Early Kidney Injury Markers in Patients with Seronegative Spondyloarthropathies: A Retrospective Cross-Sectional Comparative Study

Background Patients with seronegative spondyloarthropathies (SpA) are at increased risk of kidney involvement due to chronic inflammation, comorbidities and pharmacotherapy. There is a need for early kidney injury markers (EKIMs) to identify subclinical renal damage, potentially enabling timely intervention and preventing irreversible kidney disease progression. Objectives This study aimed to comprehensively evaluate the concentrations of various established and emerging early kidney injury markers, including Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), Retinol Binding Protein 4 (RBP4), Fibroblast Growth Factor 23 (FGF23), N-acetyl-β-D-glucosaminidase (NAG), and Interleukin-18 (IL-18), in serum and urine of SpA patients without clinically recognized kidney disease, comparing them to healthy controls (HC) and analyzing their associations with SpA subtypes and therapeutic regimens. Methods This was a retrospective cross-sectional comparative study involving 125 patients with SpA (50 with ankylosing spondylitis, 41 with psoriatic arthritis, 34 with non-radiographic spondyloarthritis) and 53 healthy individuals serving as controls. Demographic data, clinical characteristics, and treatment regimens were collected. Serum and urinary levels of EKIMs (NGAL, KIM-1, RBP4, FGF23, NAG, and IL-18) were measured. Statistical analyses, including the Mann-Whitney U test and Kruskal-Wallis test with post-hoc analysis, were performed to assess differences between groups and identify significant associations. Results Our findings indicate subclinical kidney involvement in SpA patients. Serum and urinary KIM-1 levels were significantly elevated in SpA patients compared to HC (serum: p = 0.039; urine: p = 0.024), suggesting early tubular damage. Urinary RBP4 was significantly higher in SpA patients (p = 0.005), while serum RBP4 was significantly lower (p < 0.001) compared to HC, pointing to altered RBP4 handling. Urinary FGF23 concentrations were significantly higher in SpA patients than in HC (p < 0.001), reflecting early tubular stress. Serum NAG levels also differed significantly between SpA and HC (p = 0.018). While no overall differences were observed for urinary NGAL or IL-18 between the SpA group and HC, subgroup analyses revealed specific differences. Notably, psoriatic arthritis patients showed distinct profiles, including lower serum FGF23 (p = 0.028 vs nr-axSpA and HC), lower serum NAG (p = 0.013 vs HC), and higher urinary IL-18 (p = 0.012 vs HC) compared to healthy individuals. Levels of most EKIMs did not significantly differ between patients on first-line versus second-line therapies, except for serum FGF23, which was lower in patients receiving bDMARDs/tsDMARDs (p = 0.018). Conclusions Patients with seronegative spondyloarthropathies without overt kidney disease demonstrate early, subclinical tubular injury and altered biomarker profiles, particularly involving KIM-1, RBP4, FGF23, and NAG. These findings underscore the potential utility of these novel markers in detecting kidney compromise at an early stage in SpA, which is crucial for timely management. Further longitudinal studies are needed to validate the predictive value of these EKIMs for long-term renal outcomes and to explore their role in monitoring disease progression and therapeutic response in SpA.