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     

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.     

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.     

Acute tubulointerstitial nephritis in 21 Japanese children

PATIENTS AND METHODS: We studied 21 Japanese children aged 1.2 to 14.9 years with biopsy-proven acute tubulointerstitial nephritis (ATIN; 5 drug-induced, 7 infection-related, 3 tubulointerstitial nephritis and uveitis syndrome (TINU), and 6 unclassified) for clinical presentation, laboratory findings, and outcome to clarify the clinical features of the entity. All developed acute renal failure with peak BUN values from 25 to 164 mg/dl (mean 83 mg/dl) and peak serum creatinine values from 1.5 to 15.1 mg/dl (mean 6.5 mg/dl). All the 7 infection-related ATIN were associated with Yersinia pseudotuberculosis infection. Four of the 21 patients underwent dialysis therapy for anuria and 1 patient in the unclassified ATIN showed progression to chronic renal failure. RESULTS: In 20 patients, renal insufficiency lasted for 6 to 73 days: 5 drug-induced; median and ranges 25 (12-33) days, 7 infection-related; 15 (6-22) days, 3 TINU; 65 (55-73) days, and 5 unclassified; 24 (6-34) days. Oral steroid therapy was introduced to the 3 TINU patients because of the prolonged renal dysfunction. Although it was effective in all, 2 of them showed a deterioration of clinical symptoms or renal function after reducing the dosage of steroid. CONCLUSION: Consequently, TINU patients required a longer period of time for the improvement of renal function compared to the other etiologies.     

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 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.     

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 (TINU): a step forward to understanding an elusive oculorenal syndrome

In this issue of NDT, Sartelet et al. [1] provide an interestingstudy on Tubulointerstitial Nephritis and Uveitis syndrome (TINU),an oculorenal syndrome the pathophysiology of which is stillpoorly understood. TINU is a rare disease, first described in 1975 by Dobrin [2]in two adolescent girls, in whom non-caseating granulomas werefound in the bone marrow and in the lymph nodes, in associationwith anterior uveitis and tubulointerstitial nephritis. Sincethen, more than 200 cases have been reported in the ophthalmologicand paediatric literature,     

Serial renal biopsies in three girls with tubulointerstitial nephritis and uveitis syndrome

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 β₂-microglobulin levels (7583–19,313 μg/l) and high serum creatinine levels (0.93–1.3 mg/dl). The elevated β₂-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.     

Severe hypertensive sequelae in a child with Seckel syndrome (bird-like dwarfism)

 We report a 19-year-old male with Seckel syndrome (bird-like dwarfism) who presents with malignant hypertension associated with hypertensive nephrosclerosis, dilated cardiomyopathy, and a ruptured cerebral artery aneurysm. Although end-organ injury due to chronic hypertension occurs frequently in adults, no previous reports of renal insufficiency due to hypertension exist in children or adolescents. We speculate that this patient may have been particularly prone to hypertensive end-organ injury due to his extreme short stature. Received: 6 May 1998 / Revised: 7 August 1998 / Accepted: 8 August 1998     

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.     

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.     

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.     

Nephrotic syndrome at 5 months: no definitive treatment or complications for 12 years

We describe a patient who developed nephrotic syndrome at 5 months, with extensive glomerular and tubular damage on biopsy. The patient was treated with diuretics and was asymptomatic for a decade despite unremitting proteinuria. A repeat biopsy at 13 years of age showed remarkable healing with histopathological features consistent with ”minimal change” nephrotic syndrome. This patient illustrates a favorable clinical outcome, without specific treatment, of nephrotic syndrome of long duration. Received: 17 August 1998 / Revised: 17 November 1998 / Accepted: 17 November 1998     

Tubulointerstitial nephritis and uveitis (TINU) syndrome caused by the Chinese herb “Goreisan”

A 58-year-old man was admitted to our hospital complaining of fever and arthralgia. His clinical course and marked ciliary hyperemia led us to suspect tubulointestinal nephritis and uveitis (TINU) syndrome, which was confirmed ophthalmologically and by renal biopsy. Results of a drug-induced lymphocyte-stimulating test were positive for the Chinese herb “Goreisan.” This is the first case in which the use of “Goreisan” was causally related to TINU 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.     

Membranous nephropathy associated with childhood sarcoidosis

 Sarcoidosis is a chronic multisytemic granulomatous disease of unknown etiology. It is relatively rare in children. Renal involvement in sarcoidosis is described less commonly than other organ involvement such as pulmonary, eye, musculoskeletal, and skin. We report a 13-year-old girl with sarcoidosis and nephrotic syndrome. Renal biopsy showed findings of membranous nephropathy. She received intravenous pulse methylprednisolone and oral cyclophosphamide with resolution of the symptoms of fever and edema, and improvement of the proteinuria. Her condition is stable with no progression of her renal disease. To the best of our knowledge, this is the first report of membranous nephropathy associated with childhood sarcoidosis. Received: 27 March 1998 / Revised: 31 August 1998 / Accepted: 31 August 1998