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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 4  |  Page : 655-657
Short course of cyclophosphamide therapy may reduce recurrence in patients with tubulointerstitial nephritis and uveitis syndrome

1 Department of Internal Medicine, Isfahan School of Medicine, Isfahan, Iran
2 Department of Pathology, Isfahan School of Medicine, Isfahan, Iran

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Date of Web Publication8-Jul-2009


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 Top

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 Top

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 Top

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 Top

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.  Back to cited text no. 1    
2.Gafter U, Kalechman Y, Zevin D, et al. Tubulo­interstitial nephritis and uveitis: association with suppressed cellular immunity. Nephrol Dial Transplant 1993;8:821.  Back to cited text no. 2  [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.  Back to cited text no. 3  [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.  Back to cited text no. 4    
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.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195.  Back to cited text no. 6  [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.  Back to cited text no. 7  [PUBMED]  
8.Paul E, Van Why S, Carpenter TO. Hyper­thyroidism: a novel feature of the tubulointers­titial Nephritis and uveitis syndrome. Pediatrics 1999;104:314.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Iida H, Terada Y, Nishino A, et al. Acute inters­titial nephritis with bone marrow granulomas and uveitis. Nephron 1985;40:108.  Back to cited text no. 9  [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.  Back to cited text no. 10    
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.  Back to cited text no. 11    
12.Azar R, Verove C, Boldron A, Delayed onset of uveitis in TINU syndrome, J Nephrol 2000;13 (5):381-3.  Back to cited text no. 12    
13.Filler G, Hansen M, LeBlanc C, et al. Pharmaco­kinetics of mycophenolate mofetil for autoimmune disease in children. Pediatr Nephrol 2003;18: 445-9.  Back to cited text no. 13  [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.  Back to cited text no. 14    
15.Gion N, Stavrou P, Foster CS, Immunomodu­latory therapy for chronic tubulointerstitial nephritis associated uveitis. Am J Ophthalmol 2000;129(6):764-8.  Back to cited text no. 15    

Correspondence Address:
Shahram Taheri
Internal Medicine Department, St. Al Zahra University Hospital, Soffeh Ave., Isfahan
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PMID: 19587511

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