WBR0812

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 45 year old Caucasian male patient is referred by the primary care physician to the nephrologist's office for nephrotic-range proteinuria. Physical examination is remarkable for high blood pressure and lower extremity edema. Following appropriate work-up, the patient is found to have elevated levels of anti-phospholipase A2 receptor (PLA2R) antibodies. The patient undergoes a kidney biopsy that shows subepithelial deposits and capillary wall thickening with normal cellularity. Anti-PLA2R IgG antibodies and C3 deposits are also observed on immunofluorescence. What is the most likely diagnosis of this patient's condition?]]
Answer A	AnswerA::Membranoproliferative glomerulonephritis often shows glomerular basement membrane (GBM) splitting on pathology due to mesangial ingrowth.
Answer A Explanation	AnswerAExp::These are not the classical findings of membranoproliferative glomerulonephritis.
Answer B	AnswerB::Membranous nephropathy
Answer B Explanation	AnswerBExp::Membranous nephropathy is characterized by the presence of antibodies against phospholipase A2 receptor. (PLA2R)
Answer C	AnswerC::IgA nephropathy
Answer C Explanation	AnswerCExp::In IgA nephropathy, 30-50% of patients have elevated IgA1 levels.
Answer D	AnswerD::Rapidly progressive glomerulonephritis
Answer D Explanation	[[AnswerDExp::These are not the classical findings of rapidly progressive glomerulonephritis (RPGN). RPGN usually presents with hematuria and rapidly worsening kidney function over only a few weeks. On pathology, RPGN is characterized classically by crescent formation.]]
Answer E	AnswerE::Lupus nephritis
Answer E Explanation	AnswerEExp::These are not the classical findings of lupus nephritis. Lupus nephritis has a wide range of presentations and several sub-types.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Membranous nephropathy (MN) or membranous glomerulonephritis (MGN) is a common glomerulonephritis that usually presents with nephrotic-range proteinuria, edema, and hypertension. MN is generally classified as primary (idiopathic) or secondary to other systemic disease, such as infections, malignancies, vasculitides etc. Primary MN has been recently associated with the presence of a newly discovered phospholipase A2 receptor (PLA2R) nephrotigenic antigen on the membrane surface of glomerular podocytes and anti-PLA2R antibodies. Kidney biopsy remains the gold standard for the diagnosis of MN, showing subepithelial deposits with capillary wall thickening and IgG deposition under immunofluorescence. On electron microscopy, MN shows a "spike and dome" appearance with subepithelial deposits. While MN is widely considered a chronic condition with a waxing and waning course, it is usually self-limited in the majority of the cases. Heavy proteinuria, a significant marker of prognosis, indicates the need for intervention, usually with corticosteroids and immunosuppressive therapy. Educational Objective: Anti-phospholipase A2 receptor antibodies are recently discovered to be the nephritogenic antibodies implicated in membranous nephropathy. They are classically present in sera of patients with membranous nephropathy and as IgG deposits on podocyte surfaces. Reference: Beck LH Jr, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11-21. Qin W, Laurence H, Beck LH Jr, Zeng C, et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol. 22:1137-1143. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::membranous, WBRKeyword::nephropathy, WBRKeyword::PLA2R, WBRKeyword::antibodies, WBRKeyword::antibody, WBRKeyword::phospholipase, WBRKeyword::A2, WBRKeyword::receptor, WBRKeyword::receptors, WBRKeyword::subepithelial, WBRKeyword::deposits, WBRKeyword::IgG, WBRKeyword::C3, WBRKeyword::complement, WBRKeyword::glomerulonephritis, WBRKeyword::nephrotic, WBRKeyword::syndrome, WBRKeyword::proteinuria, WBRKeyword::hypertension, WBRKeyword::edema, WBRKeyword::spike, WBRKeyword::dome, WBRKeyword::immunofluorescence, WBRKeyword::renal, WBRKeyword::kidney, WBRKeyword::biopsy, WBRKeyword::light, WBRKeyword::microscopy, WBRKeyword::electron
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