Approach to proteinuria (pediatrics): Clinical sciences

Proteinuria 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.

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 mg/m2/day for a child younger than 6 months of age; or greater than 150 mg/m2/day for children 6 months or older.

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 and assess the urine protein to urine creatinine ratio based on your patient’s age.

Okay, 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. 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 and 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 2 or more. 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 2; 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.

Okay, indications for a renal biopsy include age of onset less than 1 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 C3 and C4 would be another reason to consider a renal biopsy in a child.

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.