Nephrotic syndrome
and Minimal Change, FSGS, Post-Infectious Glomerulonephritis, MPGN, IgA nephropathy (Bergers Disease))

• proteinuria
• hypoalbuminemia
• edema
• hypercholesterolemia.
• hypercoaguability (due to loss of Antithrombin III)
• Note: Many patients who have NS may display low serum sodium values, primarily during relaspes. Hypernatremia is rarely observed in NS.

Etiologies: minimal change disease (most common), FSGS, MPGN, and associated with systemic diseases (e.g., SLE, HSP, HUS). The first step in the evaluation is to obtain a thorough medical history and family history. In general, diseases that cause NS are not familial in origin, but the presence of disease in a family member may provide clues to the ultimate diagnosis.

Physical examination should focus on vital signs because severe NS may be indicated by:

• increased respiratory rate (possible pulmonary edema or pneumonia)
• significant tachycardia (possible intravascular depletion)
• elevated blood pressure.

PE:

• Often present with asymptomatic edema
• Lungs: assess for pulmonary edema
• evaluation of heart sounds, especially for the S3 component (possible fluid overload)
• palpation of the abdomen (ascites, fluid wave, and tenderness may indicate peritoneal infection)
• assessment for the severity of peripheral edema

Look at the pee:

• If the diagnosis of NS is suspected, a urinalysis must be obtained.
• If evidence of proteinuria on urine dipstick: get urine protein:creatinine. This may not aid in determining the etiology of NS, but it is a good reference point for future comparison.
• Determination of the presence of red blood cells (RBCs) in the urine is essential.
• Proteinuria in the absence of hematuria suggests such glomerular diseases, such as:
  • minimal-change nephrotic syndrome (MCNS) (note: 50% of children w/ MCNS may have RBCs intermittently)
  • membranous nephropathy
  • Children who have focal segmental glomerulosclerosis (FSGS) also may exhibit RBCs in the urine sporadically.
• The persistence of RBCs in the urine with proteinuria must alert the physician to the presence of nephritis in addition to nephrosis. Nephrotic vs Nephritis Chart
• Diseases characterized by RBCs in the urine with or without proteinuria:
  • PIAGN Post-Infectious Glomerulonephritis
  • MPGN membranoproliferative glomerulonephritis
  • LN lupus nephritis
  • IgANIgA nephropathy (Bergers Disease) (
  • tubulointerstitial nephritis

Complications

• infection, spontaneous bacterial peritonitis
• thrombosis because of hypercoagulability

Nephrotic Syndrome in Infants:

• prognosis is guarded; etiology is rarely minimal change before 6 months of age
• often due to secondary causes (e.g., infections, drug reactions, toxins, etc.)

Congenital Nephrotic Syndrome:

• poor prognosis
• often don’t respond to steroids or cytotoxic therapy
• many infectious complications

Treatment

• Children who have NS almost uniformly are treated with oral steroids
• The response to such treatment aids in determining the etiology of the NS.
• 98% of MCNS will experience complete resolution of edema and proteinuria after 4 weeks of oral steroid therapy.
• If proteinuria persists after 4 weeks of therapy, as for the boy described in the vignette, a diagnosis other than MCNS must be considered. Although a renal biopsy would be indicated at this point, the presence of RBCs in the urine and findings on other laboratory tests may aid in the diagnosis.
  • Gross hematuria suggests glomerulonephritis, including MPGN and IgAN.
  • Microscopic hematuria, with or without episodes of gross hematuria, always is present in children who have LN.
  • The complete absence of RBCs in the urine implies either FSGS or membranous nephropathy.
  • Serum complement (C3, C4) levels may be reduced in PIAGN (usually only reduced C3), LN, and MPGN.

Note:  The incidence of FSGS is on an exponential rise in children and must be suspected in any child who has NS and does not undergo a remission within 4 weeks of beginning steroid therapy.

References:
Kashgarian M, Hayslett JP, Seigel NJ. Lipoid nephrosis and focal
sclerosis: distinct entities or spectrum of disease. Nephron.
1974;13:105-108
Levy M, Gonzalez-Burchard G, Broyer M, et al. Berger's disease in
children. Natural history and outcome. Medicine. 1985;64:157-180
Nephrotic syndrome in children: prediction of histopathology from
clinical and laboratory characteristics at time of diagnosis. A report
of the International Study of Kidney Disease in Children. Kidney Int.
1978;13:159-165
Southwest Pediatric Nephrology Study Group. Comparison of idiopathic
and systemic lupus erythematosus-associated membranous
glomerulonephropathy in children. Am J Kidney Dis. 1986;7:115-124
Wyatt RJ, Forristal J, West CD, Sugimoto S, Curd JG. Complement
profiles in acute post-streptococcal glomerulonephritis. Pediatr
Nephrol. 1988;2:219-222