Clinicopathologic Features and Prognostic Factors in Biopsy-Confirmed Renal Involvement in Primary Sjőgren Syndrome

Baseline kidney function and chronic structural injury strongly predicted both renal recovery and long-term clinical outcomes. Tubulointerstitial nephritis was the predominant lesion in Sjögren syndrome with renal involvement. Early detection and management of renal involvement in Sjögren syndrome are critical to preventing irreversible kidney damage.

Renal involvement in primary Sjögren syndrome (SS) is uncommon but clinically consequential. Previous 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.

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 end point: newly developed or progressive CKD, ESKD, or all-cause mortality.

Fifty-six patients were included (median age 57 years; 91% female). Extraglandular manifestations occurred in 76% and baseline CKD in 65%. The median sCr at baseline and biopsy was 1.3 and 1.6 mg/dl, respectively. Anti-Sjogren's syndrome antigen A, often linked with Ro ribonucleoprotein 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 (interquartile range, 1.4-7.2), 43% reached the composite end point. Baseline sCr ≥2 mg/dl, 24-hour proteinuria ≥1 g, and presence of segmental glomerulosclerosis were associated with lower odds of recovery (odds ratio=0.16, 0.13 and 0.11, P = 0.02, 0.001 and 0.008, respectively) and higher long-term risk (hazard ratio=4.51, 2.92 and 3.52; P = 0.002, 0.01 and 0.02, respectively). Moderate/severe arteriosclerosis also increased long-term risk (hazard ratio=2.56; P = 0.03).

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.