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Year : 2020  |  Volume : 2  |  Issue : 1  |  Page : 39

Tubulointerstitial nephritis and uveitis syndrome: An atypical case

1 Department of Ophthalmology, Setúbal Hospital Center, Setúbal, Portugal
2 Department of Ophthalmology, Cascais Hospital, Cascais, Portugal

Date of Submission21-Sep-2020
Date of Acceptance12-Oct-2020
Date of Web Publication10-Dec-2020

Correspondence Address:
Dr. Silvia Cunha Diniz
Quinta da Matela - Batudes, 2950-056 - Palmela, Setúbal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_51_20

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Tubulointerstitial nephritis and uveitis syndrome is an uncommon clinical entity. Usually, renal involvement is moderate, and uveitis is acute, bilateral, anterior, and nongranulomatous (revised). We present the case of a 55-year-old female patient who went to the emergency department with complaints of asthenia, myalgia, and paresthesia. One week later, she complained of photophobia and was diagnosed with bilateral nongranulomatous acute anterior uveitis. The next day, due to hypotension and acute kidney injury, the patient was hospitalized. Renal biopsy showed tubulointerstitial nephritis. The patient was started on oral prednisolone, achieving uveitis resolution and renal function stability. After slow corticoid reduction, the patient presented uveitis recurrence complicated with bilateral optic disc (revised) edema and cystoid macular edema (CME) in the left eye. After oral prednisolone reduction, the patient suffered another relapse with CME worsening. We decided to initiate methotrexate 7.5 mg/week, achieving ocular and renal function stability.

Keywords: Acute kidney injury, corticoid, tubulointerstitial nephritis, uveitis

How to cite this article:
Diniz SC, Gomes PP, Matias IF, Pina BS, Neves PP, Ornelas MC. Tubulointerstitial nephritis and uveitis syndrome: An atypical case. Pan Am J Ophthalmol 2020;2:39

How to cite this URL:
Diniz SC, Gomes PP, Matias IF, Pina BS, Neves PP, Ornelas MC. Tubulointerstitial nephritis and uveitis syndrome: An atypical case. Pan Am J Ophthalmol [serial online] 2020 [cited 2021 Nov 27];2:39. Available from: https://www.thepajo.org/text.asp?2020/2/1/39/303005

  Introduction Top

Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon clinical entity, affecting predominantly adolescents and young women.[1] Risk factors include genetic susceptibility and precipitating factors, such as the use of antibiotics and nonsteroidal anti-inflammatory drugs.[2] Various human leukocyte antigens (HLA) have been associated with TINU syndrome, such as HLA-A220, HLA-DQA1*0121, HLA-DQB1*0521,22, HLA-DRB1*121,22, and HLA-DRB1*010223, but small sample size and heterogeneity between reports prevent robust conclusions.[3] HLADRB1*0102 haplotype is strongly associated with TINU syndrome and bilateral, sudden-onset anterior uveitis.[4] Typically, uveitis occurs after the episode of nephritis, but in about 21% of cases, uveitis precedes nephritis, and in 15% of cases, both occur simultaneously.[5] Renal involvement tends to be moderate and self-limited, and patients may be asymptomatic or present constitutional symptoms similar to flu-like condition, such as weight loss, malaise, fever, rash, arthralgia, abdominal/flank tenderness/pain, polyuria, and nocturia.[6] Uveitis can be asymptomatic, especially in children, but it is usually anterior, bilateral, and nongranulomatous, with sudden onset of ocular redness, pain, and photophobia.[7] Posterior involvement of uveitis is rare and can be characterized by macular and optic disc (revised) edema, choroiditis, and choroidal neovascularization.[8] Typically, bilateral anterior uveitis with or without intermediate/posterior uveitis occurs within 2 months before or 12 months after the onset of interstitial nephritis.[8]

The authors describe a case of TINU syndrome in a 55-year-old female patient.

  Case Report Top

A 55-year-old female patient was admitted to the emergency room (ER) complaining of anorexia, asthenia, myalgia, and paresthesia, with 1 week of evolution. Her past medical history included major depression, thyroidectomy after follicular thyroid carcinoma, cholecystectomy, dyslipidemia, and overweight. Blood tests revealed serum creatinine, urea, and C-reactive protein elevation. Renal and adrenal gland ultrasounds were normal. The patient denied any allergies. She claimed to have started taking rosuvastatin pills a fortnight before. She was discharged from the ER with an indication of rosuvastatin suspension. One week later, the patient went to the ER with a sudden onset of visual acuity (VA) reduction, red eyes, and bilateral photophobia, and was diagnosed with bilateral nongranulomatous acute anterior uveitis (AAU). Topical therapy with dexamethasone and atropine was started. The next day, due to hypotension and worsening of renal function (RF), the patient was hospitalized. The aadditional investigation included negative tests for rheumatoid factor, antinuclear antibodies, antineutrophil cytoplasmatic antibodies, HIV, hepatitis A, B, and C, and normal pattern for serum protein electrophoresis. Rickettsia conorii,brucellosis, Borrelia, Coxiella burnetii, syphilis, and Toxoplasma gondii (revised) infections were excluded; there was past contact with cytomegalovirus (CMV) (positive IgG with negative IgM). During the 5 days of hospitalization, there was a progressive improvement in RF. Due to the persistence of inflammatory reaction in the anterior chamber with bilateral synechiae, the patient was started on prednisolone 1 mg/kg–60 mg/day 15 days after the diagnosis of bilateral AAU. TINU syndrome was suspected and kidney biopsy requested (revised), showing active tubulointerstitial nephritis. Three weeks after the initiation of prednisolone, there was AAU resolution and improvement of RF. Slow corticosteroid tapering was started, with a 10 mg reduction every 2 weeks. Furthermore, HLA genotyping showed HLA-DRB1*0102 allele presence. After completing 16 weeks of prednisolone treatment, when the patient was on 5 mg/day, she was admitted to the ER because of left eye (LE) redness and photophobia; bilateral uveitis relapse complicated with optic disc (revised) edema and cystoid macular edema (CME) in the LE was detected [Figure 1], [Figure 2], [Figure 3], [Figure 4]. Prednisolone was elevated to 40 mg/day and topical dexamethasone and cyclopentolate were started. Two weeks later, VA was 10/10 (decimal scale) in both eyes, with no anterior chamber reaction, CME regression in the LE, and slight improvement in optic disc (revised) edema. It was decided to reduce the dose of prednisolone to 20 mg/day. Two weeks later, there was worsening of macular edema with snowballs in the LE and anterior chamber reaction in both eyes. Topical corticoid frequency and oral prednisolone were increased to 40 mg/day. Sixteen weeks later, with slow corticoid tapering to 20 mg/day, there was a normalization of the ophthalmological issues and stabilization of the RF; however, the patient developed weight gain. After a multidisciplinary discussion, it was decided to initiate methotrexate 7.5 mg/week, to reduce the dosage and dependence on prednisolone. The patient remains stable from a nephrological and ophthalmological point, presenting corrected VA of 10/10 in both eyes, with no anterior or posterior inflammation or complications after 1 month of methotrexate and 20 mg/day prednisolone treatment [Figure 5] and [Figure 6].
Figure 1: Left eye posterior synechia

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Figure 2: Fundus photograph showing optic disc edema

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Figure 3: Optical coherence tomography image showing nasal and temporal peripapillary retinal thickening in both eyes

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Figure 4: Optical coherence tomography image showing cystoid macular edema in the left eye

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Figure 5: Fundus photograph 1 month after methotrexate treatment

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Figure 6: Optical coherence tomography image 1 month after methotrexate treatment

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  Discussion Top

Diagnosis of TINU syndrome may be significantly delayed or unrecognized because patients may be asymptomatic or exhibit nonspecific symptoms that do not lead to RF test performance.[7] As uveitis and renal disease are usually asynchronous, even when both are symptomatic, connection between them may be missed.[7] Therefore, TINU syndrome can be underdiagnosed and its prevalence is higher than previously thought.

Investigation of other causes of uveitis (revised) such as sarcoidosis, systemic lupus erythematosus, Sjogren's syndrome, granulomatous polyangiitis, Behcet's disease, tuberculosis, and syphilis is required.[8] A kidney biopsy is the only confirmatory test.[9] Elevated urinary beta-2 microglobulin (β2 M) has emerged as a sensitive noninvasive test useful in the diagnosis of TINU syndrome.[9]

Treatment of anterior uveitis exclusively with topical corticoids is ineffective in about 80% of cases, requiring an association with systemic corticoids.[10] After the suspension of systemic treatment, uveitis tends to relapse with more severe involvement.[11] In cases resistant to corticoids or to avoid their adverse effects, immunomodulators such as methotrexate, cyclosporine, azathioprine, and mycophenolate mofetil should be considered.[12]

This case of TINU syndrome, atypical because of the patient's age and evolution, reflects well the difficulty in stabilizing the patient's uveitic condition, compared to the favorable evolution of the renal disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Liakopoulos V, Ioannidis I, Zengos N, Karabatsas C, Karasavvidou F, Salmas M, et al. Tubulointerstitial nephritis and uveitis (TINU) syndrome in a 52-year-old female: A case report and review of the literature. Ren Fail 2006;28:355-9.  Back to cited text no. 1
Santoro D, Vita G, Rovito S, Venuto L, Cavallari V, Vita R, et al. Drug-induced TINU syndrome and genetic characterization. Clin Nephrol 2012;78:230-6.  Back to cited text no. 2
Macau R, Barreto S, Martins J, Silva J, Fraga F , Manso R, et al. Tubulointerstitial nephritis and uveitis syndrome (TINU): À propos of 2 cases. Port J Nephrol Hypert 2018;32:184-90.  Back to cited text no. 3
Mackensen F, David F, Schwenger V, Smith LK, Rajalingam R, Levinson RD, et al. HLADRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone. Br J Ophthalmol 2011;95:971-5.  Back to cited text no. 4
Mandeville JT, Levinson RD, Holland GN. The tubulointerstitial nephritis and uveitis syndrome. Surv Ophthalmol 2001;46:195-208.  Back to cited text no. 5
Parameswaran S, Mittal N, Joshi K, Rathi M, Kohli HS, Jha V, et al. Tubulointerstitial nephritis with uveitis syndrome: A case report and review of literature. Indian J Nephrol 2010;20:103-5.  Back to cited text no. 6
[PUBMED]  [Full text]  
Okafor LO, Hewins P, Murray PI, Denniston AK. Tubulointerstitial nephritis and uveitis (TINU) syndrome: A systematic review of its epidemiology, demographics and risk factors. Orphanet J Rare Dis 2017;12:128.  Back to cited text no. 7
Pakzad-Vaezi K, Pepple KL. Tubulointerstitial nephritis and uveitis. Curr Opin Ophthalmol 2017;28:629-35.  Back to cited text no. 8
Provencher LM, Fairbanks AM, Abramoff MD, Syed NA. Urinary β2-microglobulin and disease activity in patients with tubulointerstitial nephritis and uveitis syndrome. J Ophthalmic Inflamm Infect 2018;8:24.  Back to cited text no. 9
Silva F, Correia S, Castro A, Moreira C, Santos S, Malheiro J, et al. Acute tubulointersticial nephritis with uveitis: A report of two cases. Portuguese J Nephrol Hypertension 2018;32:191-5.  Back to cited text no. 10
Purt B, Hiremath S, Smith S, Erzurum S, Sarac E. A rare case of tubulointerstitial nephritis and uveitis syndrome treated with a multi-specialty approach. Am J Case Rep 2016;17:869-73.  Back to cited text no. 11
Gion N, Stavrou P, Foster CS. Immunomodulatory therapy for chronic tubulointerstitial nephritis-associated uveitis. Am J Ophthalmol 2000;129:764-8.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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