Kidney Involvement in Primary Sjögren Syndrome: Focus on Tubulointerstitial Nephritis

Background and Objectives: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with heterogeneous extraglandular involvement, including the kidney. Tubulointerstitial nephritis (TIN) is the hallmark kidney lesion of pSS, but its clinical and histological features, compared with other causes of TIN, remain incompletely characterized. This study aimed to describe the clinical, laboratory, and histological features of biopsy-proven pSS-associated TIN (pSS-TIN) and to compare them with TIN of other etiologies. Materials and Methods: We retrospectively analyzed native-kidney biopsies (2015-2025) with histological diagnosis of TIN, from adult and pediatric patients, excluding cases with neoplasms or concomitant acute glomerular injury. Clinical, laboratory, and histological data of pSS-TIN patients were compared with other TIN etiologies using the Mann-Whitney U test, Fisher's exact test, and Spearman's correlation; p < 0.05 was significant. Results: Among 690 native-kidney biopsies, 35 showed TIN; after excluding cases with glomerular involvement, 14 patients with pSS-TIN and 16 patients with no-pSS-TIN patients were analyzed. All pSS-TIN patients were female, and biopsy occurred after a significantly longer interval from disease diagnosis than patients with no-pSS-TIN (p = 0.018). Acute kidney injury was less frequent (p = 0.021) and kidney function was better preserved in pSS-TIN, while the urea-to-creatinine ratio was similar between groups. Standard urinalysis was abnormal in only about half of patients in both groups. Longer disease duration correlated with lower eGFR in pSS-TIN (p = 0.033). Predominantly chronic histological damage was associated with higher proteinuria (p = 0.037) across the entire cohort, and germinal-center-like lymphoid structures were observed in two pSS-TIN patients with extensive acute damage. In our cohort, no statistically significant association was detected between kidney function indices and the severity of chronic damage. Conclusions: In this biopsy-based cohort, pSS-TIN showed a predominantly chronic presentation, less acute kidney injury, and a longer diagnostic interval than other TIN forms. Routine urinary and functional parameters may not reliably reflect chronic tubulointerstitial damage, highlighting the importance of careful renal screening and timely nephrological assessment, with kidney biopsy when clinically indicated.