A pathophysiologic study of the kidney tubule to optimize organ preservation solutions

Ahmad, Niaz; Hostert, Lutz; Pratt, Julian R.; Billar, Katharine J.; Potts, David J.; Lodge, J. Peter A.
July 2004
Kidney International;Jul2004, Vol. 66 Issue 1, p77
Academic Journal
A pathophysiologic study of the kidney tubule to optimize organ preservation solutions. Background. Tissue damage at the time of organ transplantation has a negative impact on the subsequent success of the procedure, both in the immediate and longer term. Hypothermia is the principal element used to prolong organ viability ex vivo, but paradoxically also induces cellular edema through inhibition of energy-dependent adenosine triphosphatases (ATPases). This induces an electrolyte imbalance that leads to fluid influx and cell swelling. It is important, therefore, that improvements are made in the preservation of ischemic organs to reduce this injury. Methods. This study has applied a novel in vitro system to model cold and warm ischemic-induced renal tubule swelling that characterizes tissue damage in ischemia/reperfusion injury. Biochemical blockade of ATPases in this system using strophanthidin modeled the effects of energy depletion and induced cell swelling. By measuring such tubule swelling and changes to tubular cell volume in isolated rabbit renal proximal tubules, an analysis was made that defined the basis on which an optimal preservation solution may be developed. Results. The data show that our model could reproduce ischemically induced cell swelling and characterized the response at the cellular level of tubules to different components of preservation solutions. The data indicate that an isosmolar, phosphate-buffered, sucrose solution prevented tubule swelling more effectively than Euro-Collins, hyperosmolar citrate, or University of Wisconsin solutions that are in routine clinical use. Conclusion. Future developments in organ preservation may significantly improve transplant outcomes. Our novel analysis forms the basis of future whole-organ studies that ultimately may allow us to propose an optimum platform for improved preservation solutions.


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