Background: Renal involvement in primary Sjögren’s syndrome (SS) is uncommon but clinically consequential. Prior studies have been limited by small samples and incomplete biopsy data. We evaluated a large biopsy-confirmed cohort to characterize clinicopathologic features of SS with renal involvement and identify predictors of renal recovery and long-term outcomes. Methods: We retrospectively identified adults with SS and kidney biopsy at Mayo Clinic (2012–2025). Clinical, laboratory, and histologic data were extracted. Predictors of complete renal recovery within 6 months, defined as serum creatinine (sCr) returning to within 25% of baseline or <1.4 mg/dL if baseline was unknown, were evaluated using logistic regression. Cox regression assessed long-term risk of a composite endpoint: newly developed or progressive chronic kidney disease (CKD), end-stage kidney disease, or all-cause mortality. Results: Fifty-six patients were included (median age 57 years; 91% female). Extraglandular manifestations occurred in 76%, and baseline CKD in 65%. Median sCr at baseline and biopsy were 1.3 and 1.6 mg/dL, respectively. Anti-Ro/SSA was positive in 80%. Low C3 occurred in 14% and low C4 in 25%. Tubulointerstitial nephritis was the predominant lesion (71%). Moderate/severe interstitial fibrosis/tubular atrophy and arteriosclerosis were present in 36% and 41%, respectively. Immunosuppressive therapy was applied in 84%. Complete recovery occurred in 67%. Over a median 3.9 years (IQR 1.4-7.2), 43% reached the composite endpoint. Baseline sCr ≥2mg/dL, 24-hour proteinuria ≥1g, and presence of segmental glomerulosclerosis were associated with lower odds of recovery (OR=0.16, 0.13 and 0.11, P =0.02, 0.001 and 0.008, respectively) and higher long-term risk (HR=4.51, 2.92 and 3.52, P =0.002, 0.01 and 0.02, respectively). Moderate/severe arteriosclerosis also increased long-term risk (HR=2.56, P =0.03). Conclusions: In biopsy-confirmed SS-related renal involvement, the severity of kidney dysfunction and the extent of chronic glomerular and vascular injury strongly predict renal prognosis. Early detection and targeted management of high-risk features may improve long-term renal outcomes.
Thongprayoon et al. (Fri,) studied this question.