Objective Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management.

Methods Patients diagnosed with pSS-FS via renal biopsy at Peking Union Medical College Hospital from 1993 to 2024 were enrolled. Data collected included age, sex, clinical symptoms (xerostomia, xerophthalmia, skin purpura, arthralgia, polyuria, and systemic symptoms), laboratory findings serum immunoglobulin G (IgG) and IgM, complement (C3, C4), antinuclear antibody, anti-Sjögren's syndrome-associated antigen A antibody (SSA), anti-SSB antibody, 24-hour urinary protein quantification, tubular proteinuria, serum creatinine, serum electrolytes, treatment, and follow-up information. Systematic assessments included the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score, pulmonary involvement (including non-infectious interstitial pneumonia, pulmonary fibrosis, pulmonary hypertension, etc.), hematological involvement (anemia, leukopenia, thrombocytopenia), etc. Efficacy evaluations encompassed improvements in immunological parameters, renal function, and tubular function. Group comparisons were performed using chi-square/Fisher's exact tests, t-tests, or non-parametric tests. Changes over time were analyzed using paired t-tests, and repeated measures during follow-up were assessed using mixed linear models.

Results A total of 38 patients with pSS-FS were included, with 37(97.4%) being female. The median age at pSS diagnosis was 43(37, 57) years. Xerostomia (76.3%) and xerophthalmia (71.1%) were the predominant clinical symptoms. The most common renal tubular dysfunctions were generalized aminoaciduria (96.9%), tubular proteinuria (96.0%), and hypokalemia (94.7%). The median eGFR was 52.57(32.04, 76.10)mL/(min·1.73 m²), with 60.5% (23/38) of patients having an eGFR below 60 mL/(min·1.73 m²).After six months of immunosuppressive therapy, including moderate-to-high-dose glucocorticoids, significant improvements were observed in immunological parameters (improvement rate: 69.2%), renal tubular function (89.5%), and renal function (44.4%). Following immunosuppressive treatment, the median eGFR increased from 54.95(33.06, 76.10)mL/(min·1.73 m²) to 65.56(56.24, 83.58)mL/(min·1.73 m²).Compared to patients with normal or mildly impaired baseline eGFR ≥ 60 mL/(min·1.73 m²), those with significantly decreased baseline eGFR < 60 mL/(min·1.73 m²) were older (46 years vs. 37 years), had higher ESSDAI scores (16 vs.13), higher 24-hour urinary protein levels (1.16 g/d vs.0.48 g/d), but lower positivity rates of serum anti-SSA antibody (36.4% vs.86.7%) and anti-SSB antibody (22.7% vs.73.3%). Moreover, this group showed more pronounced renal function improvement after 6 months (58.8% vs.20.0%) and 12 months (66.7% vs.25.0%) of immunosuppressive therapy.

Conclusions This study reports the clinical characteristics of the largest single-center cohort of pSS-FS patients internationally, characterized by varying degrees of proximal renal tubular dysfunction and renal impairment. Timely initiation of immunosuppressive therapy, including glucocorticoids, is crucial, particularly for patients with significantly reduced eGFR, who may experience more substantial renal function improvement.