Halle Field

Natallia Maroz

Journal of Medical Case Reports

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CASE REPORT Open Access
Necrotizing crescentic glomerulonephritis
related to sarcoidosis: a case report
Natallia Maroz1,2,3* and Halle Field3
Abstract
Introduction: Renal injury due to sarcoidosis develops in less than a quarter of patients with this systemic disease.
In most cases, granulomatous tissue alters the production of vitamin D, which leads to hypercalciuria, nephrocalcinosis,
and nephrolithiasis. Granulomatous interstitial nephritis is another well-recognized pathological process associated with
sarcoidosis. However, a glomerular pathology is very rarely noted, and only a few cases are reported to have cellular
crescentic glomerulonephritis.
Case presentation: We describe the case of a 26-year-old African American woman with systemic sarcoidosis, with a
unique constellation of renal lesions, including noncaseating epithelioid granulomatous necrotizing interstitial nephritis,
cellular crescent formation, and necrotizing vasculitis. Immunosuppressive therapy was helpful for alleviating her
nephrotic syndrome and maintaining the stability of her renal function over a 30-month period.
Conclusion: Glomerular involvement of sarcoidosis needs to be considered in the differential diagnosis in cases
of rapidly progressive glomerular nephritis.
Keywords: Crescentic glomerulonephritis, Rapidly progressive glomerular nephritis, Sarcoidosis
Introduction
Sarcoidosis is a chronic systemic granulomatous disorder
with various clinical presentations. Although lung in-
volvement is the most common morbidity in such cases,
severe extrapulmonary manifestations are also observed.
Renal pathology may also be associated with sarcoidosis,
and is observed in approximately 4–22 % of cases [1].
The spectrums of renal disorders include hypercalciuria,
nephrocalcinosis, and nephrolithiasis, which are the
most common causes of renal failure in sarcoidosis [2].
The second most-common manifestation of renal dis-
ease in sarcoidosis is granulomatous interstitial nephritis
(GIN); its prevalence is reported to be 7–27 % [3]. Cases
with glomerular lesions are rare, and only few cases have
been reported to have evidence of crescentic glomerulo-
nephritis [4]. In the present report, we describe a case
wherein a patient with multisystem sarcoidosis exhibited
a constellation of renal lesions, including GIN, crescentic
glomerulonephritis, and necrotizing vasculitis.
Case presentation
A 26-year-old African American woman with accidental
ankle subluxation presented to our emergency depart-
ment with foot pain. As a part of her work-up, she was
incidentally found to have an elevated serum creatinine
level of 2.2 mg/dL and proteinuria. Therefore, our patient
was referred to a nephrologist for further evaluation.
Her medical history included morbid obesity, hyper-
tension, and hyperlipidemia. The hypertension had been
present for 5 years, and was controlled with metoprolol
(25 mg, twice a day) and amlodipine (10 mg, daily). Her
other medications included ranitidine (150 mg, daily),
lovastatin (20 mg, daily) and norgestimate ethinyl estra-
diol (one tablet, daily). Moreover, she took ibuprofen
once a month, as needed, for shoulder pain. We did not
note any personal or family history of kidney disease,
autoimmune disease, or diabetes. The results of her
physical examination were relatively unremarkable, except
for obesity and moderate edema limited to her lower ex-
tremities. Her blood pressure was 140/90 mmHg. Examin-
ation of a 24-hour urine collection showed 11 g of urinary
protein and hematuria. Her serum albumin level was
1.8 g/dL.
* Correspondence: natallia.maroz@wright.edu
1Renal Physicians Inc., One Elizabeth Place, Suite 190, Dayton, OH 45418, USA
2Department of Medicine, Wright State University, Boonshoft School of
Medicine, 128 E. Apple St., 2nd Floor, Dayton, OH 45409, USA
Full list of author information is available at the end of the article
JOURNAL OF MEDICAL
CASE REPORTS
© 2015 Maroz and Field. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Maroz and Field Journal of Medical Case Reports  (2015) 9:282 
DOI 10.1186/s13256-015-0764-8
A kidney ultrasonography indicated normal size kidneys.
Thereafter, she underwent a kidney biopsy, which showed
severe noncaseating epithelioid granulomatous necrotiz-
ing interstitial nephritis(Fig. 1), necrotizing vascular lesion
(Fig. 2), and cellular crescent formation (Fig. 3) that were
related to the underlying sarcoidosis. Immunofluorescence
studies were negative for immunoglobulin (Ig) IgA, IgM,
kappa, lambda, C1q, C3, and fibrinogen but mild diffuse
linear glomerular capillary staining for IgG was suggestive
of pauci-immune crescentic glomerulonephritis.
Electron microscopy revealed no immune complex
deposits. Mycobacterium tuberculosis studies indicated
negative results. Serologic testing showed normal comple-
ment levels and negative results for anti-nuclear antibody,
double-stranded DNA, antineutrophil cytoplasmic anti-
body (ANCA), human immunodeficiency virus, Sjogren’s
syndrome, rapid plasma reagin, and viral hepatitis. Urine
protein electrophoresis showed nonselective proteinuria
related to combined glomerular and tubular damage. Her
level of rheumatoid factor was <3 units/mL. Moreover, she
was found to have elevated levels of angiotensin converting
enzyme of 78 U/L (normal, 16–68U/L), but her levels of
calcium, vitamin D, and parathyroid hormone were normal.
A subsequent computed tomography (CT) scan of her
chest showed patchy ground-glass opacities within both
the lower lobes, with multifocal air trapping, as well as mild
thickening of the bronchioles and mild hilar fullness,
consistent with stage II pulmonary sarcoidosis. CT of her
abdomen showed diffuse pelvic, para-aortic, and mesen-
teric lymphadenopathy. Examination of a pelvic lymph
node biopsy specimen demonstrated no evidence of any
lymphoproliferative disorder. Flow cytometry reported a
predominance of T-cells in the tissue, with a normal 3.9:1
ratio of CD4 and CD8. Her lactate dehydrogenase level was
within normal limits. Childhood records indicated a history
of bilateral uveitis, which was treated with prednisolone.
Owing to the multisystem involvement, our patient was
referred to a university-based sarcoidosis center. Because
the renal pathology was predominant in her case, the man-
agement of immunosuppression was deferred to a neph-
rologist. She was initially treated with prednisone (60 mg,
daily for 1 month), along with the subsequent addition of
azathioprine (150 mg, daily). The prednisone administra-
tion was gradually tapered to 5 mg/day over 12 months.
Subsequently, her nephrotic syndrome improved, her
serum albumin levels improved to 3.8 g/dL, and her urinary
protein levels markedly reduced from 11 g/24 hours to 1 g/
24 hours. After 1 year, the concentration of interlukin-2 re-
ceptor in her peripheral blood was assessed, and the find-
ings were suggestive of persistent disease activity. Hence,
her azathioprine dose was increased to 200 mg/day.
Thirty months after diagnosis, our patient remains in
partial renal remission, with stable stage 4 chronic kidney
Fig. 2 Necrotizing vasculitis in renal parenchyma (hematoxylin and
eosin, 20X)
Fig. 1 Granulomatous interstitial nephritis. Black line separates
the zone of diffuse interstitial inflammation from the area
with granulomatous responce. Arrows point toward epithelioid
noncaseating granulomas (hematoxylin and eosin, 40X) Fig. 3 Cellular crescent formation (periodic acid-Schiff, 40X)
Maroz and Field Journal of Medical Case Reports  (2015) 9:282 Page 2 of 4
disease (creatinine, 2.5 mg/dL; glomerular filtration rate,
28 mL/min/1.73 m2) and minimal proteinuria.
Discussion
Crescentic or rapidly progressive glomerular nephritis
(RPGN) represents a nephrological emergency. It may be
commonly linked to ANCA vasculitis, anti-glomerular
basement membrane disease, or complement-mediated
cases of lupus nephritis, cryoglobulinemia, IgA nephropa-
thy, and post-infectious glomerulonephritis. The major
clinical characteristics of the disease may include a
marked decline in renal function along with active urinary
sediment. Renal pathology demonstrates the presence of
cellular crescents at the beginning of the disease, which
frequently progress to fibrocellular crescents. If these pa-
tients are not promptly treated with immunosuppressive
therapy, RPGN will lead to irreversible damage and end-
stage renal disease [5].
Sarcoidosis is a chronic systemic granulomatous dis-
order with various clinical presentations and an unclear
etiology. The pathological activity of T-cells appears to
be an important event in the formation of noncaseating
granulomas, although the triggering mechanism is un-
clear. Lung involvement is the most common morbidity,
but extrapulmonary manifestations are also observed
[6]. It is more prevalent in young women, and is often
diagnosed around the age of 40 years. In the USA, this
condition has a 3–10-fold greater incidence in African-
American individuals than in Caucasians [2, 7]. At
present, no universal diagnostic criteria have been devel-
oped for sarcoidosis; hence, diagnosis generally requires a
biopsy and clinical exclusion of other granulomatous
diseases [7].
The extrapulmonary manifestations of sarcoidosis
affect the skin, eyes, nervous system, lymphatic system,
joints, heart, and liver. Renal disease can also be associ-
ated with sarcoidosis, although such cases are less com-
mon and are observed in about 4–22 % of cases [1].
Moreover, hypercalciuria is noted in half of these patients
as a result of calcitriol production in the granulomas. This
further leads to nephrocalcinosis and nephrolithiasis,
which are the most common causes of renal failure in sar-
coidosis [2, 8]. The second most-commonly observed
manifestation of renal disease in sarcoidosis is GIN; its
prevalence is reported to be 7–27 % [3, 8]. In a retrospect-
ive analysis of 47 patients with sarcoidosis with renal in-
volvement, 37 patients were reported to have noncaseating
GIN. Granulomas with a lymphoma-like appearance may
also be observed in renal sarcoidosis, and presents as a
mass in the kidney parenchyma on imaging [8].
Glomerular lesions are very rarely observed, and include
membranous nephropathy, focal segmental sclerosis,
mesangioproliferative glomerulonephritis, IgA nephropa-
thy, and crescentic glomerulonephritis [1, 9–11]. Among
the cases of crescentic glomerulonephritis, half of the pa-
tients showed ANCA antibody positivity, raising concerns
regarding the accuracy of the diagnosis and the similarity
in the pathogenesis between two granulomatous diseases
[8]. The presence of noncaseating necrotizing granulomas
within the wall of small, medium, and even large vessels
has been described in rare cases of systemic vasculitis
from sarcoidosis [9, 10].
The presentation of renal involvement in sarcoidosis is
unusual in our case. Our patient had a combination of
GIN, RPGN, and necrotizing vasculitis in the absence
of any other autoimmune disease. Moreover, she also
presented with extensive extrarenal manifestations of
sarcoidosis.
Sarcoidosis is not routinely considered to be a part of
the differential diagnosis for RPGN or any other glom-
erular pathology; instead, it is diagnosed based on the
exclusion of other possible conditions. Considerable lit-
erature is available to guide the management of RPGN
not related to sarcoidosis, including the initial use of
cytotoxic agents as induction therapy followed by the
use of maintenance agents. It is unclear whether this
treatment can be applied to the management of RPGN
from sarcoidosis. Extrapulmonary manifestations of sar-
coidosis are very responsive to prednisone therapy; how-
ever, successful use of cytotoxic agents has been reported
in steroid-resistant cases [2, 12, 13, 14, 15]. Considering
the severity of our patient’s renal manifestations and extra-
renal disease, we started treatment with azathioprine along
with prednisone. After 30 months, she showed partial renal
remission and stabilization of other manifestations.
Although the therapeutic strategies for sarcoidosis-
related RPGN need to be defined, a positive response to
prednisone therapy is well recognized. A randomized
multicentric clinical trial, “Treatment of renal sarcoid-
osis by methylprednisone bolus,” is currently recruiting
patients to determine the required dose and duration of
treatment with steroids. Use of adrenocorticotropic hor-
mone (ACTH) gel appears to be an attractive alternative
to corticosteroid therapy in extrarenal sarcoidosis via its
effect on different subtypes of mineralocorticoid recep-
tors (MCR). Positive renal effects were reported through
the stimulation of MC1R in podocytes, reduced renal
lymphocyte infiltration, effect on phospholipase A2 recep-
tor, attenuation of glomerular immune complex depos-
ition [16]. Different types of MCR have been identified in
tubular epithelial cells and endothelial cells [17]; however,
the validity of ACTH use in renal sarcoidosis should be
confirmed through clinical evidence.
In the present case, our patient achieved partial renal
remission with azathioprine and a low maintenance-dose
of prednisone. Ideally, the use of prednisone-sparing
agents is desired in order to avoid long-term corticoster-
oid toxicity. Studies regarding whether sarcoidosis can
Maroz and Field Journal of Medical Case Reports  (2015) 9:282 Page 3 of 4
be managed with a prednisone-free regimen need to be
conducted. Moreover, elucidating the etiology of sarcoid-
osis is essential to define the therapeutic aim and to de-
velop targeted therapy.
Conclusions
Glomerular involvement of sarcoidosis is a rare cause of
RPGN. In certain cases, renal manifestations may pre-
cede the diagnosis of systemic sarcoidosis [5]. The man-
agement of sarcoidosis-related RPGN remains a clinical
challenge. Therapeutic algorithms cannot be simply ex-
trapolated from non-sarcoidosis types of RPGN. In the
present case, we observed that the use of induction
immunosuppressive therapy with cytotoxic agents was
not required to achieve remission in a patient with
sarcoidosis-related MPGN. Accumulating evidence via
case reports of successful and unsuccessful strategies
is important to achieve better outcomes in patients
with sarcoidosis and RPGN.
Consent
Written informed consent was obtained from the patient
for the publication of this case report and accompanying
images. A copy of the written consent is available for re-
view by the Editor-in-Chief of this journal.
Competing interests
The authors declare they have no competing interests.
Authors’ contributions
Both authors have contributed equally to the writing of the manuscript. Both
authors read and approved the final manuscript.
Author details
1Renal Physicians Inc., One Elizabeth Place, Suite 190, Dayton, OH 45418,
USA. 2Department of Medicine, Wright State University, Boonshoft School of
Medicine, 128 E. Apple St., 2nd Floor, Dayton, OH 45409, USA. 3Department
of Medicine, Kettering Medical Center, 3535 Southern Blvd Kettering, Dayton,
OH 45429, USA.
Received: 23 August 2015 Accepted: 8 November 2015
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Necrotizing crescentic glomerulonephritis related to sarcoidosis: a case report

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Necrotizing crescentic glomerulonephritis related to sarcoidosis: a case report

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