PROJECT SUMMARY/ABSTRACT This proposal details work for the third cycle (2023-2028) of the Chronic Kidney Disease Prognosis Consortium (CKD-PC). A global public health problem, CKD affects >10% of the world population and is a leading cause of death. The CKD-PC – a global group of ~300 investigators representing >100 cohorts with >30 million individuals from >40 countries – has played an important role in facilitating major advances in the staging of CKD, the identification of surrogate endpoint for clinical trials, and the establishment of a range of risk tools for use in clinical care (ckdpc.org). The CKD-PC uses an efficient, fluid consortium structure, centralized analytics, and innovative meta-analysis methods to advance epidemiologic research in CKD prognosis at the highest level of rigor, productivity, and clinical impact. In this phase, we aim to inform guidelines in kidney disease with evidence on CKD prevalence and progression; elucidate the role of CKD in the risk of heart failure, arrhythmias, infections, cancer, frailty, and dementia; and evaluate the performance of kidney and CKD-related risk tools in different clinical settings. Current challenges include: quantifying the implications of the 2021 CKD- EPI equations world-wide; determining when and how often cystatin C should be tested; and identifying situations in which local adaptations of risk calculators for kidney and CKD-related outcomes are warranted. We will work to continue to increase regional representation, enhancing generalizability, and to incorporate additional clinical trials in order to map observed risks to real-world data to inform guideline-recommended thresholds for treatment. We remain flexible and efficient in responding to high priority topics set forth by guideline organizations and regulatory bodies such as the US Food and Drug Administration, and for collaboration with other consortia, including the Global Burden of Disease. Our overarching aim is to improve the health of patients with or at risk for CKD.