son-years. Person years defined as starting at the date of entry into study until first of death, emigration, nephrolithiasis diagnosis or end of study. IQR; interquartile range, IR; incidence rate, CI; confidence interval. doi:10.1371/journal.pone.0113602.t002 Confounders and predictors of nephrolithiasis in AS patients Among AS patients anti-TNF treatment, IBD, and a previous history of NL 
) were identified as predictors of NL during follow-up. 8 / 14 Kidney Stones in Ankylosing Spondylitis When comparing AS patients to general population subjects with adjustment for age, IBD, and prior NL, AS remained a highly significant risk factor with a HR of 2.1. Moreover an even higher risk of NL was found in AS patients treated with antiTNF with a multivariate HR of 3.0 compared to the general population group. When excluding patients and matched subjects with the identified predictors from the analysis, the remaining AS patients had an increased risk of 2.0. Sensitivity analysis In order to control for selection bias and detection bias, various sensitivity analysis were performed. A subgroup analysis showed a persistently increased risk of NL in AS compared to general population subjects in both prevalent AS and incident AS. When excluding patients with prior NL, the risk of de novo NL remained increased for incident AS patients.When excluding AS patients and PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19681699 comparator subjects with observation time less than a year, AS patients still had an increased risk for NL compared to general population. Moreover, when studying the subgroup of patients and comparators having attended hospital care prior to study entry for other common reasons not associated with NL, AS patients remained at increased risks for NL. 9 / 14 Kidney Stones in Ankylosing Spondylitis Discussion This study demonstrates a more than two-fold increased risk of kidney stone diagnosis in AS patients compared to the general population, confirming our prespecified hypothesis. Male sex, prior diagnosis of IBD, prior diagnosis PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19683642 of NL, and patients receiving anti-TNF therapy were identified as predictors of NL in AS patients. These findings are consistent with previously established risk factors of NL. Notably, the risk of NL in AS patients remained more than two-fold increased after adjusting for these confounders. This suggests that AS in itself or through other closely related factors may contribute to the process of kidney stone formation. Comorbidities such as renal insufficiency and calcium metabolic disorders did not significantly predict risk of NL. The crude incidence rate of NL in general population subjects of 2.1/1,000 py found in this study, is comparable to incidence rates reported in other studies on populations in industrialized countries which supports the validity of our findings. In this study we used treatment with TNF-inhibitors as a MedChemExpress K-858 surrogate marker of more severe AS. The fact that patients receiving TNF-inhibitors had a 1.6-fold increased risk of NL compared to other AS patients and 3-fold increased risk compared to general population subjects, suggests that disease severity may be associated with a greater risk for NL. However less likely, we cannot rule out the possibility that TNF-inhibitor treatment in itself increases the risk of NL. Consistently, the various sensitivity analyses supported the increased risk of NL in AS patients. Importantly, incident AS patients without any prior history of NL at baseline had a 1.8 fold increased risk of NL compared to matche
