Nephrotic Syndrome

Nephrotic Syndrome: Excerpt from The 5-Minute Pediatric Consult

Lawrence Copelovitch, MD

Nephrotic Syndrome - BASICS

Nephrotic Syndrome - description

Nephrotic syndrome (NS) applies to any glomerular disorder associated with heavy proteinuria, hypoproteinemia, edema, and hypercholesterolemia. Nephrotic-range proteinuria is found when there is 4+ protein on the urine dipstick, which usually correlates with proteinuria of >40 mg/m²/hr or 50 mg/kg/d

Nephrotic Syndrome - epidemiology

• Minimal change nephrotic syndrome (MCNS) is the most frequent cause of nephrotic syndrome in younger children.
  • Occurs mainly between the ages of 2 and 8 years, with a peak at 3 years of age.
  • Boys are more commonly affected than girls (3:2).
  • Atopy and minimal change nephrotic syndrome have an association.
  • HLA-DR7 is most common MHC haplotype associated with MCNS.
• Focal segmental glomerulosclerosis (FSGS) is the 2nd most frequent cause of nephrotic syndrome in childhood
  • Children with FSGS are more likely than children with MCNS to have steroid dependant or steroid resistant nephrotic syndrome (SRNS)
• Examples of congenital NS are Finnish, diffuse mesangial sclerosis (DMS) mesangiosclerotic, and syphilitic nephrosis.

Nephrotic Syndrome - incidence

• 2–7 per 100,000 in children <16 years
• Black children have a higher incidence of focal segmental glomerulosclerosis (FSGS) than do white and Asian children.

Nephrotic Syndrome - prevalence

16 per 100,000 in children <16 years

Nephrotic Syndrome - risk factors

Immunologic abnormalities:

• A number of immunologic abnormalities are seen with NS that predispose to infection.
  • These include defective opsonization, decreased serum levels of complement factors D and B, abnormal humoral immunity, decreased delayed hypersensitivity and proliferative responses, and increased suppressor-cell activity and suppressor lymphokine levels.

Nephrotic Syndrome - genetics

A positive family history is present in 3.5% of patients.

Nephrotic Syndrome - pathophysiology

MCNS:

• The glomerular tuft and size are normal.
• Mesangial expansion is absent or minimal.
• Immunofluorescence is usually negative, although scanty staining for C3, IgM, and IgA may occasionally be found; these patients are usually steroid dependent.
• Electron microscopy reveals widening and effacement of the visceral epithelial foot processes, which are reversible, occur in association with proteinuria, and are not specific for MCNS.

Nephrotic Syndrome - etiology

• Most pediatric cases are primary; 5–10% are secondary to other diseases.
• The most common primary cause of NS in childhood is MCNS. It is characterized by minimal histologic changes on light microscopy, and is usually a steroid sensitive nephrotic syndrome (SSNS).
• Other causes of primary nephrotic syndrome include focal segmental glomerulosclerosis and membranous and membranoproliferative glomerulonephritis (GN).
• Secondary causes of NS include infections, vasculitis, diabetes, drugs (e.g., NSAIDS), and hereditary disorders.

Nephrotic Syndrome - DIAGNOSIS

Nephrotic Syndrome - signs & symptoms

• Fatigue and general malaise
• Reduced appetite
• Weight gain and facial swelling
• “Puffy eyes”
• Abdominal swelling or pain
• Urine that is foamy
• Atopy
• Pitting-dependent edema
• Fluid accumulation in body spaces (ascites, pleural effusions, scrotal swelling)
• White nails, lusterless hair, soft ear cartilage
• Hepatomegaly
• Mild hypertension

Nephrotic Syndrome - history

• Inquire about known atopy or food intolerance.
• Inquire about drug exposure (especially NSAI agents).
• Inquire about any infections or hernias.

Nephrotic Syndrome - physical exam

Look for edema in the most dependent area of the child:

• Legs
• Lumbar spine
• Scalp
• Soft ear cartilage

Nephrotic Syndrome - tests

Nephrotic Syndrome - lab

• The urine dipstick usually shows 2,000 mg/dL (4+) of protein.
  • In small children with NS, the urine dipstick may show <4+.
• Timed or spot urine protein collection:
  • 24-hour urine shows >50 mg/kg/d.
  • Spot urine protein/creatinine ratio is >2.
• Monitor complications of glucocorticoid therapy:
  • Growth failure
• Home testing:
  • The 1st morning urine is tested for protein.

Nephrotic Syndrome - imaging

In complicated cases, renal ultrasound to evaluate kidney size and parenchymal architecture

Nephrotic Syndrome - differencial diagnosis

• Edema:
  • CHF
  • Liver failure
  • Protein-losing enteropathy
  • Protein energy malnutrition (Kwashiorkor)
• Minimal change nephrotic syndrome:
  • Focal glomerulosclerosis (FSGS)
  • Membranous GN
  • Membranoproliferative GN
  • Diffuse mesangioproliferative GN

Nephrotic Syndrome - TREATMENT

Nephrotic Syndrome - general measures

• Corticosteroids are the first-line therapy (see “Medications”).
• Influenza vaccination yearly
• Pneumococcal vaccination according to the “high-risk” schedule (23 valent pneumococcal vaccine)

Nephrotic Syndrome - diet

Restrict salt intake while in relapse or on daily corticosteroids.

Nephrotic Syndrome - medication

Nephrotic Syndrome - first line

Corticosteroids used as 1st-line agents. There are a number of similar regimens:

• On presentation: Daily corticosteroids for 4 weeks, followed by alternate-day therapy for 4 weeks
• On relapse: Daily corticosteroids until in remission, followed by alternate-day therapy for 8–12 weeks

Nephrotic Syndrome - second line

• Alkylating agents (cyclophosphamide, chlorambucil)
• Mycophenolate mofetil (MMF)
• Calcineurin inhibitors (cyclosporine A, tacrolimus)
• Diuretics
• Albumin

• Live vaccines are contraindicated while daily corticosteroids or alkylating agents are being given.
• Children in relapse, on corticosteroids, or on alkylating agents and who are nonimmune and exposed to varicella should receive VZIG.
• Albumin and/or Lasix must be used cautiously to prevent fluid overload or intravascular dehydration.

Nephrotic Syndrome - FOLLOW UP

• When to expect improvement:
  • Remission occurs 2–4 weeks after starting corticosteroids in MCNS.
• Signs to watch for:
  • Fever, abdominal pain, oliguria
• Pitfalls:
  • Recognize situations in which hypovolemia may occur.

Nephrotic Syndrome - prognosis

The prognosis for MCNS is excellent, with a mortality rate of <1%.

Nephrotic Syndrome - complications

• Most complications are secondary to steroid therapy and include growth retardation, glaucoma, posterior lens cataracts, obesity, mood changes, hirsutism, osteoporosis, and infection.
• Primary peritonitis and cellulitis may occur de novo or with steroid therapy.
• Diarrhea and vomiting may result in rapid severe hypovolemia.
• Vascular thromboses are found with NS in relapse, especially if hypovolemia is present.
• Acute reversible renal failure is an uncommon complication of NS of childhood.
• MCNS does not result in chronic renal failure.

Nephrotic Syndrome - bibliography

Barratt TM, Clark G. Minimal change nephrotic syndrome and focal segmental glomerulosclerosis. In: Holliday M, Barratt TM, Avner ED, eds. Pediatric Nephrology. 3rd ed. Baltimore: Williams & Wilkins; 1994:767–787.
1. Chesney RW. The idiopathic nephrotic syndrome. Curr Opin Pediatr. 1999;11:158–161.
2. Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. 2003;362:629–639.
3. Hodson EM, Knight JF, Willis NS, et al. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database of Syst Rev. 2000;(4):CD001533.
4. Hodson EM, Knight JF, Willis NS, et al. Corticosteroid therapy for nephrotic syndrome in children [update of Cochrane Database Syst Rev. 2001;(2):CD001533]. Cochrane Database Syst Rev. 2003;CD001533.
5. McEnery PT, Strife CF. Nephrotic syndrome in childhood. Pediatr Clin North Am. 1982;89:875–885.
Meyers KEC, Kaplan BS. Minimal-change nephrotic syndrome. In: Neilson EG, Couser WG, eds. Immunologic Renal Diseases. Philadelphia: Lippincott-Raven; 2001:969–985.
6. Robson WLM, Leung AKC. Nephrotic syndrome in childhood. Adv Pediatr. 1993;40:287–323.
7. Vande Walle JG, Donckerwolcke RA. Pathogenesis of edema formation in the nephrotic syndrome. Pediatr Nephrol. 2001;16:283–293.

Nephrotic Syndrome - CODES

Nephrotic Syndrome - icd9

581.9 Nephrotic syndrome

Nephrotic Syndrome - PATIENT TEACHING-MED

Educate the family about urine testing, complications, diet, and therapy.

Nephrotic Syndrome - FAQ

• Q: Will the MCNS recur?
• A: The clinical course tends to be one of multiple remissions and relapses. Relapses usually stop about the time of puberty.
• Q: Can the NS return in adult life?
• A: Yes, this does occur.
• Q: Is macroscopic hematuria ever found with MCNS?
• A: Gross hematuria suggests a renovascular event or a diagnosis other than MCNS. Microscopic hematuria occurs in ~25% of cases.
• Q: What other agents are used to treat NS?
• A: Cyclosporin A, tacrolimus, mycophenolate mofetil (MMF), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers are used in children with steroid-dependent or -resistant NS.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Nephrotic syndrome

• Back to disease: Nephrotic syndrome: Introduction
• Next Book Extract About Nephrotic syndrome: Surveys relating to Nephrotic syndrome
• More Book Extracts: All Online Books for Nephrotic syndrome

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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