Tubulointerstitial nephritis is an inflammatory disease that mainly affects the kidney tubules and interstitium. Various factors can cause this condition, including medications, infections, metabolic disorders, and autoimmune diseases. When this condition follows a chronic course, it is classified as chronic tubulointerstitial nephritis. Since tubulointerstitial nephritis encompasses a range of kidney conditions resulting from diverse causes, the WHO classification (see Table 1), which takes into account these causes, is widely used for identification of specific disease type. This article specifically focuses on tubulointerstitial nephritis with uveitis (TINU) syndrome.
TINU syndrome is a condition characterized by the combination of tubulointerstitial nephritis and uveitis, an inflammation of the uvea, a part of the eye. It is believed to be triggered by abnormalities in the immune system, although the exact cause remains unknown. First reported in 1975, the concept and diagnostic criteria for TINU syndrome were proposed in 2001.
In TINU syndrome, individuals may experience general symptoms such as fever, fatigue, loss of appetite, and weight loss, as well as kidney-related symptoms such as flank pain, excessive thirst, and frequent urination. However, these symptoms are not always present and are common in many other conditions, making it difficult to suspect tubulointerstitial nephritis based solely on symptoms. Eye symptoms caused by uveitis include red eye, photophobia, eye pain, and decreased vision.
If TINU syndrome is suspected, the diagnosis is made based on examination findings. Blood tests often show impaired kidney function, while urine tests typically reveal an increase in tubular proteinuria (elevated urinary β2-microglobulin is a key diagnostic marker), along with leukocyturia, hematuria, proteinuria, and glucosuria, which also support the diagnosis. A kidney biopsy—a procedure in which a small sample of kidney tissue is taken and examined under a microscope—can confirm the diagnosis. Please also refer to the Q&A section.
Both eye and kidney symptoms are experienced in approximately 20% of cases at the time of diagnosis. Kidney symptoms may appear after eye symptoms, or vice versa, sometimes with a delay between the two. Therefore, regular urine tests are essential during the treatment and monitoring of uveitis, and regular ophthalmologic examinations are crucial during the follow-up of tubulointerstitial nephritis.
Currently, there are no established guidelines for treating TINU syndrome. While kidney symptoms may resolve on their own, cases with severe kidney dysfunction or systemic symptoms are managed with steroids or immunosuppressive drugs. The response to treatment can be favorable; however, some patients may experience residual kidney dysfunction or persistent proteinuria as long-term effects.
For uveitis, steroid eye drops or local steroid injections often lead to improvement. However, treatment can sometimes be challenging, requiring systemic administration of steroids or immunosuppressive drugs.
A. While precise data for Japan is unavailable, TINU syndrome is estimated to account for 0.2–2% of patients diagnosed with uveitis and 5–28% of those diagnosed with tubulointerstitial nephritis.
A. TINU syndrome is more common in females, with a female-to-male ratio of 3 to 1, and it is often observed during adolescence and early adulthood. However, cases have also been reported in the elderly.
A. The exact cause of TINU syndrome is still unknown. It is believed to result from an autoimmune response, in which the immune system mistakenly attacks the body’s own cells and proteins. The autoimmune targets in TINU syndrome are the kidneys and eyes.
A. Doctors may suspect TINU syndrome if the patient experiences general symptoms such as fever or eye-related issues, or if abnormalities are found during school urine screenings. However, routine urine tests, including those conducted during school screenings, often fail to detect abnormalities that lead to the diagnosis of TINU syndrome. When TINU syndrome is suspected, more detailed urine tests, eye examinations, and, if necessary, a kidney biopsy (a procedure in which a small sample of kidney tissue is taken and examined under a microscope) are performed for diagnosis.
Sarcoidosis is another condition that can cause both tubulointerstitial kidney lesions and eye symptoms. This makes differentiating between the two necessary, which can sometimes be challenging. Both interstitial nephritis and uveitis can have various underlying causes, and further investigation is often required even after diagnosing the kidney or eye conditions.
Table 1. Excerpt from the Revised WHO Classification of Tubulointerstitial Vascular Lesions
Table 2. Diagnostic and Treatment Guidelines for TINU Syndrome (for Healthcare Professionals)
| Acute Interstitial Nephritis | Uveitis | |
|---|---|---|
| Definite | Histopathological or clinical diagnosis meeting all three TIN criteria | Typical |
| Probable | Histopathologically diagnosed TIN TIN meeting any of the three clinical criteria |
Atypical Typical |
| Possible | TIN meeting any of the three clinical criteria | Atypical |
(Mandeville JT, et al: The tubulointerstitial nephritis and uveitissyndrome. Surv Ophthalmol. 2001; 46: 195-208 より)
