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| Year : 2009 | Volume
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| Issue : 1 | Page : 131-133 |
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| Granulomatous interstitial nephritis after prolonged use of phenytoin |
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Rapur Ram, G Swarnalatha, Neela Prasad, Aruna Prayaga, KV Dakshina Murthy
Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, India
Click here for correspondence address and email
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How to cite this article:
Ram R, Swarnalatha G, Prasad N, Prayaga A, Dakshina Murthy K V. Granulomatous interstitial nephritis after prolonged use of phenytoin. Saudi J Kidney Dis Transpl 2009;20:131-3 |
How to cite this URL:
Ram R, Swarnalatha G, Prasad N, Prayaga A, Dakshina Murthy K V. Granulomatous interstitial nephritis after prolonged use of phenytoin. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2020 Oct 29];20:131-3. Available from: https://www.sjkdt.org/text.asp?2009/20/1/131/44722 |
To the Editor,
A 25-year-old gentleman had been using phenytoin sodium 100 mg thrice a day since the age of 14 years, when he suffered two episodes of generalized tonic clonic seizures. He never suffered tuberculosis in the past.
At present admission he had complaints of fatigue and swelling of feet and face of three months duration. He also complained of breathlessness, vomiting, anorexia, and constipation of one week duration. He was afebrile, and had no urinary symptoms or skin rash. On examination, lymph nodes were not palpable and eye and systemic examinations were unremarkable. His investigations revealed: hemoglobin 8.0 g/dL, total leucocyte count 14700/mm 3 , absolute eosinophilic count 440/mm 3 , serum creatinine 12.8 mg/dL, blood urea 223 mg/dL, serum calcium 7.3 mg/dL, angiotensin converting enzyme levels 34 IU/L (normal range: 20-68 IU/L), 1,25 Vitamin D levels 43 pg/mL (normal range: 15-60 pg/mL), urine examination: albumin 2+, 5-6 RBC/ hpf, 18-20 WBC/hpf, leukocyte casts and urine eosinophils were negative. 24-hour urinary protein was 1.0 gm and calcium excretion 154 mg. Blood and urine cultures for aerobic and mycobacterium (BACTEC 9000 Blood Culture Series) were negative. Throat swab culture and serum antistreptolysin titres were also negative. Ultrasound abdomen showed right kidney of 10.9 × 4.4cm and left kidney of 9.5 × 3.9cm with increased parenchymal echogenecity. Radiograph and CT scan of chest were normal; tuberculin skin testing with 5 TU was negative after 48 hours. HBs Ag, AntiHCV antibodies and HIV were all negative. Anti-CMV IgG positive and IgM negative, cANCA, pANCA, ANA, antidsDNA, anti SCL-70, and cryoglobulin, were also negative. C3 and C4 levels were within normal range.
A renal biopsy after three sessions of dialysis showed 19 glomeruli of which three were sclerosed. One glomerulus showed periglomerular fibrosis, one had mesangial thickening and one glomerulus revealed a granuloma in the Bowman's capsule [Figure 1]. A few epitheloid cell granulomas were also seen in the interstitium, consisting of Langerhan's giant cells and histiocytes. The granulomas did not have areas of necrosis. There was no angiocentricity and; silver stain for fungus and Ziehl-Neelsen's stain for acid-fast bacilli was negative. Immunofluorescent stains for IgG, IgA, IgM and complements were negative.
Phenytoin sodium was replaced with sodium valproate, and intravenous methyl prednisolone 1.0 g per day was administered for three days followed by oral steroid 0.5mg/kg. The patient's urine improved gradually and hemodialysis was withdrawn 3 weeks later. Prednisolone was continued for 6 months and serum creatinine remained stable at 2.1 mg/dL.
The incidence of granulomatous interstitial nephritis (GIN) is reported around 0.95% [1] and 5.9%. [2] In a recent series, only 46 GIN (0.5%) out of 9,779 renal biopsies, were identified. [3]
Mignon et al [1] classified GIN into two groups: GIN with or without vasculitis or glomerulonephritis. The first group includes drug-induced GIN (28% of total GIN), sarcoidosis (10%), tuberculosis (10%) and GIN without clear etiology (25%); the later group is mainly composed of Wegener's granulomatosis (16%). Antibiotics, particularly sulpha drugs, penicillin, NSAIDs, diuretics, allopurinol, and anti-convulsant drugs are the leading drug offenders. A few cases of oliguric acute renal failure and interstitial nepritis have been reported with phenytoin. [4],[5],[6],[7],[8] Yoshikawa et al reported sodium valproate induced interstitial nephritis 6 years after the initiation of drug therapy. [9] In our patient, the use of medicine and exclusion of other causes implicate phenytoin sodium resulting in GIN and one must always exclude medications as the cause of renal disease in patients presenting with acute renal failure.
 References | |  |
| 1. | Mignon F, Mery JP, Mougenot B, Ronco P, Roland J, Morel-Maroger L. Granulomatous interstitial nephritis. Adv Nephrol Necker Hosp 1984;13: 219-45.  |
| 2. | Viero RM, Cavallo T. Granulomatous interstitial nephritis. Hum Pathol 1995; 26(12):1347-53. |
| 3. | Bijol V, Mendez GP, Nose V, Rennke HG.. -interstitial nephritis: a clinicopathologic study of 46 cases from a single institution. Int J Surg Pathol 2006;14(1):57-63. |
| 4. | Sheth KJ, Casper JT, Good TA. Interstitial nephritis due to phenytoin hypersensitivity. J Pediatr 1977;91(3):438-41. |
| 5. | Agarwal BN, Cabebe FG, Hoffman BI. Diphenylhydantoin induced acute renal failure. Nephron 1977;18(4):249-51. |
| 6. | Hymen LR, Ballow M, Knieser MR. Diphenyl-hydantoin interstitial nephritis: Role of cellular and humoral immunologic injury. J Pediatr 1978;92(6):915-20. |
| 7. | Maston JR, Krous HF, Blackstock R. Diphenylhydantoin induced hypersensitivity reaction with interstitial nephritis. Hum Pathol 1985;16(1):94-7. |
| 8. | Gaffey CM, Chun B, Harvey JC, Manz HJ. Phenytoin-induced systemic granulomatous vasculitis. Arch Pathol Lab Med 1986;110(2): 131-5. |
| 9. | Yoshikawa H, Watanabe T, Abe T. Tubulo-interstitial nephritis caused by sodium valproate. Brain Dev 2002;24 (2):102-5. |
Correspondence Address:
Rapur Ram
Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad
India
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PMID: 19112234 
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