Sunday, May 1, 2011

The organization is key

There are a number of glomerulopathies that feature organized deposits of nonbranching fibrils, some more common than others. The diseases make their first major separation into Congo Red positive (amyloid) and Congo Red negative categories. Amyloid fibrils are randomly arranged, and are 8-12nm in diameter. The Congo Red negative fibrillary diseases are more diverse, and since they are more rare but are favored by those who write the boards, I found a review to be helpful. Fibrillary Glomerulonephritis:
  • Randomly arranged fibrils 12-30nm in diameter
  • Usually polyclonal IgG
  • Presents usually with proteinuria. 50% have nephrotic syndrome at presentation.
  • 50% of patients progress to ESRD within a few years
  • Treatment often unsuccessful. Steroids, cytoxan, and rituxan have been used with varying success.
  • Does not usually recur in transplants
Immunotactoid glomerulopathy:
  • parallel deposits of straight, hollow-lumen fibrils (microtubules) >30nm in diameter
  • usually monoclonal IgG
  • usually secondary
  • Deposits occur on subepithelial surface of basement membrane, can be indistinguishable from membranous on light microscopy
  • Presents with nephrotic syndrome, hypertension, hematuria.
  • Recurs in transplants
  • randomly arranged curved microtubules 25-35nm in diameter
Fibronectin glomerulopathy:
  • 10-15nm fibrils
  • Hereditary, autosomal dominant
  • Presents with proteinuria, hematuria, hypertension
Collagenofibrotic glomerulopathy
  • Banded collagen fibrils
  • Hereditary, autosomal recessive, most cases from Japan
  • Presents with edema and nephrotic syndrome
  • Progresses to ESRD
Diabetes can also be associated with fibril deposition, usually 5-20nm in diameter. Lupus can cause fibril formation, and these generally are around the same size as the deposits in fibrillary GN and are arranged in a fingerprint pattern.This article contains an outstanding flow chart for the differential diagnosis of glomerular diseases with organized deposits.

For the boards, it may be helpful to remember that the fibril diameter of the more common fibrillary diseases- amyloid, fibrillary GN, and immunotactoid GP are correlated with their position in the alphabet- (A= 8-12nm, F= <30nm, usually 18-20, and I= >30nm, usually 45-55nm).


Stan said...

Here is a nice case report and review on fibrillary diseases of the kidney.

And here is a newer case series from cJASN. 66 patients reviewed, and they noted 36% recurrence in 14 transplanted patients.

emily petersen said...

Sorry, that last comment (and this one) was from Emily Petersen- my father in law has leftt himself signed into google on my computer :)

Andrea Angioi said...

A very interesting work has been published in KI in 2003 by the Columbia University Department of Pathology group supporting the "morphological" classification of Organized deposits GN, especially focusing to fibrillary glomerulonephritis and immunotactoid glomerulopathy, two entities that are hard to define clearly for its frequent overlapping troubles.

Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, Appel GB, D'Agati VD.
Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different
clinical and pathologic features. Kidney Int. 2003 Apr;63(4):1450-61. PubMed
PMID: 12631361.

By the way, the supporters of "etio-pathological" classification of kidney diseases related with organized deposits (me encluded) could appreciate the old-fashioned study of Pronovost et al, NDT 1996 that approached the previous problem in a different way.