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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2017  |  Volume : 28  |  Issue : 5  |  Page : 1157-1161
Acute kidney injury with granulomatous interstitial nephritis and vasculitis revealing sarcoidosis

1 Department of Medicine A, Charles Nicolle Hospital, Tunis, Tunisia
2 Department of Laboratory of Renal Pathology LRSP001, Charles Nicolle Hospital, Tunis, Tunisia

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Date of Web Publication21-Sep-2017


Sarcoidosis is an inflammatory disease that affects mostly the lungs and lymph glands. Renal involvement is rare and especially vasculitis. We report a case who presented an acute kidney failure and had sarcoidosis with vasculitis and nodular splenic involvement. A 35-year-old woman presenting a Lofgren syndrome was hospitalized for acute renal failure with cervical lymphadenopathy without other clinical findings. Laboratory data disclosed elevated angiotensin converting enzyme serum level. Abdominal ultrasound showed a multinodular spleen. Renal histology revealed granulomatous interstitial nephritis with necrotizing vasculitis. Outcome was favorable after the institution of high dose corticosteroids along with cyclophosphamide. Renal involvement is rare in sarcoidosis. However, the diagnostic delay should be avoided to improve the outcome.

How to cite this article:
Harzallah A, Kaaroud H, Boubaker K, Barbouch S, Goucha R, Hamida FB, Abdallah TB. Acute kidney injury with granulomatous interstitial nephritis and vasculitis revealing sarcoidosis. Saudi J Kidney Dis Transpl 2017;28:1157-61

How to cite this URL:
Harzallah A, Kaaroud H, Boubaker K, Barbouch S, Goucha R, Hamida FB, Abdallah TB. Acute kidney injury with granulomatous interstitial nephritis and vasculitis revealing sarcoidosis. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2022 Nov 27];28:1157-61. Available from: https://www.sjkdt.org/text.asp?2017/28/5/1157/215120

   Introduction Top

Sarcoidosis is a systemic granulomatous disease of unknown cause involving generally lung and lymph nodes.[1] Renal involvement is rare and can be polymorphic including several manifestations most commonly due to disorders in calcium homeostasis.[2] Granulo-matous tubulointerstitial nephritis (GIN) is a less common cause of renal impairment, diagnosed only with biopsy.[3] Involvement of small blood vessels in the kidney is not usually seen in sarcoidosis. We present an interesting case of a patient with acute kidney injury (AKI) with biopsy findings of a vasculocentric GIN with evidence of small-vessel vasculitis and a nodular splenic involvement.

   Case Report Top

A 35-year-old woman was admitted to our department who presented with Lofgren syndrome (erythema nodosum and arthralgia). She has no significant medical history and has not been taking any medication. On admission, she had cervical lymphadenopathy. There were no other remarkable clinical findings especially nasal or ocular. Blood pressure was normal.

The initial laboratory tests [Table 1] showed advanced renal failure with an eGFR, calculated according to the modification of diet in renal disease renal disease equation, of 8.4 mL/min/1.73 m2 (serum creatinine: 536 μmol/L). Serum calcium was normal and serum angiotensin-converting enzyme level was raised at 118 UI. Proteinuria was less than 0.5 g/day with no hematuria. Liver function tests were normal. Her erythrocyte sedimentation rate was 82 mm at 1 h. Chest X-ray was normal. Urine and sputum cultures for tuberculosis were all negative. Renal ultrasound showed normal kidney size and echogenicity with no evidence of obstruction or nephro-lithiasis. Ultrasonography of the abdomen showed a normal spleen size with a multiple hypoechoic lesions. A computed tomography scan of the chest showed two infracentimetric mediastinal ganglions. Bronchoalveolar lavage showed a higher level of lymphocytosis at 78%, with the lymphocyte T CD4/CD8 ratio at 0.1. Salivary gland biopsy showed a tuber-culoid noncaseating granuloma with moderate inflammation. Light microscopic evaluation of the kidney biopsy specimen was performed with hematoxylin and eosin, periodic acid–Schiff, Wilder’s reticulin staining modified by Callard, Masson’s trichrome, and crystal violet staining. There were 40 nonglobally sclerosed glomeruli, several of which showed focal ischemic tuft retraction. No glomeruli with hyper-cellularity, fibrinoid necrosis, or crescents were identified. There were multiple interstitial noncaseating granulomas comprising of epithelioid histiocytes, Langhans type giant cells with an interstitial fibrosis and moderate interstitial lymphocytic and granulomatous inflammation with tubulitis [Figure 1].
Table 1: Laboratory data at presentation

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Figure 1: Granulomatous interstitial inflammation.

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There was necrotizing vasculitis of the arteries with thrombosis and parietal disruption surrounded by a noncaseating granuloma [Figure 2] and [Figure 3]. Routine immunofluore-scence was negative for all immunoglobulins and C1q, with the exception of nonspecific mesangial positivity for C3 and IgM involving a few glomeruli. Antineutrophil cytoplasmic antibody serologic test results were negative.
Figure 2: Necrotic vasculitis of the arteries with thrombosis.

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Figure 3: Parietal disruption of arteries surrounded by a noncaseating granuloma.

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Although granulomatous arteritis is rarely seen in sarcoidosis, the diagnosis of systemic sarcoidosis with renal granulomatous vasculitis was finally retained.

The treatment consisted of intravenous pulse methylprednisolone, 500 mg daily for three days, followed by oral prednisone (1 mg/kg daily) associated with six pulses of cyclophos-phamide (15 mg/kg/month). During the eight next days, she improved her renal function with a decrease of the serum creatinine to 294 μmol/L (eGFR: 16.2 mL/min/1.73 m2).

After six months, she continues on maintenance prednisone therapy at 10 mg daily along with azathioprine 100 mg/day, with the improvement of kidney function (serum creatinine: 142 μmo/L, eGFR: 39 mL/min/1.73 m2) [Table 2]. At the last follow-up, her eGFR was 38 mL/min/1.73 m2 on prednisone (5 mg daily) without any relapse and with a normal ultrasound of the abdomen.
Table 2: Evolution of renal function.

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   Discussion Top

We present a case who had an AKI with a Lofgren syndrome suggestive of sarcoidosis. The kidney biopsy findings of GIN showed the unusual feature of vasculocentric granulomatous inflammation centered around arterioles with necrosis and thrombosis consistent with vasculitis. Multisystem organ involvement by a granulomatous process was suggested by imaging abnormalities of the abdomen showing of a nodular spleen. Such clinical presentation and the exclusion of other possible causes of granulomatous disease established a clinicalpathologic diagnosis of renal sarcoi-dosis. In addition, the improvement in kidney function with glucocorticoids and immuno-suppressive therapy corroborate our diagnosis.

Granulomatous inflammation can be observed in various conditions such us infections, lymphoma, or granulomatous with polyangiitis. In patients with systemic sarcoidosis who underwent kidney biopsy, 15%–40% of the cases had GIN, although cases of isolated renal sarcoidosis also have been reported,[4],[5] especially by Robson et al.[6]

In the study of Mahévas et al, 47 adult patients with renal sarcoidosis were assessed. Thirty-seven patients presented with GIN, and 10 with interstitial nephritis without granulomas.[7] Then, GIN is the most typical histologic feature observed in patients with renal sarcoidosis.

A vascular involvement with GIN is rare. Several conditions may lead to this, like infections especially tuberculosis, drug-induced allergic interstitial nephritis, Churg-Strauss syndrome or polyangiitis. Vasculopathy in sarcoidosis can be either by compression of granuloma with disruption of the lamina of the adjoining blood vessels or a vascular injury termed necrotizing sarcoid granulomatosis characterized by confluent granulomas with necrosis that was primarily described in lungs.[8]

To the best of our knowledge, only three cases were reported over the literature including sarcoidosis associated with histologic features of vasculitis in the kidney [Table 3].[9],[10],[11] Our case is particular because of the associated nodular spleen. In fact, the involvement of the spleen in sarcoidosis was reported in only 15%–24% of cases.[12],[13]
Table 3: Granulomatous interstitial nephritis with renal vasculitis: literature review.

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Corticosteroids seem to be the treatment of choice in renal sarcoidosis. Most authors recommend generally corticosteroids only at doses of 0.5–1 mg/kg/day of oral prednisone as the initial regimen.[14] Although steroids improved the renal function of a large majority of patients, only a minority of them recovered normal renal function. These data are according to those obtained by Mahévas et al,[7] in a series of 47 patients and with those of Rajakariar et al.[14] However, methylprednisolone seems to have been more beneficial. In fact, in the study of Mahévas et al, there was a better response to intravenous high-dose steroids than to oral steroids. A similar response has been reported for sarcoidosis with vascular involvement.[8]

Other alternative regimens were tested in certain cases such as mycophenolate and azathioprine with good result. Furthermore, cytotoxic agents have been added to corticosteroid therapy in some cases that allowed a remission-maintenance, using lower doses of corticosteroids.[15],[16],[17]

Thus, we choose to treat our patient with pulses of methylprednisolone plus an immuno-suppressive regimen. She indeed improved her renal function, but at the end of follow-up, the eGFR was <60 mL/min/1.73m2.

Moreover, it seems that renal function improvement is inversely related to the initial fibrosis score. In the study of Mahévas et al, patients with an extensive interstitial fibrosis F3 score were unresponsive to treatment.[7] This observation was in accordance with that of Rajakariar et al.[14] They also demonstrated that the renal function response at one month was highly predictive of the long-term response.

   Conclusion Top

Sarcoidosis is a disease of granulomatous inflammation in which renal involvement such us GIN is rare. A small-vessel vasculitis can also be a feature of renal sarcoidosis. That is why kidney biopsy must be performed in cases of acute renal failure as far as possible, to improve renal prognosis by instituting early and adequate therapy.

Conflict of interest: None declared.

   References Top

Mayock RL, Bertrand P, Morrison CE, Scott JH. Manifestations of sarcoidosis. Analysis of 145 patients, with a review of nine series selected from the literature. Am J Med 1963;35:67-89.  Back to cited text no. 1
Chapelon-Abric C. Rare sites of sarcoidosis: Clinical aspects and reflections on the diagnostic approach. Rev Med Interne 1995;16: 271-7.  Back to cited text no. 2
Berliner AR, Haas M, Choi MJ. Sarcoidosis: The nephrologist’s perspective. Am J Kidney Dis 2006;48:856-70.  Back to cited text no. 3
Joss N, Morris S, Young B, Geddes C. Granulomatous interstitial nephritis. Clin J Am Soc Nephrol 2007;2:222-30.  Back to cited text no. 4
Bergner R, Hoffmann M, Waldherr R, Uppenkamp M. Frequency of kidney disease in chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2003;20:126-32.  Back to cited text no. 5
Robson MG, Banerjee D, Hopster D, Cairns HS. Seven cases of granulomatous interstitial nephritis in the absence of extrarenal sarcoid. Nephrol Dial Transplant 2003;18:280-4.  Back to cited text no. 6
Mahévas M, Lescure FX, Boffa JJ, et al. Renal sarcoidosis: Clinical, laboratory, and histologic presentation and outcome in 47 patients. Medicine (Baltimore) 2009;88:98-106.  Back to cited text no. 7
Fernandes SR, Singsen BH, Hoffman GS. Sarcoidosis and systemic vasculitis. Semin Arthritis Rheum 2000;30:33-46.  Back to cited text no. 8
Agrawal V, Crisi GM, D’Agati VD, Freda BJ. Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis. Am J Kidney Dis 2012;59:303-8.  Back to cited text no. 9
Miller BW, Miller SB, McKenzie CR, Davila RM. Granulomatous interstitial nephritis: Drug hypersensitivity, infection, or sarcoidosis? Am J Kidney Dis 1997;30:586-8.  Back to cited text no. 10
Shintaku M, Mase K, Ohtsuki H, Yasumizu R, Yasunaga K, Ikehara S. Generalized sarcoidlike granulomas with systemic angiitis, crescentic glomerulonephritis, and pulmonary hemorrhage. Report of an autopsy case. Arch Pathol Lab Med 1989;113:1295-8.  Back to cited text no. 11
Warshauer DM, Dumbleton SA, Molina PL, Yankaskas BC, Parker LA, Woosley JT. Abdominal CT findings in sarcoidosis: Radiologic and clinical correlation. Radiology 1994;192:93-8.  Back to cited text no. 12
Taavitsainen M, Koivuniemi A, Helminen J, et al. Aspiration biopsy of the spleen in patients with sarcoidosis. Acta Radiol 1987;28:723-5.  Back to cited text no. 13
Rajakariar R, Sharples EJ, Raftery MJ, Sheaff M, Yaqoob MM. Sarcoid tubulo-interstitial nephritis: Long-term outcome and response to corticosteroid therapy. Kidney Int 2006;70: 165-9.  Back to cited text no. 14
Dykhuizen RS, Smith CC, Kennedy MM, McLay KA, Cockburn JS, Kerr KM. Necro-tizing sarcoid granulomatosis with extrapulmonary involvement. Eur Respir J 1997;10:245-7.  Back to cited text no. 15
Lynch JP 3rd, Sharma OP, Baughman RP. Extrapulmonary sarcoidosis. Semin Respir Infect 1998;13:229-54.  Back to cited text no. 16
Watson I, Hill CM, Biggart JD, Russell CJ, Garrett PJ. Sarcoidosis and primary systemic vasculitis. Nephrol Dial Transplant 1996;11: 1631-3.  Back to cited text no. 17

Correspondence Address:
Amel Harzallah
Department of Medicine A, Charles Nicolle Hospital, Tunis
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Source of Support: None, Conflict of Interest: None

PMID: 28937078

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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