and triglycerides at presentation, and should be evaluated annually thereafter or 2-3 months after a change in treatment or other conditions known to cause dyslipidemia. Elevated levels of total and LDL cholesterol are associated with cardiovascular disease in chronic renal disease.

The National Cholesterol Expert Panel on Children (NCEP-C) treatment guidelines should be followed for children with CKD (stages 1-4) and prepubertal children on dialysis. The approach for pubertal children with Stage 5 CKD is similar to that for adults, but higher thresholds are used for treating LDL and non-HDL cholesterol. Recommendations for adolescents are discussed in detail elsewhere

Hepatic 3-methylglutaryl coenzyme A reductase inhibitors (statins), fibrates, plant stanols, bile acid–binding resins, and dietary manipulation are options for individualized treatment.

Hypertension

Hypertension is a highly significant and independent predictor for progression of CKD in children. The most recent data available (2003) indicate that at least 38% of children with CKD in the United States are receiving antihypertensive therapy.¹⁰

The optimal target blood pressure for children with chronic renal failure is currently recommended to be below the 90th percentile for age. Treatment of even mild hypertension is important in patients with chronic renal failure to protect against both progressive renal failure and cardiovascular disease, which is markedly increased in even moderate chronic renal disease.

Treatment of hypertension in children, with and without CKD, is based on 3 factors: degree of blood pressure elevation, the presence of cardiovascular risk factors, and the presence of end-organ damage. Additionally, the initial antihypertensive agent may be selected based on cause of CKD and age.

ACE inhibitors and angiotensin II receptor blockers have an additional benefit in at least some patients with chronic renal disease, slowing the rate of progressive renal injury, independent of the activity of the underlying disease.

Metabolic acidosis

The kidneys play a critical role in acid-base homeostasis by excreting an acid load (produced by cellular metabolism and skeletal growth in children) and preventing bicarbonate loss in the urine. An increasing tendency to retain hydrogen ions has been observed among patients with chronic renal disease, eventually leading to a progressive metabolic acidosis. In children, overt acidosis is characteristically present when the eGFR is less than 30 mL/min per 1.73 m² (stage 4).

The acidosis in CKD in children can be associated with an increased or normal anion gap. Current guidelines recommend maintaining a serum bicarbonate level of 22 mmol/L. If necessary, the authors recommend supplementation with sodium bicarbonate. Sodium bicarbonate therapy is started at 1-2 mEq/kg/d in 2-3 divided doses; the dose is titrated to the clinical target.

Growth

Disruption of the hypothalamic-pituitary growth hormone axis contributes to the growth hormone–resistant state in uremia. Long-term growth hormone treatment in children with CKD induces catch-up growth, and most patients may achieve normal adult height if treatment is initiated prior to ESRD.

Based on the current K/DOQI guidelines, treatment with recombinant human growth hormone (hGH) should be considered under the following conditions:⁹

• Children whose height for chronological age varies by more than 2 negative standard deviation scores (SDS)
• Children whose height velocity for chronological age varies by more than 2 negative SDS
• Children with growth potential documented by open epiphyses
• No other contraindication for recombinant hGH use

Additionally, the following nutritional and metabolic imbalances should be corrected prior to use of recombinant hGH:

• Insufficient intake of energy, protein, and other nutrients
• Acidosis
• Hyperphosphatemia (correct serum phosphorus level to <1.5 times the upper limit for age)
• Secondary hyperparathyroidism

Surgical Care

Surgical intervention is often recommended in children with obstructive uropathy to relieve acute kidney failure due to initial or recurrent obstruction. These children should be provided follow-up because, despite surgical intervention, they have persistent underlying CKD. In those children who opt for hemodialysis, an arteriovenous fistula needs to be created by the vascular surgery team as an access for hemodialysis.

Diet

Dietary management is of paramount importance in children with CKD. These patients have an altered metabolic milieu due to deranged kidney function. The challenge for pediatricians is to optimize the growth and development of children in this setting. The challenge for both pediatricians and dietitians is to make the diet interesting and palatable in order to ensure compliance. The goal is not only to add years to life but also to life to years.

• Energy
• • Energy requirement should meet at least recommended dietary allowance (RDA) for normal children of same height age.
  • If protein energy malnutrition (PEM) is present, it needs to be increased further to improve weight gain and linear growth. Calorie intake should be enough to enhance the efficiency of protein (protein-sparing effect) and to prevent the patient from lapsing into a catabolic state.
  • Poor intake is common in these patients due to anorexia, nausea and dietary restrictions.
  • When use of chronological age does not account for the growth, height age should be the basis for energy estimation. Supplementation can be used as per requirement (enteral or parenteral nutrition as needed).
• Protein
• • The diet should include 1.1-1.2 g/kg/d protein, with 60-70% protein from high biological value origin.
  • Protein is required to maintain positive nitrogen balance for growth and maintain body protein turn over.
  • The protein intake must be carefully controlled, avoiding protein malnutrition from an excessively restricted diet while avoiding toxicity from nitrogenous waste products from an excessively generous diet.
  • High biological value proteins are of utmost importance because they are beneficial in promoting muscle anabolism and decreasing muscle wasting.
• Phosphorus and calcium
• • As the GFR progressively declines, excretion of phosphate decreases, and, hence, serum phosphorus levels increase. Because of this, care must be taken for the following:
  • • Dietary phosphorus restriction
    • Regular phosphate binders with the meals
  • The elemental calcium intake recommended for pediatric patients with CKD is as follows: 
  • • Age 1-10 years: 500-600 mg/d
    • Age 11-18 years: 800-1000 mg/d
  • High amounts of phosphorus affects growth in children and, if levels are high over a long period, may cause renal osteodystrophy. Prolonged elevation of serum calcium and phosphorus levels leads to vascular calcification. The daily elemental calcium requirement is about 80-100 mg/kg/d.
• Potassium
• • The potassium requirement should be individualized depending on the serum potassium levels. Approximately 1600-2400 mg of potassium can be given.
  • Close watch should be kept on the potassium levels, and modifications can be made accordingly.
  • Hyperkalemia may occur due to excessive intake of high-potassium foods, catabolism, and other causes.
  • Special attention should be given if the child is anuric.
  • Leaching of pulses and vegetables should be suggested if the child is hyperkalemic.
  • Daily bowel movements are important because the GI route accounts for as much as 30% of potassium excretion in patients with chronic renal failure.
• Sodium and fluid
• • No added salt (NAS) and restriction of salty snacks is recommended. 
  • If the child is hypertensive and edematous, further restriction of salt and fluid is emphasized. However, exceptions include diseases in which sodium is lost in the urine (salt-losing nephropathies).
  • The allowance of salt depends on the presence of edema, hypertension, and administration of sodium-containing medications. Salt intake should be kept to less than 2400 mg/d.
  • Once these children progress to dialysis or opt for kidney transplantation, a dietician should be consulted again because the dietary requirements change.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Iron salts

These agents are used to replenish iron stores. The body stores iron in compounds called ferritin and hemosiderin for future use in the production of hemoglobin. Iron absorption is a variable of the existing body iron stores, the form and quantity in foods, and the combination of foods in the diet. The ferrous form of inorganic iron is more readily absorbed.

Drug Category: Hematopoietic growth factors

These agents are used to stimulate blood cell production. Endogenous erythropoietin stimulates RBC hematopoiesis. Recombinant human erythropoietin (epoetin alfa) and darbepoetin stimulate erythropoiesis in anemic conditions.

Drug Category: Phosphate binders

These agents are indicated if phosphate elevation is uncontrolled by dietary phosphate restriction. Calcium phosphate binders are typically the initial therapy for hyperphosphatemia. Calcium supplements and calcitriol may possibly also be used for hypocalcemia.

Drug Category: Vitamin D analogs

Hyperparathyroidism is treated with calcitriol or other active vitamin D analogs. These drugs may also be used to treat hypocalcemia.

Drug Category: Growth hormones

These agents are used pharmacologically as a growth-promoting agent to help optimize growth in developing children with chronic kidney disease (CKD).

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• All children require regular follow-up on an outpatient basis in a dedicated chronic kidney disease (CKD) clinic until initiation of long-term renal replacement therapy. This involves a multidisciplinary team approach that involves the nephrologist, primary care physician, renal dietitian, nurse, and social worker. They should work in close coordination with the primary pediatrician or family physician.

Transfer

• Patients with any complications require transfer to a center with a pediatric nephrology unit where acute dialysis can be performed if required.

Prognosis

• Once CKD occurs, progression to end-stage renal disease (ESRD) appears certain. However, the rate of progression depends on the underlying diagnosis, on the successful implementation of secondary preventive measures, and on the individual patient.
• Once the eGFR declines to less than 30 mL/min per 1.73 m² and the child has stage 4 CKD, the child and the family should be prepared for renal replacement therapy. The family should be provided with information related to preemptive kidney transplantation, peritoneal dialysis, and hemodialysis. When preemptive transplantation is not an option, the choice between the 2 forms of dialysis is generally dictated by technical, social, and compliance issues, as well as family preference. Peritoneal dialysis is much more common in infants and younger children.
• Patients on long-term dialysis have a high incidence of morbidity and mortality.
• Preemptive renal transplantation should be the goal of management in these children.

Patient Education

• Children with CKD and their families should receive education about the importance of compliance with secondary preventative measures, natural disease progression, prescribed medications (highlighting their potential benefits and adverse effects), diet, and types of long-term renal replacement modalities.
• For excellent patient education resources related to kidney disease, visit eMedicine's Kidneys and Urinary System Center. These resources may be printed free of charge.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Some medications such as NSAIDs and radiocontrast agents are contraindicated in these children because of the risk of deterioration of kidney function. Dose modification is required for a wide variety of drugs belonging to different categories.
• Unexplained anemia or short stature is sometimes the only presentation in a child. A high index of suspicion is required for early diagnosis.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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3. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. Feb 2002;39(2 Suppl 1):S1-266. [Medline].
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14. Mak RH. Chronic kidney disease in children: state of the art. Pediatr Nephrol. Oct 2007;22(10):1687-8. [Medline].
15. Saland JM, Ginsberg H, Fisher EA. Dyslipidemia in pediatric renal disease: epidemiology, pathophysiology, and management. Curr Opin Pediatr. Apr 2002;14(2):197-204. [Medline].
16. Salusky IB. A new era in phosphate binder therapy: what are the options?. Kidney Int Suppl. Dec 2006;(105):S10-5. [Medline].
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Article Last Updated: Jan 14, 2008