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      Diagnostic utility of kidney biopsy in patients with sarcoidosis and acute kidney injury

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          Abstract

          Background:

          Sarcoidosis is an idiopathic multisystem disease characterized by noncaseating granulomatous inflammation. Renal biopsy is often performed to evaluate the patient with sarcoidosis and acute kidney injury (AKI). Diagnosis rests on the demonstration of noncaseating granulomas and exclusion of other causes of granulomatous inflammation. This paper reports a patient with pulmonary sarcoidosis and AKI whose renal function improved after prednisone therapy despite the absence of kidney biopsy findings characteristic of sarcoidosis.

          Case report:

          A 63-year-old Caucasian male with history of hypertension was treated for pulmonary sarcoidosis with a 6-month course of prednisone. His creatinine was 1.6 mg/dL during the course. Two months after finishing treatment, he presented with creatinine of 4 mg/dL. A kidney biopsy was performed, which showed nonspecific changes without evidence of granuloma or active interstitial inflammation. He was empirically started on prednisone for presumed renal sarcoidosis, even with a nondiagnostic kidney biopsy finding. Within a month of treatment, his serum creatinine improved to 2 mg/dL, though not to baseline. He continues to be stable on low-dose prednisone. With this case as a background, we aimed to determine the incidence of inconclusive kidney biopsies in patients with sarcoidosis presenting with AKI and to identify the various histological findings seen in this group of patients.

          Methods:

          In this retrospective study, all patients who had native renal biopsies read at The Ohio State University over the period of 6 years were identified. Those patients with a diagnosis of sarcoidosis, presenting with AKI, were included for further review.

          Results:

          Out of 21 kidney biopsies done in patients with sarcoidosis over a period of 6 years, only four (19%) showed granulomatous interstitial nephritis (GIN). An equal number of patients (4 [19%]) had presence of membranous nephropathy. Nephrocalcinosis was seen in three patients (14%). Almost half of the biopsies had findings suggestive of diabetic nephropathy or other nonspecific changes not characteristic of renal sarcoidosis (48%).

          Conclusion:

          Renal sarcoidosis can be focal in nature and characteristic lesions can be missed in a small-needle core biopsy. Inconclusive renal biopsies with only nonspecific findings are frequent in patients with sarcoidosis and AKI. The presence of GIN on renal biopsy, although classic, is uncommon. Renal sarcoidosis remains a presumptive clinical diagnosis and empiric treatment with steroids may be initiated in cases with a strong clinical suspicion even in the absence of characteristic renal biopsy findings.

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          Most cited references16

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          Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999.

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            Renal sarcoidosis: clinical, laboratory, and histologic presentation and outcome in 47 patients.

            We conducted the current study to investigate the clinical, laboratory, and histologic features at presentation and the outcome of renal sarcoidosis (RS). Exhaustive retrospective data were collected by the French Sarcoidosis Group. Forty-seven adult patients were assessed (30 male/17 female, M/F ratio: 1.76). Median estimated glomerular filtration rate (eGFR) was 20.5 mL/min per 1.73 m(2) (range, 4-93 mL/min per 1.73 m(2)). Moderate proteinuria was found in 31 (66%) patients (median, 0.7 g/24 h; range, 0-2.7 g/24 h), microscopic hematuria in 11 (21.7%) patients, aseptic leukocyturia in 13 (28.7%) patients. Fifteen of 47 (32%) patients had hypercalcemia (>2.75 mmol/L). Eleven of the 22 (50%) patients diagnosed between June and September had hypercalcemia compared with only 4 of the 25 (16%) cases diagnosed during the other months (p < 0.001). Thirty-seven patients presented with noncaseating granulomatous interstitial nephritis (GIN), and 10 with interstitial nephritis without granulomas. Apart from hypercalcemia, the clinical phenotype was also remarkable for the high frequency of fever at presentation. All patients initially received prednisone (median duration, 18 mo), 10 received intravenous pulse methylprednisolone. eGFR increased from 20 +/- 19 to 44 +/- 24.7 mL/min per 1.73 m(2) at 1 month (p < 0.001, n = 38), to 47 +/- 19.9 mL/min per 1.73 m(2) at 1 year (p < 0.001, n = 46), to 49.13 +/- 25 mL/min per 1.73 m(2) at last follow-up (p < 0.001, n = 47). A complete response to therapy at 1 year and at last follow-up was strongly correlated with complete response at 1 month (p < 0.01). Renal function improvement was inversely related to initial histologic fibrosis score. A complete response to therapy at 1 year was strongly correlated with hypercalcemia at presentation (p = 0.003). Relapses were purely renal (n = 3) and purely extrarenal (n = 10) or both (n = 4), often a long time after presentation, with in some cases severe cardiac or central nervous system involvement. We conclude that hypercalcemia and fever at presentation are often associated with RS; RS is most often and permanently responsive to corticosteroid treatment, but some degree of persistent renal failure is highly frequent and its degree of severity in the long run is well predicted from both histologic fibrotic renal score and response obtained at 1 month.
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              Renal manifestations of sarcoidosis.

              Sarcoidosis may involve the kidneys in several ways. Most commonly, aberrations of calcium metabolism, including hypercalcemia, hypercalciuria, and nephrocalcinosis, are responsible for the renal manifestations of sarcoidosis. Granulomatous infiltration of the renal interstitium may also produce severe derangements of renal function. Glomerulonephritis can occur with sarcoidosis, although the pathogenesis remains unclear. Besides renal insufficiency and frank renal failure, nephrotic syndrome, nephrolithiasis, hypertension, and a variety of tubular defects may complicate sarcoidosis. The sensitivity of "sarcoid nephropathy" to corticosteroids usually warrants therapeutic trial.
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                Author and article information

                Journal
                Int J Nephrol Renovasc Dis
                International Journal of Nephrology and Renovascular Disease
                Dove Medical Press
                1178-7058
                2011
                26 September 2011
                : 4
                : 131-136
                Affiliations
                [1 ]Division of Nephrology
                [2 ]Division of Renal Pathology, The Ohio State University, Columbus, Ohio, USA
                Author notes
                Correspondence: Ravish Shah, The Ohio State University, Division of Nephrology, 395 W 12th Avenue, Ground Floor, Columbus, OH 43210, USA, Tel +1 614 293 4055, Fax +1 614 293 3073, Email ravish.shah@ 123456osumc.edu
                Article
                ijnrd-4-131
                10.2147/IJNRD.S22549
                3215339
                22114514
                33ca0e77-9d48-449d-bf46-42b320f6d6f4
                © 2011 Shah et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 23 September 2011
                Categories
                Original Research

                Nephrology
                renal sarcoidosis,acute kidney injury,sarcoidosis,granulomatous interstitial nephritis,kidney biopsy

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