Approach to proteinuria (pediatrics): Clinical sciences

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Introduction0:00–0:42

Protein. Urea refers to the presence of protein in the urine which occurs when the kidneys fail to filter blood properly.
It can result from disruption of the glomerular basement membrane allowing proteins to cross the filtration barrier or from injury to the renal tubules resulting in decreased protein reabsorption.
Proteinuria can be benign like with transient proteinuria or orthostatic proteinuria or it can be pathologic and persistent as the result of glomerular dysfunction or tubular dysfunction.

Urine Dipstick0:42–1:58

Now, let's discuss what to do when a pediatric patient presents with proteinuria. First, obtain a urine dipstick as an initial assessment, preferably a first morning void.
And if the dipstick is positive for protein, consider proteinuria. Your next step is to obtain a focused history and physical examination and repeat the urine dipstick test twice.
It's generally recommended to repeat the urine dipstick on two separate occasions. Again, sampling the first morning void if possible because many factors can alter the results such as a very high or low urine ph or urine that's very dilute or highly concentrated.
Now, here's a clinical pearl, a small amount of protein in urine can be normal. However, in the absence of hematuria or in an otherwise asymptomatic child protein excretion is considered abnormal when it's greater than 240 mgs per square meter per day.
For a child younger than six months of age or greater than 150 mgs per square meter per day for Children, six months or older.

Transient Proteinuria1:58–2:41

Now, if both repeat urine dipsticks are negative for protein diagnose transient proteinuria, which is a benign condition that doesn't require further work up.
Although the cause may be unknown, your patient may have a history of fever or mild illness, stress, heavy exercise, significant heat or cold exposure or dehydration on the flip side.
If repeat urine dipstick continues to be positive for protein. Obtain a first morning void spot urine collection, assess the urine protein to urine creatinine ratio based on your patients age.

Orthostatic Proteinuria2:41–3:39

Ok. Let's say your patient is between six months and two years old and the urine protein to creatinine ratio is less than 0.5 or your patient is older than two years and the ratio is less than 0.2.
In this case, consider orthostatic proteinuria also known as postural proteinuria, which is when their first morning urine sample is normal, but it becomes elevated after the child has been upright later in the day to confirm the diagnosis, obtain a random void spot urine collection and compare the results to the first morning void urine collection.
If the random void spot, urine shows an elevated protein and the first morning, void, urine contains normal protein. Diagnose orthostatic proteinuria, orthostatic proteinuria is the most common cause of proteinuria during adolescence.
Now, let's back up and take a look at patients with a high urine protein to creatinine ratio. This applies to patients between six months and two years old who have a urine protein to creatinine ratio greater than or equal to 0.5 or patients older than two years old, who have a urine protein to creatinine ratio greater than or equal to 0.2.

Persistent Proteinuria3:39–4:39

Because these individuals have consistently elevated urine protein, you can diagnose persistent proteinuria. Next, assess for nephrotic syndrome by obtaining a urinalysis with microscopy, a urine protein to serum creatinine ratio, which is based on the quantity of protein in a first morning void in the serum creatinine, a serum albumin and a lipid panel.
These lab results can help you distinguish between nephrotic syndrome and non nephrotic persistent proteinuria. Let's start with patients who have nephrotic range proteinuria defined as a urine protein to serum creatinine ratio of two or more.

Nephrotic Syndrome4:39–6:05

In cases of nephrotic syndrome. The urinalysis will be positive for protein.
The urine protein to serum creatinine ratio will be greater than or equal to two. The serum albumin will be low and the lipid panel will show elevated lipids.
Your next step is to assess for renal biopsy indications. Now, here's a high yield fact, the loss of protein in the urine results in a decrease in oncotic pressure.
And so the physical exam often reveals edema most commonly around the eyes called periorbital edema, as well as edema in the lower extremities, scrotum labia or abdomen.
Ok. Indications for a renal biopsy include age of onset, less than one year or greater than 12 years.
A markedly elevated serum creatinine gross hematuria or marked hypertension. Now, here's a clinical pearl.
Although we haven't highlighted it here, low levels of C three and C four would be another reason to consider a renal biopsy in a child.

Minimal Change Disease6:05–6:38

If your patient does not have indications for a renal biopsy, you can diagnose minimal change disease, which is the most common cause of nephrotic syndrome in Children.
Here is a clinical pearl to keep in mind while the renal biopsy is not generally needed to diagnose minimal change disease.
If you do order one, the sample will appear normal under light microscopy, but you will see a basement of podocyte foot processes on electron microscopy.
However, if your patient has indications for renal biopsy, examine the tissue using both light microscopy and electron microscopy and consider obtaining genetic testing.

Focal Segmental Glomerulosclerosis/Membranous Nephropathy6:38–7:34

This will help you distinguish between focal segmental glomerulosclerosis and membranous nephropathy. If light microscopy reveals segmental sclerosis and hyalinosis, electron microscopy shows effacement of podocyte foot processes and genetic testing is positive for a mutation, diagnose focal segmental glomerulosclerosis.
On the other hand, if light microscopy reveals diffuse capillary and glomerular basement membrane thickening, while electron microscopy reveals a spike and dome appearance of subepithelial deposits.
And genetic testing is negative, diagnosed membranous nephropathy. Now let's go back and discuss a patient with proteinuria but not enough to be considered nephrotic syndrome.

Non-nephrotic, persistent proteinuria7:34–8:38

In these patients, the urinalysis will be positive for protein. The urine protein to serum creatinine ratio will be less than two.
The serum albumin may or may not be low and the lipid panel might show elevated lipids if so, you can diagnose non nephrotic persistent protein urea.
You will then want to assess for urinary casts. Now, here's a clinical pearl.
We often obtain additional labs to evaluate for kidney damage, including urinary low molecular weight proteins, like beta two microglobulin alpha one microglobulin lysozyme and retinol binding protein.
These are often positive in cases of non nephrotic persistent proteinuria. And as you might expect, the serum creatinine will be elevated in these cases too.

Fanconi Syndrome8:38–9:43

Ok. Let's start with cases where there are nonspecific or no casts such as in Fanconi Syndrome.
These individuals typically report thirst, fatigue weakness and frequent urination. Meanwhile, the urinalysis may show no or nonspecific tests.
If so consider Fanconi syndrome, then order a 24 hour urine collection. If it demonstrates elevated levels of amino acids, phosphate bicarbonate and glucose diagnose Fanconi syndrome.
This is a condition resulting from a proximal tubule defect that prevents appropriate electrolyte in substances absorption.
It can be acquired or inherited such as in proximal or type two retinal tubular acidosis in Children. Fanconi syndrome.
Is usually the result of genetic conditions such as cystinosis, polycystic kidney disease or Wilson disease. All right, switching gears and moving on to acute interstitial nephritis or a.

AIN9:43–10:25

In for short. In this case, the urinalysis will demonstrate white blood cells, white blood cell casts and eosinophils obtain a renal biopsy which may show interstitial edema, eosinophils and an interstitial infiltration of inflammatory cells.
If so diagnose a, these patients often have a history of recent use of medications such as nsaids, penicillin, or cephalosporins affected individuals may also report a recent infection, rash or fever.

ATN10:25–11:13

Finally, let's look at when the urinalysis shows muddy brown casts as in acute tubular necrosis or A TN. For short here, you'll want to obtain a fractional excretion of sodium or phena if the phena is greater than 2% diagnose atn, these patients may also report the use of medications such as aminoglycosides, amphotericin B nsaids or sulfonamides or they may have been exposed to a radio contrast medium.
Often, elements of the history suggest renal hypoperfusion which could result from hypovolemia due to vomiting, diarrhea and dehydration.
All right, as a quick recap. If a patient presents with proteinuria, obtain repeat urine dipsticks.

Review11:13–12:19

If the protein is not present on repeat urine dipstick tests, diagnose transient proteinuria. On the other hand, if the proteinuria continues, compare the quantity of protein in a first morning urine collection to a random spot urine collection.
If the protein is higher in the random spot collection, diagnose orthostatic proteinuria on the flip side. If the proteinuria does not resolve and is consistently elevated throughout the day.
Diagnose persistent proteinuria, then assess the underlying cause. The most important causes of nephrotic range proteinuria include minimal change, disease, focal segmental glomerulosclerosis and membranous nephropathy.
While the most important causes of non nephrotic persistent proteinuria include fanconi syndrome A and ATN.