32. DIFFERENTIAL DIAGNOSIS OF PROTEINURIA

Question 1

Physiologic proteinuria:

Answer 1

Protein may be found in the urine of healthy children, does not exceed 0.15
g/24h OR <4g/m2/hour OR Uprotein/Ucreatinine <0.2)

Question 2

Nephrotic proteinuria in children is defined as protein greater than:

Answer 2

40mg/m2/hour or Upr/Ucr >2.0

Question 3

Urinary protein/ urinary creatinine values:

Answer 3

A Upr/Ucr >0.2 on a first morning specimen excludes orthostatic proteinuria.

Upr/Ucr >2.0 indicates nephrotic range proteinuria

Question 4

Transient proteinuria:

Answer 4

Transient proteinuria can be seen after vigorous exercise, fever, dehydration, seizures, and adrenergic agonist therapy.

Proteinuria is usually mild (Upr/cr<1), glomerular in origin, and always resolves within a few days.
It does not indicate renal disease.

Question 5

Postural (orthostatic) proteinuria:

Answer 5

Postural (orthostatic) proteinuria is a benign condition defined by normal protein excretion while recumbent but significant proteinuria when upright. It is glomerular in nature, more common in adolescents and tall, thin individuals, and not associated with progressive renal disease.

Question 6

Tubular proteinuria:

Answer 6

Tubular proteinuria is characterized by preponderance of low-molecular-weight proteins in the urine and is suspected with acute tubular necrosis, pyelonephritis, structural renal disorders, polycystic kidney disease, and tubular toxins such as antibiotics or chemotherapeutic agents.
The combination of tubular proteinuria with evidence of tubular electrolyte wasting and glycosuria is termed Fanconi syndrome.

Question 7

Glomerular proteinuria:

Answer 7

Glomerular proteinuria is characterized by a combination of large- and small-molecular-weight proteins in the urine, variable levels of proteinuria, and often evidence of glomerular disease (hematuria, red blood cell casts, HTN, and renal insufficiency)
Causes of glomerular proteinuria include
Glomerular capillary disruption (HUS, crescentic glomerulonephritis)
Glomerular capillary immune complex deposition (poststreptococcal glomerulonephritis and lupus nephritis)
Altered glomerular capillary permeability (MCNS, congenital NS)

Question 8

Clinical manifestations of membranous glomerulonephritis:

Answer 8

Proteinuria (non-nephrotic or nephrotic range proteinuria) is the most common manifestation of the disease.
It may be high-grade in 40-75% of children (nephrotic range) and in these cases leads to clinically recognized oedema.
Sometimes there is a micro-/macrohematuria.
Some patients have high blood pressure at diagnosis

Question 9

Membranous glomerulonephritis - light microscopy:

Answer 9

Light microscopy shows a thickening of the glomerularbasement membrane with characteristic spikes (visible with silver stain and PAS-reaction).
Immunofluorescence reveals subepithelial deposits of immune complexes (100%) and C3 complement fraction (77%) in the form of granules.
Immune complexes are composed mainly of gG (IgG4 and IgG1).

Question 10

Membranous glomerulonephritis - electron microscopy:

Answer 10

Electron microscopy verifies a number of fine, electronically dense subepithelial deposits between podocyte foot processes.
Sometimes histological findings allow to determinethe type of MGN - idiopathic or secondary.

Question 11

Treatment of membranous glomerulonephritis:

Answer 11

Children with asymptomatic non-nephrotic range proteinuria should receive conservative treatment (ACE inhibitors, ARB).
In children with nephrotic syndrome, a 6-month follow-up and conservative treatment is recommended beforeinitiating immunosuppressive therapy because there is a high rate of spontaneousremissions.

Disease is often steroid-resistant and treatment includes alkylating agent + CSs or CNls with or without CSs.
Remission is achieved in 75% of children.