Nephritic syndromes (pediatrics): Clinical sciences

Nephritic syndrome refers to a group of symptoms that result from glomerulonephritis, or inflammation and damage to the kidney’s glomeruli. This damage results in edema, hypertension, decreased urine output, and hematuria. Various underlying conditions can lead to nephritic syndrome, including infections, genetic conditions, and autoimmune diseases.

When a pediatric patient presents with a chief concern suggesting nephritic syndrome, first perform an ABCDE assessment to determine if the patient is unstable.

If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, put your patient on continuous vital sign monitoring including heart rate, blood pressure, and pulse oximetry, and provide supplemental oxygen if needed.

Here’s a clinical pearl to keep in mind! While you’re stabilizing your patient, also evaluate for and correct electrolyte abnormalities, like hyperkalemia, that can occur with nephritic syndrome.

Now, let’s go back to the ABCDE assessment and look at stable patients.

First, obtain a focused history and physical examination, which can help you distinguish nephritic syndrome from nephrotic syndrome. Keep in mind that these two conditions can have overlapping symptoms and even occur simultaneously.

First, let’s discuss nephrotic syndrome.

Patients with nephrotic syndrome usually report swelling, often in combination with malaise, headache, fatigue, or irritability. If the physical examination reveals edema, you should suspect nephrotic syndrome.

To confirm the diagnosis, obtain a urinalysis; a urine protein-to-creatinine ratio; a serum albumin; and a lipid panel. If the urinalysis is positive for protein, the protein-to-creatinine ratio reveals nephrotic range proteinuria, the serum albumin is low, and serum lipids are elevated, diagnose nephrotic syndrome.

Now, let’s discuss nephritic syndrome.

These patients have frankly bloody urine, cola-colored, or tea-colored urine and decreased urine output. The physical exam reveals elevated blood pressure and edema. With these findings, suspect nephritic syndrome and order a urinalysis with microscopy. If urinalysis demonstrates blood with or without protein; and microscopy shows RBCs and RBC casts with or without protein, diagnose nephritic syndrome.

Here’s another clinical pearl! Red blood cell casts are clumps of red blood cells that are pathognomonic of glomerulonephritis!

Once you confirm nephritic syndrome, your next step is to assess for glomerulonephritis by obtaining labs. These include serum creatinine; as well as disease-specific labs, like complements C3 and C4; antistreptolysin O titer; serum IgA; and galactose-deficient IgA1. Additionally, check for autoantibodies, including cytoplasmic antineutrophil cytoplasmic antibody or c-ANCA; perinuclear antineutrophil cytoplasmic antibody or p-ANCA; anti-glomerular basement membrane antibody or anti-GBM antibody; antinuclear antibody or ANA; anti-double stranded DNA antibody or Anti-dsDNA antibody; and anti-Smith antibody. Next, revisit your patient’s history to assess for a recent acute infection. This will help you recognize post-streptococcal glomerulonephritis and IgA nephropathy.

Let’s start with patients who report a recent streptococcal infection, such as strep pharyngitis or impetigo. In this case, suspect poststreptococcal glomerulonephritis. Labs usually reveal a low C3, normal C4, and a positive ASO titer. Based on these findings, diagnose post-streptococcal glomerulonephritis.

Here’s a clinical pearl! While you don’t usually need a kidney biopsy to diagnose post-streptococcal glomerulonephritis, if you obtain one, immunofluorescence will show a granular appearance from the IgG, IgM, and C3 deposits, which is referred to as a “lumpy bumpy” or a “starry sky” pattern.

Now, treatment of post-streptococcal glomerulonephritis is mainly supportive and includes sodium and water restriction, as well as loop diuretics. Thankfully, the disease is generally self-limited and resolves in a few weeks.

Now, here’s a high yield fact to keep in mind! Although treating strep pharyngitis with penicillin can prevent rheumatic fever, keep in mind that antibiotics do not prevent post streptococcal glomerulonephritis. However, antibiotics may prevent the spread of nephrogenic strains of Streptococcus pyogenes such as Group A β-hemolytic Streptococcus!

Now let’s switch gears and discuss patients who report a recent viral upper respiratory infection. In this case, suspect IgA nephropathy. Affected patients might also report recurrent episodes of grossly bloody urine. Labs may reveal elevated levels of creatinine, galactose-deficient IgA1, and serum IgA; as well as an increased IgA-to-C3 ratio. To evaluate further, obtain a renal biopsy with immunofluorescence. The presence of mesangial IgA immune deposits confirms IgA nephropathy.

For patients with IgA nephropathy, treatment involves lowering blood pressure and decreasing proteinuria, so you’ll need to start your patient on an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.

However, if proteinuria persists, or if your patient has a progressive loss of kidney function despite these medications, consider adding glucocorticoids. If IgA nephropathy advances to end-stage renal disease, your patient may require dialysis or kidney transplantation.

Now, let’s consider patients who do not report a recent acute infection with sensorineural hearing loss.

In this case, you should suspect Alport syndrome. Affected individuals might also have abnormalities that involve the cornea, lens, and retina; so patients often report light sensitivity, blurred vision, and eye pain. In addition, there is often a family history of deafness and renal failure.

Labs may reveal an elevated serum creatinine. To confirm the diagnosis, obtain a renal biopsy with electron microscopy and immunofluorescence.

If electron microscopy reveals glomerular basement membrane splitting; as well as thinning and thickening of the glomerular basement membrane with a “basket-weave” appearance; and if the immunofluorescence shows an absence of the type IV collagen chains, diagnose Alport syndrome.

Now, here’s a clinical pearl to keep in mind! Alport syndrome is associated with an abnormality in type IV collagen, which is a protein that provides structural support to the eyes, ears, and kidneys. You can also diagnose Alport syndrome from a skin biopsy, which will demonstrate an absence of type IV collagen, or through genetic testing, which may reveal the COL4A5 mutation.