eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Chronic Kidney Disease

Sanjeev Gulati, MBBS, MD, DNB(Peds), DM, DNB(Neph), FIPN(Australia), FICN, FRCPC(Canada), Associate Professor, Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences; Senior Consultant in Pediatric Nephrology, Department of Nephrology and Transplant Medicine, Fortis Hospitals, India

Updated: Aug 12, 2009

Introduction

Background

Chronic kidney disease (CKD) is characterized by an irreversible deterioration of renal function that gradually progresses to end-stage renal disease (ESRD). Chronic kidney disease 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 chronic kidney disease in children has steadily increased, with poor and ethnic minority children disproportionately affected.

The major health consequences of chronic kidney disease 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 chronic kidney disease–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 (KDOQI) working group of the National Kidney Foundation of the United States defined chronic kidney disease 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."^2,3,4

Pathophysiology

Despite the diverse etiologies, once chronic kidney disease 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 chronic kidney disease.

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 chronic kidney disease 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 chronic kidney disease is the basis for the common management plan for children with chronic kidney disease, 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 m².⁵ In the past decade, the incidence of the disease has steadily increased among all ethnic groups.

International

The prevalence of chronic kidney disease 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 chronic kidney disease seen in a referral hospital.⁶ 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.⁷ However, underreporting due to lack of recognition may suggest an even higher prevalence in children.

Mortality/Morbidity

About 70% of children with chronic kidney disease develop ESRD by age 20 years. Children with ESRD have a 10-year survival rate of about 80% and an age-specific mortality rate of about 30 times that seen in children without ESRD. The most common cause of death in these children is cardiovascular disease, followed by infection. Of the deaths due to cardiovascular causes, 25% were attributed to cardiac arrest (cause uncertain), 16% to stroke, 14% to myocardial ischemia, 12% to pulmonary edema, 11% to hyperkalemia, and 22% to other cardiovascular causes, including arrhythmia. Data from the Australia and New Zealand (ANZ) 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.⁸

Race

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

Choi et al found that rates of ESRD among black patients exceeded those among white patients at all levels of baseline eGFR.⁹ Similarly, mortality rates among black patients were equal to or higher than those among white patients at all levels of eGFR. Risk of ESRD among black patients was highest at an eGFR of 45-59 mL/min/1.73 m² (hazard ratio, 3.08), as was the risk of mortality (hazard ratio, 1.32).

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 chronic kidney disease increases with age and is much more common in adults than children. Among children, chronic kidney disease 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.⁵

Clinical

History

Chronic kidney disease (CKD) is asymptomatic in its earliest stages (stage I and stage II), although urinalysis findings or blood pressure may be abnormal. As chronic kidney disease 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 chronic kidney disease in an otherwise healthy-looking child who has tubulointerstitial kidney disease.
• The signs and symptoms in advanced chronic kidney disease 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, estimated glomerular filtration rate (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 chronic kidney disease 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

Differential Diagnoses

Other Problems to Be Considered

Acute renal failure
Rapidly progressive glomerulonephritis

Workup

Laboratory Studies

• Initial testing must include an examination of the urine and estimation of the glomerular filtration rate (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 chronic kidney disease. 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 chronic kidney disease have broad hyaline casts. Characteristic findings on microscopic examination of the urine sediment may suggest a diagnosis other than chronic kidney disease. 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 chronic kidney disease–related complications.
• Anemia is an important clinical finding in chronic kidney disease, 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 KDOQI guidelines state that estimates of GFR are the best overall indices of the level of kidney function.⁴ The reference range of GFR in young adults is 120-130 mL/min per 1.73 m². However, the reference range of estimated GFR (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 (age 2-12 y in children and adolescent girls and 0.7 y in adolescent boys)
  • Therefore, all children with chronic kidney disease 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 chronic kidney disease.
  • 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 chronic kidney disease 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 chronic kidney disease or acute kidney failure. If a child has small shrunken kidneys, a kidney biopsy is often unnecessary to establish a diagnosis of chronic kidney disease.

Histologic Findings

• In advanced stages of chronic kidney disease, 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 KDOQI recommended classification of chronic renal disease by stage:^10,4

• Stage I disease is defined by a normal GFR (>90 mL/min per 1.73 m²) and persistent albuminuria.
• Stage II disease is characterized by a GFR of 60-89 mL/min per 1.73 m² and persistent albuminuria.
• Stage III disease is characterized by a GFR of 30-59 mL/min per 1.73 m².
• Stage IV disease is characterized by a GFR of 15-29 mL/min per 1.73 m².
• Stage V disease is characterized by a GFR of less than 15 mL/min per 1.73 m² or end-stage renal disease (ESRD).

Treatment

Medical Care

According to the recommendations of the Pediatric Work Group of KDOQI for chronic kidney disease (CKD), all children with evidence of CKD should be referred to a pediatric nephrologist for consultation and comanagement.⁴

Patients with chronic kidney disease 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 chronic kidney disease 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 chronic kidney disease, 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 chronic kidney disease 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 chronic kidney disease–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%.¹¹

Iron supplementation is essential to ensure an adequate response to erythropoietin. This is targeted to maintain a transferrin saturation level of 20% or higher and serum ferritin level of 100 ng/dL or higher in children with chronic kidney disease. The pediatric dose of oral iron is 2-3 mg/kg/d 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 stage II chronic kidney disease 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 chronic kidney disease 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 III disease).

The 2 major types of bone disease commonly encountered in patients with chronic kidney disease prior to maintenance dialysis include enhanced bone resorption (osteitis fibrosa) and osteomalacia/rickets. As chronic kidney disease 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 II) 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 chronic kidney disease, even those with mild disease who often have evidence of abnormalities in bone metabolism. Vitamin D insufficiency and deficiency are very prevalent in pediatric patients across all stages of chronic kidney disease, particularly in nonwhite and obese patients, and may contribute to growth deficits during the earliest stages of chronic kidney disease.¹²

For calcium and phosphorus measurements, the KDOQI guidelines recommend monthly measurements in stage V disease, whereas PTH measurements should be obtained at least every 3 months.^10,4 Early detection of bone metabolic abnormalities ensures that therapeutic interventions can be initiated, thereby preventing or minimizing renal osteodystrophy.

According to the KDOQI 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.^10,4 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 chronic kidney disease are uncertain, the KDOQI guidelines recommend targeted levels of serum intact PTH in stage V disease to be 200-300 pg/mL.^10,4

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 left ventricular hypertrophy (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 chronic kidney disease, and elevated homocysteine levels are associated with cardiovascular disease. The effect of dietary fortification with folic acid on homocysteine levels in chronic kidney disease 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 KDOQI guidelines on dyslipidemias recommend that all children as well as adults with chronic kidney disease should be evaluated for dyslipidemia.^10,4 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 chronic kidney disease (stages I-IV) and prepubertal children on dialysis. The approach for pubertal children with stage V chronic kidney disease 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 chronic kidney disease in children. The most recent data available (2003) indicate that at least 38% of children with chronic kidney disease in the United States are receiving antihypertensive therapy.¹³

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 chronic kidney disease, 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 chronic kidney disease 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 IV).

The acidosis in chronic kidney disease 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 chronic kidney disease induces catch-up growth, and most patients may achieve normal adult height if treatment is initiated prior to ESRD.

Based on the current KDOQI guidelines, treatment with recombinant human growth hormone (hGH) should be considered under the following conditions:^10,4

• 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 chronic kidney disease. In those children who opt for hemodialysis, an arteriovenous fistula needs to be created by the vascular surgery team as an access for hemodialysis.

Major clinical predictors to be used for the perioperative management of a patient with chronic renal failure.

Intermediate clinical predictors to be used for the perioperative management of a patient with chronic renal failure.

Minor clinical predictors to be used for the perioperative management of a patient with chronic renal failure.

Diet

Dietary management is of paramount importance in children with chronic kidney disease. 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.
  • Protein restriction is not recommended in children because it has not been shown to influence the decrease in renal function in children with chronic kidney disease.
• 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 chronic kidney disease 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

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.

Ferrous sulfate (Feosol, Feostat)

Source of iron for hemoglobin synthesis in treating anemia of chronic renal failure. Also used with erythropoietin to prevent iron stores depletion. PO solutions and chewable tabs of ferrous iron salts are available for use in pediatric populations.

Dosing

Adult

325 mg (60 mg elemental iron) PO qd/tid

Pediatric

2-6 mg/kg/d PO; may administer qd or divided bid

Interactions

Absorption is enhanced by ascorbic acid; interferes with tetracycline absorption; food and antacids impair absorption

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

GI tract upset; iron toxicity is observed with ingestion of large amount and can be fatal, especially in children

Sodium ferric gluconate complex (Ferrlecit)

Used to treat microcytic hypochromic anemia due to iron deficiency when PO administration is unfeasible or ineffective. Used to replenish iron stores in individuals on erythropoietin therapy who cannot take or tolerate PO iron supplementation.

Dosing

Adult

125 mg (as elemental iron)/dose IV diluted in 100 mL of 0.9% NaCl solution and infused over at least 1 h with each hemodialysis session; may repeat for a total of 8 doses
Can be administered in combination with erythropoietin

Pediatric

<6 years: Not established
>6 years: 1.5 mg elemental Fe (0.12 mL) per kg IV; dilute in 25 mL 0.9% NaCl and infuse over 1 h for 8 consecutive dialysis sessions; not to exceed 125 mg/session

Interactions

Alpha tocopherol may decrease stores if administered in combination; coadministration with ACE inhibitors may increase adverse events with IV iron therapy

Contraindications

Documented hypersensitivity; anemias that are not involved with iron deficiency; hemochromatosis; hemolytic anemia; acute phase of infectious kidney disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Contains benzyl alcohol (do not use in neonates); serious hypersensitivity reactions may occur, including first dose; may cause hypotension, malaise, fatigue, weakness, or pain in chest, back, flanks, or groin during administration; monitor Hgb to avoid iron overload

Iron sucrose (Venofer)

Polynuclear iron (III) hydroxide in sucrose for IV use. Contains no preservatives or dextran polysaccharides. Used to treat microcytic hypochromic anemia due to iron deficiency when PO administration is unfeasible or ineffective. Used to replenish iron stores in individuals on erythropoietin therapy who cannot take or tolerate PO iron supplementation.

Dosing

Adult

100 mg (as elemental iron)/dose undiluted by slow IV injection (20 mg iron/min) or IV infusion (6.7 mg iron/min; diluted in 100 mL of 0.9% NaCl solution) with each hemodialysis session; may repeat for a total of 8 doses; typically requires a minimum cumulative dose of 1000 mg of elemental iron to achieve a favorable hemoglobin or hematocrit response; not to exceed 3 doses per wk
Can be administered in combination with erythropoietin

Pediatric

Not established

Interactions

Alpha tocopherol may decreased stores if administered in combination; coadministration with ACE inhibitors may increase adverse events with IV iron therapy; decreases bioavailability of PO administered iron

Contraindications

Documented hypersensitivity; anemia unrelated to iron deficiency; hemochromatosis; hemolytic anemia; acute phase of infectious kidney disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hypersensitivity reactions have been reported with injectable iron products; may cause hypotension (related to IV administration rate or cumulative dose), cramps, headache, nausea, vomiting, or diarrhea; monitor Hgb to avoid iron overload

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.

Epoetin alfa (Epogen, Procrit)

Stimulates division and differentiation of committed erythroid progenitor cells. Induces release of reticulocytes from bone marrow into blood stream.

Dosing

Adult

50 U/kg IV/SC 3 times qwk initially; depending on Hct target, may gradually increase dose each mo up to 150 U/kg IV/SC 3 times qwk

Pediatric

<1 month: Not established
>1 month: 50 U/kg IV/SC 1-3 times qwk initially; depending on Hct target, may gradually increase dose each mo up to 250 U/kg 3 times qwk if needed

Interactions

None reported

Contraindications

Documented hypersensitivity; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypertension, history of seizures, or porphyria; decrease dose if Hct increase exceeds 4 U in any 2-wk period or approaching Hct upper target of 36%; caution in iron deficiency or folate/B12 deficiency; do not use multidose vial (contains benzyl alcohol) in premature or young infants; treatment results depend on adequate iron supplementation

Darbepoetin alfa (Aranesp)

Indicated for treatment of hyperphosphatemia secondary to chronic renal failure. Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. Calcium acetate 667 mg equivalent to 169-mg elemental calcium.
Stimulates division and differentiation of committed erythroid progenitor cells. Induces release of reticulocytes from bone marrow into blood stream.

Dosing

Adult

0.45 mcg/kg/wk SC

Pediatric

<11 years: Not established
>11 years (based on European Best Practice Guidelines): 0.45 mcg/kg/wk SC/IV

Interactions

Coadministration with thalidomide increases thromboembolic risk

Contraindications

Documented hypersensitivity; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypertension, history of seizures, porphyria, liver disease, sickle cell anemia, hypercoagulable disorders, red cell aplasia, or conditions with enhanced thrombotic tendency; decrease dose if Hct increase exceeds 2.5 g/dL in any 4-wk period; complete iron repletion before initiating

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.

Calcium acetate (Calphron, PhosLo)

Indicated for treatment of hyperphosphatemia secondary to chronic renal failure. Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. One cap or tab of calcium acetate 667 mg is equivalent to 169-mg elemental calcium (ie, 1 g calcium acetate equivalent to 250-mg of elemental calcium).

Dosing

Adult

1334 mg (2 tab/cap) PO tid pc; increase to bring serum phosphate value to 6 mg/dL as long as hypercalcemia does not develop

Pediatric

50-150 mg/kg/d (as elemental calcium) PO divided tid pc for hyperphosphatemia; administer between meals for hypocalcemia

Interactions

May increase effect of quinidine; may decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels

Contraindications

Documented hypersensitivity; hypercalcemia; hypophosphatemia; renal calculi

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypercalcemia or hypercalcuria may occur when therapeutic amounts are administered

Calcium carbonate (Caltrate, Tums)

Used to treat hyperphosphatemia in chronic renal failure. Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. Also indicated for hypocalcemia. Calcium carbonate 1 g is equivalent to 400 mg of elemental calcium.

Dosing

Adult

1-2 g/d PO tid pc; increase dose to lower serum phosphate value to 6 mg/dL as long as hypercalcemia does not develop

Pediatric

50-150 mg/kg/d (as elemental calcium) PO divided tid pc for hyperphosphatemia; administer between meals for hypocalcemia

Interactions

May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels

Contraindications

Renal calculi; hypercalcemia; hypophosphatemia; renal or cardiac disease; digitalis toxicity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypercalcemia or hypercalcuria may occur at therapeutic doses

Sevelamer (Renagel)

Indicated to reduce serum phosphorous in patients with ESRD. Binds dietary phosphate in the intestine, thus inhibiting its absorption. Reduces incidence of hypercalcemic episodes in patients on hemodialysis compared with patients receiving calcium acetate treatment.

Dosing

Adult

Initial: 800-1600 mg PO tid pc
Maintenance: Increase or decrease by 400-800 mg per meal q2wk to maintain serum phosphorous at 6 mg/dL or less

Pediatric

Not established; limited data suggest 800-1200 mg PO tid pc

Interactions

May reduce absorption of drugs coadministered with sevelamer; when changes in absorption of PO medications may have clinical consequences (eg, antiseizure or antiarrhythmic drugs), medications should be taken 1 h before or 3 h after a dose of sevelamer

Contraindications

Documented hypersensitivity; bowel obstruction; hypophosphatemia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with dysphagia, severe GI tract motility disorders, or swallowing disorders; does not contain calcium or alkali supplementation (monitor serum calcium, bicarbonate, and chloride levels); may cause or worsen metabolic acidosis with high doses

Vitamin D analogs

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

Calcitriol (Rocaltrol, Calcijex)

Primary active metabolite of vitamin D-3. Increases calcium levels in serum by promoting absorption of calcium in intestines and retention in kidneys. Decreases excessive serum phosphatase levels and parathyroid levels. Decreases bone resorption.
Should be used in patients with renal failure who are unable to convert the inactive prohormone forms to the active metabolite. Available in PO and parenteral form. Active form of vitamin D. Used in cases of pRTA as multitherapy with large quantities of alkali and potassium supplementation.
Used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in CRF by increasing intestinal calcium absorption.

Dosing

Adult

0.25 mcg PO qd/qod
0.5 mcg IV qd 3 times qwk
Increase at 4- to 8-wk intervals by 0.25 mcg/d to achieve target PTH level

Pediatric

<3 years: 0.01-0.05 mcg/kg/d PO qd
>3 years: 0.25-0.5 mcg PO qd

Interactions

Cholestyramine and other bile acid–binding resins decrease absorption; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects

Contraindications

Documented hypersensitivity; hypercalcemia; hyperphosphatemia; hypervitaminosis D; malabsorption syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adequate response in improving hypocalcemia depends on adequate dietary calcium intake; serum calcium phosphate product must not exceed 55 mg/dL to minimize metastatic tissue and blood vessel calcification; avoid hypercalcemia

Paricalcitol (Zemplar)

Formed through the removal of the 19th carbon group and modifications to the side chain of calcitriol, thus reducing the calcemic effect. It has been reported to suppress PTH without significant impact on calcium, phosphorus, or calcium-phosphorus product. Increases calcium levels in serum by promoting absorption of calcium in intestines and retention in kidneys.
Decreases excessive serum phosphatase levels and parathyroid levels. Decreases bone resorption.
Should be used in patients with renal failure who are unable to convert the inactive prohormone forms to the active metabolite. Available in PO and parenteral form. Active form of vitamin D.
Used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in CRF by increasing intestinal calcium absorption.

Dosing

Adult

Initial dose based on the serum PTH levels:
<500 pg/mL: 1 mcg/d PO
>500 pg/mL: 2 mcg/d PO
Increase at 2- to 4-wk intervals to achieve target PTH level

Pediatric

<5 years: Not established
5-19 years: Data limited; one clinical trial suggests initial dose based on PTH levels:
PTH <500 pg/mL: 0.04 IV 3 times/wk
PTH >500 pg/mL: 0.08 mcg/kg IV 3 times/wk
Adjust dose at 2- to 4-wk intervals based on PTH levels

Interactions

Cholestyramine and other bile acid-binding resins decrease absorption; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects; do not use phosphate or vitamin D-related compounds concomitantly with paricalcitol; caution if administered with digoxin (digitalis toxicity is potentiated by hypercalcemia)

Contraindications

Documented hypersensitivity; hypercalcemia; hyperphosphatemia; hypervitaminosis D; malabsorption syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adequate response to paricalcitol in improving hypocalcemia depends on adequate dietary calcium intake; serum calcium phosphate product must not exceed 55 mg/dL to minimize metastatic tissue and blood vessel calcification; avoid hypercalcemia; caution in breastfeeding; adverse effects include GI tract distress, dry mouth, lightheadedness, edema, chills, or fever

Doxercalciferol (Hectorol)

Vitamin D analog (1-alpha-hydroxyergocalciferol) that does not require activation by kidneys. Requires hydroxylation in liver to be converted to an active vitamin D metabolite. Controls intestinal absorption of dietary calcium, tubular reabsorption of calcium by kidneys, and in conjunction with parathyroid hormone, the mobilization of calcium from skeleton. Indicated for treatment of secondary hyperparathyroidism in ESRD.

Dosing

Adult

10 mcg PO 3 times/wk at dialysis; adjust dose as needed to lower blood iPTH to 150-300 pg/mL; increase dose by 2.5 mcg/8 wk if iPTH is not lowered by 50% and fails to reach the target range; not to exceed 20 mcg PO 3 times/wk
Alternatively, 4 mcg IV 3 times/wk; may adjust dose by 1-2 mcg/8 wk to maintain iPTH levels

Pediatric

Not established

Interactions

Cholestyramine and mineral oil may reduce absorption; concurrent use with other vitamin D supplements or magnesium containing antacids (or supplements) may increase toxicity

Contraindications

Documented hypersensitivity; hyperphosphatemia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Discontinue other forms of vitamin D before initiating therapy; avoid overdose; monitor calcium levels carefully; hyperphosphatemia may reduce effects; caution in hepatic impairment

Growth hormones

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

Growth hormone (Nutropin, Saizen)

hGH produced by recombinant DNA technology. Results in stimulation of linear growth.
Stimulates erythropoietin, which increases red blood cell mass.
Currently widely available in SC injection form. Adjust dose gradually based on clinical and biochemical responses assessed at monthly intervals, including body weight, waist circumference, serum IGF-1, IGFBP-3, serum glucose, lipids, thyroid function, and whole body dual-energy x-ray absorptiometry. In children, assess response based on height and growth velocity. Continue treatment until final height or epiphysial closure or both have been recorded.

Dosing

Adult

Not indicated

Pediatric

0.35 mg/kg/wk SC initially, divided into daily or 6 times qwk SC injections

Interactions

Glucocorticoids may decrease growth-promoting effects

Contraindications

Documented hypersensitivity; closed epiphysis; intracranial lesion; malignancy; acidosis; malnutrition

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause injection site pain, lipodystrophy, headache, or intracranial hypertension

Calcimimetic Agent

These agents reduce PTH levels. A small clinical trial by Muscheites et al in children showed an 80% decrease in serum PTH levels.¹⁴

Cinacalcet (Sensipar)

Directly lowers iPTH levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

Dosing

Adult

30 mg PO qd initially; titrate upward slowly (no more frequent than q2-4wk intervals) by 30 mg increments to target iPTH of 150-300 pg/mL
Take with meals or immediately following; do not crush, chew or cut tablets

Pediatric

Not established, but 0.25 mg/kg PO qd for 4 wk has been shown to lower circulating PTH levels (Muscheites et al, 2008)

Interactions

Strong CYP450 2D6 inhibitor; may increase serum levels of CYP 2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP450 3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease cinacalcet clearance

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2 mo (parathyroid carcinoma); do not initiate treatment if serum calcium below 8.4 mg/dL; adynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting

Follow-up

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 chronic kidney disease 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 estimated glomerular filtration rate (eGFR) declines to less than 30 mL/min per 1.73 m² and the child has stage IV chronic kidney disease, 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 chronic kidney disease 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

Medicolegal Pitfalls

• Some medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents are contraindicated in children with chronic kidney disease (CKD) 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.

Multimedia

Media file 1: Major clinical predictors to be used for the perioperative management of a patient with chronic renal failure.

Media file 2: Intermediate clinical predictors to be used for the perioperative management of a patient with chronic renal failure.

Media file 3: Minor clinical predictors to be used for the perioperative management of a patient with chronic renal failure.

References

1. Collins AJ, Kasiske B, Herzog C, et al. Excerpts from the United States Renal Data System 2003 Annual Data Report: atlas of end-stage renal disease in the United States. Am J Kidney Dis. Dec 2003;42(6 Suppl 5):A5-7. [Medline].

2. [Guideline] Kopple JD. National kidney foundation K/DOQI clinical practice guidelines for nutrition in chronic renal failure. Am J Kidney Dis. Jan 2001;37(1 Suppl 2):S66-70. [Medline].

3. [Guideline] 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].

4. [Guideline] KDOQI. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 update. Executive summary. Am J Kidney Dis. Mar 2009;53(3 Suppl 2):S11-104. [Medline].

5. Seikaly MG, Ho PL, Emmett L, et al. Chronic renal insufficiency in children: the 2001 Annual Report of the NAPRTCS. Pediatr Nephrol. Aug 2003;18(8):796-804. [Medline].

6. Gulati S, Mittal S, Sharma RK, Gupta A. Etiology and outcome of chronic renal failure in Indian children. Pediatr Nephrol. Sep 1999;13(7):594-6. [Medline].

7. Ardissino G, Dacco V, Testa S, et al. Epidemiology of chronic renal failure in children: data from the ItalKid project. Pediatrics. Apr 2003;111(4 Pt 1):e382-7. [Medline].

8. Craven AM, Hawley CM, McDonald SP, et al. Predictors of renal recovery in Australian and New Zealand end-stage renal failure patients treated with peritoneal dialysis. Perit Dial Int. Mar-Apr 2007;27(2):184-91. [Medline].

9. [Best Evidence] Choi AI, Rodriguez RA, Bacchetti P, Bertenthal D, Hernandez GT, O'Hare AM. White/black racial differences in risk of end-stage renal disease and death. Am J Med. Jul 2009;122(7):672-8. [Medline].

10. [Guideline] Hogg RJ, Furth S, Lemley KV, et al. National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics. Jun 2003;111(6 Pt 1):1416-21. [Medline].

11. [Guideline] Noordzij M, Korevaar JC, Boeschoten EW, Dekker FW, Bos WJ, Krediet RT. The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guideline for Bone Metabolism and Disease in CKD: association with mortality in dialysis patients. Am J Kidney Dis. Nov 2005;46(5):925-32. [Medline].

12. Seeherunvong W, Abitbol CL, Chandar J, Zilleruelo G, Freundlich M. Vitamin D insufficiency and deficiency in children with early chronic kidney disease. J Pediatr. Jun 2009;154(6):906-11.e1. [Medline].

13. Swinford RD, Portman RJ. Measurement and treatment of elevated blood pressure in the pediatric patient with chronic kidney disease. Adv Chronic Kidney Dis. Apr 2004;11(2):143-61. [Medline].

14. Muscheites J, Wigger M, Drueckler E, Fischer DC, Kundt G, Haffner D. Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Pediatr Nephrol. Oct 2008;23(10):1823-9. [Medline].

15. Eknoyan G. The importance of early treatment of the anaemia of chronic kidney disease. Nephrol Dial Transplant. 2001;16 Suppl 5:45-9. [Medline].

16. Fogo AB. Mechanisms of progression of chronic kidney disease. Pediatr Nephrol. Jul 24 2007;[Medline].

17. Haffner D, Schaefer F, Nissel R, et al. Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. N Engl J Med. Sep 28 2000;343(13):923-30. [Medline].

18. Mak RH. Chronic kidney disease in children: state of the art. Pediatr Nephrol. Oct 2007;22(10):1687-8. [Medline].

19. 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].

20. Salusky IB. A new era in phosphate binder therapy: what are the options?. Kidney Int Suppl. Dec 2006;(105):S10-5. [Medline].

21. Sanchez CP. Secondary hyperparathyroidism in children with chronic renal failure: pathogenesis and treatment. Paediatr Drugs. 2003;5(11):763-76. [Medline].

22. Soergel M, Schaefer F. Effect of hypertension on the progression of chronic renal failure in children. Am J Hypertens. Feb 2002;15(2 Pt 2):53S-56S. [Medline].

Keywords

chronic kidney disease, CKD, end-stage renal disease, ESRD, end-stage kidney disease, ESKD, chronic renal disease, CRD, chronic renal insufficiency, CRI, adaptive hyperfiltration, end-stage kidney failure, proteinuria, progressive kidney insufficiency, anemia, osteodystrophy, systemic hypertension, intraglomerular hypertension, glomerular hypertrophy, metabolic acidosis, hyperlipidemia, tubulointerstitial disease, systemic inflammation, altered prostanoid metabolism, cardiac arrest, myocardial ischemia, pulmonary edema, hyperkalemia, obstructive uropathy, polydipsia, nocturia, treatment, diagnosis

Contributor Information and Disclosures

Author

Sanjeev Gulati, MBBS, MD, DNB(Peds), DM, DNB(Neph), FIPN(Australia), FICN, FRCPC(Canada), Associate Professor, Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences; Senior Consultant in Pediatric Nephrology, Department of Nephrology and Transplant Medicine, Fortis Hospitals, India
Sanjeev Gulati, MBBS, MD, DNB(Peds), DM, DNB(Neph), FIPN(Australia), FICN, FRCPC(Canada) is a member of the following medical societies: American Society of Pediatric Nephrology, Indian Academy of Pediatrics, International Society of Nephrology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Laurence Finberg, MD, Clinical Professor, Department of Pediatrics, University of California at San Francisco and Stanford University
Laurence Finberg, MD is a member of the following medical societies: American Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Frederick J Kaskel, MD, PhD, Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine
Frederick J Kaskel, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)