A 21-year-old male presents to your office with hematuria 3 days after the onset of a productive cough and fever. Following renal biopsy, immunofluorescence shows granular IgA deposits in the glomerular mesangium. Which of the following do you suspect in this patient?

Poststreptococcal glomerulonephritis

A 12-year-old boy is brought to an outpatient clinic by his mother, who noticed that her son’s urine has been dark for the past 4 days. She initially attributed this to inadequate hydration, so she monitored her son’s fluid intake and encouraged him to drink more water. However, she noticed that the color of the urine kept getting darker until it began to resemble cola. The boy’s medical history is significant for a sore throat approx. 2 weeks ago, which resolved without medication or treatment. The boy has also been complaining of pain in his ankles, which he first noticed shortly after soccer practice 1 week ago. He has had no pain during urination or urethral discharge, however, and does not have any history of previous episodes of cola-colored urine or passage of blood in the urine. However, the boy has been experiencing intermittent episodes of abdominal pain for the past 3 days. The boy also has wheals on his torso, legs, and buttocks, which his mother attributes to seasonal allergies. Physical examination reveals an alert child who is not in obvious distress but who has a mild conjunctival pallor. Vital signs include: respiratory rate is 22/min, temperature is 36.7°C (98.0°F), and blood pressure is 130/90 mm Hg. Examination of the musculoskeletal system reveals multiple skin lesions (see image). Which of the following laboratory findings is most likely associated with this patient’s clinical presentation?

Elevated IgM-IgG immune complex rheumatoid factor

24-hour urinary protein of more than 4 g

Elevated levels of serum IgG and C3 protein

A 61-year-old man comes to the physician because of progressively worsening swelling of his ankles. He says he has felt exhausted lately. Over the past 3 months, he has gained 5 kg. He has smoked one pack of cigarettes daily for 30 years. His pulse is 75/min and his blood pressure is 140/90 mmHg. Examination shows 2+ pitting edema in the lower extremities. Neurologic exam shows diminished two-point discrimination in the fingers and toes. A urine sample is noted to be foamy. Laboratory studies show a hemoglobin A1c of 7.9% and creatinine of 1.9 mg/dL. A biopsy specimen of the kidney is most likely to show which of the following?

Split glomerular basement membrane

A 47-year-old woman comes to the physician because of a 2-week history of gradually worsening facial and lower extremity swelling. She has had a 4-kg (8.8-lb) weight gain during this time. Her blood pressure is 150/88 mm Hg. Examination shows periorbital edema and 2+ pretibial edema bilaterally. A 24-hour collection of urine shows 4.0 g of proteinuria. Microscopic examination of a kidney biopsy specimen shows thickening of the glomerular basement membrane. Electron microscopy shows dense subepithelial deposits. Further evaluation is most likely to show which of the following?

Anti-phospholipase A2 receptor antibodies

Anti-myeloperoxidase antibodies

Anti-collagen type IV antibodies

A 57-year-old woman presents to her family physician because of sinusitis and nasal drainage for 3 months. The nasal drainage is purulent and occasionally hemorrhagic. She has only temporary improvement after trying multiple over the counter medications. Over the last 2 weeks, she also has fatigue and joint pain, mainly affecting the ankles, knees, and wrists. Vital signs include: temperature 36.9°C (98.4°F), blood pressure 142/91 mm Hg, and pulse 82/min. On examination, there is inflammation and bleeding of the nasal mucosa, along with tenderness to percussion over the maxillary sinuses. Urine dipstick reveals 4+ microscopic hematuria and 2+ proteinuria. Which of the following is the most likely diagnosis?

Granulomatosis with polyangiitis

A 62-year-old man presents to the emergency department with hematuria and hemoptysis that started in the morning. He notes that he has had frequent lung infections throughout his adult life, the most recent being 2 weeks ago. He also mentions that he has had hematuria twice before but never as severe as he is having currently. His medical history is otherwise non-significant, and his only medication is acetaminophen as needed. His blood pressure is 136/92 mm Hg, heart rate is 86/min, respiratory rate is 16/min, and temperature is 37.0°C (98.6°F). Chest radiography shows a resolving right middle lobe airspace opacity. His initial laboratory tests are notable for elevated erythrocyte sedimentation rate and C-reactive protein level. While in the examination room, the patient develops a spontaneous nosebleed. What is the most likely diagnosis?

Granulomatosis with polyangiitis

Post-streptococcal glomerulonephritis

Glomerulonephritis classification for USMLE Step 3: High-Yield Internal Medicine Lessons

Nephritic vs. Nephrotic - The Great Divide

Nephritic (Inflammatory): Glomerular inflammation (immune complex deposition).
- Presents with: Hematuria (RBC casts), HTN, oliguria, azotemia.
- Proteinuria: Mild-to-moderate (< 3.5 g/day).
Nephrotic (Non-inflammatory): Podocyte damage leading to ↑ permeability.
- Presents with: Massive proteinuria (> 3.5 g/day), hypoalbuminemia, severe edema, hyperlipidemia/lipiduria (oval fat bodies).
- 📌 Mnemonic: PALE (Proteinuria, hypoAlbuminemia, Lipidemia, Edema).

Acute Glomerulonephritis Classification and Management

⭐ Nephrotic syndrome causes a hypercoagulable state due to urinary loss of Antithrombin III, increasing risk for thromboembolism.

Nephrotic Syndromes - The Protein Leakers

Hallmarks: Proteinuria >3.5 g/day, hypoalbuminemia, severe edema, hyperlipidemia/lipiduria (oval fat bodies).
Minimal Change Disease (MCD):
- Most common cause in children; often follows infection.
- LM: Normal. EM: Diffuse effacement of podocyte foot processes.
- Excellent, rapid response to corticosteroids.
Focal Segmental Glomerulosclerosis (FSGS):
- Most common cause in adults (esp. African American).
- Sclerosis in segments of some glomeruli.
- Associations: HIV, heroin use, sickle cell, obesity.
Membranous Nephropathy (MN):
- Subepithelial immune complex deposits → "spike and dome" on EM.
- Associated with anti-PLA2R Abs, HBV, NSAIDs, malignancy.

⭐ In an adult with new-onset nephrotic syndrome, especially Membranous Nephropathy, always consider and screen for an underlying solid tumor (e.g., lung, colon).

EM of podocyte foot process effacement in MCD

Nephritic Syndromes - The Inflammatory Crew

Hallmark: Glomerular inflammation & bleeding.
Presentation: Hematuria (cola-colored urine), RBC casts, hypertension, oliguria, and mild proteinuria (< 3.5 g/day).

RBC casts and dysmorphic RBCs in urine sediment

Classification by Complement (C3) Levels:

Normal C3
- IgA Nephropathy (Berger's Disease): Most common cause worldwide. Often follows URI/GI infection.
- Pauci-Immune GN: ANCA-associated (e.g., GPA, MPA).
- Alport Syndrome: Hereditary (Type IV collagen defect); associated with deafness & ocular findings.
Low C3
- Post-Streptococcal GN (PSGN): Follows GAS infection (1-3 weeks post-pharyngitis, 3-6 weeks post-impetigo).
- Membranoproliferative GN (MPGN): "Tram-track" appearance on histology.

⭐ Exam Tip: IgA nephropathy presents with hematuria syn-pharyngitically (concurrently with infection), while PSGN has a significant latency period after the infection resolves.

Mixed Pictures - Nephritic-Nephrotic Overlap

Presents with features of both nephritic (hematuria, HTN) and nephrotic (>3.5 g/day proteinuria, edema) syndromes.
Membranoproliferative Glomerulonephritis (MPGN): Thickened glomerular basement membrane (GBM) & mesangial proliferation.
- Classic "tram-track" appearance on light microscopy.
- Can be primary or secondary (e.g., HCV, SLE, cryoglobulinemia).
Diffuse Proliferative Glomerulonephritis (DPGN): Most common & severe lupus nephritis (Class IV).
- Features "wire-loop" lesions from subendothelial deposits.

MPGN tram-track appearance (light and electron microscopy)

⭐ MPGN Type I is strongly associated with Hepatitis C virus (HCV), while Type II (Dense Deposit Disease) is linked to C3 nephritic factor, an autoantibody that stabilizes C3 convertase, leading to persistent complement activation and low C3 levels.

Nephritic syndrome = inflammation (hematuria, HTN). Nephrotic syndrome = podocyte damage (massive proteinuria >3.5 g/day, edema).

Linear IgG deposits on immunofluorescence are pathognomonic for Goodpasture's syndrome.

Subepithelial "humps" are classic for Post-streptococcal GN.

"Spike and dome" appearance on electron microscopy indicates Membranous Nephropathy.

Crescent formation signifies Rapidly Progressive Glomerulonephritis (RPGN), a nephrologic emergency.

IgA Nephropathy is the most common primary glomerulonephritis worldwide.

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