View source for WBR231

{{WBRQuestion
|QuestionAuthor={{Rim}} (Reviewed by Will Gibson)
|ExamType=USMLE Step 1
|MainCategory=Histology, Pathology
|SubCategory=Renal
|MainCategory=Histology, Pathology
|SubCategory=Renal
|MainCategory=Histology, Pathology
|SubCategory=Renal
|MainCategory=Histology, Pathology
|MainCategory=Histology, Pathology
|MainCategory=Histology, Pathology
|SubCategory=Renal
|MainCategory=Histology, Pathology
|SubCategory=Renal
|MainCategory=Histology, Pathology
|SubCategory=Renal
|MainCategory=Histology, Pathology
|SubCategory=Renal
|MainCategory=Histology, Pathology
|MainCategory=Histology, Pathology
|SubCategory=Renal
|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?

[[File:Diabetic_nephropathy.png|300px]]
|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 [[immunoglobulin]]s, [[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.
|AnswerA=Amorphous pink deposits of amyloid in renal cortex
|AnswerAExp=Amyloidosis is characterized by [[amyloid]] deposition that is positive for Congo red stain.
|AnswerB=Immune response mediated by CD4 and CD8 lymphocytes
|AnswerBExp=Immune response mediated by [[CD4]] and [[CD8]] [[lymphocytes]] describes the mechanism of renal rejection following [[transplantation]].
|AnswerC=Cystic distribution throughout the renal parenchyma
|AnswerCExp=[[Polycystic kidney disease]] is characterized by cystic distribution throughout the renal parenchyma.
|AnswerD=Immune complex deposition activating the complement pathway
|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.
|AnswerE=Non-enzymatic glycosylation of proteins
|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. 
|EducationalObjectives=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.<br>
Kalia K, Sharma S, Mistry K. Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy. Clin Chim Acta. 2004;347(1-2):169-76.<br>
First Aid 2015 page 543
|RightAnswer=E
|WBRKeyword=Diabetes, Diabetes Mellitus, DM, Glucose, Glycosylation, Glycation, AGEs, Histology, Nephropathy, Renal, Kidney, Histology
|Approved=Yes
}}