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Tubulointerstitial nephritis and uveitis syndrome (TINU) is a specific form of intraocular inflammation (uveitis) combined with kidney disease that was first described in two patients by Dobrin et al. in 1975. Since then, approximately 200 more cases have been published. The cause of the disease is still unknown. A hypersensitivity reaction is suspected, especially an infection or very rarely a medication reaction is thought to trigger the disease. It is considered to be a rare disease and thus unfortunately is still unfamiliar to most ophthalmologists. Therefore, it is frequently overlooked in the differential diagnosis. In this review we want to show advances in diagnostics and treatment as well as progress in deciphering the pathogenesis.Beta-2 microglobulin (Ub2MG) analysis in urine and human leukocyte antigen (HLA) typing is helpful to diagnose TINU cases. A high association of HLA-DRB1*01 has been shown with TINU. A first single case report suggests a common antibody production against ocular and renal proteins.TINU is a common cause of uveitis among patients who present with bilateral, anterior uveitis of sudden onset. It is more frequent in children and apparently in boys. Although the activity of the eye disease can persist for many months, it is usually controlled with little treatment and the outcome is very good.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is considered to have a good prognosis even without any immunosuppressive therapy, although there is no histological evidence to support this. The objective of this study was to evaluate, retrospectively, serial renal biopsy findings in three girls with TINU syndrome who were treated with prednisolone. At presentation, all patients had significantly elevated urinary beta(2)-microglobulin levels (7583-19,313 microg/l) and high serum creatinine levels (0.93-1.3 mg/dl). The elevated beta(2)-MG and creatinine levels persisted for 1 month, and renal biopsies were performed to establish a definitive diagnosis. The initial biopsy specimens of all patients revealed marked interstitial enlargement consisting of infiltration of lymphocytes; there was also notable tubulitis and infiltration of eosinophils. All patients received prednisolone therapy following the diagnosis. A second renal biopsy was performed 9 months after the first biopsy for two of three patients, and 2 years later for the third patient. The biopsy specimens taken at 9 months still showed histological changes of acute inflammation; in contrast, that taken at 2 years showed a lower degree of acute inflammation, but scar formation was observed in some regions. Based on these results, we conclude that selected TINU syndrome patients require some immunosuppressive therapy.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare autoimmune disease and the pathogenesis is still unknown. We report a case of TINU syndrome with high ASLO titer. Uveitis improved and urine β2-MG normalized with low dose systemic predonisolone and cyclosporin A. The high ASLO titer in early phase suggested that streptococcal infection might have triggered TINU syndrome. Lymphocyte phenotypes normalized after treatment with low dose systemic predonisolone and cyclosporin A.

Uveitis is defined as an intraocular inflammation induced by different etiologies. Though the precise pathogenesis is still unknown, accumulating evidence shows that both innate and adaptive immune responses may be predominant mechanisms involved in the development of uveitis. Toll-like receptors have been shown to be expressed in the human eye and play an important role in infectious uveitis. The NOD proteins, expressed mainly in the cytosol by APCs, recognize the products of bacteria and participate in the development of uveitis. HLA genes have been associated with some uveitis entities, including acute anterior uveitis (HLA-B27), Behcet disease (HLA-B51), birdshot retinochoroidopathy (HLA-A29), Vogt-Koyanagi-Harada syndrome (HLA-DR4), sarcoidosis, sympathetic ophthalmia, juvenile idiopathic arthritis, tubulointerstitial nephritis and uveitis (TINU) syndrome, and pars planitis (HLA-DR15). The exact mechanism whereby certain HLA genes predispose to a certain uveitis entity has not yet been elucidated. In addition, several studies have demonstrate that polymorphisms in certain immune response genes, such as tumor necrosis factor (TNF), MHC class I polypeptide-related sequence A (MICA), interleukin-1 (IL-1), and some chemokines, may contribute to the development of human uveitis. Polymorphisms in the gene coding for the costimulatory molecule known as cytotoxic T-lymphocyte antigen 4 (CTLA-4) were recently found in Chinese patients with VKH syndrome but not in patients with Behcet disease. Further developments in the unraveling of immune response genes may lead to a better understanding of human uveitis and will hopefully allow the development of novel treatment regimes.

Acute tubulointerstitial nephritis is demonstrated in 2–3% of all native renal biopsies, increasing to 10–15% if the biopsy is performed in the setting of acute renal failure [1]. It is most commonly related to medication or infection [1,2]. An increasingly recognized entity is tubulointerstitial nephritis with uveitis (TINU) syndrome. We outline the clinical course of a patient with TINU syndrome and review the changes in epidemiology, diagnosis and management.

Tubulointerstitial nephritis and uveitis (TINU) is the association of acute interstitial nephritis (AIN) with uveitis, although the two do not need to occur at the same time. There should be no other systemic inflammatory disease (either putative autoimmune or infectious processes) to explain the concurrence of uveitis and interstitial nephritis.

We report a case of tubulointerstitial nephritis and uveitis (TINU syndrome) with full type Fanconi syndrome. A 32-year-old woman presented with fatigue, anorexia and weight loss. Laboratory findings showed anemia, polyclonal hypergammaglobulinemia and moderate renal dysfunction. Tubular function abnormalities were normoglycemic glucosuria, panaminoaciduria, phosphaturia and kaliuresis leading to hypokalemia. Renal tubular acidosis and hypouricemia were also evident. Serum antistreptolysin O titer was high. Ocular symptoms (bilateral anterior uveitis) emerged soon after admission. Renal biopsy showed diffuse tubulointerstitial infiltration by lymphocytes and plasma cells without granuloma. Treatment with systemic steroids was given and renal function, and ocular symptom returned to normal with 3 months. Although tubular abnormalities involving TINU syndrome has already been reported, the disease associated with full type Fanconi syndrome has rarely been seen, and systemic steroid may be beneficial in reducing the development of tubulointerstitial injury.

Granulomatous interstitial nephritis (GIN) is a rare histologic diagnosis. This series reports the presenting features, associated conditions, treatment, and outcome of patients with a diagnosis of GIN in Glasgow during a 15-yr period and compares this with the available literature. Eighteen cases were identified: Five cases were associated with sarcoidosis, two were associated with tubulointerstitial nephritis and uveitis, two were associated with medication, and nine were idiopathic. Patients presented with advanced renal failure (median estimated creatinine clearance 21 ml/min) and minimal proteinuria (urine albumin-to-creatinine ratio 9.9 mg/mmol). Sixteen patients were treated with prednisolone for a mean of 25 mo. Six patients relapsed with reduction in prednisolone dosage, and four patients required steroid-sparing agents. During the mean follow-up of 45 mo, renal function improved or stabilized in 17 patients; the rate of improvement in renal function was most marked in the first year after diagnosis with a gain in function of +1.9 ml/min per mo. The median estimated creatinine clearance at final visit was 56 ml/min. One patient required renal replacement therapy at diagnosis but recovered renal function with treatment. No patient required long-term renal replacement therapy. There was no correlation between the degree of fibrosis or inflammation on biopsy and renal outcome, and the features on biopsy did not help to determine the cause of GIN. GIN is a treatable cause of renal failure that highlights the value of renal biopsy in patients who present with renal failure even when there is minimal proteinuria. The rarity of GIN demonstrates the need for systematic data collection.

Background Inflammation is a well-known risk factor for the development of choroidal neovascularization (CNV), yet not all causes of intraocular inflammation have been documented to cause CNV. Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare cause of intraocular inflammation mostly in pediatric patients and only seldom has been associated with development of CNV. Findings A 34-year-old pregnant female with a past history of bilateral ocular inflammation secondary to TINU presents 1 year after diagnosis with vision loss in the left eye. Clinical examination and investigations show the development of CNV in the left eye. The patient was treated with ranibizumab (Genentech, San Francisco, CA) intravitreal injections with improvement in symptoms and clinical findings. Conclusions We report the first case of CNV secondary to TINU in an adult patient. The CNV associated with TINU is responsive to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.

Patient: Female, 44 Final Diagnosis: Tubulointerstitial nephritis • uveitis syndrome Symptoms: — Medication: Loxoprofen sodium hydrate Clinical Procedure: Renal biopsy Specialty: Nephrology Objective: Rare disease Background: Although TINU syndrome is characterized by idiopathic TIN with bilateral anterior uveitis, few reports have provided a comprehensive summary of the features of this disorder. Previous reports have suggested that many Japanese patients had HLA-A2 and -A24 (7), but there is no evidence. Case Report: A 44-year-old female was referred to our hospital due to renal dysfunction in March 2012. After admission, her symptoms improved spontaneously without medication within 2 weeks. In the outpatient clinic, she was diagnosed with idiopathic bilateral anterior uveitis in May, and her renal dysfunction relapsed in November. A renal biopsy showed diffuse TIN. We made a diagnosis of TINU syndrome because we could not explain the origin, and treated her with a systemic corticosteroid. Her renal function and ocular symptoms have been improving. The patient had HLA-A24, -B7, -DR1, -C*07: 02 and -DQB1*05: 01: 01. We collected 102 Japanese cases in PubMed, Ovid MEDLINE, and the Japanese Medical Abstracts Society and compared our case with the previous cases. Conclusions: This disorder affects primarily young females (median age, 14 years), and the most common symptom is fever (44/102 cases). We conducted a statistical analysis using contingency table and Pearson’s chi-square test, for HLA-A2 and A24, and calculated the odds ratio (OR). There are no significant differences (A2 was present in 7/22 cases and in 19/50 controls, p value (P) 0.61, OR 0.76 (95% confidence interval (CI)) 0.27–2.2; A24 was present in 10/22 cases and in 33/50 controls, P 0.10, OR 0.43, CI 0.16–1.2).

Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by tubulointerstitial nephritis with sudden-onset of uveitis. Currently, only over 200 cases have been described in the literature. TINU syndrome might be underestimated due to lack of recognition and under-diagnosis. The pathogenesis of TINU syndrome remains unclear, it affects predominantly adolescents. We report a case of an acute renal insufficiency at a 42 years old woman whose exploration favors the diagnosis of a TINU syndrome; she was put under cortico-steroids with recovery of a normal renal function at 73 ml/ min/1.73 m 2 . Our message is to enquire specifically for episodes of uveitis in any patient presenting with unexplained acute interstitial nephritis and to keep in mind the diagnosis of TINU syndrome.

IMPORTANCE Tubulointerstitial nephritis and uveitis (TINU) syndrome is characterized by tubulointerstitial and ocular inflammation. Thus far, the value of noninvasive diagnostic tests is not known. OBJECTIVE To determine whether urinary beta 2-microglobulin (beta 2M), urinary protein, and serum creatinine have predictive value for detecting TINU syndrome in young patients with uveitis. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study was conducted July 2010 through February 2013 at a tertiary care referral center in Utrecht, the Netherlands. Forty-five consecutive new patients with uveitis aged 22 years or younger were enrolled. EXPOSURES Urinary beta 2M, urinary protein, and serum creatinine were measured prospectively, and the estimated glomerular filtration rate was calculated. MAIN OUTCOMES AND MEASURES A post hoc analysis was performed to determine whether urinary beta 2M, urinary protein, serum creatinine, estimated glomerular filtration rate, and/or pyuria were correlated with definitive and probable cases of TINU syndrome. RESULTS Eighteen of the 45 patients (40%) in our cohort had elevated urinary beta 2M levels, and 10 patients (22%) had elevated serum creatinine levels. Twenty of 43 patients (47%) had proteinuria. Eight of the 45 patients were diagnosed by a pediatric nephrologist as having renal dysfunction that suggested acute interstitial nephritis. Of these 8 patients, 2 were definitively diagnosed as having TINU syndrome (confirmed by renal biopsy). After excluding other causes of renal dysfunction, the remaining 6 patients with uveitis and renal dysfunction fulfilled the criteria of probable TINU syndrome. The 8 patients with definitive or probable TINU syndrome had higher urinary beta 2M levels than patients with normal renal function (median beta 2M, 1.95 mg/L; 95% CI, 1.26-5.16 mg/L vs 0.20 mg/L; 95% CI, 0.19-0.21 mg/L; P < .001; Mann-Whitney U test). Our analysis revealed that the positive predictive value of increased beta 2M combined with increased serum creatinine was 100% for detecting definitive and/or probable TINU syndrome. CONCLUSIONS AND RELEVANCE These data suggest that urinary beta 2M and serum creatinine levels are sensitive and relatively simple diagnostic screening tools for detecting renal dysfunction to diagnose TINU syndrome in young patients with uveitis similar to those evaluated in this study.

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

We report for the first time the appearance of lymphoid interstitial lung disease in a patient with tubulointerstitial nephritis and uveitis (TINU) syndrome. A 41-year-old woman with a 9-month history of recurrent bilateral iridocyclitis was referred to our division for examination of renal dysfunction. Renal biopsy showed extensive interstitial CD3+ lymphocytic infiltration; glomerular structures were unaffected. After oral corticosteroid therapy, renal function remained stable during the next few years. Uveitis was controlled by using topical steroids. Five years after first presentation, the patient developed symptoms suggestive of interstitial lung disease, combined with a relapse of uveitis. Lung biopsy showed lymphofollicular bronchiolitis (CD3+) associated with florid alveolitis. There was no evidence for acute infection or systemic disease to be the cause of this pathological state. Lung disease proved to be steroid responsive. A new pulmonary flare-up 3 years later responded to renewed treatment. Accounting for the histological findings, we assume both TINU syndrome and interstitial lung disease to be manifestations of a common autoimmune disorder.

Idiopathic tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon condition, characterized by acute tubulointerstitial nephritis (TIN) with a favorable course and uveitis with a chronic relapsing course. The pathogenesis remains unclear, but a lymphocyte-mediated immune mechanism has been suggested. A 9-year-old boy was evaluated for fatigue and 2 kg of weight loss. Renal glucosuria, elevated urine beta(2)-microglobulin (MG), progressive renal dysfunction, polyclonal hypergammaglobulinemia, various autoantibodies and abnormal lymphocyte phenotypes were found. A renal biopsy revealed acute TIN. After 2 months of treatment with prednisolone, renal function and polyclonal hypergammaglobulinemia were normalized. While tapering prednisolone, anterior uveitis developed, which was improved with topical steroid. But abnormal lymphocyte phenotypes and autoantibodies persisted on low-dose prednisolone. Uveitis became aggravated, and urine beta(2)-MG increased again. The second renal biopsy (7 months later) was normal except for minimal focal interstitial fibrosis. Uveitis was not responsive to systemic steroids, but improved with additional cyclosporin. Abnormal lymphocyte phenotypes improved, and most autoantibodies disappeared. We report a rare case of idiopathic TINU syndrome with severe immunologic dysregulation, which correlated with the clinicopathological and biochemical parameters. The information about lymphocyte phenotypes and autoantibodies may provide more insight into the pathophysiology and the clinical course of uveitis in this rare disorder.

We report a case of tubulointerstitial nephritis and uveitis (TINU) syndrome in an adult male. A 40-year-old man was found to have bilateral anterior uveitis and mild renal insufficiency with high urinary beta-2 microglobulin. Work up for connective tissue and infectious diseases were negative. His kidney function normalized spontaneously and remained normal at 1 year without intervention. Uveitis responded completely to local corticosteroid treatment and has not recurred.

We report a case of tubulointerstitial nephritis and uveitis (TINU syndrome) in a 16-yearold male adolescent. He had weakness, anorexia, weight loss and malaise. He had no ocular symptom at presentation. Impairment of renal function, tubular proteinuria, anemia, increased erythrocyte sedimentation rate, eosinophilia and hypergammaglobulinemia were detected. He had HLA-DR4, HLA-A3 and HLA-B51 positivity. HLA-B27 was negative. The renal biopsy showed interstitial cell infiltrates and tubular atrophy without granulomas in interstitium. Glomeruli showed mild mesangial hypercellularity. Immunofluorescent staining was uniformly negative. After administration of systemic corticosteroids, renal, ocular and constitutional manifestations regressed. Bilateral knee arthritis developed 2 months after stopping the steroid treatment and in which ultrasonography showed a Baker’s cyst in right. Oral sulfasalazine was started and local corticosteroid was injected into the cyst. Symmetrical synovitis regressed without taking systemic steroid treatment. TINU syndrome should be considered in the differential diagnosis of patients presenting with non-specific constitutional, visual and renal manifestations. During the follow-up, synovitis may develop rarely. This is the first case report of TINU syndrome with symmetrical synovitis and Baker’s cyst.

Purpose. Tubulointerstitial nephritis and uveitis (TINU) syndrome usually shows anterior segment intraocular inflammation, but severe posterior segment intraocular inflammation is rarely observed. We report 2 children with TINU syndrome complicated by subfoveal choroidal neovascularization (CNV). Methods. Case reports. Results. Patients were a 12-year-old girl and a 12-year-old boy diagnosed with probable TINU syndrome on the basis of typical ocular findings and high value of urinary β2 microglobulin even though renal biopsy was not performed. The girl showed development of CNV with subretinal macular hemorrhage along with the exacerbation of anterior chamber inflammation in her left eye. Subretinal macular hemorrhage recurred frequently even with oral prednisolone; therefore, intravitreal injection of bevacizumab (IVB) was performed. After IVB, the subretinal proliferative tissue shrunk and subretinal hemorrhage has not recurred for 5 years. The boy showed subretinal hemorrhage from CNV with severe anterior chamber inflammation in his left eye. With oral prednisolone, anterior chamber inflammation and subretinal hemorrhage disappeared, but shrunken subretinal fibrosis in the macula remained. Final visual acuity was poor due to residual subretinal fibrosis in both cases. Conclusions. Tubulointerstitial nephritis and uveitis syndrome has a potential to develop CNV that leads to severe visual loss; therefore, prompt anti-inflammatory therapy is required, and IVB should be regarded as a potential choice of treatment.

Introduction Le tubulointerstitial nephritis and uveitis (TINU) syndrome est une maladie rare definie par l’association d’une nephrite tubulointerstitielle aigue idiopathique a une uveite. L’objectif de cette etude etait de connaitre les caracteristiques du TINU syndrome de l’adulte ainsi que son pronostic a moyen terme et les facteurs l’influencant (dont le traitement). Patients et methodes Vingt centres hospitaliers ont participe a cette etude observationnelle retrospective. Les patients avaient un diagnostic porte entre le premier janvier 1999 et le premier decembre 2015. Les donnees etaient recoltees tout au long du suivi medical du patient. Resultats Quarante et un patients ont ete inclus (25 femmes, 16 hommes, ratio de 1,6 :1). L’âge median a la declaration de la maladie etait de 46,8 ans (16,8 a 77,4) avec une creatininemie mediane de 207 μmol/L (100 a 1687) et un debit de filtration glomerulaire (DFG) median de 27 mL/min/1,73 m 2 (2 a 73). Apres une annee de suivi, le DFG median etait de 76 mL/min/1,73 m 2 (17 a 119) et 69 % des patients adultes souffraient d’insuffisance renale chronique. Les facteurs initiaux associes a une degradation du DFG un an plus tard etaient : l’âge eleve, la creatininemie elevee et la bicarbonatemie basse. Aucun marqueur anatomo-pathologique renal initial n’etait associe au pronostic renal. Durant la premiere annee, 40 % des patients recidivaient leur uveite. La corticotherapie generale etait associee a une diminution des recidives d’uveites, mais n’avait pas d’effet statistiquement significatif sur le DFG. Discussion Nous avons rapporte dans ce travail la plus grande serie de cas adultes de TINU syndrome publiee a ce jour (environ 170 cas adultes de TINU syndrome avaient ete decrits). Nous avons decrit leurs caracteristiques clinico-pathologiques, biologiques, leurs traitements et leur pronostic a moyen terme. Conclusion Dans cette etude, plus de deux tiers des patients souffraient d’insuffisance renale chronique apres une annee de suivi. Ce travail suggere aussi que la corticotherapie orale serait efficace dans le traitement des atteintes ophtalmologiques du TINU syndrome.

This study describes the pharmacokinetics of mycophenolate mofetil (MMF) in 15 pediatric patients with vasculitis and connective tissue disease involving the kidney. Patients included 10 with systemic lupus erythematosus (SLE), 1 with antiphospholipid antibody syndrome, 2 with Wegener granulomatosis, and 1 each with Goodpasture syndrome, Henoch-Schönlein-associated nephritis, and 1 with severe tubulointerstitial nephritis and uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF, which was administered for a median of 491 days. Mean starting dose of MMF was 974+/-282 mg/m(2 )in two divided doses. Pharmacokinetic monitoring of the active compound of MMF, mycophenolic acid (MPA), was performed using an EMIT assay. The mean MPA AUC after a median of 39 days was 61.8+/-31.0 micro gxh/ml, median time to maximum concentration was 60 min, and mean maximum concentration was 18.5+/-8.4 micro g/ml. At last follow-up, mean MMF dose was 900+/-341 mg/m(2) per day, and mean trough MPA concentration was 3.1+/-1.1 (range 0.6-4.6) micro g/ml. Therapy was effective in inducing remission in 4 of 9 patients with active disease. Only 1 of the 5 other patients relapsed. All 6 patients with controlled disease maintained remission. There were few side effects: one episode each of diarrhea and leukocytopenia and two viral infections. We conclude that MMF at 900 mg/m(2) per day appears to be effective in these patients.

Acute tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease usually having a good prognosis. But the recurrence of uveitis and the chronic progression of kidney injury are still main problems. We report a 15-year-old girl with TINU who showed proteinuria, pathological renal change, multiple organ dysfunction, and immune disorders. After 2 months of 1 mg/kg/day corticosteroid therapy, 24-h urine protein, liver function tests, and creatine kinase returned to normal level. In spite of this, steroid was tapered off slowly and small dose of steroid maintenance therapy lasted for 1 year. Her kidney and ocular symptoms did not recur during 5 years of follow-up. We suggest low-dose steroid maintenance therapy to decrease the recurrence of the TINU syndrome.

Background TINU syndrome probably is a frequently overlooked disease where uveitis occurs in association with acute tubulointerstitial nephritis. Diagnostic criteria have been published recently. Patients and methods In this retrospective case series the charts of four consecutive patients with TINU syndrome (follow-up 36, 23, 17, and 12 months, respectively) were analysed, including comorbidity and complications, and the literature was reviewed. Results Two patients were treated with methotrexate or ciclosporin A and mycophenolate mofetil. In one patient autoimmune thyroiditis was known. During the follow-up, symptoms indicative of rheumatoid arthritis were observed. Because of her uveitis she required methotrexate therapy. Three patients were obese (mean BMI 32.2 kg/m (2)). Ocular complications were posterior synechiae (two patients) and papillary and macular oedema (three patients). One patient developed cerebrospinal hypertension under ciclosporin A treatment which resolved after discontinuation of therapy. Conclusions Patients with definite TINU syndrome frequently suffer from other diseases and associated immune phenomena. The course of the disease can vary considerably. Complications do occur, despite overall good prognosis. Regional and systemic steroids may be sufficient; frequently steroid sparing immunosuppressives are necessary at least temporarily. Patients with this multiorgan disease do need to be followed by a paediatrician or a medical specialist.

Objective To explain fluorescein angiographic features in patients with tubulointerstitial nephritis and uveitis syndrome. Design Retrospective observational case series. Participants Four consecutive patients with tubulointerstitial nephritis and uveitis syndrome seen at Uveitis Service of Okayama University Hospital from 1995 to 2000. Methods Patients' characteristics obtained from medical records were analyzed. In addition, characteristics of 15 patients reported previously as case reports in the Japanese literature were reviewed. Main outcome measures Clinical and fluorescein angiographic features. Results The present four patients showed varying degrees of retinal capillary leakage on fluorescein angiography, ranging from capillary leakage limited to the peripheral fundus to cystoid macular edema. The same angiographic features were found in 15 patients reported previously in the Japanese literature. Conclusions Retinal capillary leakage of varying degrees was a common fluorescein angiographic feature in patients with tubulointerstitial nephritis and uveitis syndrome. Fluorescein angiography is valuable in assessing the extent of retinal involvement.

We report for the time a patient with recurrence of tubulointerstitial nephritis and uveitis (TINU) following renal transplantation. Our patient was diagnosed at the age of 8 years and, despite treatment with systemic steroids, developed established renal failure. At the age of 17 years, he underwent a live-related donor renal transplant. Immunosuppression included tacrolimus, mycophenolate mofetil and prednisolone. Having had normal renal function for 3 years after transplantation, he developed uveitis and decline in the graft function. A biopsy of the allograft demonstrated recurrent granulomatous interstitial nephritis. The recurrence of TINU following transplantation suggests a role for circulating autoantibodies in the disease pathology.

Patient: Female, 32 Final Diagnosis: Nephrogenic diabetes inspidus secondary to tubulointerstitial nephritis and uveitis (TINU) syndrome Symptoms: — Medication: — Clinical Procedure: Kidney biopsy Specialty: Nephrology Objective: Rare disease Background: Tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) is a diagnosis of exclusion based on the presence of uveitis and acute tubulointerstitial nephritis in the absence of other disease entities known to cause both of these disorders. The proximal tubule is frequently affected by this syndrome, resulting in a wide range of presentations that vary from proteinuria to full picture of Fanconi syndrome. However, distal tubular involvement is not common. Case Report: A 32-year-old female patient presented with polyuria, polydipsia and painful red eyes. Her water deprivation test and desmopressin test results were consistent with nephrogenic diabetes insipidus. Her kidney biopsy showed acute tubulointerstitial nephritis. Her eye exam was consistent with uveitis. To our knowledge, this is the first reported case of nephrogenic diabetes insipidus due to tubulointerstitial nephritis and uveitis syndrome. Conclusions: Tubulointerstitial nephritis and uveitis syndrome (TINU) syndrome can present with multiple renal tubular defects, including nephrogenic diabetes insipidus.

A 46-year-old female patient presenting with acute interstitial nephritis and anterior uveitis was admitted. The renal biopsy disclosed the presence of interstitial nephritis, confirming the clinical diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome. Treatment with oral steroids was started, with prompt improvement of symptoms and laboratory abnormalities.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, often underdiagnosed or misdiagnosed in children. We describe the case of a 12-year-old boy who presented to Severance Hospital with a 1-month history of bilateral conjunctival injection. He was first evaluated by an Ophthalmologist in another hospital and diagnosed with panuveitis. Laboratory tests indicated renal failure, and a renal biopsy confirmed the diagnosis of acute tubulointerstitial nephritis. An extensive exclusion of all possible causes allowed a diagnosis of TINU syndrome. The patient was treated with a systemic corticosteroid (initially prednisolone, 2 mg/kg and later deflazacort 1 mg/kg) and topical steroid drops for 1 month. Azathioprine was later added to the treatment regimen and the systemic steroid was slowly tapered. The final outcome of renal-ocular disease was favorable in the patient. However, long-term follow-up is necessary to properly manage frequent relapses and incomplete renal recovery. TINU should be considered as a differential diagnosis in children with uveitis or acute renal failure.

The pathogenesis of tubulointerstitial nephritis and uveitis (TINU) syndrome remains unknown, but T cell-mediated immune response has been postulated to play a role. On the other hand, TINU syndrome is characterized by hypergammaglobulinemia and high serum immunoglobulin G (IgG) levels, suggesting an involvement of humoral immunity. We describe a case of TINU syndrome in a 13-year-old girl with multiple tubular dysfunctions including renal glucosuria, tubular proteinuria, phosphaturia, uricosuria, and concentrating and acidifying defect. IgG antibody from her serum was reactive against 125-kDa human kidney protein. Immunofluorescence study using mouse kidney revealed that the antibody was against cortical renal tubular cells. The antibody disappeared as the renal symptoms resolved. We suggest that IgG antibody may contribute to tubular dysfunction in some patients with TINU syndrome.

Two Japanese sisters with persistent uveitis showed significant increased levels of urinary beta-2 microglobulin. A percutaneous renal biopsy performed in the younger sister revealed tubulointerstitial nephritis (TIN) with helper/inducer T cell infiltrates. Also, abnormal 67-gallium accumulation in the kidneys, suggesting TIN, was observed in the other one at the same time. Although patients with the syndrome of tubulointerstitial nephritis and uveitis (TINU) have been reported to date, its occurrence in siblings has rarely been seen. Both of them shared same human leukocyte antigen (HLA) DR6, suggesting the potential association between HLA-DR6 and TINU.

Purpose: To report on the occurrence of tubulointerstitial nephritis and uveitis (TINU) and HLA typing in two siblings.Design: Retrospective case study.Methods: HLA typing from two siblings with TINU syndrome and their parents was performed on DNA from peripheral blood mononuclear cells (PBMC).Results: The boy developed TINU syndrome in 2001, his sister 5 years later. Both siblings inherited the HLA alleles HLA-DRB1*1401 and HLA-DQB1*0503 on the maternal haplotype, a haplotype that had rarely been observed in patients with TINU.Conclusions: The observations support inheritance of HLA-linked risk factors of TINU, but indicate heterogeneity of the risk phenotype due to linkage with different reported haplotypes.

PURPOSE: To describe the clinical course and treatment with immunomodulatory agents in patients with tubulointerstitial nephritis and uveitis syndrome. METHODS: Retrospective analysis of the charts of six patients with tubulointerstitial nephritis and uveitis syndrome. RESULTS: The mean (±SD) age was 24.3 (±16.5) years, range 13 to 49 years. Four patients were children, and two were adults. Three were men, and three were women. Five of the six patients had anterior uveitis, and one had panuveitis. All patients had several relapses despite treatment with topical, regional, and oral steroids and methotrexate in one case. The introduction or modification of immunosuppressants (methotrexate, azathioprine, or cyclosporin A) achieved control of the uveitis and prevented relapses over a mean (±SD) follow-up period of 19.66 (±10.01) months, range 6 to 34 months. No treatment-related side effects were observed. CONCLUSIONS: Tubulointerstitial nephritis and uveitis syndrome is a distinct disease entity in which the nephritis typically resolves, but the uveitis often becomes chronic and is treatment resistant. Immunomodulatory agents can achieve control of the inflammation and prevent relapses.

Tubulointerstitial nephritis and uveitis syndrome presents with either renal or ocular manifestations, and associated weight loss. We report two adolescents with transient hyperthyroidism early in the course of the syndrome. Hyperthyroidism may represent an unrecognized feature of the disorder and potentially contributes to the accompanying weight loss. Thyroid function should be evaluated in patients with tubulointerstitial nephritis and uveitis syndrome and symptomatic therapy provided when necessary.

We identified 35 cases of tubulointerstitial nephritis and uveitis (TINU), 31 from a MEDLINE search (1966-1996) of the English literature and 4 from our hospital records (1988-1996). To meet the case definition, the patient had to be less than 18 years old and have TINU of unknown cause. Common presenting symptoms included fatigue, weight loss, fever, and abdominal pain. The uveitis was usually anterior and could occur at any time with respect to the onset of the renal disease. Common laboratory features included anemia, increased erythrocyte sedimentation rate, and decreased creatinine clearance. Most patients (33 of 35) had renal biopsies that commonly revealed an intense inflammatory interstitial infiltrate, glomerular sparing, and negative immunofluorescence studies. Of the 35 patients, 26 received systemic corticosteroid therapy (5 of 26 for eye disease); 22 had follow-up for at least 1 year; 13 of 35 patients had a recurrence of their uveitis. The outcome in all 35 cases was normal renal function with no documented visual loss. In conclusion, TINU is a unique syndrome with characteristic clinical features, laboratory changes, and renal biopsy results. Treatment is controversial, and the outcome in children, even if untreated, is excellent.

The case of a 13.5-year-old girl with acute tubulointerstitial nephritis and uveitis (TINU syndrome) is presented. The etiology of this rare syndrome, which in most cases involves female adolescents and usually regresses spontaneously, is still unknown. An infection-triggered pathological immune reaction has been considered to play a role in the pathogenesis of this disorder. Here we report for the first time the association of TINU syndrome and Epstein-Barr virus infection.

Purpose To report a case of tubulointerstitial nephritis and uveitis syndrome (TINU) with novel posterior segment features of bilateral vitritis and retinal pigment epithelial detachments. Methods This is an interventional case report with fundus photographs and fluorescein angiograms of a 9-year-old girl presenting with bilateral acute anterior uveitis 4 months after a diagnosis of acute tubulointerstitial nephritis. Results Visual acuities remained normal throughout the 6-month period of follow-up. The anterior and posterior uveitis settled, although retinal pigment epithelial detachments persisted and may be related to the underlying disease process in TINU or exogenous steroid treatment, or both. Conclusions The idiopathic inflammatory response seen in TINU is traditionally associated with an anterior uveitis. This case demonstrates that there may be more extensive ocular involvement and that posterior uveitis and retinal pigment epithelial detachments may represent emerging features of atypical cases of TINU.

Tubulointerstitial nephritis and uveitis (TINU) generally occurs at young age and has a female preponderance. Renal biopsy reveals interstitial infiltration of inflammatory cells and edema, and the associated intraocular inflammation typically consists of an anterior, bilateral uveitis. The pathogenesis of TINU likely involves both humoral and cellular immunity and is mediated by medications, infectious agents, or other unknown causes. A previous report detected a renal antigen recognized by the serum of a TINU patient. In this report the authors extend these observations to document seroreactivity against a retinal antigen of similar size.

Summary Background and objectives Tubulointerstitial nephritis and uveitis (TINU) syndrome is considered a rare cause of acute tubulointerstitial nephritis (ATIN) that is usually associated with renal recovery. This study sought to investigate the diagnosis, prognosis, and contributing factors of TINU syndrome using a large cohort of patients with prospective follow-up. Design, setting, participants, & measurements This study included patients with TINU syndrome from a prospective cohort of patients with ATIN from 2007 to 2012. Clinical-pathologic data were collected at biopsy and autoantibodies against modified C-reactive protein (mCRP-Ab) were measured. Serum levels and renal tissue expression of Kreb von den Lunge-6 were also detected. Independent risk factors for poor renal outcome at 12 months and late-onset uveitis were analyzed. Results Thirty-one patients (28%) with biopsy-proven ATIN were classified as having TINU syndrome. Of these patients, 18 (58%) developed late-onset uveitis and were misdiagnosed as having drug-induced ATIN at the time of biopsy. An abnormal level of mCRP-Ab was an independent risk factor for late-onset uveitis (odds ratio, 14.7; 95% confidence interval, 3.4 to 64.0). Patients with TINU syndrome and drug-induced ATIN had comparable levels of Kreb von den Lunge-6 in both serum and renal tissues. Ninety-two percent of patients developed stage 3–4 CKD and/or tubular dysfunction by 12 months postbiopsy. Age, serum creatine level, erythrocyte sedimentation rate, and the presence of concomitant thyroid disease or leukocyturia were related to poor renal outcome. Relapse was seen in 36% (11 of 31) of patients and potentiated poor renal outcome. Conclusions The diagnosis of TINU syndrome can be missed in a large fraction of patients with ATIN because uveitis can present well after the onset of tubulointerstitial nephritis. Elevated mCRP-Ab levels may be useful in predicting late-onset uveitis TINU syndrome. Unfortunately, patients with TINU tended to have frequent relapses and most patients had incomplete renal recovery. Long-term follow-up is needed to prevent misdiagnosis and properly manage TINU syndrome.

To describe chorioretinal lesions in pediatric uveitis that are associated strongly with the HLA-DR, DQ class II type associated with tubulointerstitial nephritis and uveitis (TINU).Retrospective, observational case series.University-based clinic.Fifteen consecutive patients with onset of bilateral panuveitis at less than 16 years of age who were seen between September 2004 and October 2012 and 6 pediatric patients with confirmed TINU.HLA-DR, DQ class II DNA typing.Detection of the HLA-DRB1*01 and HLA-DQB1*05 risk alleles for TINU.Fourteen (93%) of the 15 patients with otherwise unexplained pediatric panuveitis typed HLA-DRB1*01-HLA-DQB1*05. Eleven (73.3%) of 15 patients had bilateral sharply demarcated, usually inferior, 200- to 300-μm spots of chorioretinal atrophy, and 4 (27.7%) of 15 patients had bilateral clusters of 500- to 750-μm poorly defined orange choroidal lesions without overlying atrophy of the retinal pigment epithelium. None had interstitial nephritis. Four of the 6 definite TINU cases had class II typing and TINU risk alleles; all 6 had bilateral panuveitis. The frequency of risk alleles was statistically higher in those with pediatric panuveitis than in the North American population and in nonpanuveitis pediatric uveitis patients assumed to have the North American HLA distribution (P.0001, Fischer exact test). Positive likelihood ratios were 9.92 to 5.18, depending on assumptions regarding pretest probability of disease.Recognition of characteristic chorioretinal lesions in otherwise unexplained pediatric panuveitis, supported by selective HLA class II DNA typing, is useful in narrowing diagnostic possibilities and directing further evaluations. Panuveitis is underappreciated as a manifestation of TINU.

Tubulointerstitial nephritis and uveitis (TINU) syndrome, which was first described in 1975, has been reported in more than 130 patients, mostly in adolescent or young women. Although data concerning the etiologic background of this inflammatory disease are limited, several humoral factors, including cytokines, have been reported in association with the disease. Here, we report a case of TINU in a 14-year-old girl, whose renal and ophthalmological improvement was associated with the decrease of serum levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-8 (IL-8). This suggests the presence of T-cell-mediated immunity in this unique syndrome.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder defined by the combination of biochemical abnormalities, tubulointerstitial nephritis, and uveitis. We describe a 12-year-old female, presented with a ten-day history of fever, characterized by sudden onset and rapid spontaneous resolution in few hours, accompanied by shivering, extreme fatigue, and loss of appetite. Laboratory values were consistent with renal failure of tubular origin. Renal biopsy confirmed a tubulointerstitial nephritis, with acute tubulitis, polymorphonuclear infiltration, and microabscesses. The renal interstitium was occupied by a dense inflammatory infiltrate, consisting of lymphocytes, plasma cells, and neutrophils. Glomerular structures were preserved. Ophthalmological examination that suggested a previous asymptomatic bilateral uveitis and HLA typing (HLA-DQA1*0101/0201 and HLA-DQB1*0303/0503) further supported the suspect of TINU syndrome. TINU syndrome is probably an underdiagnosed disorder, responsible for many cases of idiopathic anterior uveitis in young patients, especially in those who have asymptomatic renal disease and when proper diagnostic tests are not performed at the time of presentation.

The authors measured serum levels of the pineal hormone melatonin to investigate the possibility of pineal dysfunction in both rats with experimental autoimmune uveitis/pinealitis (EAU/EAP) and uveitis patients. The serum melatonin concentrations of EAU/EAP rats were measured by radioimmunoassay over a 24-hour (h) period, and in uveitis patients at night (0200 h). Melatonin concentrations were assayed in six patients with Behcet's disease, four with Vogt-Koyanagi-Harada (VKH) disease, three with sarcoidosis, three with Kirisawa-type uveitis, and one with tubulointerstitial nephritis and uveitis syndrome. Nocturnal serum melatonin levels were significantly lower in Lewis rats with EAU/EAP (2200 h: 33.6±20.4 pg/ml, 0200 h: 43.2±13.9 pg/ml) than in the controls (2200 h: 117.5±25.3 pg/ml, 0200 h: 132.4±20.2 pg/ml) (p>0.01, at 2200 h and 0200 h). Melatonin levels were significantly lower in VKH disease (20.7±10.5 pg/ml) (p>0.01) and Behcet's disease (42.1±42.5 pg/ml) (p>0.05) than in the controls (79.4±36.7 pg/ml). These results suggest that there is a decrease in pineal gland function due to pinealitis in EAU/EAP rats. The markedly decreased nocturnal serum melatonin levels may also be related to the presence of retinal uveitogenic antigens in uveitis patients.

Background Non-infectious uveitis is the most common cause of blindness in children. Most studies have evaluated diagnosis criteria and treatment of JIA-associated uveitis. Objectives We analyzed treatment and outcome of childhood uveitis related to other causes than JIA. Methods A retrospective chart review of pediatric uveitis in patients Results Thirty patients (SR: 0,5; 51 eyes) were enrolled. Mean age of diagnosis was 9.6±3.5 years (3 to 15 y). Mean follow-up was 4 ±3 years. Main diagnoses were: idiopathic (60%), Behcet9s disease (BD) (13%), sarcoidosis (10%), Vogt-Koyanagi– Harada syndrome (3%), herpes simplex virus (3%) and tubulointerstitial nephritis and uveitis (TINU) syndrome (3%). Among idiopathic uveitis (n=27 eyes), 44% were anterior uveitis. Twenty eyes (74%) received systemic corticosteroid as first-line therapy, inducing inactivity for 2 eyes (10%) and remission for 1 eye (5%) at 5 years. DMARDs were needed for 18 eyes (66.6%). Methotrexate was used as first-line therapy in 14 eyes (77%) with 7.1% (n=1 eye) remission at 4 months. Infliximab was used as second-line treatment in 9 eyes (60%) with 78% of improvement and 78% of inactivity but no remissions. Ocular complications occurred in 67% of patients: posterior synechia (37%), macular edema (37%), severe vision loss (26%), cataract (22%), vasculitis (19%), and band keratopathy (16%). In BD uveitis (n=6 eyes), 83% had panuveitis. All BD patients received systemic corticosteroid therapy and azathioprine among those 50% responded with inactive uveitis. Infliximab was used as second-line therapy in 3 eyes with 100% of improvement. All BD patients developed complications: vasculitis (83%), posterior synechiae (83%), vitreous hemorrhage (50%), severe vision loss (33%) and macular edema (17%). Sarcoidosis affected 4 eyes, 75% were panuveitis and all patients received systemic corticosteroids and became steroid dependent. All of these patients received methotrexate, and 50% required infliximab as a second line with remission in 1 eye and inactivity in 3 eyes. Posterior synechiae developed in 3 eyes. Conclusions Idiopathic uveitis is the most common cause of non-JIA uveitis in children. BD and sarcoidosis are thought to be the most severe ones, but idiopathic uveitis seems very difficult to treat as two third of patients have severe complications at the end of the treatment. Most patients were steroid dependent and required a DMARD in association with infliximab. Improvement and disease inactivity were frequently obtained but remission was rare. References Jabs et al., Standardization of Uveitis Nomenclature for Reporting Clinical Data. Results of the First International Workshop. Disclosure of Interest E. Sardar: None declared, P. Dusser: None declared, M. Labetoulle: None declared, E. Barreau: None declared, B. Bodaghi: None declared, I. Kone-Paut Grant/research support from: SOBI, Roche, Consultant for: Novartis, SOBI, Pfizer, abbvie, Roche/CHUGAI

A 16-year-old female patient was admitted to our hospital due to progressive renal dysfunction with an increased serum creatinine (sCr) level of 1.7 mg/dL. Her clinical course without any ocular manifestations and results of drug-induced, lymphocyte-stimulating tests, in addition to a renal histological assessment, initially encouraged us to ascribe the patient's renal abnormalities to drug-induced acute interstitial nephritis (AIN). Four months later, she started to complain about reduced visual acuity when she was found to have anterior bilateral uveitis despite the recovered renal function with almost constant sCr levels around 0.7 mg/dL. Thus, a diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome was finally made. Our case illustrates the difficulties in distinguishing late-onset uveitis TINU syndrome from drug-induced AIN at the time of the renal biopsy, thereby suggesting the importance of a longitudinal follow-up to overcome the potential underdiagnosis of the disease. Several diagnostic conundrums that emerged in this case are also discussed.

Dobrin syndrome or tubulointerstitial nephritis and uveitis syndrome is a rare disease with excellent prognosis. We report a 60-year-old male of Indian origin who presented with acute interstitial nephritis (AIN) and unilateral anterior immune-mediated uveitis. The syndrome has been reported sporadically. This is only the third case from a patient of Indian origin. We highlight this case and evaluate the long-term use of nonsteroidal anti-inflammatory drug-induced AIN and uveitis as a potential causative factor.

The authors report the association of tubulointerstitial nephritis and uveitis (TINU) with Hashimoto’s thyroiditis in a 16-year-old boy. Oral prednisolone was administered and the renal function normalized and has remained stable for 2 years. However, two recurrences of uveitis occurred in the 2-year follow-up period.