Tubulointerstitial nephritis and uveitis (TINU syndrome)
- Geoffrey Lee, MD
Geoffrey Lee, MD
- Attending Physician
- Kingston General Hospital
- Akhtar Ashfaq, MD
Akhtar Ashfaq, MD
- Assistant Professor of Medicine
- Albert Einstein College of Medicine
A unique subset of patients with interstitial nephritis has the TINU syndrome (tubulointerstitial nephritis and uveitis). First described in 1975 , more than 250 cases have now been reported [2,3]. The majority of cases have been documented in the ophthalmology and pediatric nephrology literature via case reports and small descriptive series.
The underlying mechanisms for TINU are not well understood. Limited data suggest that modified C-reactive protein (mCRP), an autoantigen common to both the uvea and renal tubular cells, may be involved in the pathogenesis . In a study of 97 patients with various renal disorders and 40 healthy controls, the prevalence of immunoglobulin G (IgG) antibodies directed against mCRP was significantly higher among nine patients with TINU syndrome (100 percent) than among those with Sjögren’s associated interstitial nephritis (29 percent), drug-induced interstitial nephritis (36 percent), glomerulonephritis (5 percent), and healthy controls (0 percent) . Another study by the same group confirmed that the mCRP is higher among patients with TINU syndrome and late-onset uveitis compared with those with drug-induced interstitial nephritis .
The inflammation in TINU syndrome is thought to be T-lymphocyte driven, based upon the histologic findings. In contrast, immune cells in patients with TINU syndrome have a paradoxical suppression of cytokine production and a decrease in peripheral immune response, as demonstrated by anergy to skin testing. This paradox is not unique to TINU, as the presence of increased tissue inflammation with concomitant suppression of peripheral immunity is also seen in patients with sarcoidosis [5,6].
RISK FACTORS AND ASSOCIATIONS
No identifiable risk factors have been found in at least 50 percent of cases. In some instances, prior infection or the use of specific drugs (antibiotics to treat upper respiratory infections and nonsteroidal anti-inflammatory drugs [NSAIDs]) has been implicated [3,7]. The Chinese herb, "goreisan," has been associated in a case report . Although causality is unclear, concurrent Chlamydia and Epstein-Barr virus infections have been described [9,10]. TINU syndrome has also been reported in patients with autoimmune diseases like hypoparathyroidism , thyroid disease [3,12], immunoglobulin G4 (IgG4)-related autoimmune disease , and rheumatoid arthritis [11,14].
Most patients with TINU are adolescents and young women, with a median age of 15 years . It has also been reported in adults and older adults [16,17]. All series report a female-to-male predominance [3,7], with no particular racial affinity.
- Dobrin RS, Vernier RL, Fish AL. Acute eosinophilic interstitial nephritis and renal failure with bone marrow-lymph node granulomas and anterior uveitis. A new syndrome. Am J Med 1975; 59:325.
- Abed L, Merouani A, Haddad E, et al. Presence of autoantibodies against tubular and uveal cells in a patient with tubulointerstitial nephritis and uveitis (TINU) syndrome. Nephrol Dial Transplant 2008; 23:1452.
- Li C, Su T, Chu R, et al. Tubulointerstitial nephritis with uveitis in Chinese adults. Clin J Am Soc Nephrol 2014; 9:21.
- Tan Y, Yu F, Qu Z, et al. Modified C-reactive protein might be a target autoantigen of TINU syndrome. Clin J Am Soc Nephrol 2011; 6:93.
- Gafter U, Kalechman Y, Zevin D, et al. Tubulointerstitial nephritis and uveitis: association with suppressed cellular immunity. Nephrol Dial Transplant 1993; 8:821.
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- Suzuki H, Yoshioka K, Miyano M, et al. Tubulointerstitial nephritis and uveitis (TINU) syndrome caused by the Chinese herb "Goreisan". Clin Exp Nephrol 2009; 13:73.
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- Grefer J, Santer R, Ankermann T, et al. Tubulointerstitial nephritis and uveitis in association with Epstein-Barr virus infection. Pediatr Nephrol 1999; 13:336.
- Catalano C, Harris PE, Enia G, et al. Acute interstitial nephritis associated with uveitis and primary hypoparathyroidism. Am J Kidney Dis 1989; 14:317.
- Paul E, Van Why S, Carpenter TO. Hyperthyroidism: a novel feature of the tubulointerstitial nephritis and uveitis syndrome. Pediatrics 1999; 104:314.
- Yoneda K, Murata K, Katayama K, et al. Tubulointerstitial nephritis associated with IgG4-related autoimmune disease. Am J Kidney Dis 2007; 50:455.
- Iida H, Terada Y, Nishino A, et al. Acute interstitial nephritis with bone marrow granulomas and uveitis. Nephron 1985; 40:108.
- Sessa A, Meroni M, Battini G, et al. Acute renal failure due to idiopathic tubulo-intestinal nephritis and uveitis: "TINU syndrome". Case report and review of the literature. J Nephrol 2000; 13:377.
- Cacoub P, Deray G, Le Hoang P, et al. Idiopathic acute interstitial nephritis associated with anterior uveitis in adults. Clin Nephrol 1989; 31:307.
- Salu P, Stempels N, Vanden Houte K, Verbeelen D. Acute tubulointerstitial nephritis and uveitis syndrome in the elderly. Br J Ophthalmol 1990; 74:53.
- Gianviti A, Greco M, Barsotti P, Rizzoni G. Acute tubulointerstitial nephritis occurring with 1-year lapse in identical twins. Pediatr Nephrol 1994; 8:427.
- Howarth L, Gilbert RD, Bass P, Deshpande PV. Tubulointerstitial nephritis and uveitis in monozygotic twin boys. Pediatr Nephrol 2004; 19:917.
- Dusek J, Urbanova I, Stejskal J, et al. Tubulointerstitial nephritis and uveitis syndrome in a mother and her son. Pediatr Nephrol 2008; 23:2091.
- Levinson RD, Park MS, Rikkers SM, et al. Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome. Invest Ophthalmol Vis Sci 2003; 44:653.
- Rosenbaum JT. Bilateral anterior uveitis and interstitial nephritis. Am J Ophthalmol 1988; 105:534.
- Igarashi T, Kawato H, Kamoshita S, et al. Acute tubulointerstitial nephritis with uveitis syndrome presenting as multiple tubular dysfunction including Fanconi's syndrome. Pediatr Nephrol 1992; 6:547.
- Koike K, Lida S, Usui M, et al. Adult-onset acute tubulointerstitial nephritis and uveitis with Fanconi syndrome. Case report and review of the literature. Clin Nephrol 2007; 67:255.
- Simon AH, Alves-Filho G, Ribeiro-Alves MA. Acute tubulointerstitial nephritis and uveitis with antineutrophil cytoplasmic antibody. Am J Kidney Dis 1996; 28:124.
- Wakaki H, Sakamoto H, Awazu M. Tubulointerstitial nephritis and uveitis syndrome with autoantibody directed to renal tubular cells. Pediatrics 2001; 107:1443.
- Conz PA, Milan M, Bragantini L, et al. TINU syndrome associated with reduced complement levels. Nephron 2001; 89:340.
- Kase S, Kitaichi N, Namba K, et al. Elevation of serum Krebs von den Lunge-6 levels in patients with tubulointerstitial nephritis and uveitis syndrome. Am J Kidney Dis 2006; 48:935.
- Joss N, Morris S, Young B, Geddes C. Granulomatous interstitial nephritis. Clin J Am Soc Nephrol 2007; 2:222.
- Takemura T, Okada M, Hino S, et al. Course and outcome of tubulointerstitial nephritis and uveitis syndrome. Am J Kidney Dis 1999; 34:1016.
- Neilson EG, Farris AB. Case records of the Massachusetts General Hospital. Case 21-2009. A 61-year-old woman with abdominal pain, weight loss, and renal failure. N Engl J Med 2009; 361:179.
- Preddie DC, Markowitz GS, Radhakrishnan J, et al. Mycophenolate mofetil for the treatment of interstitial nephritis. Clin J Am Soc Nephrol 2006; 1:718.
- van Leusen R, Assmann KJ. Acute tubulo-interstitial nephritis with uveitis and favourable outcome after five months of continuous ambulatory peritoneal dialysis (CAPD). Neth J Med 1988; 33:133.
- RISK FACTORS AND ASSOCIATIONS
- CLINICAL AND LABORATORY MANIFESTATIONS
- Renal manifestations
- Laboratory findings
- DIAGNOSIS AND HISTOLOGIC FINDINGS
- DIFFERENTIAL DIAGNOSIS
- MANAGEMENT AND PROGNOSIS
- Renal disease
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS