204 Strengths and limitations Our study had several strengths. First, we used data from the GoYK study, which included real-life data of patients and healthcare professionals from multiple organizations in primary and secondary care organizations. This comprehensive sample closely mirrored the complexity and diversity of Dutch CKD healthcare. Second, we were the first ones to study the cost-effectiveness of an intervention focused on health literacy, an important social determinant of health with notorious negative impacts on chronic diseases, in the CKD setting. Third, we took several methodological decisions to strengthen the validity and robustness of our research, making conservative and evidence-based choices regarding model parameters. Our study also had limitations. First, the effect of GoYK on CKD progression was not assessed directly but estimated using an intermediate outcome, namely hypertension. This increased the uncertainty of our findings, as indirect estimations may fail to account for non-observed variables that might influence the associations, and because they are contingent on model assumptions and limitations. Nevertheless, we employed conservative assumptions when performing the calculation. It is also worth noting that the use of indirect estimation often gives a reliable estimation of the final outcome, the reason why it is commonly used in cost-effectiveness studies[40,46,47]. Second, we analyzed the effect of GoYK on CKD progression via one mediator only and did not take into account other related outcomes, such as cardiovascular diseases[48-50]. This approach could have led to an underestimation of the real health gains. Third, given that the majority of the individuals in GoYK were older and therefore retired, we could not collect information on non-medical costs, such as work absenteeism. This may have underestimated our findings, given that more advanced stages of CKD are related to higher absenteeism[51]. Implications We suggest that healthcare organizations implement GoYK, given its substantial potential for saving costs. However, as this is the first study to assess the costeffectiveness of a health literacy intervention in CKD, these results should be approached with caution. Therefore, GoYK should be implemented, but in
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