WBR230

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Will Gibson)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 21 year old male patient presents to the urgent care clinic for dark colored urine. Upon further questioning, the patient reports he has recently recovered from a flu-like illness 4 days prior to presentation. Patient denies dysuria, frequency, or urgency. Patient’s vital signs reveal a temperature of 36.7 degree C (98 degree F), heart rate of 68 beats per minute, and blood pressure measuring 110/85 mmHg. Patient’s physical examination is unremarkable. After appropriate work-up, renal biopsy reveals mesangial proliferation. Which finding is most consistent with the pathogenesis of the patient’s condition?]]
Answer A	AnswerA::Immunoglobulin subclass deficient in galactose
Answer A Explanation	[[AnswerAExp::IgA Nephropathy (Berger’s disease) is the most common primary glomerulonephritis worldwide. It is characterized by mesangial proliferation on light microscopy. As opposed to post-infectious glomerulonephritis, IgA nephropathy is typically “synpharyngitic” due to its manifestation immediately following a non-specific upper respiratory tract or gastrointestinal infection. The hallmark for diagnosing IgA nephropathy is IgA deposition in the glomerular mesangium. IgG and/or IgM could also be similarly present in the deposition. Complement C3, properdin, C4, C4d, mannose-binding lactin, and terminal complement complex C5b-C9 are also commonly present; while C1q is typically absent. Mesangial IgA is almost always IgA1 subclass that is deficient in galactose.]]
Answer B	AnswerB::Circulating immune complexes triggering the activation of complement pathways
Answer B Explanation	[[AnswerBExp::Circulating immune complexes that trigger the activation of complement pathways are typically seen in post-infectious glomerulonephritis and in membranoproliferative glomerulonephritis.]]
Answer C	AnswerC::Selective loss of albumin caused by basement membrane polyanion loss
Answer C Explanation	[[AnswerCExp::Selective loss of albumin is a hallmark of minimal change disease (lipoid nephrosis). Characteristically, light microscopy in minimal change disease reveals normal glomeruli. Electron microscopy shows podocyte foot process effacement.]]
Answer D	AnswerD::Deposition of protein sheets that stain positive for Congo Red
Answer D Explanation	[[AnswerDExp::Amyloidosis is an infiltrative disease that has a positive Congo red stain showing apple-green birefringence.]]
Answer E	AnswerE::Generation of advanced glycosylation end products and acceleration of aldose reductase pathway
Answer E Explanation	[[AnswerEExp::Advanced glycosylation end products (AGEs) are the hallmark of diabetic nephropathy causing microvascular complications.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation::IgA nephropathy (Berger’s disease) is the most common primary glomerulonephritis worldwide. It is characterized by mesangial proliferation on light microscopy. As opposed to post-infectious glomerulonephritis, IgA nephropathy is typically “synpharyngitic” due to its manifestation immediately following a non-specific upper respiratory tract or gastrointestinal infection. The hallmark for diagnosing IgA nephropathy is IgA deposition in the glomerular mesangium. IgG and/or IgM could also be similarly present in the deposition. Complement C3, properdin, C4, C4d, mannose-binding lactin, and terminal complement complex C5b-C9 are also commonly present; while C1q is typically absent. Mesangial IgA is almost always IgA1 subclass that contains O-glycans deficient in galactose. On light microscopy, increase in mesangial matrix and hypercellularity are common but not exclusive. Electron microscopy reveals electron-dense material corresponding to IgA immune deposits mostly seen in mesangial and paramesangial areas. The peak incidence of IgA Nephropathy is between the ages of 15 and 30. Males are affected twice as often as females. Genome-wide-association studies have linked the HLA and complement loci to disease predisposition. Optimal treatment consists of blood pressure control with an ACE-inhibitor or Angiotensin Receptor Blocker (ARB). Educational Objective: IgA nephropathy is the most common primary glomerulonephritis worldwide. IgA1 sublclass, deficient in galactose, is implicated in IgA nephropathy. It typically presents at young age immediately following an upper respiratory or gastrointestinal infection. References: Wyatt RJ, Julian BA. IgA Nephropathy. N Eng J Med. 2013;368:2402-2414 Gharavi, Ali G., et al. "Genome-wide association study identifies susceptibility loci for IgA nephropathy." Nature genetics 43.4 (2011): 321-327. First Aid 2015 page 541]]
Approved	Approved::Yes
Keyword	WBRKeyword::Renal, WBRKeyword::Nephropathy, WBRKeyword::IgA Nephropathy, WBRKeyword::Autoimmune, WBRKeyword::IgA, WBRKeyword::Kidney
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