#6543 TUBULOINTERSTITIAL NEPHRITIS AND UVEITIS (TINU) SYNDROME: A REPORT OF 6 CASES WITH RENAL BIOPSY AND ELECTRON MICROSCOPY EVALUATION.
Authors: Palamaris Kostas , Petrakis Ioannis , Dermitzaki Kleio , Pleros Christos , Kroustalakis Nikos , Destouni Maria , Stofas Anastasios , Paliouras Christos , Theochari Irene , Sarantis Panagiotis , Theodoropoulou Eleni , Stylianou Kostas , Gakiopoulou Harikleia 
Published: June 2023

Abstract

Background and Aims
Tubulointerstitial nephritis with uveitis (TINU) syndrome is a rare, but probably under-diagnosed, immune-mediated clinical entity, characterized by simultaneous renal and ocular manifestations Diagnosis requires exclusion of all other causes of tubulointerstitial nephritis (TIN). We present six patients with clinical, laboratory and renal biopsy findings consistent with TINU syndrome

Method
Medical records review. All patients underwent renal biopsy. Histochemical (pas, masson, silver, Congo-red) and immunohistochemical stains for immune cell populations (CD3, CD20, CD4, CD8, PGM1, CD138) and for the assessment of β2-microglobulin were conducted. Electron microscopy (ΕΜ) was also performed.

Results
All our patients experienced ocular and renal manifestations, defined by bilateral uveitis, photosensitivity, and decline of renal function. In some patients, increased serum creatinine was accompanied by non-nephrotic range proteinuria, glucosuria or “full blown” Fanconi syndrome. The rest of the laboratory evaluation was normal apart from the presence of elevated erythrocyte sedimentation rate and urine β2-microglobulin. Follow-up, ranged from 18 months to 10 years. Histological evaluation revealed interstitial inflammatory infiltration consisting of lymphocytes, with a T-cell predominance, along with several macrophages. Inflammation severity varied, with some showing scarce foci of immune cell clusters, while others demonstrated a dense, diffuse interstitial infiltration. Interestingly, in two cases, non-necrotic, ill-defined granulomas were detected. Tubulitis was also encountered in some patients. A divergence was noted regarding chronicity index, with different levels of tubular atrophy, interstitial fibrosis and global glomerulosclerosis among different cases. β2-Microglobulin immunohistochemical evaluation revealed diminution of cytoplasmic staining in tubular epithelial cells compared to control kidneys. A notable finding derived from ΕΜ was the presence, in one patient, of scattered granular electron-dense-deposits along tubular basement membranes. First-line treatment included steroids, supplemented in some cases by additional immunosuppressive agents. Three patients experienced partial or complete response. Progressive renal damage was observed in a case with severe chronic lesions and persistence of inflammation-triggering factor (illicit substance).

Conclusion
Our cases seem to represent progressive stages within the continuum of disease evolution. Patients with more prominent inflammation might represent a more initial state, while those with more severe chronicity index, probably depict more advanced stages. While the predominance of T-cells predicates a cell-mediated autoimmune mechanism, as the driving force of the disease occurrence, the presence of immune-complexes in more advanced stages might indicate the involvement of humoral immunity as a late event during disease course.