What is the significance of proteinuria?
Proteinuria usually implies that there is a defect in glomerular permeability. In general, proteinuria can be classified into persistent or transient.
Among the causes of persistent proteinuria there are three types: (1) glomerular, (2) tubular, or (3) overflow.
• Glomerular proteinuria includes diabetic nephropathy and other common glomerular disorders. It is caused by increased filtration of albumin and other proteins across the glomerular capillary wall. Other causes of glomerular proteinuria have a rather benign course, such as orthostatic and exercise-induced proteinuria. These latter causes are usually transient and characterized by significantly less proteinuria, usually less than 1 g a day.
• Tubular proteinuria is due to tubulointerstitial disease. Patients have decreased ability for the proximal tubules to reabsorb proteins that are normally filtered by the glomerulus. The amount of proteinuria is typically small (<2 g/day). Unlike the large macromolecules lost with glomerular proteinuria (albuminuria), in tubular proteinuria it is mostly low-molecular-weight proteins, such as β 2 -microglobulin, that are lost in the urine. These will test negative by urinary dipstick.
• Overflow proteinuria (also called overproduction proteinuria) is exemplified by multiple myeloma, in which there is an overabundance of Ig light chains in circulation secondary to overproduction. These excess Igs get filtered by the glomerulus and exceed the tubular capacity for reabsorption, resulting in proteins appearing in the urine.
Although both glomerular and tubular proteinuria are secondary to abnormalities involving the glomerular capillary and tubular walls, respectively, in overflow proteinuria, the problem lies in overproduction of certain proteins.
Quantification of proteinuria is best accomplished by performing a 24-hour urine collection. However, this can be cumbersome, especially in the elderly, children, or those with urinary incontinence. The urine protein to urine creatinine ratio (urine PCR), using a random urine specimen, has good correlation with the 24-hour urine protein determination. The 24-hour urine protein in grams is approximately equivalent to the urine PCR in g/g (for SI units, multiply PCR in g/mmol by approximately 9 to estimate g/day). See Question 18 for more details.
In transient proteinuria conditions, there is a transient change in glomerular hemodynamics, causing increased excretion of urinary protein. These are usually benign and self-limited. Examples include congestive heart failure, fevers, strenuous exercise, seizure disorders, and even extremes of stress. Orthostatic proteinuria (see Question 17) falls under this category.
