Nephrotic syndromes (pediatrics): Clinical sciences

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Introduction0:00–0:28

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 ABCD E assessment to determine if they are unstable or stable, if unstable, stabilize their airway breathing and circulation.

Unstable Patient0:28–0:54

Next, obtain IV access, put your patient on continuous vital sign monitoring and if needed, provide supplemental oxygen.

Stable Patient0:54–1:19

Now, let's 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 kidneys.

Nephritic Syndrome1:19–2:07

Glomeruli affected patients often report frankly bloody cola or tea colored urine and decreased urine output. Meanwhile, the physical examination often reveals elevated BP 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 RBC S RBC casts and possibly protein diagnose nephritic syndrome.

Nephrotic Syndrome2:07–4:12

Now, let's switch gears and discuss nephrotic syndrome. These patients usually report swelling occasionally with nonspecific 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 two or more.
The serum albumin is low and lipids are elevated diagnosed 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 mg 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 in age under one year or over 12 years.
A markedly elevated serum creatinine gross hematuria and marked hypertension. Here's another clinical pearl low C three and C four levels are another indication for renal biopsy in a child with nephrotic syndrome.

Minimal Change Disease4:12–5:04

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.

Steroid-Sensitive Nephrotic Syndrome5:04–7:10

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 three 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.
All right, let's say your patient achieves remission after tapering glucocorticoids. In this case, you should continue supportive care and monitor your patient.
Keep in mind that these Children may still relapse even during remission, especially if they acquire an upper respiratory or gastrointestinal infection.
On the other hand, your patient might experience frequent relapses, meaning more than two relapses within six months of starting treatment or more than four in a 12 month period or they might demonstrate steroid dependent disease.
Here, you should consider switching to a Glucocorticoid sparing agent, which could include cyclophosphamide mycophenolate, mofetil, riTUXimab levamisole or calin neuron inhibitors like cycloSPORINE or tacrolimus.
Be sure to teach patients and their caregivers how to use urine dipsticks to identify relapses early. Here's a high yield fact, Glucocorticoid sparing agents can help your patient avoid side effects associated with long term Glucocorticoid use such as hypertension growth failure and cushingoid appearance.

Steroid-Resistant Nephrotic Syndrome7:10–8:39

Let's switch gears and discuss patients with protein urea that persists after 4 to 6 weeks of glucocorticoid therapy. In this case, diagnose steroid resistant nephrotic syndrome and start your patient on a calcineurin inhibitor and a uranin angiotensin aldosterone system inhibitor or rossi.
Since these medications have renoprotective properties. Rossi medications include both angiotensin converting enzyme inhibitors, also called ace inhibitors and angiotensin receptor blockers or Arbs.
Additionally, refer your patient to a pediatric nephrologist for further evaluation, which may include renal biopsy, genetic testing or Glucocorticoid tapering time for a clinical pearl steroid resistant nephrotic syndrome can result from genetic conditions like Charcot Marie tooth disease or Hurler syndrome.
These Children rarely respond to immunosuppression and many progress to end stage renal disease, eventually requiring dialysis or kidney transplantation.
In other cases, steroid resistant nephrotic syndrome might be caused by secondary conditions like prolonged infections or autoimmune conditions such as systemic lupus erythematosus, which may respond to immunosuppression.

Renal Biopsy Indicated8:39–9:12

Ok. Time to discuss patients for whom a renal biopsy is indicated.
These patients are likely to have severe primary kidney disease or an underlying systemic condition to evaluate further obtain a renal biopsy with light microscopy and electron microscopy.
Also consider genetic testing, especially if there is a family history of renal disorders or if the exam reveals characteristic phenotypic features suggesting a genetic condition.

Focal Segmental Glomerulosclerosis9:12–10:25

Let's start with focal segmental glomerulosclerosis or FSGS in this condition. White microscopy reveals focal and segmental sclerosis with hyalinosis and adhesions of the bowman capsule.
While electron microscopy shows effacement of podocyte foot processes. Meanwhile, genetic testing may identify a mutation.
These findings are diagnostic of FSGS which can be primary meaning it's caused by a single gene mutation. Since primary FSGS doesn't usually respond to immunosuppression.
You should refer your patient for subspecialty care. Instead.
On the other hand, secondary FSGS is caused by an underlying condition and is more likely to respond to immunosuppression.
So, for these patients, you should consider adding glucocorticoids with or without a calci neurine inhibitor. Now, here's a high yield fact, patients who have nephrotic range proteinuria without hypoalbuminemia are more likely to have secondary FSGS.
Ok. Let's move on to membranous nephropathy.

Membranous Nephropathy10:25–11:35

In this condition, light microscopy reveals uniform widespread capillary and glomerular basement membrane thickening electron microscopy reveals a spike in dome appearance caused by subepithelial deposits of IgG and C three.
And genetic testing will be negative with these findings. You can diagnose membranous nephropathy.
This autoimmune condition can be primary meaning disease is isolated to the kidney or it can be secondary meaning it's caused by a systemic condition.
In either case, membranous nephropathy responds to immunosuppression. So start glucocorticoids and consider steroid sparing agents like cyclophosphamide.
Here's one last clinical pearl, primary membranous nephropathy is associated with the production of antibodies to the phospholipase A two receptor which is found on podocytes.
If you suspect that your patient has this membranous nephropathy, remember to test for these antibodies. All right.

Review11:35–12:33

As a quick recap if a patient has nephrotic syndrome, but there are no indications for biopsy. Suspect minimal change disease and treat with glucocorticoids.
Patients with steroid sensitive nephrotic syndrome who achieve remission should continue supportive treatment. While those with frequent relapses or steroid dependence require additional immunosuppression.
Meanwhile, steroid resistant nephrotic syndrome often requires rossi treatment, additional immunosuppression and a pediatric nephrology referral on the flip side for Children who require a renal biopsy.
Findings on light microscopy, electron microscopy and genetic testing can help you distinguish FSGS from membranous nephropathy.
For both conditions management typically consists of subspecialty care and