Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study

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 m (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 m (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.

Figure 1

Flow Chart of patients’ corticosteroid treatment.

Figure 2

Kidney lesions of TINU syndrome. (A) Low-power view showing diffuse interstitial inflammation composed of mononuclear cells, lesions of interstitial fibrosis and tubular atrophy, and no glomerular or vascular lesions (hematoxylin and eosin, magnification ×200). (B) Normal glomeruli (hematoxylin and eosin, magnification ×400). TINU = tubulointerstitial nephritis and uveitis.

Figure 3

Evaluation of renal function at 1 y of follow-up in 35 patients with TINU syndrome. (A) Renal prognosis after 1 y of follow-up. The eGFR in the normal renal function group calculated using the MDRD was above 90 mL/min per 1.73 m². The eGFR in the group with stage 2 CKD was between 60 and 90 mL/min per 1.73 m². The eGFR in the group with stage 3 CKD was between 30 and 60 mL/min per 1.73 m². The eGFR in the group with stage 4 CKD ranged from 15 to 30 mL/min per 1.73 m². CKD = chronic kidney disease, eGFR = estimated glomerular filtration rate, MDRD = modification of diet in renal disease, TINU = tubulointerstitial nephritis and uveitis.

Figure 4

Evaluation of the ophthalmological prognosis after 1 y of follow-up according to the dose of oral corticosteroids initially administered in 35 patients with TINU syndrome. Group A corresponds to patients who received oral corticosteroids at 1 mg/kg per d (n = 19); Group B a dose between 0.5 and 0.7 mg/kg per d (n = 10); Group C had no systemic treatment (n = 4). The statistical differences (P) between the groups are shown. (A) Evaluation of the number of relapses of uveitis related to TINU syndrome. The bars correspond to medians and the whiskers to the interquartile range. (B) Evaluation of persistent chronic uveitis related to TINU syndrome. The bars correspond to the percentage of patients. TINU = tubulointerstitial nephritis and uveitis.