A 42-year-old male presents with non-specific symptoms and acute renal injury with a background of focal segmental glomerulosclerosis, but has normal renal function. He had associated anterior uveitis; his renal histology showed acute tubulointerstitial nephritis and uveitis (TINU syndrome) and his vasculitic screen was negative. He was treated with high-dose steroids and had a good a response. At follow-up his renal function normalised in a two-month period. TINU should be considered in acute interstitial nephritis with ocular symptoms and in the absence of any obvious cause for the renal injury.

Presentation

The patient presents with anorexia, nausea, vomiting and lethargy, and had been generally unwell for a week. He had a background history of controlled hypertension and focal segmental glomerulosclerosis, diagnosed on a renal biopsy in 2002. His renal indices have been normal for the past six years. He had been attending the renal clinic on a four-monthly basis, and his progress was going well. On arrival at the hospital he was euvolemic, normotensive and apyrexial. His baseline bloods showed:

• A normal white cell count
• Stable haemoglobin
• Elevated inflammatory markers with an ESR 59 CRP 12.3
• A raised creatinine at 101. 

The immunological assessments showed a negative ANA and ANCA. IgG 13.50, IgA 6.0, IgM 1.5.

His septic screen, including blood cultures and MSU, was negative. CXR was clear and he was in sinus rhythm. His urine was quite active with protein and blood in it. He was treated with IV antibiotics for a presumed urosepsis. Renal ultrasound showed normal-sized kidneys with no collection or hydronephrosis. His 24-hour urinary protein was 1,608g – in a subnephrotic range – and won’t go with a flare-up. His inflammatory markers were settling, but renal function declined subsequently. His creatinine peaked to 287. He developed red painful eyes. Ophthalmology consultation revealed bilateral moderate anterior uveitis that was treated with topical steroids and mydriatics. 

Due to further renal function deterioration he underwent a renal biopsy. The histology was consistent with acute TINU and non-caseating granulomas. His ACE levels were checked as a part of the work-up for a granulomatous lesion on histology, which came back as normal. He was started on high-dose prednisolone with an excellent positive response. His creatinine almost normalised in four to six weeks time.

Discussion

TINU is a syndrome which was first described in 1975 by Dobrin. Some 150 cases have been reported to date. It is an oculorenal syndrome with an unknown aetiology. A cell-mediated immunity and delayed hypersensitivity may play a role with lymphocyte infiltration and increased CD4/CD8 count. There is association with HLA DQA1 and HLA DQB1. In more than 50% of cases it is recognised as an idiopathic condition, while other patients may have several risk factors, such as:

• An upper respiratory tract infection and treatment with an antibiotic
• NSAIDs
• Viral infections like Epstein-Barr virus
• Herpes zoster
• Chlamydia
• Autoimmune conditions such as rheumatoid arthritis
• Hyperthyroidism and hypothyroidism 
• IgG-related autoimmune conditions like pancreatitis.

Females are affected more commonly than males, with a ratio of 3:1. It commonly affects children with a median age of 15, but may affect adults as well.

Uveitis may present as eye pain, photophobia or decreased visual acuity. It is an anterior uveitis in 80% of cases and is bilateral in 77% of cases, but posterior uveitis may occur as well. In 20% of cases intraocular complications like synechiae formation, cataracts and glaucoma can result. In 35% of cases the ocular symptoms develop concurrently, and in 65% they follow the acute interstitial nephritis by a month, but can occur up to a year later.

Renal manifestations are flank pain, sterile pyuria, haematuria, proximal and distal tubular defects resulting in aminoaciduria, phosphaturia and glycosuria. The diagnosis is clinical with histological support. The differential is sarcoidosis. Most TINU patients do not have pulmonary features or any evidence of hilar lymphadenopathy. Their serum ACE level is usually in the normal range. Management is high-dose steroids with a very good response. Investigations involve baseline bloods, autoantibodies screen and histology. Prognosis is favourable, either spontaneously or with high-dose steroids. Relapses of uveitis are treated with immunosuppressives. In most cases, the acute renal injury is transient and the end result is a full renal recovery.