Nephrotic syndromes (pediatrics): Clinical sciences

Nephrotic syndrome is characterized by the combination of proteinuria, hypoalbuminemia, edema, and hyperlipidemia, which result from glomerular damage. In pediatric patients, nephrotic syndrome is often idiopathic, but it can also be caused by infections and genetic or autoimmune conditions.

If a pediatric patient presents with a chief concern suggesting nephrotic syndrome, first perform an ABCDE assessment to determine if they are unstable or stable. If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, put your patient on continuous vital sign monitoring, and if needed, provide supplemental oxygen.

Let’s now look at stable patients. When it comes to stable patients, obtain a focused history and physical examination, which can help you distinguish nephrotic syndrome from nephritic syndrome. Keep in mind that these two conditions can have overlapping symptoms, and in some cases, they occur simultaneously. First, let’s discuss nephritic syndrome.

Nephritic syndrome refers to the combination of hematuria, azotemia, hypertension, and edema caused by inflammation within the kidney’s glomeruli. Affected patients often report frankly bloody, cola- or tea-colored urine; and decreased urine output. Meanwhile, the physical examination often reveals elevated blood pressure and edema. These findings should make you suspect nephritic syndrome. To confirm the diagnosis, obtain a urinalysis with microscopy. If it’s positive for blood, with or without protein; and microscopy reveals RBCs, RBC casts, and possibly protein; diagnose nephritic syndrome.

Now, let’s switch gears and discuss nephrotic syndrome. These patients usually report swelling, occasionally with non-specific symptoms, such as malaise, headache, fatigue, or irritability. Physical exam often reveals periorbital edema; but, in more severe cases, you might also notice edema of the scrotum, labia, or abdomen; as well as lower extremity edema that becomes more pronounced throughout the day. The edema is usually generalized, pitting, and not discolored. With these findings, suspect nephrotic syndrome.

Your next step is to order labs, including a urinalysis; and a urine protein to serum creatinine ratio, which consists of the quantity of protein on a first morning void and the serum creatinine. Also, order a serum albumin level and lipid panel. If the urinalysis demonstrates protein; the urine protein to serum creatinine ratio is 2 or more; the serum albumin is low; and lipids are elevated; diagnose nephrotic syndrome.

Now, here’s a clinical pearl to keep in mind! In children, nephrotic range proteinuria can also be defined as a 24-hour urine sample with more than 40 milligrams per meter squared per hour of protein.

Once you diagnose nephrotic syndrome, consider restricting salt and fluid intake, especially if the patient has moderate to severe edema. Then, you’ll need to determine whether your patient requires a renal biopsy. Indications for biopsy include an age under 1 year or over 12 years; a markedly elevated serum creatinine; gross hematuria; and marked hypertension.

Here’s another clinical pearl! Low C3 and C4 levels are another indication for renal biopsy in a child with nephrotic syndrome.

Let’s start by discussing patients who have no indications for a renal biopsy. In this case, you should suspect minimal change disease, the most common cause of nephrotic syndrome in children.

Here’s a high yield fact! Patients with minimal change disease don’t usually require a biopsy; however, if you do obtain one, immunofluorescence will appear normal, but electron microscopy often reveals epithelial cell podocyte effacement.

Once you suspect minimal change disease, treat your patient with glucocorticoids for approximately 4 to 6 weeks. After treatment is complete, you’ll need to assess for steroid resistance. Although most children are steroid-sensitive, some do not respond to glucocorticoids.

Now, if proteinuria resolves after 4 to 6 weeks of steroid treatment, your patient has steroid-sensitive nephrotic syndrome. A positive response to steroids suggests that minimal change disease is responsible for your patient’s nephrotic syndrome.

At this point, you should continue the glucocorticoids for 8 to 12 weeks, and then assess for remission, which is defined as resolution of proteinuria, or a protein-to-creatinine ratio less than 0.2 on 3 separate occasions.

If proteinuria does resolve but subsequently recurs, it’s considered a relapse; and if proteinuria persists or worsens when glucocorticoids are tapered, then your patient’s condition is steroid-dependent.