Chronic renal failure (CRF) is an irreversible reduction in renal function, or glomerular filtration rate (GFR), with accompanying derangements in biochemical homeostasis. The term chronic kidney disease (CKD) incorporates CRF and chronic renal insufficiency, which are considered part of the spectrum of CKD. End-stage renal disease (ESRD) is defined as CRF so severe that a form of renal replacement therapy (such as peritoneal dialysis) is required. The Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation established standards for the definition and classification of CKD to promote early diagnosis (Table 111-1)¹. These standards define CKD as being present in any patient who meets one of two criteria: (1) there is evidence of kidney damage for 3 months or more, as defined by structural abnormalities of the kidney with or without decreased GFR, as evidenced by abnormalities in the composition of blood or urine, abnormalities in imaging tests, or abnormalities on kidney biopsy; (2) the GFR is less than 60 mL/minute per 1.73 m² for 3 months or more, with or without any structural changes. GFR is not adequately determined using serum creatinine alone; it should be estimated using a prediction equation such as the Schwartz equation (Table 111-3)².

The incidence of CRF in children is low, and the incidence of ESRD is 9 children per 1 million of the age-related population.¹ Unlike adults with CRF, in whom the primary causes are diabetes and hypertension, the overwhelming majority of children with CRF have primary renal disease, usually of a congenital origin.^3,4 This means that the care of children with CRF can deviate dramatically from that of adults.

There have been remarkable improvements in the treatment of children with CRF and ESRD, with a subsequent increase in the prevalence of CRF in the pediatric population. Children with CRF are more likely to have polyuria and salt wasting, complicating their care as compared to adults with CRF. Additionally, they have the requirement for growth and development. Normalization of these parameters is the key to successful treatment. These factors, along with the psychosocial issues specific to childhood, make the treatment of children with CRF challenging, but with meticulous care and attention to detail, these children can reach adulthood with minimal associated morbidity.

PATHOPHYSIOLOGY

There is a wide spectrum of causes of childhood CRF. Regardless of the underlying cause, the basic pathophysiology is the same. Damage to the nephron can be direct or as the result of adaptive hyperfiltration in which other areas try to compensate for the loss of nephrons from the initial injury. The increased filtration leads to increased glomerular pressure which over time causes inflammation and damage. Both pathways lead to glomerular scarring, tubular atrophy, and interstitial fibrosis, with an ultimate reduction in normal renal function. The consequences of decreased function are usually not evident until renal function is less than 30% to 50%. These consequences can include acidosis, hyper- or (more rarely) hypokalemia, anemia, deranged calcium-phosphorus balance (hyperphosphatemia and hypocalcemia), abnormal bone metabolism, hypertension, short stature, hyponatremia, and disrupted water homeostasis.

The clinical presentation of children with CRF varies tremendously due to both the wide range of causes and the different stages of disease at which a child may present. Stage 1 and Stage 2 patients are generally asymptomatic. Polyuria is often an early sign of many congenital anomalies and diseases that impair urine concentrating ability before GFR decreases. The most universal finding in children presenting with undiagnosed CRF is growth failure. Fatigue, anorexia, malaise, and worsening school performance are also common findings in patients with Stage 3 and above. Renal osteodystrophy can be seen, regardless of the cause of CRF. Signs and symptoms may include bone pain, refusal to walk, valgus deformities of the lower extremities, frontal bossing, and a rachitic rosary. Children with congenital uropathies or nephropathies are likely to present with the symptoms of polyuria and salt wasting: dehydration, emesis, acidosis, hyperkalemia, and either hyper- or hyponatremia, depending on the salt and water balance of the individual patient. This subset of patients rarely has hypertension. Children with juvenile nephronophthisis (chronic, progressive tubulointerstitial nephritis) can also present with signs and symptoms of polyuria, but they often have accompanying hypertension and ocular abnormalities. Children with reflux nephropathy may present initially with signs and symptoms of pyelonephritis and develop hypertension as the nephropathy progresses. Edema and hypertension are typically found in children with CRF due to a glomerulopathy. Polycystic renal disease and renal tumors may present with abdominal pain, hypertension, and an abdominal mass.

CRF should be suspected in children with marked nonhemolytic anemia, hyperparathyroidism, small kidneys on renal ultrasonography, or physical findings consistent with rickets.

There is a wide spectrum of causes of childhood CRF (Table 111-2). In developed countries, approximately two-thirds of children with CRF have congenital conditions such as posterior urethral valves or renal dysplasia.¹