Tubulointerstitial Nephritis with Uveitis in Chinese Adults

Abstract

SummaryBackground and objectives Tubulointerstitial nephritis and uveitis (TINU) syndrome is considered a rare cause of acute tubulointerstitial nephritis (ATIN) that is usually associated with renal recovery. This study sought to investigate the diagnosis, prognosis, and contributing factors of TINU syndrome using a large cohort of patients with prospective follow-up.Design, setting, participants, & measurements This study included patients with TINU syndrome from a prospective cohort of patients with ATIN from 2007 to 2012. Clinical-pathologic data were collected at biopsy and autoantibodies against modified C-reactive protein (mCRP-Ab) were measured. Serum levels and renal tissue expression of Kreb von den Lunge-6 were also detected. Independent risk factors for poor renal outcome at 12 months and late-onset uveitis were analyzed.Results Thirty-one patients (28%) with biopsy-proven ATIN were classified as having TINU syndrome. Of these patients, 18 (58%) developed late-onset uveitis and were misdiagnosed as having drug-induced ATIN at the time of biopsy. An abnormal level of mCRP-Ab was an independent risk factor for late-onset uveitis (odds ratio, 14.7; 95% confidence interval, 3.4 to 64.0). Patients with TINU syndrome and drug-induced ATIN had comparable levels of Kreb von den Lunge-6 in both serum and renal tissues. Ninety-two percent of patients developed stage 3-4 CKD and/or tubular dysfunction by 12 months postbiopsy. Age, serum creatine level, erythrocyte sedimentation rate, and the presence of concomitant thyroid disease or leukocyturia were related to poor renal outcome. Relapse was seen in 36% (11 of 31) of patients and potentiated poor renal outcome. ConclusionsThe diagnosis of TINU syndrome can be missed in a large fraction of patients with ATIN because uveitis can present well after the onset of tubulointerstitial nephritis. Elevated mCRP-Ab levels may be useful in predicting late-onset uveitis TINU syndrome. Unfortunately, patients with TINU tended to have frequent relapses and most patients had incomplete renal recovery. Long-term follow-up is needed to prevent misdiagnosis and properly manage TINU syndrome.

The ratio of urinary α1-microglobulin to microalbumin can be used as a diagnostic criterion for tubuloproteinuria

“…The diagnosis of TIN or TINU is difficult because of variable and nonspecific clinical manifestations. Studies have reported that urinary α1-microglobulin and β2-microglobulin excretion increase in patients with TINU (20,21). The current results indicated that urinary α1-microglobin increased significantly (about 100-fold above the upper limit of the normal range) in the 6 patients with ATIN and in the 4 patients with TINU, and the ratio of urinary α1-microglobulin to microalbumin was greater than 1.…”

Tubulointerstitial Nephritis and Uveitis Syndrome: Case Report and Review of the Literature

“…14,19,20 Yin Tang et al 14 and Li et al 21 demonstrated for the first time a high prevalence of serum autoantibodies against modified C-reactive protein (anti-mCRP autoantibodies) in patients with TINU syndrome. 14 The results of Ying Tang suggest that mCRP may be one of the common target autoantigens in renal and ocular tissues in patients with TINU syndrome.…”

Tubulointerstitial Nephritis and Uveitis (TINU) Syndrome, Two New Cases and Review of the Literature

“…Specific basement membrane antigens have also been found to be immunogenic in animal models of acute interstitial nephritis, and only few patients with TINU were specifically reported to have immunofluorescent tubular basement membranes (TBMs) staining indicating antibody deposition [8,11,23]. It has been also reported a tubular depositions of complement components such as C3 and the C5b-9 complex [6]. On the other hand, TINU syndrome has sometimes been associated with polyclonal hypergammaglobulinemia and elevated serum immunoglobulin IgG levels suggesting a humoral mediated immune response [24], as in our tow patients.…”

“…TINU syndrome is a disorder characterized by a combination of idiopathic acute tubulointerstitial nephritis and uveitis [4,5], Since it was first documented in 1975 [6,7], only a little more than 200 cases of TINU syndrome have been reported [8,9], with approximately 60% of cases occurring in children [6]. Most of the patients with TINU syndrome are adolescents and young women, with a median age at the onset of 15 (range 9 to 74) years and a 3:1 female-to-male predominance [2,7], but others found an older age group with a male predominance [9].…”

“…TINU syndrome is regarded as a rare cause of acute tubulointerstitial nephritis (ATIN) [6], The pathogenesis of TINU is not clear, but it is thought to be the result of an autoimmune process that might involve humoral and cellular autoimmunity [2,11]. Renal tubular and ciliary body epithelia share some similar functions, such as those pertaining to electrolyte transporters sensitive to carbonic anhydrase inhibitors.…”