WBR0748

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 40-year-old man with no past medical history presents to the physician's office for foamy urine. He takes no medications and has no allergies. He denies a history of either smoking, alcohol intake, or illicit drug use. A full physical examination is unremarkable. A 24-hour urinary collection reveals 6 grams of urinary proteins. Renal biopsy is performed, and the diagnosis of membranous nephropathy is made. Which of the following findings may distinguish primary from secondary forms of membranous nephropathy?]]
Answer A	AnswerA::Deposition of specific IgG subclasses on immunofluorescence
Answer A Explanation	[[AnswerAExp::IgG4 subtype is most commonly observed in idiopathic membranous nephropathy. In contrast, IgG1, 2, and 3 are more commonly observed in secondary forms of membranous nephropathy. The difference between the two may aid in the differentiation between primary (idiopathic) and secondary membranous nephropathy.]]
Answer B	AnswerB::Extent of glomerular crescent formation on light microscopy
Answer B Explanation	AnswerBExp::Crescent formation is usually present in rapidly progressive glomerulonephritis (RPGN), but may also be present in other forms of glomerulonephritides. The extent of crescent formation characterizes the severity of disease.
Answer C	AnswerC::Presence of gross hematuria during clinical work-up
Answer C Explanation	AnswerCExp::Gross hematuria is usually unlikely to be observed in membranous nephropathy. Microscopic hematuria is more common than gross hematuria. Hematuria does not help in differentiating between primary and secondary membranous nephropathies.
Answer D	AnswerD::Quantification of nephrotic-range proteinuria during 24-hour urinary collection
Answer D Explanation	[[AnswerDExp::The degree of proteinuria helps in identifying patients who require intervention. Patients with sub-nephrotic range proteinuria usually have higher chances of spontaneous remission. On the other hand, patients with nephrotic range proteinuria are less likely to remit spontaneously. Proteinuria is considered the most important prognostic marker. Proteinuria has a "dose-dependent" effect, where the more the proteinuria, the worse the prognosis.]]
Answer E	AnswerE::Presence of urinary IgG and IgM during clinical work-up
Answer E Explanation	AnswerEExp::Urinary IgG and IgM may be found in patients with membranous nephropathy. They may be utilized as biological biomarkers for follow-up and progression. Nonetheless, their role still needs to be validated.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Approximately 80% of patients with idiopathic membranous glomerulopathy (MGN or membranous nephropathy) present with nephrotic syndrome. A minority of patients have sub-nephrotic-range proteinuria at presentation. Patients may also have microscopic hematuria. The finding of gross hematuria, on the other hand, is unlikely in MGN, and generally suggests the need to search for alternative diagnoses. However, gross hematuria has nonetheless been described in MGN. Kidney biopsy is the gold standard for the diagnosis of MGN. On light microscopy, kidney biopsy typically demonstrates capillary wall thickening with normal cellularity. Immunofluorescence is remarkable for IgG and C3 deposits along the capillary walls. Electron microscopy shows exclusively subepithelial deposits between podocyte foot processes. IgG subtypes present on immunofluorescence may be helpful in differentiating idiopathic vs. secondary causes of MGN. In primary idiopathic MGN, the IgG4 subtype of IgG is most commonly observed, comprising approximately 80% of all idiopathic cases. However, this is not true for secondary causes of MGN. Although other features on renal biopsy are common between the 2 forms, IgG1, 2, and 3 are more commonly observed in secondary MGN. Furthermore, the location of the deposits may also provide clues to the diagnosis. While deposits in primary MGN are exclusively observed in the subepithelial region, deposits in secondary MGN may involve both the subepithelial and subendothelial regions of the capillary wall. Educational Objective: IgG subclass on immunofluorescence may differentiate primary vs. secondary membranous nephropathy. IgG4 is associated with primary membranous nephropathy, whereas IgG1, 2, and 3 are more commonly associated with secondary membranous nephropathy. References: Jennette JC, Iskandar SS, Dalldorf FG. Pathologic differentiation between lupus and nonlupus membranous glomerulopathy. Kidney Int. 1983; 24(3):377-85. Ohtani H, Wakui H, Komatsuda A, et al. Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy. Nephrol Dial Transplant. 2004; 19(3):574-9. Polanco N, Gutierrez E, Covarsi A, et al. Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol. 2010; 21(4):697-704. Menon S, Valentini RP. Membranous nephropathy in children: clinical presentation and therapeutic approach. Pediatr Nephrol. 2010; 25(8):1419-28. First Aid 2014 page 536]]
Approved	Approved::Yes
Keyword	WBRKeyword::Membranous, WBRKeyword::Nephropathy, WBRKeyword::Membranous nephropathy, WBRKeyword::Nephrotic syndrome, WBRKeyword::Subendothelial, WBRKeyword::Subepithelial, WBRKeyword::IgG, WBRKeyword::Subclass, WBRKeyword::IgG1, WBRKeyword::IgG2, WBRKeyword::IgG3, WBRKeyword::IgG4, WBRKeyword::Primary form, WBRKeyword::Secondary form, WBRKeyword::IgG subclass, WBRKeyword::IgG subclasses, WBRKeyword::Prognosis, WBRKeyword::Proteinuria, WBRKeyword::Primary, WBRKeyword::Idiopathic, WBRKeyword::Secondary, WBRKeyword::Form, WBRKeyword::Forms
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