Kidney transplant; Medication non-adherence; Immunosuppressive therapy; Psychometric scale, Factor analysis, Questionnaire design, Reliability and validity.

Introduction: Non-adherence to immunosuppressive therapy after kidney transplantation is an important factor for rejection and graft loss. Identifying nonadherence related to use of immunosuppressants is essential for treatment, however, it is not uncommon for this to occur with irreparable damage to the graft. Therefore, the prior identification of patients susceptible to this non-adherence would enable the adoption of preventive measures. However, clinical instruments have not yet been developed for this purpose. Objective: To develop and validate a psychometric scale for the assessment of propensity to non-adherence to immunosuppressant therapy in pre-kidney transplant patients. Methodology: Multicenter, prospective, observational, longitudinal and analytical study in candidate patients for kidney transplant of both sexes, over 18 years old. To develop the

psychometric scale, a set of items expressing patient statements were compiled, obtained through a literature review, focus group and an expert panel. The pilot questionnaire was administered to 541 patients from 13 healthcare centers, of which 154 repeated the questionnaire approximately 12 months later. The final questionnaire was obtained by exploratory factor analysis and internal validation included analysis of internal consistency reliability, test-retest reliability and convergent validity assessed by differentiation by known groups. For external validation, 381 patients with already scheduled surgery were included in six transplant centers and were observed in the pre-transplant and in months 3, 6 and 12 post-transplant for evaluation of criterion validity, by comparison with two medication non-adherence scales, and validity predictive of non-adherence, assessed by a combination of 3 methods (self-report, serum level of immunosuppressants and drug

withdrawal from the pharmacy). Results: The final questionnaire, called Kidney AlloTransplant Immunosuppression Therapy Adherence (KATITA) Questionnaire, consisting of 25 items in 3 uncorrelated dimensions, showed good internal consistency reliability (Cronbach's alpha 0.81). The 3 dimensions and respective Cronbach's alpha were “Carelessness” (14 items, 0.81), “Skepticism” (6 items, 0.57) and “Concern” (5 items, 0.62). Test-retest reliability showed an intraclass correlation coefficient of 0.62 (moderate agreement). The scale showed convergent validity. The longitudinal study included 381 patients and confirmed the multidimensional structure of the scale and criterion validity. The predictive validity of the scale was confirmed by an area under the ROC curve of 0.68, sensitivity of 59,8%, specificity of 68,2%, and positive predictive value of 71,8%. Conclusion: The KATITA-25 questionnaire is the first validated psychometric questionnaire assessing predisposition to nonadherence to immunosuppressive medication in candidate patients to kidney transplantation in the pre-kidney transplant setting.