Thomas Willis (1621 – 1675): First steps into kidney function

This review analyzes the pivotal but underrecognized contribution of Thomas Willis (1621 - 1675) to the foundations of kidney function in the 17^th century. By comparing his early work <i>De Urinis</i> (1659), which interpreted urinary diagnosis through humoral traditions, with his subsequent <i>Pharmaceutice Rationalis</i> (1674 - 1675) we document a paradigm shift: progress from considering the kidney a passive filter to proposing it as an active regulatory organ that balanced urinary salts through tubular function. Building on the cardiac pump and blood circulation model of William Harvey and the tubular structure of the kidney of Lorenzo Bellini, Willis rejected the Galenic physiology that the kidney attracted blood because it was in its nature to do so in favor of a mechanical model of "straining or percolation" driven by the force of circulating blood. Willis also considered diabetes a blood disorder rather than a kidney disease, noting that diabetic urine differed from imbibed fluids being sweet "as it were imbued with Honey or Sugar". These conceptual advances - developed without microscopic evidence or chemical analysis - reveal a remarkable inductive reasoning. Documented by subsequent observations, Willis' work established three critical principles: the blood-clearing function of the kidney depends on circulatory dynamics, tubules modify urine composition, and urinary changes reflect systemic physiology rather than just renal pathology. His renal model, though incomplete, provided the first systematic framework for homeostasis that would be developed in the 19^th century. His writings clearly mark the initial but fundamental first steps in the evolution of our current understanding of kidney function.