The stages and grades assigned to LY2835219 CDK inhibitor tumours may therefore differ between the studies included in the meta-analysis. This could be problematic for pT1 tumours, because some pTa tumours may have been overstaged and classified as pT1 tumours. This meta-analysis provides a good example of the effect of confounding factors that are not taken into account. Such factors may not only modify the magnitude of any association, but also create spurious associations. Larger sample sizes and more detailed data are therefore required for a valid statistical analysis. In such conditions, meta-analysis is an effective approach, making it possible to draw reliable conclusions. However, metaanalyses can only take into account the confounding factors that were actually measured. Other unknown variables may affect the relationship between the pathway and disease severity and remain undetected. All the publications retained for this analysis had a high quality of reporting, making it possible to extract the relevant information. Despite the known weaknesses of meta-analysis, the large sample and the homogeneity of the results after adjustment add weight to our conclusions: we found that FGFR3 and TP53 mutations occurred independently when stage and grade were taken into account, and that the frequency of TP53 mutation was high in pT1G3 and pT2-4 tumours, regardless of the presence or absence of FGFR3 mutations in these tumours. Thus, TP53 mutations can occur in Ta pathway tumours, when these tumours progress. However, the time frame of TP53 mutation differs considerably between the two pathways: TP53 mutations occur before basement membrane invasion in the carcinoma in situ pathway, whereas they probably occur after or during basement membrane invasion in the Ta pathway. Our findings also indicate that care is required in the analysis of bladder tumours, as both pathways of tumour progression for bladder cancers must be taken into account when interpreting data. Cardiovascular disease is the most common cause of morbidity and mortality in patients with end-stage renal disease. Since traditional risk factors, such as advanced age, hypertension, diabetes, smoking, and dyslipidemia, cannot fully account for the high prevalence of cardiovascular disease, uremia-related factors, including inflammation and oxidative stress, have been implicated in the pathogenesis of cardiovascular disease in ESRD patients. Recently, accumulating evidence has shown that disturbances in calcium-phosphorus metabolism also play a pivotal role in cardiovascular disease, partly via the development of vascular calcification. Vascular calcification is not uncommon in general elderly population; 20–30% of people older than 65 years have calcification in the aorta. In patients with chronic kidney disease, this proportion is reported to be substantially higher; more than one half of CKD patients even before the start of dialysis and up to 80–90% of ESRD patients have some form of vascular calcification. Previous studies have revealed vascular calcification is independently associated with all-cause and cardiovascular mortality in both general population and ESRD. Moreover, since vascular calcification progresses rapidly in dialysis patients, ESRD patients with the progression of vascular calcification are demonstrated to have an unfavorable outcome. Therefore, not only the identification of vascular calcification but also risk stratification of patients by the changes in vascular calcification may be important for clinicians to manage dialysis patients. To date, a number of techniques are available to detect vascular calcification.