Tubulointerstitial nephritis and uveitis (TINU) syndrome in a 52-year-old female: a case report and review of the literature

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare entity first described in 1975, affecting mainly young women and adolescents. We present a case of a 52-year-old female patient (one of the oldest in the literature) who complained of fever, anorexia, nausea, and vomiting. After she was admitted to our hospital, laboratory tests revealed tubular proteinuria, elevated erythrocyte sedimentation rate (ESR), anemia, and renal insufficiency (serum creatinine 4.2 mg/dL) with metabolic acidosis. Ophthalmologic examination revealed anterior uveitis (iritis) and renal biopsy showed acute tubulointerstitial nephritis. The diagnosis of TINU syndrome was established and the patient was treated with oral corticosteroids. All symptoms and ophthalmologic abnormalities disappeared after 6 weeks of treatment. Renal function also recovered completely and remained stable at follow-up. TINU syndrome should be considered in the differential diagnosis of unexplained tubulointerstitial nephritis, especially in the presence of ocular findings. Corticosteroid therapy is still controversial, but it helps in the quick resolution of renal and mainly eye abnormalities.     

Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome in a 52-Year-Old Female: A Case Report and Review of the Literature

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare entity first described in 1975, affecting mainly young women and adolescents. We present a case of a 52-year-old female patient (one of the oldest in the literature) who complained of fever, anorexia, nausea, and vomiting. After she was admitted to our hospital, laboratory tests revealed tubular proteinuria, elevated erythrocyte sedimentation rate (ESR), anemia, and renal insufficiency (serum creatinine 4.2 mg/dL) with metabolic acidosis. Ophthalmologic examination revealed anterior uveitis (iritis) and renal biopsy showed acute tubulointerstitial nephritis. The diagnosis of TINU syndrome was established and the patient was treated with oral corticosteroids. All symptoms and ophthalmologic abnormalities disappeared after 6 weeks of treatment. Renal function also recovered completely and remained stable at follow-up. TINU syndrome should be considered in the differential diagnosis of unexplained tubulointerstitial nephritis, especially in the presence of ocular findings. Corticosteroid therapy is still controversial, but it helps in the quick resolution of renal and mainly eye abnormalities.     

Delayed onset of uveitis in TINU syndrome

We report here the clinical features and outcomes of two patients who presented idiopathic tubulo-interstitial nephritis and uveitis syndrome (TINU syndrome) with ocular disease following the onset of nephropathy. The initial symptoms were renal impairment with asthenia, anorexia and weight loss. An increase in urinary beta2-microglobulin was noticed at the initial checkup in both patients. Renal biopsies showed interstitial cellular infiltration without granulomas or tubular atrophy. No glomerular and vascular alterations were seen and immunofluorescent staining was uniformly negative. Systemic steroid therapy was given and renal function returned to normal within three months. Anterior uveitis occurred in both patients eight months later and responded well to local steroid therapy. Renal involvement in TINU syndrome mostly has a favorable outcome. Despite the possibility of spontaneous regression, systemic steroids may be beneficial in reducing the development of interstitial fibrosis.     

Acute tubulointerstitial nephritis with uveitis syndrome presenting as multiple tubular dysfunction including Fanconi's syndrome

We describe an 11-year-old male patient with acute tubulointerstitial nephritis with uveitis (TINU) syndrome. He presented with easy fatigability, pallor, nocturia and weight loss. laboratory examination disclosed anaemia, polyclonal hypergammaglobulinaemia, low molecular weight proteinuria, glycosuria, aminoaciduria, proximal and distal renal tubular acidosis, a urine concentration defect and decreased creatinine clearance. The multiple renal tubular dysfunction and slight glomerular dysfunction subsided spontaneously. Bilateral anterior uveitis was manifested 7 months after the onset of the disease. This is the first reported case of TINU syndrome with multiple proximal and distal tubular dysfunction including a complete type of Fanconi's syndrome.     

Tubulointerstitial nephritis and uveitis syndrome (TINU) with Fanconi's syndrome

We report a 57-year-old woman with concurrent tubulointerstitial nephritis and uveitis syndrome (TINU) and Fanconi's syndrome. She presented with sudden onset of bilateral ocular pain, blurred vision, acute renal failure, glucosuria and proteinuria. Slit lamp examination revealed acute bilateral anterior uveitis. Tubulointerstitial nephritis was confirmed by kidney biopsy. Laboratory examination revealed normoglycemic glucosuria, proteinuria, normal anion-gap metabolic acidosis, phosphaturia, urinary uric acid wasting and kaliuresis leading to hypokalemia. Her vision and renal function improved gradually after systemic steroid therapy. There have been rare reports of TINU syndrome which had features of Fanconi's syndrome. The prevalence of TINU syndrome may be underestimated, and its association with Fanconi's syndrome requires further investigation.     

Tubulointerstitial nephritis and uveitis in monozygotic twin boys

We describe monozygotic male twins who developed tubulointerstitial nephritis and uveitis (TINU) almost 2 years apart. They presented with non-specific symptoms and were noted to have glycosuria and renal impairment. Both children have uveitis. One had biopsy-proven interstitial nephritis and the other had biochemical evidence of transient tubular dysfunction. While the renal parameters improved, they are still under treatment for uveitis. The occurrence of TINU in identical twins at an interval of just under 2 years supports a strong genetic element in the aetiology of this syndrome. We believe this is the first report of male twins with TINU.     

A case of adult-onset tubulointerstitial nephritis and uveitis (“TINU syndrome”) associated with sacroileitis and epstein-barr virus infection with good spontaneous outcome

The authors report a case of tubulointerstitial nephritis and uveitis (TINU syndrome) in a 48-year-old woman. The patient's ocular symptoms (relapsing bilateral uveitis) began 4 months before the renal disease was diagnosed and were treated successfully with local steroid therapy. The main baseline laboratory findings were anemia, a rapid sedimentation rate, and a decreased renal function. Urinalysis results showed mild proteinuria and some hyaline and hyaline-granular casts. Immunoglobulin (Ig) G and IgM antibodies to Epstein-Barr virus (EBV) were present. The renal biopsy showed interstitial lymphocytes and infiltration by rare plasma cells, tubular atrophy without granulomas, and slight expansion of the mesangium; electronic microscopy showed rare electron-dense deposits in the mesangium; no vascular alterations were seen, and immunofluorescent staining was uniformly negative. X-ray of the pelvis showed bilateral sacroileitis, which has been previously described in only 1 case of TINU syndrome; human leukocyte antigen B27 was negative. After 6 months without any therapy, all laboratory findings were normal; after 30 months, renal function was still normal, uveitis had not relapsed, but sacroiliac involvement was still present; EBV-viral capsid antigen (VCA) IgM were still high (28 UA/mL), and the EBV IgG titers were increased (VCA>170, EBV-nuclear antigen 108 UA/mL). This case confirms that this rare entity, originally observed in children, may occur and have a favorable spontaneous renal outcome also in the adult; EBV may play a role, as previously suggested. This is, to the authors’ knowledge, the first reported case of TINU syndrome with the association of a well-documented bilateral sacroileitis.     

A case of tubulointerstitial nephritis and uveitis syndrome with severe immunologic dysregulation

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 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 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.     

Drug-induced TINU syndrome and genetic characterization

Tubulointerstitial nephritis and uveitis (TINU) syndrome is due to a disregulation of cell-mediated immunity and genetical predisposition due a particular molecular characterization. We report the case of a 50-year-old woman who was admitted for acute renal failure. She had recently taken flurbiprofen for 10 d for recurrent bronchitis. A renal biopsy revealed acute tubulointerstitial nephritis. Prednisone was started and prognosis was favorable. Three months later the patient developed transitory blurred vision. The diagnosis was bilateral uveitis and she received topic and systemic corticosteroid therapy, with resolution of ocular symptoms. Recurrent episodes of uveitis experienced during the next 12 months were treated with same therapy. Genomic haplotype in our patients was HLA A*0278/2631,-B*1517/3802,- Cw*0701/1202, -DRB1*0101/1359 (DRB3* 52), -DQA1*0102/0102, DQB1*0603/0603. TINU syndrome is characterized by tubulointerstitial nephritis that tends to be selflimiting, whereas uveitis tends to relapse. HLA-DQA1*01 and -DQB1*06 haplotypes are strongly associated with TINU syndrome. This is the first report of TINU syndrome induced by flubiprofen intake. Our case emphasizes the importance of the association between drug exposure and strong susceptibility to TINU syndrome giving the molecular characterization.     

Successful treatment of progressive renal injury due to granulomatous tubulointerstitial nephritis with uveitis

Acute tubulointerstitial nephritis and bilateral uveitis (TINU) syndrome is a rare disease usually occurring in young women. We report the exceptional case of a 48-year-old man with TINU syndrome who had a 10-month history of interstitial nephritis before the onset of uveitis. Findings from the renal biopsy specimen indicated tubular atrophy, dense infiltration of lymphocytes, granulomatous infiltration with multinucleated giant cells, and disruption of the vessel wall. The patient was initially diagnosed to have chronic kidney disease; interstitial nephritis could not be diagnosed until blurred vision occurred. However, he was successfully treated with steroid pulse and oral maintenance therapy. Steroid therapy may be effective to treat TINU syndrome irrespective of the onset of the disease.     

Tubulointerstitial nephritis and uveitis syndrome with transient hyperthyroidism in an elderly patient

A 69-year-old Japanese woman without any specific medical or family history was admitted to our hospital for renal insufficiency with proteinuria. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 34.9 mg/dL and creatinine level was 1.78 mg/dL) and elevated urinary levels of N-acetyl-β-d-glucosaminidase (23.4 U/L) and β2-microgloblin (20200 μg/L) were observed. We performed a renal biopsy. The biopsied specimen showed severe diffuse infiltration of mononuclear cells into the interstitium, with normal glomeruli, and these findings were compatible with acute tubulointerstitial nephritis (ATIN). At that time, ATIN seemed to be idiopathic. We performed gallium scintigraphy, and the results revealed uptake by the bilateral kidneys, thyroid gland, and right parotid gland. Serum thyroid stimulating hormone (TSH) was undetectable, free triiodothyronine was normal (3.11 pg/mL), and free thyroxine was elevated to 2.4 ng/dL. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Two months later, burning pain and conjunctival congestion developed in both eyes. She had uveitis, as diagnosed by slit-lamp examination. Topical corticosteroid was used for the uveitis with success. We could not detect any cause of the uveitis, so a diagnosis of tubulointerstitial nephritis and uveitis syndrome (TINU syndrome) with associated hyperthyroidism was made. Treatment was started with 15 mg/day of prednisolone. Now her renal function is slowly recovering. There are few reports of TINU syndrome with transient hyperthyroidism. This case suggests the possibility of thyroid dysfunction in patients with TINU syndrome. A laboratory evaluation of thyroid function should be considered in the diagnostic evaluation of TINU syndrome.     

Excellent outcome of tubulointerstitial nephritis and uveitis: case report and five-year follow-up

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.     

A Case of Tubulointerstitial Nephritis and Uveitis in an Adult Male

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 β-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.     

Excellent Outcome of Tubulointerstitial Nephritis and Uveitis: Case Report and Five-Year Follow-Up

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.     

Repeat renal biopsy in tubulointerstitial nephritis and uveitis syndrome: report of a case

A Japanese girl aged 12 years who presented with a month history of uveitis developed a significant elevation of urinary beta 2 microglobulin (beta 2MG) up to 13,933 micrograms/l. A percutaneous renal biopsy revealed a dense CD4-positive T-cell infiltration with focal tubulitis in the interstitium. The tubulointerstitial score (TI score) described by Foster et al. was 7 points. She was diagnosed as having tubulointerstitial nephritis and uveitis syndrome (TINU). Due to the severe interstitial infiltration, a 6-month course of prednisolone at the dose of 30 mg per alternate day was started. The levels of urinary beta 2MG dramatically decreased following treatment and the renal function remained normal. The second renal biopsy performed 6 months later revealed mild persistent CD4-positive T-cell infiltration associated with 19% periglomerular thickening, with the TI score of 4 points. These clinical observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with TINU. Since persistent interstitial infiltration has been known to be harmful to the kidney, we therefore speculate that prompt administration of corticosteroids might be beneficial to these patients. Although the renal outcome of TINU has been reported to be favorable to date, patients with severe interstitial infiltration should be followed under close observation. Study of similar patients is needed to clarify our understanding of effective therapy for TINU.     

Tubulointerstitial Nephritis and Uveitis Syndrome: Use of Gallium Scintigraphy in its Diagnosis and Treatment

Prompt diagnosis and treatment with corticosteroids of the tubulointerstitial nephritis with uveitis (TINU) syndrome may assist in the preservation of renal function. We present a case illustrating the characteristic clinical features of this syndrome. Gallium scintigraphy assisted in the diagnosis and management of this case, which was complicated by relapsing pyelonephritis.     

Repeat renal biopsy in a girl with tubulointerstitial nephritis and uveitis syndrome

A Japanese girl aged 8 years who presented with a 2-month history of uveitis subsequently developed tubulointerstitial nephritis. A percutaneous renal biopsy revealed massive interstitial mononuclear cell infiltrates consisting of CD4-positive T cells. Despite administration of topical corticosteroids, the ocular symptoms persisted. Systemic corticosteroid therapy dramatically reduced the ocular symptoms and urinary β₂-microglobulin (β 2MG) concentration. However, reducing the prednisolone dosage induced recurrence of uveitis associated with increased levels of urinary β 2MG. The CD4-positive T cell infiltration persisted in the second renal biopsy performed 6 months after the first renal biopsy. These observations suggest that the interstitial cell infiltration persists for a relatively long time in a proportion of patients with tubulointerstitial nephritis and uveitis syndrome (TINU). Although the renal outcome of TINU has been reported to be favorable, prolonged interstitial cell infiltration may affect long-term renal outcome. Selected patients with TINU should be followed with close observation. Received: 7 February 2001 / Revised: 8 June 2001 / Accepted: 27 June 2001     

Tubulointerstitial nephritis and uveitis syndrome in a mother and her son

A mother and her son, both with tubulointerstitial nephritis and uveitis syndrome (TINU) are reported. The nephritis presented itself at 13 years in the mother and at 10 years in her son. Glomerular filtration (GFR) decreased in both, and renal biopsies confirmed the diagnosis. Nephritis preceded the onset of uveitis in both. Clinical course and renal function improved quickly on oral steroids in the boy. The mother’s hyperazotemia decreased spontaneously (without steroids), but not to normal range, and remained stable for 35 years of follow-up. Local steroids due to recurrences of uveitis were repeatedly needed in both. We believe this is the first report on familial occurrence of inherited TINU syndrome in two generations.     

Tubulointerstitial nephritis and uveitis in children and adolescents

 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. Received: 21 May 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998