Pediatric Nephrotic Syndrome: Definition and Diagnosis

Study Notes

Nephrotic Syndrome Definition

Nephrotic syndrome is characterized by:
- Generalized edema
- Proteinuria (>40 mg/hour/m2 or >2g/m2/day)
- Hypoproteinemia (total serum protein < 5.6 g/dl, serum albumin ≤ 2.5 g/dl)
- Hypercholesterolemia (> 200 mg/dl)
- Hyperlipidemia (> 900 mg/dl)

Classification

Classification of nephrotic syndrome:
- Nephrotic syndrome: Edema, uPCR > 2000 mg/g, or > 300 mg/dl, or 3+ protein on urine dipstick, hypoalbuminaemia ≤ 2.5 g/dl
- Complete remission: Proteinuria reduction of 50% or greater from the presenting value and absolute uPCR between 200 and 2000 mg/g
- Partial remission: Failure to reduce urine protein excretion by 50% from baseline or persistent excretion uPCR > 2000 mg/g
- No remission: Attainment of complete remission within initial 4 weeks of corticosteroid therapy
- Initial responder: Attainment of complete remission within initial 4 weeks of corticosteroid therapy
- Initial nonresponder/steroid resistance: Failure to achieve complete remission after 8 weeks of corticosteroid therapy
- Relapse: uPCR > 2000 mg/g or > 3+ protein on urine dipstick for 3 consecutive days
- Infrequent relapse: One relapse within 6 months of initial response, or one to three relapses in any 12-month period
- Frequent relapse: Two or more relapses within 6 months of initial response, or four or more relapses in any 12-month period
- Steroid dependence: Two consecutive relapses during corticosteroid therapy, or within 14 days of ceasing therapy

Age Classification

Classification of nephrotic syndrome by age:
- Congenital nephrotic syndrome (onset in the first 3 months of life)
- Infantile nephrotic syndrome (onset between 4 months and 1 year)
- Child and adolescent nephrotic syndrome

Treatment of Congenital Nephrotic Syndrome

Treatment of congenital nephrotic syndrome:
- Finnish-type congenital NS: proper nutrition, bilateral nephrectomy, albumin, peritoneal dialysis, ACEI, kidney transplantation, thyroid hormones
- Other forms of congenital NS: treatment of infections, bilateral nephrectomy, corticosteroid therapy for those with minimal damage or FSGS

Primary and Secondary Nephrotic Syndrome

Primary (idiopathic) nephrotic syndrome:
- Classified according to the histological lesions:
  - Minimal change disease (MCD)
  - Focal and segmental glomerulosclerosis (FSGS)
  - Membranoproliferative glomerulonephritis (MPGN)
  - Membranous nephropathy (MGN)
Secondary nephrotic syndrome:
- Due to circulatory disorders:
  - Renal vein thrombosis
  - Constrictive pericarditis
  - Congestive heart failure
- Due to toxins or drugs:
  - Penicillamine
  - Gold salts
  - Nonsteroidal anti-inflammatory drugs (NSAIDs)
  - Wasp sting
- Due to infections:
  - Group A streptococci
  - Hepatitis B and C
  - HIV
  - Syphilis
  - Malaria
  - Infected ventriculoperitoneal shunt
  - Bacterial endocarditis
- Due to systemic diseases:
  - SLE
  - Other vasculitis (Henoch-Schonlein purpura)
  - Diabetes
  - Amyloidosis

Pathophysiology

Pathophysiology of nephrotic syndrome:
- Different mechanisms depending on the etiology:
  - Immune complex diseases (Ag+Ab→CIC)
  - Anti-GBM antibodies
  - Direct toxic mechanism on GBM
  - Disturbances of cellular-mediated immunity
- Protein permeability alteration of GBM
- ↑ protein filtration with exceeding maximum transport capacity of TCR
- Proteinuria, hypoproteinemia, and dysproteinemia
- Redistribution of water in the intracellular and intravascular compartments
- Hypovolemia and inadequate secretion of ADH
- Edema and water retention

Diagnostic Algorithm

Diagnostic algorithm:
1. Specify renal etiology of edema, excluding other causes
2. Identify other renal diseases associated with edema
3. Confirm nephrotic syndrome
4. Establish the etiology of nephrotic syndrome (primary or secondary)

Diagnostic Workup

Diagnostic workup:
- Case history and clinical examination
- Urine analysis: urinalysis, dosing urinary protein, albumin/creatinine ratio, urinary ionogram
- Blood tests: complete blood count, inflammation tests, protein/albumin, ionogram, urea, creatinine, cholesterol, total lipid panel, liver transaminases, blood clotting tests, ASLO, Complement (C3 and C4), antinuclear Ab, anti-dsDNA, HIV, toxoplasma, syphilis, CMV serology, and hepatitis B and C serology
- Abdominal ultrasound, Doppler, echocardiography, and PRB

Corticosteroid Therapy

Corticosteroid therapy:
- Indications: at diagnosis, in progress, and during treatment
- Response to therapy: good response, poor response, and steroid resistance

Treatment

Treatment of nephrotic syndrome:
1. Diet and activity measures:
  - Bed rest
  - Normocaloric diet
  - Protein restriction
  - Carbohydrate and lipid restriction
  - Na+ restriction
2. Adjuvant therapy:
  - Edema treatment: diuretics, albumin, and plasma expander
  - Treatment of HBP: ACEI, beta blockers, calcium channels blockers
  - Antiplatelet drugs and anticoagulant treatment
  - Infection treatment
3. Corticosteroid therapy:
  - PREDNISONE 1,5-2 mg/kg/day orally
  - METILPREDNISOLONE 500-1000 mg/m2/day
4. Immunomodulatory drugs:
  - LEVAMISOL 2,5 mg/kg alternative

Description

Test your knowledge on the definition and diagnosis of pediatric nephrotic syndrome, including the characteristics of generalized edema, proteinuria, and lipid abnormalities. Learn about the classification and criteria for this kidney disorder.