7 December 2005 Case of the Week #30


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We thank Dr. Dylan Miller, Mayo Clinic, Rochester, Minnesota (USA) for contributing this case. We invite you to contribute a Case of the Week by sending an email to NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case. Please only send cases with a definitive diagnosis.


Case of the Week #30


Clinical History


A 41 year old man with diabetes presented with renal failure one week after an upper respiratory infection. A renal biopsy was obtained, and processed for H&E and electron microscopy.


Micro description: H&E, PAS stain, Jones methenamine silver


Electron microscopy: image (m: mesangial nodule, arrow: subepithelial hump)


What is your diagnosis?


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Diabetic nodular glomerulosclerosis with superimposed post-infectious glomerulonephritis.




This case features two distinct lesions consistent with the patients history of diabetes and streptococcal infection (an ASO titer was elevated).


Patients with diabetes have numerous renal lesions, including nodular glomerulosclerosis, also called intercapillary glomerulosclerosis or Kimmelstiel-Wilson disease. These are ovoid, spherical, laminated hyaline masses in the periphery of the glomerulus that are PAS positive (additional image #1). They may eventually obliterate the glomerular tuft, causing end stage renal disease. They are relatively specific for diabetes, but may also be found in membranoproliferative glomerulonephritis, light-chain disease and amyloidosis.


Other microscopic diabetic renal lesions include (a) basement membrane thickening and increased mesangial matrix, in all patients; (b) diffuse glomerulosclerosis, identified by an increase in PAS+ mesangial matrix associated with basement membrane thickening, that eventually obliterates mesangial cells; (c) profound hyalinization of afferent arterioles (insudative lesion-intramural), which is specific for diabetes at this site (image); (d) organizing fibroepithelial crescents, associated with an aggressive clinical course; and (e) diffuse thickening of the tubular basement membrane, tubular atrophy and interstitial fibrosis.


Post-streptococcal glomerulonephritis is a diffuse type of endocapillary proliferative glomerulonephritis. It is also called post-infectious glomerulonephritis, because similar histologic findings are seen with endemic malaria, toxoplasmosis, hepatitis B and C, HIV, varicella, spirochetes, staphylococci, meningococci and other bacteria. The deposition of immune complexes from antibodies against organisms elicits an acute inflammatory response and nephritic syndrome. Post-streptococcal disease is decreasing in the US, where post-Staphylococcal aureus infection is more frequent, but it is common elsewhere. Histologically, the glomeruli are globally and diffusely enlarged and hypercellular due to neutrophils and macrophages, and the proliferation of mesangial and endothelial cells. Capillary lumina are obstructed by swollen endothelial cells and inflammatory cells. Immunofluoresence shows a granular (lumpy-bumpy) deposition of IgG, IgM and C3 in peripheral glomerular loops. EM shows subepithelial humps (finely granular, dome-shaped, electron dense material, representing immune complex deposits), and the obliteration of epithelial cell foot processes.


A case of IgA dominant, post-staphylococcal glomerulonephritis complicating diabetic nephropathy has been reported (Hum Path 2003;34:1235).


Additional references: Hum Path 1993;24:77 (pathogenesis of Kimmelstiel-Wilson nodule). Also see our Kidney-Non tumor chapter (click here)





Nat Pernick, M.D.
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