Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults

Abstract

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8–77.4) with a median serum creatinine level at 207 μmol/L (range 100–1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m2 (range 2–73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10–2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m2 (range 17–119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = −0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = −0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis.

Tubulointerstitial nephritis and uveitis

“…Interstitial nephritis is usually associated with systemic symptoms such as fever, weight loss, and fatigue, but may be asymptomatic. The renal course is thought to be independent from ocular disease as neither the severity nor the prognosis of nephritis is influenced by the presence of uveitis [3*,9]. Asymptomatic uveitis in the context of pediatric tubulointerstitial nephritis may be under-recognized, with one prospective study identifying uveitis in 50% of patients with biopsy-proven interstitial nephritis in [10].…”

“…However, no guidelines or recommendations for proactive ocular screening in patients with interstitial nephritis have been made to date. TINU has not been identified with higher frequency in any ethnic group [5], and gender is no longer believed to contribute to disease predisposition [2,3*,5,6**,8]. In addition to bilateral anterior chamber cell and flare, posterior synechiae, cystoid macular edema, disc edema (especially in the young), elevated intraocular pressure, and cataract are common ocular complications found in patients with TINU and may be seen at presentation [2,5,11].…”

“…Subsequent to initial descriptions, reports of TINU cases of many ages [2,3*] with a broad range of ocular manifestations including intermediate and panuveitis has challenged early classification [2,3*,5,6**,12-14**]. Some of the first reports of posterior segment involvement included isolated macular and disc edema [5], which are manifestations that would not be classified as posterior uveitis under the Standardization of Uveitis Nomenclature (SUN) [15].…”

“…Some of the first reports of posterior segment involvement included isolated macular and disc edema [5], which are manifestations that would not be classified as posterior uveitis under the Standardization of Uveitis Nomenclature (SUN) [15]. However, more recent reports using SUN criteria have identified TINU patients with intermediate and panuveitis [3*,6**,14**] suggesting that these presentations could have been previously underappreciated. Other rare descriptions of posterior findings in the most recent literature include small hypopigmented chorioretinal scars [14**,16], delayed multifocal choroiditis [17], acute posterior multifocal placoid pigment epitheliopathy [18], choroidal neovascular membranes [19], and neuroretinitis [14,20].…”

“…Since the first description in 1975, tubulointerstitial nephritis and uveitis syndrome (TINU) has become increasingly recognized as not only an important cause of uveitis in the pediatric and young adult age-groups, but also in older adults [1-3*]. It comprises approximately 1–2% of cases in subspecialty practices, but may represent up to a third of bilateral acute-onset anterior uveitis in patients younger than 20 [2,4-7**].…”