eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Chronic Kidney Disease

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
Contributor Information and Disclosures

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

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