Baylor University Medical Center Proceedings July 2017 - 351

Medullary angiitis and pauci-immune crescentic
glomerulonephritis
Jeffrey Klein, MD, William Rodriguez, MD, Michael Kuperman, MD, and Harold Szerlip, MD

Although almost all pathological diagnoses made from a native kidney
biopsy come from careful examination of the renal cortex, certain diseases have a characteristic medullary component. Medullary angiitis
has histological features of interstitial hemorrhage in the medulla with
an associated polymorphonuclear leukocyte infiltrate. These findings
are primarily found in the setting of antineutrophil cytoplasmic antibodyassociated vasculitis. Medullary angiitis identified in the setting of negative immunofluorescence is most suggestive of pauci-immune crescentic
glomerulonephritis, as presented in this case.

he gold standard for evaluation and proper classiﬁcation
of kidney disease is microscopic examination of renal tissue. As noted by Pirani, "the adequacy of a needle biopsy
is determined not by size (length) but by the presence
of renal cortex" (1). Glomerulonephritis can have characteristic
cortical ﬁndings, namely in the glomeruli. However, certain
disease entities remain elusive without close inspection of the
medulla. Medullary angiitis is an uncommon ﬁnding on renal
biopsies with rare descriptions in the literature (2, 3). These ﬁndings are thought to be due to thrombosis of the vasa recta with
subsequent medullary hemorrhage. Medullary angiitis is most
commonly associated with antineutrophil cytoplasmic antibody
(ANCA)-associated vasculitis (AAV). Increased awareness of
this pathologic ﬁnding is needed, as medullary angiitis can be
ignored or misdiagnosed as acute interstitial nephritis (4). This
case describes the association between medullary angiitis and
systemic vasculitis with a discussion of the underlying etiology.
CASE DESCRIPTION
A 64-year-old man with prior hypertension, obesity, gout,
and chronic kidney disease was admitted for evaluation of a rising
creatinine. Two years earlier, his baseline creatinine was 1.2 to 1.5
mg/dL with 132 mg of albumin in a 24-hour urine collection.
These ﬁndings remained stable until his creatinine increased from
1.5 to 2.2 mg/dL with 2+ hematuria over a 1-month period. The
patient admitted to frequent use of nonsteroidal antiinﬂammatory drugs (NSAIDs) for gout during that period. At that time, his
allopurinol was decreased from 450 mg to 300 mg daily and the
patient remained oﬀ NSAIDs. Three weeks later, the creatinine
was 3.5 mg/dL with 5.2 g of protein in a 24-hour urine collection.
Proc (Bayl Univ Med Cent) 2017;30(3):351-352

A kidney biopsy disclosed 12 glomeruli. None were globally sclerosed; one had a cellular crescent, two had ﬁbrocellular
crescents, and three had ﬁbrous crescents. The glomeruli had
normal size and cellularity. There was severe acute tubular injury
consisting of tubular cell necrosis with sloughing and apical
blebbing. The medulla had extensive interstitial hemorrhage
and leukocytoclasia of neutrophils (Figure 1). Tubular atrophy
and interstitial ﬁbrosis involved 40% to 50% of the cortex. Immunoﬂuorescence was negative. Electron microscopy revealed
normal glomerular basement membrane thickness without deposits. Approximately 80% of the glomerular basement membrane surface had podocyte foot process eﬀacement.
Based on the kidney biopsy ﬁndings, the patient was diagnosed with pauci-immune glomerulonephritis with medullary
angiitis. ANCA was positive with a titer of 1:320. Antigen testing was positive for myeloperoxidase.
The induction regimen included intravenous cyclophosphamide 1000 mg with intravenous Solu-Medrol 500 mg. After
6 doses of monthly cyclophosphamide and prednisone taper,
his serum creatinine fell to 1.7 mg/dL with 2 g of proteinuria.
Due to persistent proteinuria, the patient was transitioned to
intravenous rituximab 1000 mg monthly with reduction of
proteinuria to 200 mg after the second dose. After 4 doses of
rituximab, he remains oﬀ corticosteroids with continued microalbuminuria and stable kidney function.
DISCUSSION
Medullary angiitis found on renal biopsy warranted further
diagnostic testing in this patient with acutely worsening renal
function and heavy NSAID use (5-7). Less than 20% of AAV
specimens describe ﬁndings of necrotizing arteritis on histology
(2, 7, 8). Watanabe et al originally described necrosis of the renal
papilla in 5 of 23 cases of granulomatosis with polyangiitis (3).
In addition to the classic necrotizing crescentic lesions typical
of the cortex, these 5 cases demonstrated ﬁbrinoid necrosis of
From the Division of Nephrology (Klein, Szerlip) and the Department of Pathology
(Kuperman), Baylor University Medical Center, Dallas, Texas; and Austin Kidney
Associates, Austin, Texas (Rodriguez). Dr. Klein is now at the University of Kansas.
Corresponding author: Jeffrey Klein, MD, Division of Nephrology and Hypertension,
Department of Internal Medicine, University of Kansas Medical Center, 3901
Rainbow Blvd., Mail Stop 3002, Kansas City, KS 66160 (e-mail: jklein@kumc.edu).
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