Elsevier

Survey of Ophthalmology

Volume 46, Issue 3, November–December 2001, Pages 195-208
Survey of Ophthalmology

Major review
The Tubulointerstitial Nephritis and Uveitis Syndrome,☆☆,

https://doi.org/10.1016/S0039-6257(01)00261-2Get rights and content

Abstract

The world's medical literature on tubulointerstitial nephritis and uveitis (TINU) syndrome was reviewed, and data on 133 patients with TINU syndrome were identified. The median age of onset was 15 years (range 9–74 years) with a 3:1 female-to-male predominance. Common laboratory abnormalities included elevated Westergren erythrocyte sedimentation rates and elevated urinary beta-2-microglobulin levels. Ocular symptoms preceded systemic symptoms in 21% of cases, and followed systemic symptoms by up to 14 months in 65% of cases. Uveitis involved only the anterior segment in 80% of cases. Uveitis was bilateral at presentation in 77% of cases. Patients were treated with systemic corticosteroids in 80% of cases and with immunosuppressive drugs in 9% of cases. Uveitis recurred or followed a chronic course in 56% of patients and persisted for several years in some cases. Ocular complications (including posterior synechiae, cataracts, and elevated intraocular pressure) were reported in 21% of cases. The visual prognosis appears to be good. Persistent renal dysfunction was reported in 11% of cases, including five patients who required renal dialysis. TINU syndrome is a distinct clinical entity that may be under-recognized and may account for some cases of unexplained chronic or recurrent uveitis. It is important for ophthalmologists, nephrologists, and primary care providers to be familiar with this disorder to ensure early diagnosis and appropriate treatment.

Section snippets

Demographics

1. Sex

There has been a female predominance in reported cases of TINU syndrome, with a 3:1 female-to-male ratio (Table 1). There has been an increasing number of reports of male patients with TINU syndrome in the more recent literature; however, whereas male patients constituted only 18% of patients reported prior to 1990, they comprised 34% of patients reported since 1990. There may have been an early ascertainment bias favoring female patients, as the initial reports of TINU syndrome

Onset of ocular symptoms

Among 120 cases for which information was available, ocular findings preceded (21%), developed concurrently with (15%), or followed (65%) the onset of interstitial nephritis, with a median onset of ocular symptoms one month after the onset of systemic symptoms, as shown in the Fig. 1. Uveitis was documented up to 2 months before, or up to 14 months after the onset of systemic symptoms. Of the 65% of patients who developed ocular symptoms after the onset of systemic symptoms, the median time to

Pathology

Although a reliable diagnosis of tubulointerstitial nephritis can be made from clinical and laboratory findings,7, 11, 13, 65, 73, 80, 94, 99 renal biopsy is required for the definitive diagnosis of tubulointerstitial nephritis, which must be distinguished from other causes of acute renal failure. All 118 patients with TINU syndrome who underwent renal biopsies had findings consistent with tubulointerstitial nephritis, which is characterized by interstitial edema and infiltration by

Differential Diagnosis

A number of diseases can cause both renal disease and uveitis, including sarcoidosis, Sjögren syndrome, syphilis, systemic lupus erythematosis, Wegener granulomatosis, Behçet disease, Epstein–Barr virus-associated infectious mononucleosis, tuberculosis, toxoplasmosis, brucellosis, and histoplasmosis. The majority of disorders listed here do not result in anterior uveitis alone, which is the most common ocular manifestation of TINU syndrome. Of these disorders, many have typical ocular findings

Laboratory Investigations

A variety of abnormal laboratory values have been reported for patients with TINU syndrome. For illustrative purposes, we have calculated mean values for selected tests, using patient results from multiple publications if laboratory values were reported using the same units. We recognize, however, that methodology and normal ranges may vary among laboratories. Typical normal ranges, based on multiple reports, are listed for purposes of general comparison.

Initial laboratory testing in patients

Therapy

No prospective, randomized studies have addressed the efficacy of treatment for acute interstitial nephritis. It may resolve spontaneously, after discontinuance of an inciting drug or treatment of an underlying infection. Systemic corticosteroids are generally reserved for cases of progressive renal failure. In the cases reported here, there was no clear relationship between age and response to treatment.

The anterior uveitis of TINU syndrome has been treated most commonly with topical

Dilemmas in evaluation and diagnosis

In evaluating patients with TINU syndrome, a search must be made for diseases that are known to cause both acute interstitial nephritis and uveitis, such as sarcoidosis and Sjögren syndrome. The initial description of TINU syndrome by Dobrin and associates17 included granulomata and eosinophils in the kidney and bone marrow, which are not found in the majority of cases in the literature. It is unknown whether acute interstitial nephritis from any cause is capable of generating uveitis, but the

Summary

In summary, TINU syndrome is a distinct entity that tends to affect young women, although both sexes and older patients may also be affected. The renal disease is characterized by acute interstitial nephritis with a predominantly T-lymphocyte infiltrate, whereas the ocular disease is most often a bilateral anterior uveitis that may occur before, simultaneous with, or after the onset of renal disease. Cell-mediated immune dysfunction has been implicated in the pathogenesis of TINU syndrome, but

Method of Literature Search

Articles cited in this review were identified from a MEDLINE search of the years 1966–1999, using the keywords interstitial nephritis and uveitis and from a review of the reference lists from each article. Two articles identified in this search33, 51 were not cited in the review because they were not available through the interlibrary loan services at either the University of California, Los Angeles or the National Library of Medicine. Also included with permission of the authors were two

Outline

I. Patient characteristics

A. Demographics

1. Gender

2. Age

3. HLA types

4. Clustering

B. Risk factors and pathogenesis

C. Clinical features

1. Systemic features

2. Ocular features

II. Course of disease

A. Onset of ocular symptoms

B. Recurrences

C. Complications

D. Outcomes

III. Pathology

IV. Differential diagnosis

V. Laboratory investigations

VI. Therapy

VII. Discussion

A. Dilemmas in evaluation and diagnosis

B. Possible pathogenic mechanisms

C. Diagnostic criteria

VIII. Summary

References (99)

  • F Montagnon et al.

    Acute interstitial nephritis with uveitis. A case report

    Rev Med Interne

    (1992)
  • R.S Moorthy et al.

    Drug-induced uveitis

    Surv Ophthalmol

    (1998)
  • J.T Rosenbaum

    Bilateral anterior uveitis and interstitial nephritis

    Am J Ophthalmol

    (1988)
  • M.D Sherman et al.

    Interstitial nephritis and uveitis syndrome presenting with bilateral optic disk edema

    Am J Ophthalmol

    (1999)
  • A.H Simon et al.

    Acute tubulointerstitial nephritis and uveitis with antineutrophil cytoplasmic antibody

    Am J Kidney Dis

    (1996)
  • A Spital et al.

    Acute idiopathic tubulointerstitial nephritisreport of two cases and review of the literature

    Am J Kidney Dis

    (1987)
  • T.I Steinman et al.

    Acute interstitial nephritis and iritis. Renal-ocular syndrome

    Am J Med

    (1984)
  • T Takemura et al.

    Course and outcome of tubulointerstitial nephritis and uveitis syndrome

    Am J Kidney Dis

    (1999)
  • R.M Ten et al.

    Acute interstitial nephritisimmunologic and clinical aspects

    Mayo Clin Proc

    (1988)
  • P Ashorn et al.

    Tubulo-interstitial nephritis and uveitis in a 13-year old boy

    Duodecim

    (1992)
  • F Auclin et al.

    Interstitial tubulo-nephritis and uveitis (Nitu syndrome). Apropos of a case

    J Fr Ophtalmol

    (1989)
  • J.A Bagon

    Tubulointerstitial nephropathy with uveitis

    Acta Clin Belg

    (1996)
  • N Belovezhdov et al.

    Acute interstitial nephritis with concomitant iridocyclitis

    Vutr Boles

    (1979)
  • F Ben Hamida et al.

    Adult uveitisapropos of 1 case with acute idiopathic interstitial nephritis

    Nephrologie

    (1995)
  • D BenEzra

    Bilateral anterior uveitis and interstitial nephritis

    Am J Ophthalmol

    (1988)
  • R Birnbacher et al.

    Tubulointerstitial nephritis and uveitisan immunological disorder?

    Pediatr Nephrol

    (1995)
  • T.E Bunchman et al.

    A syndrome of acute interstitial nephritis and anterior uveitis

    Pediatr Nephrol

    (1993)
  • R Burghard et al.

    Acute interstitial nephritis in childhood

    Eur J Pediatr

    (1984)
  • M Burnier et al.

    Idiopathic acute interstitial nephritis and uveitis in the adult

    Report of

    (1986)
  • P Cacoub et al.

    Idiopathic acute interstitial nephritis associated with anterior uveitis in adults

    Clin Nephrol

    (1989)
  • S Cavazza et al.

    Bilateral intermediate uveitis and acute interstitial nephritis (TINU syndrome). Ultrasonographic documentation of a case

    J Fr Ophtalmol

    (1994)
  • H.C Chen et al.

    Acute tubulo-interstitial nephritis and uveitis with anti-neutrophil cytoplasmic antibodies in an adultan autoimmune disorder?

    Nephron

    (1998)
  • D.N Cruz et al.

    Drug-induced acute tubulointerstitial nephritisthe clinical spectrum

    Hosp Pract (Off Ed)

    (1998)
  • P Finielz et al.

    Acute interstitial nephritis with uveitis

    Presse Med

    (1990)
  • T Fried

    Acute interstitial nephritis. Why do the kidneys suddenly fail?

    Postgrad Med

    (1993)
  • U Gafter et al.

    Anterior uveitis, a presenting symptom in acute interstitial nephritis

    Nephron

    (1986)
  • U Gafter et al.

    Tubulointerstitial nephritis and uveitisassociation with suppressed cellular immunity

    Nephrol Dial Transplant

    (1993)
  • L Garcia de Cortazar et al.

    Interstitial nephritis syndrome and uveitis

    Rev Chil Pediatr

    (1991)
  • A Gianviti et al.

    Acute tubulointerstitial nephritis occurring with 1-year lapse in identical twins

    Pediatr Nephrol

    (1994)
  • F Gohlke et al.

    Tubulointerstitial nephritis-uveitis syndrome (TINU syndrome)

    Dtsch Med Wochenschr

    (1995)
  • S Gomez Garcia et al.

    Interstitial nephritis associated with uveitis

    An Esp Pediatr

    (1990)
  • J Grefer et al.

    Tubulointerstitial nephritis and uveitis in association with Epstein–Barr virus infection

    Pediatr Nephrol

    (1999)
  • N Hausmann et al.

    Acute recurrent uveitis and idiopathic interstitial nephritis—a nosologic entity (tubulo-interstitial nephritis and uveitis)

    Klin Monatsbl Augenheilkd

    (1988)
  • K Hirano et al.

    A case of acute tubulointerstitial nephritis and uveitis syndrome with a dramatic response to corticosteroid therapy

    Am J Nephrol

    (1989)
  • N.P Huttunen et al.

    Interstitial nephritis and uveitis coexisting in a school-aged child

    Duodecim

    (1988)
  • T Igarashi et al.

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

    Pediatr Nephrol

    (1992)
  • H Iida et al.

    Acute interstitial nephritis with bone marrow granulomas and uveitis

    Nephron

    (1985)
  • T Iitsuka et al.

    HLA tissue types in patients with acute tubulointerstitial nephritis accompanying uveitis

    Nippon Jinzo Gakkai Shi

    (1993)
  • N Itami et al.

    Acute tubulointerstitial nephritis with uveitis

    Arch Intern Med

    (1990)
  • Cited by (0)

    Min-Sik Park, DVM, Immunogenetics Laboratory, Department of Pathology and Laboratory Medicine, UCLA School of Medicine, performed the analysis of HLA types. Minhtri Nguyen, MD, Division of Nephrology, Department of Medicine, UCLA School of Medicine, provided suggestions regarding appropriate criteria for diagnosis of acute interstitial nephritis. James T. Rosenbaum, MD, Departments of Ophthalmology, Medicine, and Cell Biology, Oregon Health Sciences University, participated in the formulation of diagnostic criteria for TINU syndrome. The following individuals translated articles published in non-English language journals: Adil Abduragimon, PhD, Gabriele Dillman, PhD, Yasmin B. Harvey, Takao Hashimoto, MD, PhD, Jana Hatch, Sandy Y. Lee, MD, Bettina S. Prost, JD, Federico Velez, MD, and Mirka Vuollo.

    ☆☆

    Supported in part by Research to Prevent Blindness, Inc. (Dr. Holland), the Skirball Foundation, Los Angeles, CA (Dr. Holland), and the David May II Endowed Professorship (Dr. Holland). Dr. Holland is a recipient of a Research to Prevent Blindness, Inc.—Lew R. Wasserman Merit Award.

    The authors have no proprietary or commercial interest in any product or idea discussed in this article.

    View full text