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| Year : 2009 | Volume
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| Issue : 4 | Page : 655-657 |
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| Short course of cyclophosphamide therapy may reduce recurrence in patients with tubulointerstitial nephritis and uveitis syndrome |
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Shahram Taheri1, Diana Taheri2
1 Department of Internal Medicine, Isfahan School of Medicine, Isfahan, Iran
2 Department of Pathology, Isfahan School of Medicine, Isfahan, Iran
Click here for correspondence address and email
| Date of Web Publication | 8-Jul-2009 |
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 Abstract | | |
We report a 43-year-old woman with tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) presented with a 5-day complaint of chills and fever, anorexia, nausea, and vomiting. She had elevated BUN and creatinine and urinalysis revealed decreased concentration, proteinuria, hematuria, and pyuria. A kidney biopsy showed non-caseating granulomatous tubulointerstitial nephritis. She suffered from anterior uveitis one month before, which was managed with local ophthalmic steroids. She received two months of oral high dose prednisolone, which was tapered over the next two months, and two months of 2 mg/kg cyclophosphamide. Her renal function recovered during the first two months. Her kidney and ocular symptoms did not recur during one year of follow-up. We suggest short course of cyclophosphamide and prednisolone for treatment of TINU syndrome to decrease the recurrence of kidney and ocular involvement.
How to cite this article:
Taheri S, Taheri D. Short course of cyclophosphamide therapy may reduce recurrence in patients with tubulointerstitial nephritis and uveitis syndrome. Saudi J Kidney Dis Transpl 2009;20:655-7 |
How to cite this URL:
Taheri S, Taheri D. Short course of cyclophosphamide therapy may reduce recurrence in patients with tubulointerstitial nephritis and uveitis syndrome. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2021 Jan 17];20:655-7. Available from: https://www.sjkdt.org/text.asp?2009/20/4/655/53295 |
| Introduction | |  |
Tubulointerstitial nephritis and uveitis (TINU) syndrome was first described by Dobrin and associates in 1975. [1] Till now more than 140 cases of this syndrome have been reported. TINU syndrome has been documented more in the ophthalmology and pediatric nephrology literature and less in adult patients via case reports and small case series.
As we reviewed, there is no study of therapy that may provide protection from recurrence of this disease in together eyes and kidneys.
| Case History | | |
A 43- year- old woman presented on October 3 rd , 2006 with a 5 day complaint of chills, fever, anorexia, nausea, and vomiting. Her past medical history was unremarkable until one month ago, when she complained of headache and felt severe pain in her eyes especially in left side. She was diagnosed anterior uveitis, and she received local ophthalmic steroid therapy.
Laboratory tests done at the first presentation included: BUN: 51 mg%, Cr: 4.2 mg%, FBS: 76 mg/dL, WBC: 6980/µL9 (neutrophils: 80%, lymphocytes: 9%, monocytes: 5%, eosinophils :4%, and LUCs: 2%). Urinalysis showed: SG: 1005, pH: 7, protein = 2+, blood = 1+, RBC = 6-8 and WBC =15-20 per high power field. Urine culture was negative. Urine protein to creatinine ratio = 1.2. Other laboratory tests included: Ca: 7.5mg/dL, P: 4.5 mg/dL, serum al bumin: 3 g/dL, ALT: 21 IU/mL, AST: 17 IU/mL, alkaline phosphatase: 148 IU/mL, antinuclear antibody: 3.9 IU/mL (negative < 10), antibody to dsDNA: 9.9 IU/mL (negative :5 20), ANCA: negative. Serum complement level was normal. Hepatitis B antigen and antibodies to hepatitis C and HIV were negative. Serum protein electrophoresis showed polycolonal hypergamaglobulinemia. Urine smear and culture for tuberculosis were negative. Chest X-ray and plain abdominal film were unremarkable.
After admission to our hospital a percutaneous kidney biopsy was done to evaluate the acute renal failure in this patient. The biopsy revealed 9 glomeruli, and all showed trivial increase in mesangial cellularity, and some contained 1-4 polymorphonuclear cells. The interstitium showed diffuse mild edema with accompanying mononuclear and polymorphonuclear cells, occasional infiltration with eosinophilic cells, and numerous epitheloid nodules with giant cells (non caseating granulomas) [Figure 1]. Immunofluorescent study was unremarkable.
The patient received initially high dose of pulse methylprednisolone and oral 2 mg/kg/day cyclophosphamide. Oral prednisolone 1 mg/kg/day and cyclophosphamide were continued for 2 months and after that cyclophosphamide was discontinued, and the prednisolone dose was tapered and discontinued over the next 2 months. The patient's renal function improved after two months of starting treatment. During the following year her renal function remained stable and her ocular manifestation did not recur. After 1 year of follow-up her serum Cr was 1.2 mg/dL and BUN: 21 mg/dL. Her urinalysis was unremarkable, and 24-hour urine protein excretion was 78 mg.
| Discussion | | |
Different mechanisms for TINU have been suggested. Delayed-type hypersensitivity and suppressed cell-mediated immunity with predominance of T-lymphocytes likely play a major role in the pathogenesis of this disorder. [2] ,[3] Proliferation and activation of T-lymphocytes by IL-2 have been proposed.
Cell mediated immunity disturbances have been noted such as anergy, an increased CD4/ CD8 ratio, and good response to corticosteroids. Although cause and effect relationship is not established, association with Chlamydia and Epstein Barr virus infection has been shown. [4] ,[5] In about 50% of the cases, no risk factor has been described; prior infection and use of specific drugs such as antibiotics and NSAIDs have been described in some reports. [6] Autoimmune diseases such as hypoparathyroidism, [7] hyperthyroidism, [8] and rheumatoid arthritis have also been reported in some articles. [7] ,[9] In a series of 18 patients, an association with HLA-DQA1*01, HLA-DQB1*05, and HLA-DQB1*01 was noted. [10] There is a case report of a patient with HTLV-1 carrier and TINU syndrome. [11]
In the differential diagnosis of interstitial nephritis that occurs in association with ocular involvement, sarcoidosis, Sjogren's syndrome, systemic lupus erythematosus, Wegener's granulomatosis, Behcet's disease, and infectious diseases, such as tuberculosis, Brucellosis More Details, toxoplasmosis, and histoplasmosis should be considered.
In many reports, renal involvement in TINU syndrome has a favorable outcome. There is possibility of spontaneous remission, but systemic steroids may be beneficial in reducing the development of interstitial fibrosis. [12] In one study, mycophenolate mofetil was used in a patient with TINU syndrome unresponsive renal disease to prednisolone therapy. [13]
In contrast, frequent recurrence of ocular involvement was described, and immunotherapy with methotrexate, cyclosporine A, and azathioprine was suggested. [14] ,[15]
In our case report, the patient presented with typical symptoms and signs of TINU syndrome.
To our knowledge, this is for the first time that short course (2 months) cyclophosphamide was added to the treatment protocol of the patients suffering from TINU syndrome with a favorable outcome for both kidney and ocular disease preventing it from recurrence after one year of follow-up. However, it needs further evaluation before it is recommended as a standard therapy for TINU syndrome.
| References | | |
| 1. | Dobrin RS, Vernier RL, Fish AL. Acute eosinophilic interstitial nephritis and renal failure with bone marrow lymph node granulomas and anterior uveitis. A new syndrome. Am J Med 1975;59:325.  |
| 2. | Gafter U, Kalechman Y, Zevin D, et al. Tubulointerstitial nephritis and uveitis: association with suppressed cellular immunity. Nephrol Dial Transplant 1993;8:821. [PUBMED] [FULLTEXT] |
| 3. | Yoshioka K, Takemura T, Kanasaki M, et al. Acute interstitial nephritis and uveitis syndrome: activated immune cell infiltration in the kidney. Pediatr Nephrol 1991;5:232. [PUBMED] |
| 4. | Stupp, R, Mihatsch, MJ, Matter, L, Streuli, RA. Acute tubulo interstitial nephritis with uveitis (TINU syndrome) in a patient with serologic evidence for Chlamydia infection. Klin Wochenschr 1990;68:971. |
| 5. | Grefer J, Santer R, Ankermann T, et al. Tubulointerstitial nephritis and uveitis in association with Epstein-Barr virus infection. Pediatr Nephrol 1999;13:336. [PUBMED] [FULLTEXT] |
| 6. | Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195. [PUBMED] [FULLTEXT] |
| 7. | Catalano C, Harris PE, Enia G, et al. Acute interstitial nephritis associated with uveitis and primary hypoparathyroidism. Am J Kidney Dis 1989;14:317. [PUBMED] |
| 8. | Paul E, Van Why S, Carpenter TO. Hyperthyroidism: a novel feature of the tubulointerstitial Nephritis and uveitis syndrome. Pediatrics 1999;104:314. [PUBMED] [FULLTEXT] |
| 9. | Iida H, Terada Y, Nishino A, et al. Acute interstitial nephritis with bone marrow granulomas and uveitis. Nephron 1985;40:108. [PUBMED] |
| 10. | Levinson RD, Park MS, Rikkers SM et al. Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome. Invest Ophthalmol Vis Sci 2003;44:653. |
| 11. | Hiroko E, Tsugio A. A case of tubulointerstitial nephritis and uveitis syndrome (TINU syndrome): A girl with HTLV-1 carrier. Ophthalmology 2000;42(7):947-52. |
| 12. | Azar R, Verove C, Boldron A, Delayed onset of uveitis in TINU syndrome, J Nephrol 2000;13 (5):381-3. |
| 13. | Filler G, Hansen M, LeBlanc C, et al. Pharmacokinetics of mycophenolate mofetil for autoimmune disease in children. Pediatr Nephrol 2003;18: 445-9. [PUBMED] [FULLTEXT] |
| 14. | Sanchez Roman J, Gonzalez Reina I, Castillo Palma MH, Rocha Castilla JL. Posterior uveitis associated with acute tubulointerstitial nephritis with favorable response to cyclosporin. Pathogenic implications. Med Clin (Barc) 1995;104: 118. |
| 15. | Gion N, Stavrou P, Foster CS, Immunomodulatory therapy for chronic tubulointerstitial nephritis associated uveitis. Am J Ophthalmol 2000;129(6):764-8. |
Correspondence Address:
Shahram Taheri
Internal Medicine Department, St. Al Zahra University Hospital, Soffeh Ave., Isfahan
Iran
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PMID: 19587511 
[Figure 1] |
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| This article has been cited by | | 1 |
Excellent outcome of tubulointerstitial nephritis and uveitis: Case report and five-year follow-up |
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Autoimmunity of patients with TINU syndrome |
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| Tan, Y. and Yu, F. and Zhao, M.-H. | | Hong Kong Journal of Nephrology. 2011; 13(2): 46-50 | | [Pubmed] | |
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