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International audience; Introduction: Tubulointerstitial nephritis (TIN) and uveitis (TINU) syndrome is a rare disease. The renal prognosis is generally thought to be better in children with TINU syndrome than in adults. However, data are scarce. We aimed to investigate the long-term renal prognosis in a French cohort of children with TINU syndrome.Methods: We performed a national retrospective study including 23 French pediatric nephrology centers enrolling patients with TINU syndrome diagnosed between January 2000 and December 2018.Results: A total of 46 patients were included (52% female, median age 13.8 years). At diagnosis of TIN, the median estimated glomerular filtration rate (eGFR) was 30.6 ml/min per 1.73 m2 (4.9-62.8). The median time between diagnosis of uveitis and TIN was 0.4 months (-4.1; +17.1). All patients had anterior uveitis, but 12 (29%) were asymptomatic. Nearly all patients (44 of 46) received steroid treatment, and 12 patients (26%) received a second-line therapy. At last follow-up (median 2.8 years), the median eGFR was 87.5 ml/min per 1.73 m2 (60.3-152.7) and

Background Tubulointerstitial nephritis with uveitis syndrome is a rare disease affecting mainly children and young women. Tubulointerstitial nephritis with uveitis is a diagnosis of exclusion, requiring a high degree of clinical suspicion. Studies report recent infections or certain drugs as precipitating factors of a lymphocytic oculorenal immune response. The prognosis is usually favorable with topical and systemic corticosteroid therapy. Case presentation We report a literature review and the case of a 14-year-old white girl, who presented to the ophthalmology department with features of one-sided uveitis. Upon transfer of patient to nephrological care, diagnostic work-up revealed renal involvement. Renal biopsy showed a mixed-cell and granulomatous tubulointerstitial nephritis with some noncaseating granulomas, leading to a diagnosis of tubulointerstitial nephritis with uveitis syndrome. With topical ocular and systemic corticosteroid therapy, the patients’ condition improved over several weeks. Conclusions Our case highlights the importance of early recognition and treatment of this syndrome, where cross-specialty care typically leads to a favorable outcome.

Objectives This paper looks at patients with a diagnosis of tubulointerstitial nephritis and uveitis (TINU) presenting to the Northern Ireland regional adult and paediatric uveitis service in the Belfast Health and Social Care Trust. The demographic distribution, treatment required and the visual and renal outcomes of these patients are documented. Methods Data were collected retrospectively on 24 patients with TINU using the Northern Ireland Electronic Care Record, central pathology records alongside the adult and paediatric uveitis databases from 2011 to 2021. Patients were categorised into two groups using the Mandeville classification system. Standard Uveitis Nomenclature (SUN) was used to classify the uveitis. Results The population prevalence is at least 12.6 cases per million based on a population of 1.9 million. Nineteen of 24 cases were definite TINU and five of 24 probable. Seventeen out of 24 had biopsy-positive TIN, all of which met all of the Mandeville clinical diagnostic features required for a definite diagnosis. All but one presented with acute bilateral anterior uveitis. The paediatric cases ranged from age 12 to 18 at age of onset with a mean age of 14. Of the 18 adult onset cases, the age ranged from 20 to 76 years. The mean age of onset for the adult cases was 53 years. Of these patients 71% were female; 42% required second-line immunosuppression for ocular disease. Visual acuity was maintained. Follow-up time ranged from 3 months to 16 years. No patient developed long-term renal impairment. Conclusions TINU is a cause of uveitis in both the paediatric and adult populations. In Northern Ireland average age with TINU was older than much of the published literature. Long-term immunosuppression for uveitis may be required as ongoing ocular, rather than renal inflammation seemed to require treatment.

Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare oculorenal inflammatory entity with a probable autoimmune etiology. Interstitial nephritis may be asymptomatic and usually has a benign course with spontaneous resolution. Uveitis, instead, is classically anterior, bilateral, and nongranulomatous, but it can be unilateral and presents as posterior uveitis or panuveitis, sometimes with a chronic or recurrent evolution. The frequent time lag of ocular and renal manifestations makes this diagnosis particularly challenging. The authors describe four cases of this rare entity, two with tubulointerstitial nephritis preceding ocular manifestations and the remaining, instead, with uveitis preceding renal involvement. The therapeutic approach included systemic corticosteroids in all cases. The addition of immunosuppressive therapy was required in three patients to achieve uveitis control. TINU is probably an underrecognized entity and should always be considered in the differential diagnosis of a chronic or recurrent idiopathic uveitis, especially in young patients who may have mild and asymptomatic renal disease.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare and poorly understood condition that is likely underdiagnosed. The possibility that uveitis and acute tubulointerstitial nephritis do not occur simultaneously may make diagnosis more difficult. Treatment consists of systemic corticosteroids and potentially non-steroid immunosuppressants. Renal disease usually resolves spontaneously or with appropriate treatment, however, ocular manifestations may be chronic or relapsing. We report a case of tubulointerstitial nephritis and uveitis syndrome in a 12-year-old female.

Background Sarcoidosis is characterized by granulomatous inflammation in multiple organs. Renal involvement is rare, and granulomatous tubulointerstitial nephritis (TIN) is the predominant histologic feature. TIN is also a hallmark of tubulointerstitial nephritis and uveitis (TINU) syndrome. Diagnoses of both sarcoidosis and TINU syndrome are usually made by exclusion and by combining clinical and histological findings, and often remain misdiagnosed. The aim of this retrospective study was to determine the characteristics of renal sarcoidosis and TINU syndrome in Slovenia in the last decade (2010 - 2020). Materials and methods A thorough search of the national database of renal biopsies from January 2010 to December 2020 was performed. Inclusion criteria were TIN and a clinical history of either sarcoidosis or TINU syndrome. To compare the characteristics of our cohort with others, we also reviewed the global literature reported since 2010. Results 13 patients (9 female, 4 male) were included in our study. Indications for kidney biopsy were acute kidney injury (n = 8), acute exacerbation of chronic kidney disease (n = 4), and proteinuria (n = 1). Seven patients had clinical and histological evidence of sarcoidosis, and 6 patients were classified as having TINU syndrome. All patients were treated with corticosteroids. Of the 13 patients, 11 had improved kidney function 6 months after treatment, and proteinuria decreased in 9 patients. One patient was on dialysis at the time of diagnosis and remained so thereafter. Conclusion Renal sarcoidosis and TINU syndrome are rare but important causes of kidney injury, with a favorable long-term prognosis if properly diagnosed and treated in a timely manner.

Background Acute interstitial nephritis (AIN) is an emerging cause of acute kidney disease. While this disease usually follows an acute course, it may occasionally recur, representing a major challenge for the clinician. Methods We performed a retrospective, observational cohort study in 13 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients with biopsy-proven AIN between 1996 and 2018 were included. Results The study group consisted of 205 patients with AIN, 22 of which developed recurrent AIN (RAIN) after a median of 111 days from diagnosis. RAIN was due to a surreptitious reintroduction of a previously known implicated drug or toxic in six patients (27%), sarcoidosis in two (9%), Sjögren’s syndrome in three (14%), light-chain-mediated AIN in two (9%) and tubulointerstitial nephritis and uveitis syndrome in two (9%), while in the rest of cases (32%), no precise cause could be identified. Microscopic haematuria was more frequent in patients with underlying systemic diseases. The first RAIN episode was treated with a repeated course of corticosteroids in 21 patients (95%). In six cases (27%), azathioprine and mycophenolate mofetil were added as corticosteroid-sparing agents. During a median follow-up of 30 months, 50 patients (27%) with no recurrences and 12 patients (55%) with RAIN reached Stages 4 and 5 chronic kidney disease (CKD). By multivariable logistic regression analysis, RAIN was independently associated with the risk of reaching Stages 4 and 5 CKD, even after adjusting for potential covariables. Conclusions RAIN is infrequent but is associated with poor kidney survival. RAIN should prompt clinicians to search for an underlying aetiology other than drug induced. However, in a large percentage of cases, no precise cause can be identified.

BackgroundAcute tubulointerstitial nephritis (AIN) is an uncommon cause of acute kidney injury in children, accounting for less than 10% of cases. There is limited information regarding the range of underlying diagnoses and how these may differ geographically.We undertook a retrospective case note review of consecutive cases of biopsy-proven AIN, presenting to a single UK tertiary paediatric centre, to describe the range of AIN in our caseload, define key characteristics and response to treatment, with the aim of informing paediatric nephrology practice.MethodsCases were identified retrospectively from departmental records. Data extracted included demographics, presenting clinical and biochemical features, renal biopsy histology, treatment and follow-up.ResultsTen cases were identified over 8 years (2007–2014). Age range 6–16 years. Male:Female ratio 1:9. Final diagnoses included 6 tubulointerstitial nephritis and uveitis syndrome (TINU), 2 idiopathic, 1 sarcoidosis, 1 child with Streptococcal disease. Of the TINU cases, timing of eye symptoms varied in relation to AIN presentation. Cases had a varied investigative work-up.Median presenting plasma creatinine was 303 μmol/l (range 152–932 μmol/l). Renal function improved spontaneously in 1 idiopathic case and improved with antimicrobial treatment in a child with Streptococcal disease.Eight cases received immunosuppressive treatment with intravenous methylprednisolone (approximately 10 mg/kg for 3–5 days) and / or oral prednisolone (1–2 mg/kg initially, reducing over 7–28 days).At 1 month, median creatinine had fallen to 91 μmol/l (range 41–120 μmol/l) with median eGFR 61 ml/min/1.73m2(range 51-103 ml/min/1.73m2). At last follow-up (median 18.5 months, range 2–70 months), median creatinine was 71 μmol/l (range 47–90 μmol/l) with median eGFR 80 ml/min/1.73m2, range 63 to 101 ml/min/1.73m2).Two patients received antihypertensives at diagnosis and 1 further patient at 1 month follow-up. Eight patients received electrolyte supplementation. Median time to discontinuing electrolyte supplementation was 3.5 months (range 1–12 months).ConclusionTo our knowledge, this is the only contemporary UK case series of biopsy-proven AIN in children. Our population has a high proportion of TINU. Treatment was accompanied by improvement of renal function, however 7/10 patients had an eGFR 2at last follow-up. We suggest a standardised investigative work-up and recommend long-term follow-up.

Background Tubulointerstitial nephritis and uveitis syndrome is a rare lymphocyte-related oculorenal inflammatory disease presumed to be associated with drug use and infectious agents. Toxoplasma gondii is one of such pathogens that could exhibit encephalitis, meningitis, and uveitis in immunocompromised or in some immunocompetent individuals. If the immunoglobulin M of Toxoplasma is positive on screening, the interpretation of the result is not simple, especially when immunoglobulin M stays positive persistently. Case presentation A 34-year-old Asian male developed fever, headache, and lymphadenopathy with tenderness, which was initially diagnosed as meningitis. Antibiotics were started, and diclofenac sodium was used for the fever. Although his symptoms were alleviated in a week by the treatment, gradual decline in renal function was noted, prompting a renal biopsy that indicated acute granulomatous interstitial nephritis. A week later, tenderness in both eyes with blurred vision appeared and revealed iritis and keratic precipitations in both eyes; hence, the diagnosis of acute tubulointerstitial nephritis and bilateral uveitis syndrome was made. Toxoplasma gondii-specific immunoglobulin G and immunoglobulin M titers were both positive. Although we could not rule out recent infection of Toxoplasma gondii, which may cause uveitis initially, Toxoplasma immunoglobulin G avidity test indicated a distant infection, which allowed us to rule out meningitis and uveitis as responsible for the complication of recent Toxoplasma gondii infection. Drug-induced lymphocyte stimulation test, or lymphocyte transformation test of diclofenac sodium, was solely positive among the tested drugs. Uveitis was alleviated only with ophthalmic steroid, and renal function returned to normal without administration of systemic steroid. Conclusions We experienced a case of diclofenac-induced tubulointerstitial nephritis and uveitis syndrome. In ruling out infections, Toxoplasma immunoglobulin M was persistently positive, and Toxoplasma immunoglobulin G avidity test indicated a “distant” infection. From these two results, we ruled out recent infection. However, it should be noted that “distant” infection indicated by commercial immunoglobulin G avidity is still a multiplex profile consisting of reinfection, reactivation, and latent infection. Narrowing down the infection profile of Toxoplasma is challenging in some cases. Therefore, careful diagnosis and extended follow-up of such patients are needed.

Purpose: To describe subclinical chorioretinal lesions revealed by indocyanine green angiography (ICGA) and their evolution under systemic treatment in tubulointerstitial nephritis and uveitis (TINU) patients.Methods: Retrospective case series of three patients with TINU syndrome. Choroidal and retinal involvement were assessed by fluorescein angiography (FA) and ICGA.Results: Three patients were analyzed. FA demonstrated hot disc, associated in two cases with retinal vascular leakage, and ICGA revealed subclinical chorioretinal dots in all three cases. Given the presence of posterior uveitis and deterioration of kidney function, asystemic treatment by oral methylprednisolone was started. Persistence of retinal and choroidal inflammations under systemic corticosteroids required association with immunosuppressive agent to control the disease activityConclusion: Multimodal imaging and more precisely ICGA is useful to assess subclinical choroidal inflammation and monitor treatment response in TINU syndrome. Immunosuppression needs to be revised and adapted when uveitis and/or kidney function are unresponsive to systemic steroidsAbbreviations: TINU: tubulointerstitial nephritis and uveitis; TIN: tubulointerstitial nephritis; ACE: angiotensin-converting enzyme; RF: rheumatoid factor; Uβ2M: urinary β-2microglobulin; AMPPE: acute multifocal placoid pigment epitheliopathy; FA: fluorescein angiography; ICGA: indocyanine green angiography; CT: computed tomography.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a distinct oculorenal disorder of immune origin and accounts for some cases of unexplained recurrent uveitis. We report three cases of TINU syndrome, one of which had primarily come to us with uveitis. It is the occurrence of tubulointerstitial nephritis and uveitis in a patient in the absence of other systemic diseases that can cause either interstitial nephritis or uveitis. TINU syndrome is a diagnosis of exclusion. Our aim in reporting these cases is to highlight the association of nephritis and uveitis, which together form a distinct clinical disorder called the TINU syndrome.

A 16-year-old boy presented with uveitis in both eyes with recurrent febrile illness and renal ailments. The patient was referred to a nephrologist. Subsequent investigations revealed acute tubulointerstitial nephritis in a renal biopsy and raised urinary beta-2 microglobulin (B2M). Based on his clinical findings and laboratory investigations, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was made. Since, the literature on TINU through India is sparse, the two available case reports were published through nephrology setup. Our case illustrates how ophthalmologist can aid in the diagnosis of such a rare clinical entity using interdisciplinary approach.

Objectives This study aims to investigate the etiologic spectrum, demographic features, and long-term follow-up results of children with noninfectious uveitis (NIU). Patients and methods Files of patients with NIU were reviewed between May 2010 and September 2017. The cohort consisted of 54 juvenile uveitis patients (26 males, 28 females; mean age 7.7 years; interquartile range [IQR] 9.2 years) with 93 affected eyes. Location of uveitis, laterality, age at onset of uveitis, complications of uveitis, duration of follow-up, associated systemic diseases, pertinent laboratory tests, medications used, and status of uveitis at the time of enrollment were recorded from the files. All patients had final systemic and ocular examination at the last month of enrollment. Results Twenty-seven patients (50.0%) had juvenile idiopathic arthritis (JIA), 17 (31.4%) had idiopathic uveitis, six (11.1%) had Behcet disease (BD), and four (7.5%) had tubulointerstitial nephritis and uveitis (TINU) syndrome. Median duration of follow-up for uveitis was 16 (IQR: 15) months. Anterior uveitis was seen in 81.4% of the patients (65.9% had bilateral and 34.1% had unilateral anterior uveitis). Bilateral intermediate uveitis was observed in 11.2% and bilateral panuveitis in 7.4% of the patients. At the time of enrollment, 45 uveitis patients (83.3%) were under remission. Complications of uveitis were observed in 18.5% of the patients. Conclusion Patients with JIA and BD should be regularly checked for uveitis. It is challenging to find an etiology in uveitis patients referred from ophthalmologists if initial questioning and examination do not reveal an overt rheumatologic disease. However, a simple urine test may help in establishing the diagnosis of TINU syndrome.

Introduction: To report the first case of bilateral ocular decompression retinopathy after uneventful non-perforating deep sclerectomy with mitomycin C in a child with tubulointerstitial nephritis and uveitis syndrome. Case description: An 8-year-old girl affected by tubulointerstitial nephritis and uveitis syndrome developed ocular hypertension (45 mmHg in the right eye and 42 mmHg in the left eye) associated with recurrent episodes of uveitis and chronic use of steroids despite maximum hypotensive medical treatment. Bilateral non-perforating deep sclerectomy with mitomycin C (0.2 mg/mL, 1 min) was performed under general anesthesia without complications. The first postoperative day, the visual acuity was reduced to 0.6 in the right eye and 0.05 in the left eye and the intraocular pressure was 3 mmHg in both eyes. Fundoscopy revealed bilateral optic nerve swelling and diffuse retinal hemorrhages, some of them with scattered-white centers. About 2 months after surgery, the visual acuity was normal and the fundus examination showed complete resolution. Conclusion: The ocular decompression retinopathy is an uncommon complication after non-perforating deep sclerectomy. This is the first case of bilateral ocular decompression retinopathy reported after non-perforating deep sclerectomy in a child with ocular hypertension secondary to recurrent uveitis and chronic use of steroids associated with tubulointerstitial nephritis and uveitis syndrome.

A 42-year-old female with past medical history of biopsy-proven interstitial nephritis that lasted for 2 years presented with bilateral anterior uveitis that lasted 5 months. The patient was treated with systemic and local corticosteroids and local mydriatics, after which the uveitis resolved. The patient was followed for 10 years in total and had three more attacks of mild anterior uveitis and cystoid macular edema that resolved after systemic corticosteroid and topical nonsteroidal antiinflammatory (NSAID) treatment.

Tubulointerstitial nephritis and uveitis syndrome is an immune-mediated inflammation involving the kidney and the eye. Uveitis is usually bilateral, non-granulomatous anterior uveitis, but posterior segment involvement has been reported.

Tubulointerstitial nephritis and uveitis syndrome (TINU) refers to an intraocular inflammation associated with acute interstitial nephritis (AIN) [1]. Uveitis may occur concurrently with AIN onset or 2 months before or one year after the onset of the disease [2]. Uveitis observed in TINU typically shows bilateral nongranulomatous anterior segment inflammation [1, 2].

Tubulointerstitial nephritis and uveitis (TINU) syndrome combines acute inflammatory nephritis (AIN) and uveitis. Uveitis in TINU often requires systemic immunomodulatory therapy (IMT), including steroid-sparing agents. Although common for other noninfectious uveitides, the use of tumor necrosis factor-α inhibitors (TNFi) in TINU has seldom been described.This retrospective case series included patients18 years of age with TINU followed at our tertiary care pediatric hospital. Disease characteristics at time of diagnosis and subsequent ophthalmological and rheumatologic evaluations were extracted from the record. AIN was defined as the presence of abnormal renal function and urinalysis or renal biopsy findings consistent with TINU. Uveitis grading, site of inflammation, inactivity, and flare were defined according to Standardization of Uveitis Nomenclature.A total of 10 patients (median age, 12.3 years; 6 females) were included. AIN preceded uveitis onset in 6 patients. Uveitis was bilateral at onset in 7 patients. Uveitis inactivity was achieved with systemic corticosteroids (CS) in 2 and with mycophenolate mofetil (MMF) in 3 patients. Because of persistent ocular inflammation, despite CS and IMT, 4 patients were treated with TNFi. All rapidly achieved uveitis quiescence and maintained prolonged inactivity under combined treatment with TNFi and MMF.Most patients in our study cohort required a steroid-sparing immunomodulator to achieve and maintain uveitis control. In the 50% of the cohort in whom conventional IMTs were inadequate, TNFi were able to maintain quiescence. TNF inhibition might be a useful treatment in IMT-refractory uveitis in TINU patients.

The coexistence of two immune-mediated diseases in the same patient is unusual. Takayasu’s arteritis (TA), which is a chronic granulomatous vasculitis, was discovered in a 47-year-old woman followed for tubulointerstitial nephritis and uveitis syndrome (TINU syndrome). We present the first case of this association. LEARNING POINTS: Rare autoimmune diseases can coexist in the same patient. Physical examination is important so that coexisting diseases can be identified. Takayasu’s arteritis was discovered as an incidental finding in a patient followed fortubulointerstitial nephritis and uveitis syndrome.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, especially in children. Owing to the short-term observational period and the small number of patients analyzed in previous reports, the long-term clinical and laboratory characteristics and renal prognosis of children with TINU syndrome remain unclear. In this retrospective observational study, we enrolled 29 children with TINU syndrome from February 1990 to February 2019. During the median follow-up duration of 38 months, the kidney function, urinary β2 microglobulin-creatinine ratio (U-β2MG/Cr), and uveitis in the patients had significantly improved at 24, 6, and 36 months after diagnosis. Higher U-β2MG/Cr was associated with longer duration of kidney function normalization. Half of the patients required uveitis treatment for 5 years after the diagnosis. Patients with severe low-molecular weight proteinuria at diagnosis needed a longer duration to achieve improvements in kidney function. Uveitis has a much longer treatment period than tubulointerstitial nephritis. This study demonstrates the good prognosis of children with TINU syndrome in terms of their long-term clinical and laboratory characteristics.

Background Tubulointerstitial nephritis and uveitis (TINU) syndrome is defined as the occurrence of tubulointerstitial nephritis (TIN) and uveitis in the absence of other systemic diseases. The most comprehensive review on this condition was published in 2001. Methods We conducted a systematic review of the literature for cases of TINU syndrome. MEDLINE and Embase databases were screened. Full-length articles or letters reporting cases with both TIN and uveitis were selected. We investigated differences between males and females and paediatric and adult cases. Multivariate analysis was performed to identify potential risk factors for chronic kidney disease (CKD) development. Results A total of 233 articles reporting 592 TINU cases were retained for the analysis. The median age of the included subjects was 17 years (interquartile range 13–46) with a female predominance (65%). Uveitis most frequently (52%) followed renal disease and was mostly anterior (65%) and bilateral (88%). Children tended to have more ocular relapses, while they were slightly less likely than adults to suffer from acute kidney injury and to develop CKD. Adult age as well as posterior or panuveitis were associated with an increased risk of developing CKD. Conclusions TINU affects both children and adults, with some differences between these two categories. Adult age and the presence of a posterior uveitis or panuveitis appear to be associated with the development of CKD.

To describe clinical manifestations of patients with tubulointerstitial nephritis and uveitis syndrome (TINU) with a focus on posterior segment findings. Retrospective chart review. 17 patients wer...

Background: The syndrome of tubulointerstitial nephritis and uveitis (TINU) is an uncommon and multisystemic autoimmune disorder. This review reports a rare case of TINU being superimposed on thrombotic microangiopathy (TMA) and, by comparing with the available literature, also summarizes the clinical features, associated conditions, treatment, and outcome of patients with TINU. Summary: Herein, we report the case of a 37-year-old male patient with acute kidney injury (AKI) clinicopathologically identified as malignant hypertension-induced TMA superimposed by acute tubulointerstitial nephritis, which was suspected to be related to drug hypersensitivity. After treatment with oral prednisone combined with a renin-angiotensin system inhibitor, the patient achieved partial renal recovery and was withdrawn from hemodialysis. Recurrent AKI concomitant with new-onset asymptomatic uveitis was detected during routine clinical follow-up after cessation of prednisone. TINU was then diagnosed, and prednisone followed by cyclophosphamide was prescribed. The patient achieved better renal recovery than in the first round of treatment and maintained stable renal function afterward. By reviewing the literature, 36 cases were reported as TINU superimposed on other conditions, including thyroiditis, osteoarthropathy, and sarcoid-like noncaseating granulomas. Key messages: TINU could be complicated by many other conditions, among which TMA is very rare. When presented as AKI, kidney biopsy is important for differential diagnosis. The case also shows that recurrent AKI with concomitant uveitis after prednisone withdrawal strongly suggested the need for long-term follow-up and elongated prednisone therapy for TINU syndrome.

This chapter reviews cystoid macular edema and retinal vasculitis, common complications of pediatric uveitis. Anatomic features of juvenile idiopathic arthritis, multiple sclerosis, tubulointerstitial nephritis and uveitis (TINU), pars planitis, and Behct syndrome, as well as their imaging findings, are discussed.

Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury with various origins. HLA-DQA1, -DQB1, and -DRB1 have been associated with development of tubulointerstitial nephritis and uveitis (TINU) syndrome in case reports and small case series, but information about HLA genetic susceptibility to drug hypersensitivity–related ATIN (D-ATIN) or other types of ATIN is limited. In this article, we genotyped 154 patients with ATIN of different causes and 200 healthy controls at HLA-DQA1, -DQB1, and -DRB1 loci. We found that there was no difference between patients with D-ATIN and TINU in the carrier’s frequency of HLA-DQA1, -DQB1, or -DRB1. Patients with Sjogren’s syndrome–ATIN and IgG4-related ATIN presented a different pattern of tested HLA alleles. HLA-DQA1*0104 (p value corrected by false discovery rate method [Pc] = 4.72 × 10−22, odds ratio [OR] = 13.81), -DQB1*0503 (Pc = 1.95 × 10−14, OR = 9.51), and -DRB1*1405 (Pc = 8.06 × 10−19, OR = 12.80) were significant risk alleles for the occurrence of D-ATIN and TINU. There were no significant associations between tested HLA alleles and ATIN induced by other causes. Patients with D-ATIN/TINU carrying HLA-DQA1*0104/DQB1*0503/DRB1*1405 had higher peak serum creatinine and more severe renal tubulointerstitial inflammatory impairment. They also had significantly higher levels of tubular HLA-DR and HLA-DQ expression, which were correlated with the numbers of interstitial CD4+ T lymphocytes (r = 0.975, p < 0.001 and r = 0.832, p = 0.005, respectively) and monocytes/macrophages (r = 0.721, p = 0.004 and r = 0.615, p = 0.02, respectively). In conclusion, patients with D-ATIN or TINU have genetic susceptibility in HLA-DQA1, -DQB1, and -DRB1 alleles. HLA-DQA1*0104/DQB1*0503/DRB1*1405 serves as a significant risk haplotype for development of D-ATIN and TINU, which might facilitate renal tubulointerstitial inflammation by enhancing Ag-presenting capacity of renal tubular cells.

The syndrome of tubulointerstitial nephritis and uveitis (TINU) is a multisystemic autoimmune disorder that may occur in response to various environmental triggers, including drugs and microbial pathogens. Evidence exists of HLA antigen-related genetic predisposition to developing TINU. The resulting inflammation affects chiefly the ocular uvea and renal tubules, although other organs may be involved. TINU is uncommon; only about 200 cases are on record since its original description 40 years ago, although it is possible that new ones are no longer being reported. Although its incidence is highest in children and adolescents, all ages may be affected. Renal and ocular inflammation may be clinically severe and persistent, but the prognosis for the majority of patients with TINU is favorable. Owing to its low prevalence, no standard therapeutic protocols have been established, but most reported cases have been treated with corticosteroids or other immunomodulatory agents. TINU has many features in common with sarcoidosis, the main clinical entity from which it must be distinguished. This article begins with an illustrative case vignette, followed by an overview of the syndrome and current theories regarding its pathogenesis.

Tubulointerstitial nephritis and uveitis syndrome is a rare and probably underdiagnosed condition. Renal and ocular manifestations may not occur simultaneously, making the diagnosis more difficult. Nephritis may be asymptomatic; therefore, renal function evaluation is essential for diagnosis. Urinary β2-microglobulin levels may be particularly useful. Uveitis, mostly anterior, nongranulomatous and bilateral, occurs usually after the onset of nephritis. Treatment includes corticosteroids and, eventually, other immunosuppressant agents. Renal disease is usually benign and resolves spontaneously or after treatment with systemic corticosteroids. Uveitis, however, may be chronic or recurrent. The authors described the cases of three pediatric patients diagnosed with tubulointerstitial nephritis and uveitis syndrome. The goal of this paper was to warn the medical community over the need to screen patients with uveitis for renal disease. RESUMO A síndrome nefrite tubulointersticial e uveíte é uma doença rara, provavelmente subdiagnosticada. As manifestações renais e oculares podem não ocorrer simultaneamente, tornando o diagnóstico mais difícil. A nefrite é geralmente assintomática, tornando fundamental a avaliação da função renal em doentes com uveíte. O doseamento da excreção urinária de β2-microglobulina é particularmente útil para o diagnóstico. A uveíte, tipicamente anterior, não granulomatosa e bilateral, manifesta-se após a nefrite na maioria dos casos. O tratamento inclui corticoides e, por vezes, outros imunossupressores. A doença renal tem evolução benigna, resolvendo-se espontaneamente ou com terapêutica com corticoides sistêmicos na maioria dos casos, no entanto, a uveíte pode ser crônica ou recorrente. Os autores descrevem três casos de síndrome nefrite tubulointersticial e uveíte, diagnosticados em idade pediátrica, e pretendem alertar para a necessidade de pesquisar sempre alterações renais nos doentes com uveíte.

Tubulointerstitial nephritis and uveitis (TINU) is a rare syndrome in which idiopathic interstitial nephritis coexists with chronic recurrent uveitis. This syndrome often represents systemic disorders such as arthralgia, rash, prolonged fever, anaemia and ocular symptoms that require medication including glucocorticoid administration. Recently, novel urinary biomarkers, such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and liver-type fatty acid-binding protein, were shown to be associated with tubulointerstitial damage and were elevated in interstitial nephritis. We evaluated these urinary biomarkers in a case of TINU syndrome before and during treatment and found that their levels were elevated at onset and decreased during treatment, especially NGAL. We conclude that these urinary biomarkers are useful to evaluate and predict prognosis in interstitial nephritis.

Purpose: To describe an atypical presentation of Tubulointerstitial Nephritis and Uveitis (TINU), with challenges in treatment course. Observations: A 12-year-old Hispanic female presented to the National Eye Institute's Uveitis clinic with bilateral blurred vision, red eyes and photophobia, not responsive to topical steroids. On exam, she had bilateral severe panuveitis with areas of subretinal fluid. During her evaluation, she was noted to have elevated serum creatinine. A kidney biopsy confirmed the presence of severe tubulointerstitial nephritis and interstitial fibrosis. She was treated with oral steroids with excellent resolution of symptoms and subretinal fluid. She continued to have anterior segment flares with attempts to taper oral prednisone which lead to treatment with multiple immunomodulatory agents. Associated hypertension and kidney damage complicated the choice of a secondary immunosuppressive agent. Conclusions and Importance: Although rare, TINU can present as panuveitis with choroidal involvement which may or may not be preceded by tubulointerstitial nephritis. A renal biopsy is required for definitive diagnosis, but abnormal urinalysis or renal function should raise suspicion for TINU. Keywords: Immunosuppression, Inflammation, Tubulointerstitial nephritis, Uveitis

Case report Two cases of tubulointerstitial nephritis and uveitis are presented. Immunosuppressive therapy was required to control the uveitis. Contrary to that usually described, uveitis became chronic, which made immunosuppressive therapy necessary. Nephritis was successfully treated with steroids. Discussion Tubulointerstitial nephritis and uveitis syndrome is an under-diagnosed disorder and requires clinical suspicion due to there being no specific laboratory study available. Recurrences and relapses of ocular inflammation are common. Immunosuppressive therapy is not often needed.

Purpose: To analyze the clinical features and long-term prognosis of uveitis in tubulointerstitial nephritis and uveitis (TINU) syndrome in a cohort of Chinese patients. Methods: A total of 32 patients with TINU syndrome between 2000 - 2016 were analyzed retrospectively. Results: Mild anterior inflammation was observed in all cases. Ultra-wide-field fluorescence angiography (UWFA) was conducted on 13 patients, and peripheral vascular leakage was observed in 22/26 eyes (84.62%) compared with active anterior chamber inflammation in 13/26 eyes (50%). Three patients received increased corticosteroid dosage therapy on their first episode of uveitis guided by UWFA had stopped steroids without recurrence. Conclusion: The uveitis in TINU syndrome was mild. Corticosteroids were efficient in most cases, but a slower tapering and long-term treatment were required. UWFA is sensitive in detecting the activity of uveitis and might be useful in monitoring disease progression. Complete withdrawal of medication was difficult to achieve in some cases.