Research in chronic kidney diseases (CKD) has reached a tipping point not seen in our field for a generation. We finally can develop a comprehensive understanding of the convergence of disease mechanisms driving both the progression to organ failure as well as cardiovascular morbidity and mortality. The Keystone conference will be a critical accelerator for our efforts to save kidneys and lives, by aligning the rapidly progressing knowledge streams within CKD research. We will explore a fundamentally novel view of the kidney’s cellular architecture through the lens of multi-scalar data generated by global kidney tissue atlas networks. We will discuss how the unprecedented deep tissue-level understanding of CKD biology in humans is driving a precision medicine drug discovery pipeline forward, from systems level target identification to definition of appropriate model systems. The impact of pursuing these emerging therapeutic targets will be examined from a molecular and societal level through the interplay of kidney failure with environmental and social determinants of health. We will evaluate successes and failures in the current CKD drug development pipeline and present innovative strategies for next generation trial design. For the first time, CKD trials will be used as discovery engines to define the mode of action of the targeted intervention in humans, using the kidney atlas knowledgebase to close the discovery loop. Immersing investigators in a diverse, rapidly expanding CKD knowledgebase in the Keystone conference setting is expected to generate cross-cutting interventional strategies impacting how we treat kidney disease for years to come.