Proteinuria testing among patients with diabetes mellitus is associated with bladder cancer diagnosis: potential for unmeasured confounding in studies of pioglitazone and bladder cancer

作者：Lewis James D^*; Habel Laurel; Quesenberry Charles; Mamtani Ronac; Peng Tiffany; Bilker Warren B; Hedderson Monique; Nessel Lisa; Vaughn David J; Strom Brian L; Ferrara Assiamira

来源：Pharmacoepidemiology and Drug Safety, 2014, 23(6): 636-645.

DOI：10.1002/pds.3619

• bladder cancer
• diabetes mellitus
• thiazolidinedione
• pharmacoepidemiology
• proteinuria

BackgroundThe observed association between pioglitazone and bladder cancer could be causal or because of bias in the design of prior studies. We hypothesize that proteinuria testing may lead to detection bias if routine test results for proteinuria lead to a full urinalysis. MethodsWe reanalyzed patients with diabetes mellitus within Kaiser Permanente Northern California. Logistic and Cox regression adjusted for age, sex, race, and smoking were used to assess the association of proteinuria testing with pioglitazone use, subsequent full urinalysis, and diagnosis with bladder cancer. ResultsPatients treated with pioglitazone were more likely than others with diabetes to undergo testing for proteinuria (p%26lt;0.001). The odds of positive tests for proteinuria were higher among pioglitazone-treated patients (OR=1.41, 95%CI 1.36-1.46). A positive proteinuria test was associated with increased odds of completing a urinalysis in the following 6months (OR=1.78, 95%CI 1.73-1.85). Negative and positive proteinuria test results were inversely (hazard ratio (HR) 0.63, 95%CI 0.52-0.75) and positively associated (HR 2.45, 95%CI 2.12-2.82) with bladder cancer risk, respectively. Adjustment for negative and positive proteinuria testing reduced the magnitude of association between pioglitazone and bladder cancer by only 5 to 10% (ever-exposed HR: from 1.06 to 1.01 and %26gt;4years exposure HR: from 1.38 to 1.28). ConclusionsProteinuria testing may be a confounder in studies of pioglitazone and bladder cancer but does not fully explain the association between pioglitazone and bladder cancer in this cohort. Optimal adjustment for proteinuria testing likely requires knowledge of the test result.

• 出版日期2014-6
• 单位rutgers