WBR231

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Will Gibson)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Histology, MainCategory::Pathology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 68 year old Caucasian male patient presents to his physician for his annual check-up. The patient’s past medical history is significant for hypertension controlled on lisinopril and advanced diabetes mellitus type II poorly controlled on daily insulin injections. Routine work-up reveals elevated serum creatinine. A renal biopsy is performed, the results of which are shown below. The histologic findings could be best explained by which of the following pathologic processes? ]]
Answer A	AnswerA::Amorphous pink deposits of amyloid in renal cortex
Answer A Explanation	[[AnswerAExp::Amyloidosis is characterized by amyloid deposition that is positive for Congo red stain.]]
Answer B	AnswerB::Immune response mediated by CD4 and CD8 lymphocytes
Answer B Explanation	[[AnswerBExp::Immune response mediated by CD4 and CD8 lymphocytes describes the mechanism of renal rejection following transplantation.]]
Answer C	AnswerC::Cystic distribution throughout the renal parenchyma
Answer C Explanation	[[AnswerCExp::Polycystic kidney disease is characterized by cystic distribution throughout the renal parenchyma.]]
Answer D	AnswerD::Immune complex deposition activating the complement pathway
Answer D Explanation	[[AnswerDExp::The pathogenesis of several primary glomerulonephritides, including post-infectious glomerulonephritis and membranoproliferative glomerulonephritis, is characterized by immune complex deposition that activates the complement pathway.]]
Answer E	AnswerE::Non-enzymatic glycosylation of proteins
Answer E Explanation	[[AnswerEExp::Diabetic nephropathy is a common microvascular complication in advanced diabetes mellitus. Renal biopsy under light microscopy would reveal characteristic eosinophilic nodules in the glomerular tuft called “Kimmelsteil-Wilson” lesion. Chronic hypercalcemia causes non-enzymation glycosylation (glycation) of proteins.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::Diabetic nephropathy is a common microvascular complication in advanced diabetes mellitus. Renal biopsy under light microscopy typically reveals characteristic eosinophilic nodules in the glomerular tuft called “Kimmelsteil-Wilson” lesion. Chronic hypercalcemia causes non-enzymation glycosylation (glycation) of proteins, which are collectively called advanced glycation end products (AGEs). Glycation is the irreversible attachment of reducing sugars to amino acids in proteins. The resulting AGEs trap extravasated immunoglobulins, albumin, LDL, and other proteins via cross-linking to the extra vascular matrix. These accumulated products cause generalized cellular dysfunction and can initiate inflammatory cascades, leading to further tissue damage. Educational Objective: Diabetic nephropathy is a microvascular complication of uncontrolled diabetes mellitus. It is characterized by Kimmelsteil-Wilson lesions, which are eosinophilic nodules in glomerular tufts. The pathogenesis of diabetic nephropathy is believed to be due to accumulation of advanced glycation end products (AGEs). References: Tan, Adeline LY, Josephine M. Forbes, and Mark E. Cooper. "AGE, RAGE, and ROS in diabetic nephropathy." Seminars in nephrology. Vol. 27. No. 2. WB Saunders, 2007. Kalia K, Sharma S, Mistry K. Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy. Clin Chim Acta. 2004;347(1-2):169-76. First Aid 2015 page 543]]
Approved	Approved::Yes
Keyword	WBRKeyword::Diabetes, WBRKeyword::Diabetes Mellitus, WBRKeyword::DM, WBRKeyword::Glucose, WBRKeyword::Glycosylation, WBRKeyword::Glycation, WBRKeyword::AGEs, WBRKeyword::Histology, WBRKeyword::Nephropathy, WBRKeyword::Renal, WBRKeyword::Kidney, WBRKeyword::Histology
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