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In rheumatology, kidney stones are usually associated with gout or psoriatic arthritis due to hyperuricemia.
Recent studies, however, show that patients with rheumatoid arthritis also have nearly twice the risk for kidney stones. Both conditions are linked to systemic inflammation, with higher systemic immune-inflammatory index values correlating with increased kidney stone risk.
RA is marked by elevated TNF, IL-1, and IL-6, which drive RANK expression and osteoclast activation, contributing to osteoporosis (OP). Kidney stones are also tied to OP and low bone mineral density, often via shared mechanisms such as hypercalciuria.
A key player in both diseases is osteopontin (OPN), a bone-derived phosphoglycoprotein. In RA, OPN promotes inflammatory cell recruitment, Th1 differentiation, osteoclast activation, and synovial proliferation, leading to joint damage. In kidney stones, OPN supports crystal adhesion and aggregation in renal tubules, alters epithelial integrity, and fosters inflammation and fibrosis.
Glucocorticoids, long used in RA, add another layer of complexity. Although effective anti-inflammatories, glucocorticoids contribute to secondary OP. Their main mechanism is induction of Annexin A1 (lipocortin I), a Ca2+-dependent phospholipid-binding protein. Annexin A1 suppresses phospholipase A2, blocking prostaglandin and leukotriene synthesis, and broadly inhibits leukocyte-driven inflammation.
However, under high-calcium conditions, increased Annexin A1 expression in renal tubular cells can enhance calcium oxalate crystal adhesion, promoting kidney stone formation. Interestingly, caffeine consumption reduces kidney stone risk, possibly by shifting Annexin A1 from the tubular surface into the cytoplasm, reducing its crystal-binding activity.
Together, these findings highlight shared pathways between RA and kidney stones. Osteopontin and Annexin A1 represent promising targets for future mechanistic studies and therapeutic strategies.
David A. McLain, MD, MACR, FACP, FRCP
Executive director, Alabama Society for the Rheumatic DiseasesSymposium director, Congress of Clinical Rheumatology
Disclosures: McLain reports no relevant financial disclosures.
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