Spondyloarthropathy: an independent risk factor for kidney stones.

PURPOSE: To better stratify risk and to verify previous prevalence reports, we conducted a retrospective cohort study comparing the lifetime incidence of nephrolithiasis in patients with spondyloarthropathies (SpA) and rheumatoid arthritis (RA). PATIENTS AND METHODS: Patients with SpA or rheumatoid factor-positive RA were identified from the rheumatology clinics of two Veterans Affairs hospitals and the University of Minnesota. Among them, 168 were confirmed to meet the American College of Rheumatology criteria and gave informed consent to participation. They were sent a survey regarding their rheumatologic diagnosis, coexistent conditions, medications, and history of kidney stones. Of the total, 143 patients responded and met the criteria for analysis. Rheumatoid arthritis patients were age and sex matched with SpA patients as controls. RESULTS: Populations were similar in all categories except that RA patients were more likely to have used prednisone (P < 0.001), bisphosphonates (P < 0.001), and calcium supplementation (P = 0.03). Kidney stones were reported by 23 (29.11%) of the 79 SpA patients compared with 8 (12.5%) of the 64 RA patients (chi (2) = 5.75; P = 0.025). Subgroup analysis of self-reporting stone history in 85 patients was found to be reliable on imaging review (sensitivity 82%; specificity 100%). CONCLUSIONS: Self-reporting of kidney stones by patients is a reliable measure. Despite adjusting for medication use and matching two similar arthritic populations, patients with SpA had a higher incidence of kidney stones than those with RA. This finding suggests that SpA is an independent risk factor for nephrolithiasis. Future studies will evaluate urinary risk factors and polymorphisms in the ANKH gene that may predispose to stone formation in this high-risk group.

Linked deficiencies in extracellular PP(i) and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression.

Osteopontin and PP(i) both suppress hydroxyapatite deposition. Extracellular PP(i) deficiency causes spontaneous hypercalcification, yet unchallenged osteopontin knockout mice have only subtle mineralization abnormalities. We report that extracellular PP(i) deficiency promotes osteopontin deficiency and correction of osteopontin deficiency prevents hypercalcification, suggesting synergistic inhibition of hydroxyapatite deposition. Nucleotide pyrophosphatase phosphodiesterase (NPP) isozymes including PC-1 (NPP1) function partly to generate PP(i), a physiologic calcification inhibitor. PP(i) transport is modulated by the membrane channel protein ANK. Spontaneous articular cartilage calcification, increased vertebral cortical bone formation, and peripheral joint and intervertebral ossific ankylosis are associated with both PC-1 deficiency and expression of truncated ANK in ank/ank mice. To assess how PC-1, ANK, and PP(i) regulate both calcification and cell differentiation, we studied cultured PC-1 -/- and ank/ank mouse calvarial osteoblasts. PC-1 -/- osteoblasts demonstrated approximately 50% depressed NPP activity and markedly lowered extracellular PP(i) associated with hypercalcification. These abnormalities were rescued by transfection of PC-1 but not of the NPP isozyme B10/NPP3. PC-1 -/- and ank/ank cultured osteoblasts demonstrated not only comparable extracellular PP(i) depression and hypercalcification but also marked reduction in expression of osteopontin (OPN), another direct calcification inhibitor. Soluble PC-1 (which corrected extracellular PP(i) and OPN), and OPN itself (> or = 15 pg/ml), corrected hypercalcification by PC-1 -/- and ank/ank osteoblasts. Thus, linked regulatory effects on extracellular PP(i) and OPN expression mediate the ability of PC-1 and ANK to regulate calcification.