Isolated perfusion of pig kidney segments to study renal function: a translational model for human kidneys

Isolated kidney perfusion forms the bridge between in vitro and in vivo experiments and is mainly performed with rodent kidneys. It enables the controlled investigation of kidney function without systemic influences and is therefore currently, for instance, considered the gold standard for investigating the regulation of renin release, a central regulator of blood pressure. Renin secretion is controlled by several intrarenal signalling cascades and thus cannot be fully modelled in cell cultures. On the other hand, the in vivo investigation of renin release is confounded by systemic counter-regulatory systemic mechanisms. For ethical and logistical reasons, human kidney tissue has not been used for isolated organ perfusion yet. To reduce the use of rodents and to achieve the translation to larger species, including humans, we developed a method for isolated perfusion of slaughterhouse pig kidney segments. This method allows for future use with human kidney segments obtained from nephrectomies. Pig kidney segments were perfused at constant pressure and renin secretion was determined. The sympathomimetic agent isoproterenol, the Ca²⁺ chelator ethylene glycol tetraacetic acid, the NO-donor S-nitroso-N-acetylpenicillamine and the loop diuretic bumetanide stimulated renin release while angiotensin II suppressed it. These responses were similar to those observed in isolated perfused rodent kidneys, demonstrating that central regulatory mechanisms of renin release are conserved across species and in tissue segments. Moreover, the newly developed model of perfusion of kidney segments of large animals is suitable for the investigation of renin release from human kidneys and provides an ethical method for isolated kidney perfusion in accordance with animal welfare.