Renal Disease in Children (Nephrotic and Nephritic Syndrome)
Essentials
Suspect renal disease and perform urine dipstick tests if a child develops oedema.
Proteinuria in association with oedema suggests nephrotic syndrome, proteinuria and haematuria nephritic syndrome.
Any child with significant proteinuria and/or haematuria shown by dipstick test and oedema should be referred as an emergency case to specialized care.
Idiopathic nephrotic syndrome in children
The most common glomerular disease in children
The aetiology is unknown.
The usual age at onset is 2 to 5 years. About 80% of patients are younger than 6 years old.
The incidence is about 2/10 000 children, and the disease is more common in boys (3:2).
In infants, particularly those below the age of 6 months, nephrotic syndrome is due to congenital and often hereditary diseases.
Symptoms and findings
Generalized oedema is usually observed in the lower extremities, the face, particularly the periorbital area, and the abdomen. Gravity affects the location of oedema: in the morning, oedema can be found particularly in the facial area, in the evening in the ankles.
There may be ascites or pleural effusion without other oedema.
There may be oedema in the scrotal or vulvar area.
Increase in weight
The circulating blood volume should be assessed because in prolonged conditions there may be hypovolaemia. The patient may have concomitant oedema and hypovolaemia.
A demarcation line in the temperature of the extremities is a good indicator of hypovolaemia. Capillary refill of the nail bed is also reduced in these cases.
Abdominal pain may be another indicator of hypovolaemia.
Oedema is rare in patients with plasma albumin levels exceeding 20 g/l.
Blood pressure is usually normal.
Diagnosis
A urine dipstick test is sufficient in outpatient care. If clear proteinuria is found in a patient with oedema, they should be referred for further hospital examinations.
Hypoalbuminaemia will develop if the level of proteinuria is so high that the liver is not capable of producing new albumin to replace the loss. In a patient of adult size, this occurs at a protein excretion equivalent to about 3-5 g/day.
The amount of protein excreted in urine may be as high as 30-50 g/day.
At the primary stage, plasma albumin concentrations are usually < 25 g/l and often well below this.
Patients typically have no significant haematuria. Microscopic haematuria is found in about 20% of patients.
Casts (epithelial cell or fatty casts) may be found in urine.
A urinary sodium test will help to assess hypovolaemia.
In patients with clear circulating hypovolaemia, fluid should be administered in the form of albumin 5% (1 g/kg, e.g. a child weighing 15 kg would be given 15 g = 300 ml albumin 5%) over 2-4 hours.
Due to increased risk of thrombosis, bed rest should not be recommended.
For patients with oliguria and clearly increasing weight or significant oedema, ascites or pleural effusion, albumin 20% at a dosage of 1 ml/kg in 20-30 min + 0.5 mg/kg (up to 20 mg) furosemide can be given intravenously 4-6 times a day.
Blood pressure and pulse should be monitored regularly during treatment to assess the circulating blood volume.
If the patient has no volume depletion, the amount of maintenance fluid can be limited to 70% of the calculated maintenance fluid requirement (calculated according to the Holliday-Segar method) to reduce loss of protein.
A diet low in salt (no added salt) should be followed, as far as possible.
Pharmacological treatment of the first episode
Prednisolone at a dosage of 60 mg/m2 /day (up to 80 mg) in 2-3 doses for 4-6 weeks, and subsequently 40 mg/m2prednisolone as single doses every other morning for 6 weeks
PPI as stomach protection is not needed as routine medication, but it may be started if abdominal symptoms appear.
Indications for referral to paediatric nephrologist at a university hospital
No remission during 4 weeks of treatment
Age < 12 months or > 12 years
Persistent hypertension
Macroscopic haematuria
Impaired renal function
Low C3 or C4
Relapses
Relapses of idiopathic nephrotic syndrome are common. The criteria for relapse are recurrent excretion of protein in urine at a level of > 40 mg/m2 /h or a urinary protein-to-creatinine ratio of > 200 mg/mmol.
Relapses are treated by giving 60 mg/m2 (up to 80 mg) prednisolone in 2-3 doses until protein excretion has remained normal for 3 days. Subsequently 40 mg/m2 as single doses every other day for 4 weeks. Prednisolone should then be tapered off during 4 weeks.
A small proportion of patients experience relapses frequently (2 or more within 6 months) or during glucocorticoid treatment. These patients should be referred to a unit of paediatric nephrology at a university hospital for assessment of the need for biopsy.
The most common histological finding is so-called minimal change disease, where nothing abnormal is found in a renal biopsy sample analyzed by light microscopy.
Nephritic syndrome
Definition
Acute glomerular damage associated with various other clinical findings
Peripheral or pulmonary oedema, sometimes congestive heart failure
Hypertension (salt and water retention), usually with symptoms
Haematuria (microscopic or macroscopic) with red cell casts
Symptoms and findings associated with systemic disease
Haematuria and/or proteinuria and renal dysfunction
General symptoms, such as malaise, abdominal pain, vomiting, fever, weight loss, fatigue, headache, rashes, purpura or joint symptoms
In addition, there may be equivocal respiratory or cardiac symptoms or dysfunction of several organ systems.
Diagnosis
Urine dipstick tests are sufficient in outpatient care. If these show clear haematuria and/or proteinuria and there are symptoms of nephritis, the patient should be referred for further examination in specialized care.
Urine particle counting and culture
Quantitative determination of protein in urine (urinary protein, urinary creatinine)
If volume depletion is suspected, urinary sodium (not always available)
In ultrasonography of the urinary tract, the kidneys may appear swollen.
C3 is usually decreased in patients with APSGN.
C4 is usually normal in APSGN but reduced in SLE, shunt nephritis and MPGN.
AST concentration is increased in 80 to 90% of patients after streptococcal pharyngitis.
Deoxyribonuclease antibody concentrations are increased after streptococcal skin infection.
The anti-GBM antibody test is positive in patients with anti-glomerular basement membrane glomerulonephritis.
The ANCA antibody test is positive in patients with glomerulonephritis associated with Wegener's granulomatosis or microscopic polyangitis Vasculitides.
Culture of pharyngeal streptococci may not be appropriate because the result may be positive in as many as 20% of school age children.
Treatment of APSGN
Depending on the severity of the disease, patients will require monitoring in specialized care either in hospital or at an outpatient clinic.
Eradication of the microbes will not affect the severity or duration of the disease but may prevent the spread of bacterial strains associated with various types of glomerulonephritis.
Pharmacotherapy is supportive.
Restriction of salt and fluid intake, loop diuretics, short-acting antihypertensive medication, such as nifedipine
Symptoms usually disappear within 2 to 3 weeks.
The long-term prognosis is good but microscopic haematuria and/or mild proteinuria may persist for several years.