Nephritic syndromes (pediatrics): Clinical sciences

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Introduction 0:00–0:32

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.

Unstable Patient 0:32–1:19

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.

Stable Patient 1:19–1:42

Keep in mind that these two conditions can have overlapping symptoms and even occur simultaneously. First, let’s discuss nephrotic syndrome.

Nephrotic Syndrome 1:42–2:28

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.

Nephritic Syndrome 2:28–4:28

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.

Post-Streptococcal Glomerulonephritis 4:28–6:02

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.

IgA Nephropathy 6:02–7:21

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.

Hearing Loss 7:21–7:29

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.

Alport Syndrome 7:29–9:11

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.
Because there’s no specific treatment for Alport syndrome, provide supportive care, which includes ACE inhibitors or ARBs.
As disease progresses, these patients might require dialysis and kidney transplantation. Now, let’s discuss patients whose hearing is intact.
For these patients, assess for hemoptysis, which will help you identify ANCA-associated glomerulonephritis or anti-GBM disease.

ANCA-Associated Glomerulonephritis 9:11–11:31

Let’s start with ANCA-associated glomerulonephritis. In addition to hemoptysis, these patients may have a positive ANCA with or without elevated creatinine.
A positive ANCA is a key finding in vasculitides such as granulomatosis with polyangiitis and microscopic polyangiitis. This should lead you to suspect ANCA-associated glomerulonephritis.
Next, obtain a renal biopsy with light microscopy and immunofluorescence. If light microscopy reveals segmental necrotizing glomerulonephritis; and if immunofluorescence shows negative or minimal immunoglobulin and complement deposition, also referred to as pauci-immune; you can confirm ANCA-associated glomerulonephritis.
Now, to determine the subtype of ANCA-associated glomerulonephritis, you’ll need to assess the disease-specific history and physical examination, and examine the ANCA-staining pattern.
So, if your patient has a history of sinusitis, and they are c-ANCA positive, meaning the cytoplasm of the white blood cells are glowing under immunofluorescence, diagnose granulomatosis with polyangiitis.
Immunosuppressives are the mainstay of treatment, so begin treatment with glucocorticoids in combination with rituximab.
On the other hand, your patient might report abdominal pain or peripheral weakness, pain, and tingling; while the exam might reveal palpable purpura.
These findings, in combination with a positive p-ANCA, where the cytoplasm around the nucleus, called the perinuclear cytoplasma, glows under immunofluorescence, confirm microscopic polyangiitis.
Again, begin treatment with immunosuppressive agents, including glucocorticoids and rituximab. Next, let’s discuss patients with anti-GBM disease.
These patients often have respiratory symptoms, such as hemoptysis, dyspnea, or cough; and their labs may reveal anti-GBM antibodies, possibly in combination with elevated creatinine.
These findings should make you suspect anti-GBM disease. Then proceed with renal biopsy and immunofluorescence.

Anti-GBM Disease 11:31–12:31

If the biopsy reveals a linear appearance of IgG deposition along the glomerular basement membrane, diagnose anti-GBM disease.
Treatment usually involves immunosuppression with glucocorticoids and cyclophosphamide, but you can also consider plasmapheresis to filter the blood and remove anti-GBM antibodies.
Fortunately, once anti-GBM disease is treated, it rarely relapses. Finally, let’s discuss cases which don’t involve hemoptysis.
Here, you should suspect immune-complex mediated proliferative glomerulonephritis. These patients might have a history of a chronic infection, like hepatitis B or C; or an autoimmune disease, such as systemic lupus erythematosus.
Additionally, their labs may reveal a low C3 and C4, as well as positive ANA, anti-double-stranded DNA, and anti-Smith antibodies.

Immune-complex mediated proliferative glomerulonephritis 12:31–15:00

Your next step is to obtain a renal biopsy with light microscopy, along with H&E and PAS stains. Now, here’s a clinical pearl to keep in mind!
Patients with immune-complex mediated proliferative glomerulonephritis often have coexisting nephritic syndrome and nephrotic syndrome, meaning they have both hematuria and nephrotic range proteinuria!
Now let’s look at the biopsy results. If H&E and PAS stains reveal mesangial hypercellularity and basement membrane thickening, which is often described as a “tram-track” pattern, diagnose membranoproliferative glomerulonephritis.
To manage your patient, first treat the underlying infection or autoimmune condition, and begin supportive care with ACE inhibitors or ARBs.
If disease progresses, consider glucocorticoids, dialysis, or kidney transplant. On the other hand, if the light microscopy reveals a “wire loop” glomerular capillary appearance, diagnose diffuse proliferative glomerulonephritis, which usually occurs in the setting of systemic lupus erythematosus.
Again, treat the underlying condition, and begin glucocorticoids, plus either cyclophosphamide or mycophenolate mofetil.
Now, here’s one last clinical pearl to keep in mind! Any patient with glomerulonephritis can develop rapidly progressive crescentic glomerulonephritis, which has a poor prognosis and can lead to renal failure if left untreated.
To identify this condition, look for the presence of crescent-shaped glomeruli on renal biopsy. Alright, as a quick recap… If a patient presents with hematuria, edema, and hypertension, suspect nephritic syndrome and obtain a urinalysis with microscopy.
If microscopy reveals red blood cell casts, diagnose nephritic syndrome. Then, use the disease-specific patient history, labs, and, in most cases, a renal biopsy...
To distinguish between post-streptococcal glomerulonephritis, IgA nephropathy, granulomatosis with polyangiitis, Alport syndrome, microscopic polyangiitis, anti-GBM disease, and immune-complex mediated glomerulonephritis.

Review 15:00–15:59

Treatment depends on the underlying disease but often includes supportive care, ACE inhibitors or ARBs, and immunosuppressant medications.
Patients who progress to renal failure require dialysis or kidney transplantation. nephropathy granulomatosis with polyangiitis Alport syndrome microscopic polyangiitis anti gbm disease and immune complex mediated glomerulonephritis Treatment depends on the underlying disease but often includes supportive care ace inhibitors or Arbs and immunosuppressant medications Patients who progress to renal failure require dialysis or kidney
Nephritic syndromes (pediatrics): Video and Causes | Osmosis