Background: The growing burden of chronic kidney disease (CKD) places substantial financial pressures on patients, healthcare systems, and society. An understanding of the costs attributed to CKD and kidney replacement therapy (KRT) permits shaping of evidence-based policy to increase awareness of the condition and support healthcare resource allocation. Inside CKD maps and projects the economic burden of CKD across 31 countries/regions from 2022 to 2027.Methods: The Inside CKD microsimulation generated virtual populations using national demographics, relevant literature, and national renal registries for the 31 countries/regions included. Patient-level country/region-specific cost data were extracted via a pragmatic local literature review and under advisement from local experts. Direct cost projections (presented in 2022 US$) were generated for diagnosed CKD (by age, stage 3a–5), KRT (by modality), cardiovascular complications (heart failure, myocardial infarction, stroke), and comorbidities (hypertension, type 2 diabetes).Findings: For the 31 analysed countries/regions, Inside CKD projected that annual direct costs of diagnosed CKD and KRT would increase by 9·3% between 2022 and 2027, from $372·0 billion to $406·7 billion. Annual KRT-associated costs were projected to increase by 10·0% from $169.6 billion to $186·6 billion between 2022 and 2027. By 2027, patients receiving KRT are projected to constitute 5·3% of the diagnosed CKD population, but contribute 45·9% of the total costs.Interpretation: The economic burden of CKD is projected to increase from 2022 to 2027. KRT contributes disproportionately to this burden. Earlier diagnosis and proactive management could slow disease progression, potentially alleviating the substantial costs associated with later CKD stages.Funding: Sponsored by AstraZeneca.Declaration of Interest: SC, MA, AP, M-SW, FSM, JJAA are members of the Inside CKD Scientific Steering Committee and received financial support from AstraZeneca to attend Inside CKD planning and update meetings. SC has received speaker fees or honoraria for advisory board participation from AstraZeneca, Boehringer, Bayer, CSL, and Hansa. JJGS and SB are employees of AstraZeneca. JC-G, AM, and LR are employees of HealthLumen Limited and have received research support from AstraZeneca. Ethical Approval: This study was conducted in accordance with ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines. This study did not require informed consent or institutional/ethical review board approval because this is a non-interventional study based on secondary data use.