Here are excerpts from the transcript:
When to refer [to the pediatric nephrologist]
- Documented presence of hematuria and proteinuria and/or persistent proteinuria.
- Nephrotic range proteinuria.
- Nephritic symptomatology.
- Signs of systemic disease such as joint pains, rash, etc. and suspect CT disease.
- Association with impaired renal function, and/or hypertension.
- Parental anxiety.
In summary, proteinuria is a very common laboratory finding in pediatric patients. Common being common, it is generally benign – either transient or orthostatic.
It is always important to take a complete history and do a thorough physical exam because the other possibilities are serious conditions that need to be diagnosed early and potentially treated.
A good take home message is that presence of hematuria along with proteinuria is a bad sign and indicates significant parenchymal renal disease.
If there is blood AND protein in the urine, this is not benign and needs further assessment and testing.
Never be shy about contacting a pediatric nephrologist if you ever have concerns of a patient with proteinuria.
Further investigations that a subspecialist may do include imaging studies and renal biopsies as indicated.
This podcast addresses the evaluation of proteinuria in children. Proteinuria is a welldocumented and common finding on urinalysis in children in both doctor’s offices and emergency rooms. Most cases are transient or benign. At least 10% of children will have proteinuria at some time in excess of 20-30 mg/dl (or 1+ on dipstick), which decreases to 0.5% for 3 consecutive samples.
In adults, proteinuria is defined as greater than 150 mg/day of protein in the urine. However, in pediatrics it tends to vary with age and body surface area. In children, proteinuria is defined as greater than 100 mg per meter squared per day, but in neonates it is greater than 300 mg per meter squared per day.
Causes Of Proteinuria
The key evaluation tool is to determine if the proteinuria is transient or persistent.
The following are common cause of proteinuria in children.
Around 60 percent of all cases of proteinuria are due to orthostatic proteinuria, especially in adolescents.
If initial investigations are normal, an orthostatic test can be completed.
Ask the patient to empty their bladder before going to bed, lie flat all night in bed, and then urinate first thing in the morning after getting up. Additional urine samples are then collected throughout the day with a final urine sample prior to bed.
A diagnosis is confirmed if the morning sample is protein-free but the evening sample contains protein. In general, kids
with orthostatic proteinuria should have under 1 gram of protein in full 24 hours.
Nearly half of all cases of proteinuria in children are transient and resolve spontaneously.
Transient proteinuria can be due to febrile illnesses, seizures, strenuous exercise, emotional stress, serious illness like congestive heart failure and abdominal surgery.
In these circumstances, [unless] another etiology is suspected, a detailed work-up is not needed.
Proteinuria due to glomerular pathology is usually persistent and is less likely to be a benign cause.
Proteinuria can be secondary to glomerular diseases such as acute glomerulanephritis, lupus nephritis and Focal Segmental GlomeruloSclerosis.
The history, physical examination, investigations and complete urinalysis will assist to differentiate between the various etiologies.
If proteinuria is over 40 mg per meter squared per hour, or
over 3 grams in a 24 hour period, it is termed heavy or nephrotic range proteinuria.
The most common cause of nephrotic syndrome in children is minimal change disease. [Look for periorbital edema.]
Proteinuria due to tubulointerstitial pathology is also usually persistent.
Causes include interstitial nephritis, acute tubular necrosis and cystitis.
Proteinuria of tubulointerstitial disease is generally mild.
Finally, structural abnormalities should be considered with proteinuria.
This includes reflux nephropathy, renal hypoplasia or dysplasia, polycystic kidney disease or hydronephrosis.
In general, there are three pathophysiologic mechanisms by
which proteinuria can occur: leaky filter units or glomeruli, inadequate reabsorption by the kidney tubules, or too much protein in the blood.
The history will focus on any associated symptoms and a review of systems.
Make sure to inquire about any recent infections.
Ask if there is a history of skin rash, abdominal pain, bloody diarrhea and joint pains to look for evidence of lupus, or systemic lupus erythematosus (SLE).
Asking about specific urinary tract symptoms such as fever, dysuria, urinary frequency, gross hematuria or suprapubic pain is important to rule out UTI.
Attempt to determine if there is a history of vigorous exercise, bruising or recent injuries.
If the patient is a female and depending on age, ask about menses.
Ask about a family history of collagen vascular diseases like lupus, renal transplant or dialysis, kidney stones, or
polycystic kidney disease.
Obtain a medication history, particularly if the pt has started any new medications.
Your physical examination will focus on the key aspects of renal assessment.
Accurate height, weight and blood pressure are essential.
Assess the patients’ fluid status and look for evidence of edema in the peripheral extremities or ascites.
An abdominal exam will look for evidence of a palpable kidney.
The physical examination will also look for other signs of
skin and joint involvement.
Do not forget to examine the genitalia for scrotal or labial edema [and look for periorbital edema].
The key is to quantitate proteinuria and determine how much protein there is in the urine.
The universal method to analyze urine is the random spot urine qualitative colorimetric test strips, i.e. the urinalysis or “dipstick” These strips give a crude estimate of the amount of
The dipstick is most sensitive to albumin and poorly quantifies other types of protein.
Trace proteinuria indicates approximately 15 mg/dl, 1+ indicates 20-30 mg/dl, 2+ is 100 mg/dL, 3+ is 300 mg/dL and 4+ is greater than 2000 mg/dL.
However, it is good to be aware of situations that may give a false positive result. These include alkaline urine, highly concentrated urine, gross hematuria, pyuria, bactiuria and
False Negatives may occur if there is very dilute urine or acidic urine.
A more accurate assessment of proteinuria is the spot urine protein/creatinine ratio which correlates well with 24 hr. protein excretion. Normally, a child under the age of 3 will have
under < 10 mg protein/mmol of creatinine and a child under the age of 10 will have under 7 mg protein/mmol of creatinine.
Approach to Investigation and Management
When assessing proteinuria in afebrile child, the first step is to repeat the urinalysis when the child is afebrile.
If the dipstick remains positive despite absence of any stressors at >1+, then the child needs further evaluation as below.
If repeat urinalysis is negative for protein, then it is a transient cause and no other tests need to be done.
Once you are sure that the cause of proteinuria is persistent and not transient, the next most common diagnosis when the history and physical are unremarkable is orthostatic proteinuria.
In order to prove this diagnosis, you need to show the presence of proteinuria at a time of activity (that is, daytime) and absence of proteinuria when recumbent (i.e. right upon waking up).
The degree of proteinuria that you can get with orthostatic in the daytime can be quite high but the analysis will always be negative in the morning. If you get these results, then you have made the diagnosis and no further follow-up is necessary.
Further evaluation is indicated if there are no postural changes with proteinuria, if there is persistent proteinuria on repeated samples and lastly, if there is co-existent hematuria and/or any systemic symptoms.
This includes looking for evidence of underlying etiology
such as glomerulonephritis.
Lab work to order would include CBC, electrolytes, creatinine,
blood urea nitrogen, cholesterol, albumin, serum complement C3/C4 and ANA.
Quantification of the exact degree of protein with a 24 hour protein collection may be useful at this time.
At this point in time, it would be prudent to consult a pediatric nephrologist for further assessment and consideration of renal biopsy and appropriate therapy.