- The Daily Step 1 Newsletter
- Posts
- Which of the following is the most likely diagnosis?
Which of the following is the most likely diagnosis?
Dr. Shoaib Ahmad Baig
January 17, 2025
🔍 Question
A 41-year-old woman presents with peripheral edema and a weight gain of 6.8 kg (15 lb) over 8 weeks. She reports frothy urine and has no significant medical history or current medications. She denies tobacco, alcohol, or illicit drug use. Blood pressure is 140/90 mm Hg, pulse 80/min, and physical examination reveals generalized edema. Heart sounds are normal, and the abdomen is soft and non-tender. Laboratory tests show a serum creatinine of 1.1 mg/dL, urinalysis with 4+ protein, 0-3 leukocytes/hpf, and oval fat bodies. Serum studies detect IgG4 antibodies to phospholipase A2 receptor (PLA2R), a transmembrane protein on podocytes.
What is the most likely diagnosis?
A. Focal segmental glomerulosclerosis
B. Membranous nephropathy
C. Minimal change disease
D. Mixed cryoglobulinemia
E. Multiple myeloma
Correct Answer 🎯:B. Membranous nephropathy
⚙️ Trigger: Immune Complex Formation
⬇️
🧠 PLA2R receptor (a transmembrane protein) on podocytes targeted by autoantibodies
⬇️
⚙️ Immune Complex Deposition (IgG4 + PLA2R) at the glomerular basement membrane (GBM)
⬇️
⚙️ Activation of complement system (C5b-C9)
⬇️
⚙️ Podocyte injury → GBM becomes leaky
⬇️
🔍 Clinical Effects:
• Proteinuria: Albumin loss dominates → Frothy urine
• Hypoalbuminemia: ⬇️ Oncotic pressure → Edema (generalized)
• Normal creatinine: No significant glomerular damage yet
Think of the kidney’s glomerulus as a coffee filter:
• In membranous nephropathy, immune complexes clog the filter and punch holes in it.
• Result: Proteins (normally retained) leak out like a broken sieve.
⚖️ Explanation of Other Differentials
Differential ⚖️ | Why Incorrect? 🔴 |
|---|---|
Focal Segmental Glomerulosclerosis (FSGS) | ⚙️ Primary damage to podocytes but: • 🧠 Associated with conditions like HIV, obesity, or heroin use (none present here). • Non-selective proteinuria is common, unlike MN. |
Minimal Change Disease (MCD) | ⚙️ Podocyte Effacement on electron microscopy: • 🧠 Mostly affects children. • Selective proteinuria, but PLA2R antibodies are absent. |
Mixed Cryoglobulinemia | ⚙️ Immune complex-mediated vasculitis: • 🧠 Systemic symptoms: Rash, arthralgia, low complement levels (not seen here). • Cryoglobulins in serum—absent in this patient. |
Multiple Myeloma | ⚙️ Plasma cell malignancy: • 🧠 Symptoms: Bone pain, fractures, anemia, hypercalcemia (none seen). • Urine findings: Bence-Jones proteins, not albuminuria |
📝 Flashcards
Stay Hungry, Stay Curious!
Your Brother In This Struggle
Dr. Shoaib Ahmad
ps…Just a heads up!
We are launching our high-yield Q bank "Excel USMLE Step1: Respiratory System" this month InshaAllah.
With this Q-bank, you’ll be able to Excel any USMLE Step 1 question on respiratory section without fear of getting a wrong answer using our visual charts and flashcards.
This e-book will feature:
High-yield USMLE Step 1 questions on the respiratory system.
Conceptual clarity for every question to solidify your understanding.
Problem-solving strategies to enhance your test-taking skills.
Flashcards for each question to reinforce learning.
You can pre-order now.
Future editions covering other systems will follow shortly.
Each e-book in the series is priced individually.
Special Offer:
61% off during the pre-order period.
Money-back guarantee if you’re not satisfied—no questions asked!