Baylor University Medical Center Proceedings July 2017 - 352

a

b

pears to be regulated by endothelialspeciﬁc angiopoietins (Ang). Ang-2
can be used to measure the extent
of endothelial cell detachment, with
a strong correlation between active AAV with renal involvement as
measured by Birmingham Vasculitis
Activity Score and Ang-2 levels (16).
These complex processes are areas of
ongoing research.

1. Piranni C. Evaluation of kidney biopsy
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eds. Renal Pathology with Clinical and
Functional Correlations. Philadelphia:
John Wiley & Sons, 1989:11-42.
2. Bonsib SM, Goeken JA, Fandel T,
Houghton DC. Necrotizing medullary
lesions in patients with ANCA associated
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3. Watanabe T, Nagafuchi Y, Yoshikawa Y,
Toyoshima H. Renal papillary necrosis associated with Wegener's granulomatosis.
Hum Pathol 1983;14(6):551-557.
Figure 1. (a) Segmental fibrocellular crescent (Periodic acid-Schiff, 200×). (b) Interstitial hemorrhage within the
4. Hendricks AR, Harris AA, Walker PD,
medulla (hematoxylin and eosin [H&E], 40×). (c) Interstitial hemorrhage, neutrophils, and karyorrhectic debris (H&E,
Larsen CP. Renal medullary angiitis: a
200×). (d) Extravasated red blood cells and neutrophils (H&E, 400×).
case series from a single institution. Hum
Pathol 2013;44(4):521-525.
5. Hedger N, Stevens J, Drey N, Walker S, Roderick P. Incidence and outcome of
the vasa recta. Of the 18 cases without papillary necrosis, only
pauci-immune rapidly progressive glomerulonephritis in Wessex, UK: a 103 had both medullary interstitial changes and classic glomerular
year retrospective study. Nephrol Dial Transplant 2000;15(10):1593-1599.
lesions.
6. Holle JU, Gross WL. Treatment of ANCA-associated vasculitides (AAV).
The histologic diagnosis may prove invaluable, as medullary
Autoimmun Rev 2013;12(4):483-486.
angiitis may be the only hint of severe systemic disease. Bonsib
7. Sinico RA, Di Toma L, Radice A. Renal involvement in anti-neutrophil cytoplasmic autoantibody associated vasculitis. Autoimmun Rev
et al noted necrotizing medullary lesions in 8 of 56 renal pa2013;12(4):477-482.
thology specimens with known AAV (2). Unlike the original
8. D'Amico G, Sinico RA, Ferrario F. Renal vasculitis. Nephrol Dial Transdescriptions by Watanabe, some glomerular lesions did not corplant 1996;11(Suppl 9):69-74.
relate with the severity of the medullary lesions. Further, cortical
9. Falk RJ, Jennette JC. ANCA small-vessel vasculitis. J Am Soc Nephrol
sampling may be insuﬃcient or nondiagnostic, so medullary
1997;8(2):314-322.
angiitis may be the only ﬁnding to suggest systemic vasculitis
10. Jennette JC, Wilkman AS, Falk RJ. Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. Am J Pathol
and thus lead to proper therapy (9-11).
1989;135(5):921-930.
Medullary angiitis is associated with ANCA positivity, IgA
11. Walker PD, Cavallo T, Bonsib SM, Ad Hoc Committee on Renal Biopsy
nephropathy, and drug-induced interstitial nephritis (2). HenGuidelines of the Renal Pathology Society. Practice guidelines for the renal
dricks et al reviewed 38 patients with medullary angiitis, and 19
biopsy. Mod Pathol 2004;17(12):1555-1563.
of the 30 patients (67%) were identiﬁed as having AAV (4). The
12. Rutgers A, Slot M, van Paassen P, van Breda Vriesman P, Heeringa P,
Tervaert JW. Coexistence of anti-glomerular basement membrane antibodremaining 11 patients had IgA nephropathy (20%) and 17%
ies and myeloperoxidase-ANCAs in crescentic glomerulonephritis. Am J
had various infections treated with associated antibiotics (4).
Kidney Dis 2005;46(2):253-262.
Similar to crescentic glomerulonephritis, the ﬁnding of medul13. Woywodt A, Streiber F, de Groot K, Regelsberger H, Haller H, Haubitz
lary angiitis on renal biopsy should provoke further serologic
M. Circulating endothelial cells as markers for ANCA-associated smalltesting (12). If no immunologic factor is identiﬁed (ANCA or
vessel vasculitis. Lancet 2003;361(9353):206-210.
14. Erdbruegger U, Grossheim M, Hertel B, Wyss K, Kirsch T, Woywodt A,
IgA), then drug-induced etiologies should be considered (9).
Haller H, Haubitz M. Diagnostic role of endothelial microparticles in
While NSAID use with minimal change disease was a diﬀerenvasculitis. Rheumatology (Oxford) 2008;47(12):1820-1825.
tial consideration, it has not been implicated in AAV.
15. Hu N, Westra J, Kallenberg CG. Dysregulated neutrophil-endothelial
Diminished renal perfusion with relative medullary hypoxia
interaction in antineutrophil cytoplasmic autoantibody (ANCA)-associhas been proposed for medulla-speciﬁc peritubular capillary
ated vasculitides: implications for pathogenesis and disease intervention.
Autoimmun Rev 2011;10(9):536-543.
involvement (4). More recent investigation into endothelial
16. Kumpers P, Hellpap J, David S, Horn R, Leitolf H, Haller H, Haubitz
cell dysregulation has revealed complex microvascular interplay
M. Circulating angiopoietin-2 is a marker and potential mediator of
(13). The neutrophils stimulated by ANCA lead to endothelial
endothelial cell detachment in ANCA-associated vasculitis with renal
cell activation and vessel destruction (14, 15). This process apinvolvement. Nephrol Dial Transplant 2009;24(6):1845-1850.

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Baylor University Medical Center Proceedings

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