SummaryBackground and objectives The cross-reactive antigen(s) of tubulointerstitial nephritis and uveitis (TINU) syndrome from renal tubulointerstitia and ocular tissue remain unidentified. The authors' recent study demonstrated that the presence of serum IgG autoantibodies against modified C-reactive protein (mCRP) was closely associated with the intensity of tubulointerstitial lesions in lupus nephritis. The study presented here investigates the possible role of IgG autoantibodies against mCRP in patients with TINU syndrome.Design, setting, participants, & measurements mCRP autoantibodies were screened by ELISA with purified human C-reactive protein in 9 patients with TINU syndrome, 11 with drug-associated acute interstitial nephritis, 20 with IgA nephropathy, 19 with minimal change disease, 20 with ANCA-associated vasculitis, 6 with Sjogren's syndrome, and 12 with amyloidosis. mCRP expression was analyzed by immunohistochemistry in renal biopsy specimens from the 9 patients with TINU syndrome and 40 from disease controls. Frozen normal human kidney and iris were used to demonstrate co-localization of human IgG and mCRP from patients with TINU syndrome with laser scanning confocal microscopy. ResultsThe mCRP autoantibodies were detected in all nine patients with TINU syndrome, significantly higher than that of those with disease controls (P Ͻ 0.05). The renal histologic score of mCRP in TINU syndrome was significantly higher than that in disease controls (P Ͻ 0.05). The staining of mCRP and human IgG were co-localized in renal and ocular tissues. ConclusionsIt is concluded that mCRP might be a target autoantigen in TINU syndrome.
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.
AAN has variant phenotypes with distinct prognosis, which is determined by the variable AA medications. With better understanding of toxic and environmental causes for kidney injury, there would be a better chance to uncover the causal factors of cases of 'CKD without known causes' which is crucial for improving the disease outcomes.
CD with multicentric type and PC or mixed cellularity variant are often associated with renal complications. Thrombotic microangiopathy-like lesions are the most common pathological characteristics. Chemotherapy can reverse kidney damage in most cases.
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