Renal disease is a major cause of morbidity and mortality in children.1–3
Chronic kidney disease stage 5, previously referred to as end-stage renal disease, occurs in about 9 to 10 children per 1 million annually.
Urinary tract abnormalities, hereditary diseases of the kidney, and urinary tract infection (UTI) account for 50% to 90% of chronic kidney disease (CKD) cases in younger children. In older children, glomerulonephritis (GN) is the most prevalent cause of CKD. The available treatment for CKD stage 4 or 5 is renal transplantation and, as a temporary measure, chronic dialysis, both of which are expensive, associated with various complications, and continue to be unavailable to many children. The pediatrician should play a major role in the early diagnosis and treatment of renal disease, thus contributing to the prevention of CKD.
Presentation of Renal Disease in Children
Early diagnosis of renal disease requires a high index of suspicion because it may be asymptomatic or may present with subtle signs and symptoms that escape medical attention. Pediatricians, therefore, should be familiar with the modes of presentation of these diseases.
Renal disease in children may present with the following:
- Signs and symptoms of renal disease such as failure to thrive, edema, and unexplained fevers
- Abnormal urinalysis
- Electrolyte and acid-base abnormalities
- Decreased renal function
- Glomerular disease
- Renal tubular defects
- Congenital abnormalities of the kidney or urinary tract
- Renal involvement in systemic diseases.
A thorough prenatal, postnatal, and family history should be obtained and a complete physical examination performed, including a blood pressure determination and an accurate abdominal examination. A urinalysis should be performed when indicated.
Signs and Symptoms of Renal Disease
Physicians should look for subtle signs and symptoms of renal disease, such as failure to thrive, unexplained fevers, vague pains, gastrointestinal symptoms, anemia, abdominal mass, edema, hypertension, and metabolic acidosis. A single umbilical artery, ear lobe anomalies, and supernumerary nipples may be associated with renal anomalies. Anemia, growth failure, hypertension, and abnormal retinal changes may be the first signs of CKD. Failure to thrive, lassitude, anorexia, and vomiting may suggest CKD or renal tubular disease. Frequency, urgency, dysuria, hesitancy, and urinary retention suggest UTI, obstructive uropathy, or urinary calculi.
Physicians should be familiar with the normal voiding pattern of children at various ages. Frequency (frequent urination) suggests UTI, whereas polyuria (passage of larger amount of urine than normal) indicates decrease in concentrating ability that occurs in diabetes mellitus, diabetes insipidus, chronic pyelonephritis or CKD. Pollakiuria (Greek pollakis, meaning “often”) is isolated daytime urinary frequency commonly affecting toilet-trained school children, especially boys. It has a sudden onset and may last from a few days to few weeks. Affected children have a normal physical examination, urinalysis, and urine culture, and do not require further investigation or treatment.
Enuresis (nocturnal incontinence) is bedwetting beyond the age when the child should be able to control urination. It is usually idiopathic and associated with a positive family history. It initially requires no other investigation than a urinalysis and urine culture. Secondary and diurnal forms of enuresis, as well as enuresis beyond the age of 12 years, may require urological evaluation. Nocturia (awakening at night to pass urine) may be normal or may suggest a decrease in urine concentrating ability or CKD.
Most renal diseases are painless. Acute pyelonephritis, renal calculi, and trauma to the kidney or bladder may present with abdominal or flank pain. Dysuria (pain on urination) is a symptom of UTI or urethritis. The pain of cystitis or prostatitis is usually suprapubic and gradual in onset.
Abdominal masses of renal origin may represent hydronephrosis, dysplastic or polycystic kidney disease, renal vein thrombosis, Wilms’ tumor, or neuroblastoma. A history of early deafness, renal failure, hypertension, diabetes, or urologic surgery in family members might suggest the presence of renal disease in the child.
Abnormal findings in the urine may be the first sign of renal disease. A carefully performed urinalysis is an easy and informative tool for the pediatrician. Hematuria, proteinuria, and casts are common urinary findings. Hematuria may be gross or microscopic. Urinalysis and, when indicated, an audiogram on immediate family members should be performed, because recurrent benign hematuria, Alport syndrome, immunoglobulin A (IgA) nephropathy, and others may be familial. In general, the presence of persistent and recurrent gross hematuria should prompt referral to a pediatric nephrologist. Significant proteinuria (> 1 g/1.73 m2/day) or proteinuria associated with abnormal red blood cell morphology, decreased renal function, hypertension, low C3, or manifestations of systemic disease are suggestive of glomerular disease and are indications for renal biopsy.
The pediatrician can easily initiate the evaluation of the child with hematuria, and/or proteinuria, quantitate proteinuria and exclude the orthostatic type. Pyuria is usually a sign of UTI, but it may be seen also with any inflammatory process of the kidney and urinary tract, renal calculi, and urinary tract abnormalities. A defect in the concentrating ability of the kidney can occur in diabetes mellitus, diabetes insipidus, renal failure, sickle cell disease, and tubular disorders.
Because recent data suggest that routine urine screening for CKD has low diagnostic yield and rarely leads to an intervention that prevents morbidity and/or mortality, the American Academy of Pediatrics (AAP) recommended in 2007 to discontinue routine urine screening of children.4
Urinary Tract Infection
UTI is the most common bacterial disease responsible for long-term morbidity in children.5 Accurate and prompt diagnosis and treatment are crucial in the prevention of renal scarring, pyelonephritis, and CKD. Diagnosis of UTI requires a high degree of suspicion because of the nonspecific nature of symptoms in younger children, such as unexplained fevers, gastrointestinal symptoms, and irritability. The diagnosis is established on the basis of a urinalysis showing pyuria or bacteriuria and a positive quantitative urine culture. The AAP emphasizes that the urine sample needs to be obtained by bladder puncture or urethral catheterization; samples obtained by a urine bag are valid only when they are negative.
In the author’s opinion, the pediatrician should use discretion and clinical judgment because these procedures might be difficult to perform in a busy pediatric practice. The AAP and the National Institute for Health and Clinical Excellence (NICE) in the UK now recommend a marked reduction in the imaging that children younger than 3 years with UTI should undergo.6,7 Both the AAP and NICE agree that prophylactic antibiotic treatment should not be routinely used in these children, including those with major vesicoureteral reflux.
Electrolyte and Acid-Base Abnormalities
Electrolyte and acid-base abnormalities are commonly seen in pediatric practice. They usually present with nausea, vomiting, diarrhea, decreased intake of fluids, irritability, lethargy, weight loss, dry skin and mucus membranes, elevated pulse, seizures, and coma. The most common cause of acid-base disorder in children is metabolic acidosis secondary to dehydration. Dehydration is the result of fluid loss because of vomiting, fever, upper respiratory infection, diabetes mellitus, diabetes insipidus, and renal disease with loss of concentrating ability. Affected children may present with a very complex clinical picture, and the treating physician should be familiar with the intricacies of their diagnosis and management.
Decreased Renal Function
Serum creatinine and blood urea nitrogen are the most commonly used blood biomarkers to monitor a decrease in renal function. Azotemia is elevated serum urea nitrogen, renal failure is reduction in renal function, and uremia, although a misnomer, is the syndrome that encompasses the overt consequences of CKD such as anemia, osteodystrophy, acidosis, growth delay, and central nervous system, gastrointestinal, and other manifestations. Acute kidney injury (AKI; abrupt severe reduction in glomerular filtration) is characterized by a rise in serum creatinine. Patients with AKI present with acidosis, anemia, and fluid overload. The etiology of AKI should be determined promptly, because some causes are reversible. Affected patients should be referred promptly to a pediatric nephrologist.
Growth retardation, anemia, history of underlying renal disease, renal osteodystrophy, or contracted kidneys suggest the presence of CKD, which is defined as the stage at which the kidneys are irreversibly damaged and unable to maintain body homeostasis. The true prevalence of CKD in children is uncertain. Congenital renal abnormalities of the urinary tract are the most prevalent cause of CKD in young children, whereas GN is more prevalent in adolescents.8
These patients should also be referred to the pediatric nephrologist because they frequently progress to CKD stage 5 (previously termed end-stage renal disease), which requires chronic dialysis and renal transplantation. Early diagnosis and treatment of these conditions is crucial because many causes of CKD in children are potentially preventable (eg, congenital abnormalities of the kidney and UTI). The stages of CKD are presented in Table 1.
Table 1. Stages of Chronic Kidney Disease
Glomerular disease may be associated with serious morbidity and possible progression to CKD. Pediatricians should be able to recognize acute GN, nephrotic syndrome, and chronic GN. The majority of children with GN present with proteinuria, hematuria, hypertension, edema, reduced renal function, or the nephrotic syndrome. Abnormal urinalysis may be the only presenting sign of chronic GN, but routine screening in children has a low diagnostic yield.
Post-streptococcal acute GN is familiar to the practicing pediatrician. Most affected children have a benign course and can be treated easily by the primary care physician on an ambulatory basis. A nephrology consultation should be obtained on patients with hyperkalemia, nephrotic syndrome, cardiac overload, and prolonged oliguria or renal insufficiency.
Nephrotic syndrome occurs in 1 in 50,000 children per year. It is characterized by proteinuria ≥ 40 mg/m2/hr (or 50 mg/kg/day), serum albumin < 2.5 g/dL, and variable degrees of edema. Random urine protein-to-creatinine ratio is above 2. The most common form of nephrotic syndrome in children is minimal change, which is characterized by response to corticosteroids and good prognosis, although most patients have one or more relapses. Patients with this type of nephrosis may be treated by the primary care physician, whereas those who are steroid-resistant or steroid-dependent, those with a suspected structural glomerular abnormality, and those associated with systemic disease should be referred to the pediatric nephrologist, because they usually require a kidney biopsy and knowledge of the current therapeutic regimens.
Renal Tubular Disease
Renal tubular diseases (eg, renal glucosuria, Fanconi syndrome with or without cystinosis, aminoacidurias, renal tubular acidosis, nephrogenic diabetes insipidus, and others) are rare, usually inherited, and present with growth failure.9 They may also present with acidosis, glucosuria, aminoaciduria, phosphaturia, rickets, and inability to concentrate the urine. It is important to diagnose these disorders correctly, because some of them are benign and require no treatment. Pediatricians will probably need the help of a pediatric nephrologist in the diagnosis and management of major renal tubular disorders.
Congenital Abnormalities of the Kidney and Urinary Tract
With the prevalence of routine prenatal ultrasound performed as early as 12 to 16 weeks of gestation, the pediatrician is now confronted with kidney and urinary tract abnormalities presenting in the neonatal period. A common abnormality is mild isolated hydronephrosis. This anomaly usually needs follow-up with ultrasound, but usually resolves spontaneously.10 Severe hydronephrosis should be investigated and followed closely by a urologist. This could be caused by a uretero-pelvic junction stenosis, vesicoureteral stenosis, posterior urethral valves, or vesicoureteral reflux. Recent evidence shows that decrease in urinary epidermal growth factor may indicate an increase in hydronephrosis grade over time.
Congenital abnormalities of the kidney and urinary tract may be minor and discovered incidentally, or major and complicated by infection, obstruction, stone formation, and pyelonephritis leading to renal scarring and CKD. They represent 25% of the total ultrasonographically diagnosed malformations occurring in 0.25% to 0.7% of fetuses, and occur in 5% to 10% of the population, 23% of patients with chromosomal aberrations, and two-thirds of patients with abnormalities of other organ systems.11 They are also responsible for one-third to two-thirds of CKD in children.
Urinary tract abnormalities should be suspected in any child with UTI, congenital anomalies of other organ systems (cardiovascular, gastrointestinal, central nervous system and others), chromosomal aberrations, various malformation syndromes, and those with single umbilical artery. Hundreds of genetic conditions and syndromes may be associated with renal and urogenital abnormalities.1
Hypertension, which occurs in < 1% to 5.1% of children, is defined as an average systolic and/or diastolic blood pressure at the 95th percentile or above for age and sex measured on at least three separate occasions.12 The most common symptoms of hypertension in children are headache, difficulty falling asleep, tiredness, and chest and abdominal pain.
Although pediatric hypertension was previously assumed to be secondary to renal, cardiovascular, or endocrine causes, there is now increased evidence that it could be a part of a spectrum of essential hypertension, mainly linked to an epidemic of pediatric obesity. Diagnosis of hypertension in children relies upon blood pressure distribution tables adjusted for gender, age, and height. Blood pressure should be measured routinely in every child starting at age 3 years and in children with comorbid conditions such as obesity, heart or kidney disease, history of umbilical line, or UTI.13
Pediatricians can play a pivotal role in the early diagnosis and treatment of hypertension to reduce long-term cardiovascular comorbidity and mortality. Control of hypertension with pharmacological and nonpharmacological therapy, including weight reduction, dietary modification, and physical conditioning, are important in preventing future morbidity from the disease.
Renal Involvement in Systemic Diseases
Systemic vasculitis (systemic lupus erythematosis and Henoch-Schönlein purpura), nonrenal infection (hemolytic uremic syndrome and staphylococcal bacteremia) and chronic disease (sickle cell disease, diabetes mellitus, malignancy) may affect the kidney in childhood.1 The kidney should be studied in any individual with multisystem disease. Affected patients may present with arthritis, rash, hypertension, hematuria, or proteinuria. The diagnosis of renal involvement in systemic disease is based on clinical findings (hematuria, proteinuria, hypertension, decreased C3, decreased renal function) as well as renal histology.
Management of Pediatric Renal Disease
Pediatricians should have a high index of suspicion of renal disease, should take a detailed patient and family history, and should perform a complete physical examination, including blood pressure measurement, and exclude the presence of systemic diseases. They should perform a urinalysis on the patient (and on family members when needed), urine culture, other laboratory tests, and indicated imaging studies.
In the present era of managed care, pediatricians find themselves performing some duties that have traditionally been performed by the specialist. Therefore, they should be able to treat UTI, uncomplicated acute GN, conditions not associated with acute or progressive deterioration of renal function, minimal change nephrotic syndrome, mild congenital abnormalities, and other renal afflictions with which the physician is comfortable dealing.
It is difficult to clearly delineate indications for referral of patients to the pediatric nephrologist. The most common reasons for referral to a pediatric nephrologist include fluid and electrolyte disorders and hematuria/proteinuria, followed by chronic GN, nephrotic syndrome, UTI, hypertension, acute GN, and CKD.14
Pediatricians should be familiar with the modes of presentation of different renal conditions, and should have a high index of suspicion for renal disease. They may initiate evaluation and treatment of kidney disease to the extent that they are confident, referring more complicated conditions to the pediatric nephrologist. Pediatricians should play a major role in the early diagnosis and treatment of renal disease to help prevent CKD.
- Barakat AJ, Chesney RW, eds. Pediatric Nephrology for Primary Care. Elk Grove Village, IL: The American Academy of Pediatrics; 2009.
- Avner ED, Harmon WE, Niaudet P, Yoshikawa N, eds. Pediatric Nephrology. 6th ed. Baltimore: Lippincott Williams and Wilkins; 2009 doi:10.1007/978-3-540-76341-3 [CrossRef] .
- Docimo SG, Canning DA, Khoury AE. The Kelalis-King-Belman Textbook of Clinical Pediatric Urology. 5th ed. Boca Raton, FL: Taylor & Francis; 2007.
- Committee on Practice and Ambulatory Medicine. Recommendations for preventive pediatric health care. Pediatrics.1995;96(2 Pt 1):373–374.
- American Academy of Pediatrics. Practice parameter: the diagnosis, treatment and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics. 1999;103(4 pt 1):843–852.
- Tullus K. What do the latest guidelines tell us about UTIs in children under 2 years of age. Pediatr Nephrol. 2012;27(4):509–511 doi:10.1007/s00467-011-2077-5 [CrossRef] .
- Pennesi M, L’Erario I, Travan L, Ventura A. Managing children under 36 months of age with febrile urinary tract infection: a new approach. Pediatr Nephrol. 2012;27(4):611–615 doi:10.1007/s00467-011-2087-3 [CrossRef] .
- Seikaly MG, Ho PL, Emmett L, Fine RN, Tejani A. Chronic renal insufficiency in children: The 2001 Annual report of the NAPRTCS. Pediatr Nephrol. 2003;18(8):796–804 doi:10.1007/s00467-003-1158-5 [CrossRef] .
- Chesney RW. Specific renal tubular disorders. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia: WB Saunders; 2004:745–750.
- Alconsher LF, Tombesi MM. Natural history of bilateral mild isolated antenatal hydronephrosis conservatively managed. Pediatr Nephrol. 2012;27(7):1119–1123 doi:10.1007/s00467-012-2113-0 [CrossRef] .
- Barakat AY, Drougas JG. Occurrence of renal and urinary tract abnormalities in 13,775 autopsies. Urology. 1991;38(4):347–350 doi:10.1016/0090-4295(91)80150-6 [CrossRef] .
- McNiece KL, Poffenbarger TS, Turner JL, Franco KD, Sorof JM, Portman RJ. Prevalence of hypertension and prehypertension among adolescents. J Pediatr. 2007;150(6):640–644 doi:10.1016/j.jpeds.2007.01.052 [CrossRef] .
- National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The Fourth Report on the Diagnosis, Evaluation and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics. 2004;114(2 Suppl 4th Report):555–576.
- Foreman JW, Chan JC. 10-year survey of referrals to a pediatric nephrology program. Child Nephrol Urol. 1990;10(1):8–13.
- National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–S266.
Stages of Chronic Kidney Disease
||Primary disease, fluid retention, hypertension
||Primary disease, comorbid conditions
||Same as stage 3, plus hyperparathyroidism, renal osteodystrophy, anemia, acidosis, growth delay
||Same as stage 3, plus consider preemptive renal transplant when GFR < 20
||Same as stage 4, plus uremic syndrome
||Initiate dialysis, renal transplant