VA M&M Pearl: An approach to proteinuria

Pearl: There are four basic types of proteinuria.

  1. Glomerular
  2. Tubular
  3. Overflow
  4. Reactive/Post-Renal

Hi Everyone!

Yesterday at M&M, nephrologist Dr. Lowell Lo was at it again – dropping serious knowledge. He presented his basic approach to finding protein in the urine. He said that his first step in evaluating proteinuria is to consider which of the four types he is dealing with.

The four basic types of proteinuria are:

Glomerular:

  • caused by increased filtration of macromolecules (e.g. albumin) across the glomerular capillary wall
  • examples: primary glomerular disease, diabetic nephropathy, hypertensive nephrosclerosis, benign causes including orthostatic and exercise-induced proteinuria
  • degree of proteinuria: variable, can reach nephrotic range

Tubular:

  • in a normal kidney, low-molecular-weight proteins (smaller than albumin) get filtered across the glomerulus and are largely reabsorbed in the proximal tubule (examples include immunoglobulin light chains, beta-2-microglobulin)
  • diseases that cause tubulointerstitial damage limit reabsorption of these proteins in the proximal tubule, leading to proteinuria
  • increased excretion of these smaller proteins is often not detected on urine dipstick
  • the increased excretion of tubular proteins (e.g. polyclonal immunoglobulin light chains) is not injurious to the kidney
  • examples: autoimmune or allergic interstitial inflammation, medication-induced interstitial injury
  • degree of proteinuria: < 3g per day

Overflow:

  • caused by increased excretion of low-molecular-weight proteins in setting of overproduction, leading to increased filtration and excretion
  • the filtered load exceeds the proximal tubule’s normal reabsorptive capacity!
  • examples: multiple myeloma (monoclonal light chains), hemolysis (hemoglobinuria), rhabdomyolysis (myoglobinuria)
  • degree of proteinuria: variable, can sometimes reach nephrotic range

Reactive/Post-renal 

  • inflammation of the urinary tract can give rise to increases in urinary protein excretion (mechanism unknown)
  • examples: UTI, nephrolithiasis, genito-urinary tumor
  • degree of proteinuria: <1 g per day

References:

Rovin BR. “Assessment of urinary protein excretion and evaluation of non-nephrotic proteinuria in adults.” UpToDate.

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