Proteinuria

Proteinuria

Introduction

• Up to 10% of children aged 8-15 years test positive for proteinuria by urinary dipstick at some time.
• In a 24-hour urine collection:
  • Normal values: <4 mg of protein/m²/hr
  • Significant values: 4–40 mg/m²/hr
  • Nephrotic range: >40 mg/m²/hr

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Causes of Proteinuria in Children

A- Transient (Functional) Proteinuria

• Idiopathic
• Related to medical condition (e.g., fever, seizure)
• Unrelated to medical condition (e.g., exercise, stress, dehydration, cold exposure)

The majority of children found to have positive urinary dipstick values for protein have normal dipstick values on repeated measurements. The proteinuria usually does not exceed 1-2+ on the dipstick. No evaluation or therapy is needed.

B- Orthostatic (Postural)Proteinuria

• Orthostatic proteinuria is the most common cause of persistent proteinuria in school-aged children and adolescents (60%).
• Children are usually asymptomatic, and the condition is discovered on routine urinalysis.
• Patients with orthostatic proteinuria excrete normal or minimally increased amounts of protein in the supine position.
• In the upright position, urinary protein excretion may be increased 10-fold, up to 1,000 mg/24 hr (1 g/24 hr).

C- Persistent Proteinuria

• Glomerular
• Adaptation (hyperfiltration) due to nephron loss (e.g., reflux nephropathy secondary to vesicoureteric reflux)

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Y

Significant proteinuria on a first morning urine sample on 3 consecutive days (>1+ on dipstick, urine specific gravity >1.015 or protein: creatinine ratio >0.2). A child is said to have persistent proteinuria if the dipstick is positive for protein on two of three random urine samples collected at least 1 week apart. Proteinuria indicates renal disease and may be caused by either glomerular or tubular disorders.

Initial evaluation of a child with persistent proteinuria should include:

• Measurement of serum creatinine and electrolyte
• First morning urine protein: creatinine ratio
• Serum albumin level
• Complement levels.

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Glomerular ProteinuriaY

• Glomerular proteinuria results from alterations in the permeability of any of the layers of the glomerular capillary wall to normally filtered proteins.
• Glomerular proteinuria can range from <1 g to >30 g/24 hr.
• Glomerular proteinuria should be suspected in any patient with:
  • First morning urine protein: creatinine ratio >1.0.
  • Proteinuria accompanied by:
    • Hypertension
    • Hematuria
    • Edema
    • Renal dysfunction

Tubular ProteinuriaY

• A variety of renal disorders that primarily involve the tubulointerstitial compartment of the kidney can cause low-grade fixed proteinuria (protein: creatinine ratio <1.0).
• Injury to the proximal tubules can result in:
  • Diminished reabsorptive capacity.
  • Loss of these low molecular weight proteins in the urine.
• Tubular proteinuria is seen in acquired and inherited disorders and may be associated with other defects of proximal tubular function, such as:
  • The Fanconi syndrome (glycosuria, phosphaturia, bicarbonate wasting, and aminoaciduria).
  • Dent disease (X-linked recessive disorder of the proximal tubules characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, kidney stones, kidney failure, and rickets).

Tubulointerstitial

• Acute tubular necrosis: aminoglycosides, cisplatin, amphotericin B, NSAIDs, radiocontrast media

• Acute tubulointerstitial nephritis:

  • NSAIDs
  • penicillin
  • cephalosporins
  • quinolones
  • sulfonamides
  • cimetidine [Tagamet]
  • allopurinol [Zyloprim]

• Polycystic kidney disease

• Proximal renal tubular acidosis:

  • Fanconi syndrome (global proximal tubule dysfunction)
  • cystinosis
  • Lowe syndrome
  • galactosemia
  • Wilson disease

• Pyelonephritis

• Toxins:

  • lead
  • copper
  • mercury

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Glomerular Versus Tubular Proteinuria

• Asymptomatic patients having persistent proteinuria generally have glomerular rather than tubular proteinuria.
• In occult cases, glomerular and tubular proteinuria can be distinguished by electrophoresis of the urine.
• In tubular proteinuria, little or no albumin is detected, whereas in glomerular proteinuria the major protein is albumin.

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Clinical Approach

• The initial workup should begin with a complete history and physical examination.
• The physician should elicit a history of recent infections (pharyngitis, impetigo), UTIs, oliguria or hematuria, and family history of renal disease.
• The physical examination should be focused on looking for hypertension (glomerulonephritis), edema (nephrotic syndrome), rash or arthritis (vasculitis), and short stature (chronic renal disease).

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Clinical Approach

• Laboratory investigations should include a urine dipstick, a urine analysis including microscopic examination, and a random urine protein-to-creatinine ratio.
• The dipstick measures the concentration of protein in urine.
• A 24-hour urine collection can be done by asking the child to void as soon as he or she wakes up and discarding the specimen; then every void should be collected for the next 24 hours, including the first void the next morning.
• A random urine specimen can be analyzed for protein and creatinine concentration.

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Management

• If the initial workup suggests the presence of an underlying renal disease, a referral to a pediatric nephrologist should be made.
• A referral should be made in the following situations:
  • Persistent fixed (i.e., nonorthostatic) proteinuria
  • Family history of glomerulonephritis
  • Systemic complaints (e.g., fever, rash, arthralgias)
  • Hypertension
  • Edema
  • Cutaneous vasculitis or purpura
  • Hematuria
  • Abnormal renal function
  • Abnormal renal ultrasound
  • Increased parental anxiety