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JussiMerenmies

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.
  • The patient has marked proteinuria. The protein-to-creatinine ratio in urine is > 200 mg/mmol Interpretation of Urine Test Results in Children.
  • 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.
    • Urinary sodium concentrations < 10 mmol/l strongly suggest a reduced blood volume.
    • In patients with urinary sodium > 20 mmol/l hypovolaemia is unlikely (unless the patient has been given diuretics).
    • However, urinary sodium tests are rarely available during on-call hours.
  • Haemoglobin and haematocrit levels also help to assess hypovolaemia.
  • Urinary creatinine concentration may be increased, suggesting reduced excretion of urine.
  • Hyperlipidaemia is a common finding.
  • IgG levels are low, IgM levels usually elevated.
  • Complement levels are normal.
  • Plasma urea and creatinine concentrations are usually normal but may be slightly increased in patients with hypovolaemia (prerenal azotaemia).
  • Plasma sodium and potassium concentrations are normal.

Treatment Corticosteroids for Nephrotic Syndrome in Children, Non-Corticosteroid Treatment for Steroid-Sensitive Nephrotic Syndrome in Children, Interventions for Idiopathic Steroid-Resistant Nephrotic Syndrome in Children

  • Treatment is usually started in hospital.
  • 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/m2 prednisolone 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.
  • Calcium and vitamin D supplements for bone protection
  • Glucocorticoids should be tapered off within four weeks.
  • Towards the end of glucocorticoid treatment, the ACTH test should be performed to examine the function of the suprarenal glands.

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
    • Proteinuria that may be of nephrotic level
    • Reduced glomerular filtrate (oliguria, uraemia, increased creatinine levels)

Acute poststreptococcal glomerulonephritis (APSGN)

  • The most common cause in children, in about 80% of cases
  • Develops 1-2 weeks after streptococcal pharyngeal infection or about 6 weeks after skin infection.
  • Symptoms vary from asymptomatic haematuria to acute renal failure (macroscopic haematuria, oliguria, hypertension, oedema).

Other aetiology

  • Other bacterial infections: Staphylococcus aureus, Streptococcus pneumoniae, Mycoplasma pneumoniae, Escherichia coli
  • Viral infections: EBV, CMV, HSV, VZV, parvovirus 19, hepatitis B and C
  • Henoch-Schönlein purpura Henoch-Schönlein Purpura
  • IgA mesangial glomerulonephritis Iga Nephropathy
  • SLE Systemic Lupus Erythematosus (Sle)
  • Membranoproliferative (mesangiocapillary) glomerulonephritis (MPGN)
  • ANCA-positive vasculitis Vasculitides
  • Anti-glomerular basement membrane antibody (anti-GBM) glomerulonephritis Glomerulonephrites
  • Shunt nephritis
  • Alport's syndrome
  • Haemolytic-uraemic syndrome

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.
  • Antinuclear and DNA antibody tests are positive in patients with SLE Systemic Lupus Erythematosus (Sle).
  • 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.

Evidence Summaries