PROTEINURIA

COMPETENCY: The resident should be able to define proteinuria and know how it is
measured, develop an appropriate management plan for a child with proteinuria, and
recognize situations in which proteinuria is non pathologic.
CASE: A concerned mother comes to your office with her athletic 16 year old son. He
recently competed in a track meet. As part of a new school drug testing program for all
varsity athletes, a urinalysis is performed during the meet shows 2+ protein. He
otherwise has no significant PMH and his blood pressure is normal. What do you do
next?
QUESTIONS:
1. What are causes of intermittent proteinuria?
2. Under what situations is a dipstick urinalysis falsely positive? Falsely negative?
3. How and when should urine samples be collected when evaluating proteinuria?
4. How do you define and manage a child with pathologic proteinuria?
REFERENCES:
Begstein JM "A practical approach to proteinuria" Pediatr Nephrol (1999) 13:697-700
Recommendations for Preventive Pediatric Health Care (RE9535), AAP Committee on
Practive and Ambulatory Medicine
Kaplan RE, Springate JE, Feld LG "Screening dipstick urinalysis: a time to change"
Pediatrics (1997) 100(6):919-921
Vogt BA, Avner ED "Conditions particularly associated with proteinuria" pp1751-1753
(2004) in Behrman: Nelson Textbook of Pediatrics, 17th edition. Elsevier.

PROTEINURIA
COMPETENCY: The resident should be able to define proteinuria and know how it is
measured, develop an appropriate management plan for a child with proteinuria, and
recognize situations in which proteinuria is non pathologic.
CASE: A concerned mother comes to your office with her athletic 16 year old son. He
recently competed in a track meet. As part of a new school drug testing program for all
varsity athletes, a urinalysis is performed during the meet shows 2+ protein. He
otherwise has no significant PMH and his blood pressure is normal. What do you do
next?
Introduction:
A urine that tests positive for protein is a frequent finding in pediatrics (perhaps as high
as 10% of all children will have a urine at one time that is positive). Yet, few of these
children actually have a pathologic state requiring referral to a nephrologist. The goal of
this outline is to help you distinguish between serious and "innocent" proteinuria
Definition:
Proteinuria is defined as the abnormal presence of protein in the urine. Normally a small
amount of protein is present in the ultrafiltrate produced by the glomerulus, but much of
this protein is absorbed by the tubules (and some additional proteins are secreted into the
urine). Ultimately, very little protein is present in the urine that leaves the kidney.
Proteinuria is often measured using a dispstick assay. In this assay, a
reagent reacts with albumin producing a color change. The dipstick is reported on a
semi-quantitative scale: negative, trace (10-20 mg/dL), 1+ (30 mg/dL), 2+ (100mg/dL),
3+ (300 mg/dL), 4+ (1000-2000 mg/dL). Of note, the dipstick test for proteinuria suffers
from both false positive errors. False negative tests are often seen in dilute urine (specific
gravity <1.005), and when a protein other than albumin is present in the urine. False
positives can be seen in a concentrated urine, a basic urine (pH >8), and a urine
contaminated by gross hematuria or by antiseptic agents (chlorhexidine or benzalkonium
chloride).
In adults, the normal value for proteinuria is <150 mg protein per day. Values in children
are assumed to be similar to adult values, and when correcting for body surface area, in a
timed urine specimen, normal urine protein is less than 4 mg/m2/hr. Using the dipstick
assay, 1+ protein may be significant in a dilute sample (Sp Gr 1.005 - 1.015), and 2+
protein may be significant in a concentrated sample (Sp Gr >1.015).
In addition to the dipstick method, the gold standard for measuring proteinuria is a 24 hr
urine, however, this test is often a logistical nightmare for both parents and hospital
personnel. Instead of a 24 hr collection, studies have shown that the ratio of protein to

creatinine in a random sample correlates with the value obtained with a 24 hr collection.
In fact, the ratio often reflects the grams of protein obtained in a 24 hr collection (i.e.
Pr:Cr 2.0 on a random sample equals 2 g/24hr). It should be noted that in small children
who do not have a lot of body mass, the Pr:Cr ratio can be falsely positive if there is only
a small amount of creatinine in the sample.
When to measure:
Given the number of different tests on a dipstick, a urinalysis is likely to be preformed
during the evaluation of febrile illness, in a child with failure to thrive, enuresis,
hypertension, and when kidney pathology is suspected. There is some debate about
whether a screening urinalysis for proteinuria should be performed. As mentioned above,
in an average pediatric cohort, up to 10% will test positive on a single sample, but less
than 1% will have multiple positive samples. Despite these facts, the AAP Committee on
Practice and Ambulatory Medicine recommends a screening U/A at age 5 and during the
teenage years.
Differential Diagnosis
If a child has isolated proteinuria, it is important to distinguish between pathologic and
non-pathologic causes. Some non-pathologic causes include orthostatic, febrile, and
exercise-induced proteinuria. Whereas pathologic proteinuria includes both tubular (e.g.
allergic-interstitial nephritis, ATN) and glomerular (nephrotic syndrome,
glomerulonephritis) causes.
Orthostatic proteinuria is a well-defined, but poorly understood phenomenon affecting
many children. The urine from these patients shows proteinuria in an upright (daytime)
sample, but normal urine in a first morning void. In adults, orthostatic proteinuria is
benign, but data in children is unavailable, so children with this form of proteinuria need
to be monitored yearly to look for signs of progression to pathologic renal disease.
It is also known that mild proteinuria (less than or equal to 2+) can be found in febrile
patients, although the mechanism is again unknown. This proteinuria can assumed to be
benign if it is not longer present on a follow-up urine after the febrile illness has resolved.
Vigorous exercise can induce both proteinuria and hematuria. These both typically
resolve spontaneously after 48 hr of rest.
A discussion of pathologic proteinuria is beyond the scope of this clinic curriculum note,
but a child with this form of proteinuria will typically display signs of systemic disease
(e.g. hypertension, edema, etc.). The urine from these patients may also contain
hematuria.
QUESTIONS:
1. What are causes of intermittent proteinuria?
Answer: fever, exercise

2. Under what situations is a dipstick urinalysis falsely positive? Falsely negative?

Answer: A highly concentrated urine, an alkaline urine, a urine with large hematuria, and
some antiseptic agents can give a false positive dipstick test. A highly dilute urine can
give a false negative dipstick test.
3. How and when should urine samples be collected when evaluating proteinuria?
Answer: It is important to collect both first morning and daytime urine samples to
evaluate for orthostatic proteinuria.
4. How do you define and manage a child with pathologic proteinuria?
Answer: If a urinalysis is positive for proteinuria, one should first make sure that the
sample is not overly concentrated, alkaline, or contaminated with antiseptic agents. After
these factors have been excluded, ask yourself if the patient has a fever or has recently
engaged in vigorous exercise. In either case, the test should be repeated at the next visit.
If the repeat dipstick is positive, then testing using random urine protein:creatinine ratios
should be performed, and orthostatic proteinuria should be considered. If orthostatic
proteinuria has been excluded, then the likelihood of renal disease increases and a serum
BUN and creatinine should be measured. A renal ultrasound should also be considered,
as well as a referral to a pediatric nephrologist. A figure from UCCH Peds Nephrology
department summarizing the approach to the patient with proteinuria is presented below.

References
Begstein JM "A practical approach to proteinuria" Pediatr Nephrol (1999) 13:697-700
Recommendations for Preventive Pediatric Health Care (RE9535), AAP Committee on
Practive and Ambulatory Medicine
Kaplan RE, Springate JE, Feld LG "Screening dipstick urinalysis: a time to change"
Pediatrics (1997) 100(6):919-921
Vogt BA, Avner ED "Conditions particularly associated with proteinuria" pp1751-1753
(2004) in Behrman: Nelson Textbook of Pediatrics, 17th edition. Elsevier.