PROTEINURIA

I. Quantification

  1. Normal = < 150mg/d; only 10-15mg = albumin; the rest is plasma protein and protein from renal tubular cells
  2. 150-3500mg/d = "proteinuria"
  3. >3500mg/d = "massive proteinuria"; usually mostly albumin
  1. If hepatic albumin synthesis can't keep up, "nephrotic syndrome" results: hypoalbuminemia, edema due to reduced intravascular oncotic pressure, and hyperlipidemia

II. Testing for proteinuria

  1. Dipsticks
  1. Respond best to albumin; may give false negatives with other proteins
  2. Use fasting morning samples to avoid false negative from dilute urine
  3. "Trace" >50mg/l protein
  4. 1+ >300 mg/l
  5. If dipstick positive, do 24h collection to quantify
  6. If 24h urine positive, do protein electrophoresis
  1. If mainly albumin, it's a glomerular lesion
  2. If lots of Bence-Jones, may be Multiple Myeloma

III. Mechanisms of proteinuria

  1. Tubular
  1. Tubules are responsible for reabsorption of low molecular weight (<40kD) serum proteins
  2. Tubular disease, e.g. tubulointerstitial nephropathy, causes excretion of these proteins with no albuminuria!
  3. Usually excrete 1-3g/d protein
  4. Albumin isn't lost, so no edema/hyperlipidemia
  5. May occur with healthy tubules from "overflow proteinuria" in cases of increased LMW protein (e.g. Ig light chains, myoglobin)
  1. Glomerular
  1. Usually very little albumin or globulin is filtered; electrostatic barrier
  2. Glomerular disease can damage various barriers to protein filtration
  3. May cause just albuminuria or albuminuria + globulinuria, depending on parts affected
  1. Transient proteinuria may be induced by fever, exercise, or acute illness
  2. "Orthostatic proteinuria"
  1. Definition: increased protein excretion (> 50mg/8h) while in the upright position, but normal protein excretion when supine; total protein excretion us < 1g/d though may go higher
  2. Common in adolescents; uncommon over age 30
  3. Pathogenesis: 3 theories proposed:
  1. Exaggeration of nl physiology (in most folks there is an increase in protein excretion with assumption of upright posture, though us. Stays in the nl range)
  2. Subtle glomerular abnormality; some are seen on renal bx
  3. Exaggerated hemodynamic response to the upright position, e.g. increases in angiotensin II and norepinephrine which can increase glomerular permeability in susceptible persons; or could be from entrapment of the renal vain by aorta and sup. Mesenteric artery
  1. Diagnosis
  1. Split urine collection: first morning void is discarded; 16h upright collection 7am-11pm (can be adjusted to regular wake/sleep times); 8h recumbent collection (note, should assume recumbent position 2h before daytime collection is finished to avoid contamination of supine collection with urine formed while in the upright position)
  2. Diagnosis of orthostatic proteinuria requires that protein excretion be normal when supine (< 50mg/8h), not merely less than when in upright position.
  1. Course: Benign, renal function tends to remain normal; tends to resolve spontaneously (50% resolution at 10y; 83% at 20y)

(Source: Harrison's 12th ed.; notes on orthostatic proteinuria from handout by Burton Rose, M.D.)