Proteinuria, Orthostatic Proteinuria

• Proteinuria is the most ominous finding in urinalysis suggestive of renal disease.
• In general, the pore size of the glomerular basement membrane (GBM) is relatively small, but a small amount of protein can be detected in the urine of any individual.
• However, if the integrity of the GBM is compromised, larger proteins may enter the urine.
• The most abundant protein in the urine usually is albumin, owing to its comparatively small size.
• Immunoglobulins, thyroid-binding globulin, transferrin, vitamin D, and antithrombin III may leak into the urine if the GBM is damaged.

If urinalysis reveals protein in the urine of any child, an evaluation is mandatory.

• The urine also should be assessed for the presence of red blood cells (RBCs), white blood cells, nitrites, and bacteria.
• RBCs and protein on urinalysis suggest renal parenchymal disease or urinary tract infection.
• Nitrites or bacteria in a clean-catch or catheterized specimen strongly indicate urinary tract infection.
• Most patients who have proteinuria do not have edema due to a reduction of oncotic pressure.

In the absence of symptoms such as edema, abdominal or flank pain, dysuria, or fever, evaluation of proteinuria can proceed in a stepwise manner.

• The most prudent initial step is to obtain a first-morning specimen and repeat the urinalysis.
• If the specimen is negative for protein, the diagnosis of orthostatic proteinuria (OP) can be made.
• If there is protein in the urine on a first-morning specimen, protein and creatinine in the urine should be quantitated.
• A urine protein:urine creatinine ratio (mg/mg), in a single voided sample, greater than 0.2 is abnormal; above 1.0 is nephrotic range proteinuria
• A P/C greater than 0.25 on the first-morning specimen warrants further evaluation.
• If the protein/creatinine (P/C) ratio is less than 0.25, observation and repeat measurement of the ratio within the next month are appropriate.
• Urine protein measured in a 12-or 24-hour urine collection:
  • Protein excretion of less than 4 mg/m2 per hour is normal
  • Protein >40 mg/m2 per hour is considered in the nephrotic range

Orthostatic Proteinuria

• total urinary protein excretion is elevated while the child is in an upright position and exceeds the rate seen in the recumbent position
• urinary protein excretion rarely exceeds 1 g/day
• diagnosis based on comparison of urine in the recumbent vs. upright position
• finding of proteinuria by dipstick on a random (mid-day) sample and a completely negative finding by dipstick on the first-morning sample.
• benign condition, does not portend long-term risk for subsequent renal disease
• Its cause remains obscure, but it may be related to compression of the renal vein from the kidney
• Regardless of the mechanism, affected patients do not require periodic evaluation.
• OP cannot be the ultimate diagnosis in a patient who has RBCs in the urine.
• A family history always is essential in the evaluation of any patient, although there is no evidence that OP is a familial disease
• The benign nature of OP obviates the need for a consultation with a nephrologist.

Caveats

• false-positive result for protein in the urine may be seen in a sample that is extremely alkaline (urine pH, >8.0).
• Proteinuria may be masked with a very dilute urine (specific gravity, >1.005).
• Protein also may be transiently present in the urine of patients who have fever or acute illness. It is prudent to re-examine the urine at a later date in these patients.

Renal ultrasonography eventually may be necessary in a patient who has proteinuria that does not disappear on the first- morning specimen. A 24-hour urine collection for protein determination also is reserved for patients who have proof of protein in the urine on the first-morning specimen.

References:
CHLA Board Review 2005
Larson TS. Evaluation of proteinuria. Mayo Clin Proc. 1994;69:1154-1158
Loghman-Adham M. Evaluating proteinuria in children. Am Fam Physician.
1998;58:1145-1152, 1158-1159
Wingo CS, Clapp WL. Proteinuria: potential causes and approach to
evaluation. Am J Med Sci. 2000;320:188-194