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Faculty of Medical Sciences

In-Situ Kidney preservation with chilled-ice-mixed solution (CHIMS) in swine model of Death Cardiac Donor (DCD) /The effect of prophylactic treatment with Sildenafil on an acute kidney injury in a rat model

Groen, J.W. (Jan-Willem) (2013) In-Situ Kidney preservation with chilled-ice-mixed solution (CHIMS) in swine model of Death Cardiac Donor (DCD) /The effect of prophylactic treatment with Sildenafil on an acute kidney injury in a rat model. thesis, Medicine.

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Abstract

This is the report, and final result of my scientific internship, which I conducted in the department of Transplantation and Nephrology of the Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubiran in Mexico City, Mexico. I originally was assigned to the protocol regarding the effects of a chilled ice-mixed solution on the preservation of the kidney during the deceased donor (DCD) transplantation, under the supervision of Dr. Aczel. However, due to unforeseen logistic and financial reasons we were unable to conduct a sufficient number of procedures needed to acquire enough results. In accordance with my faculty tutor Prof. dr.W. van Son and the chairman of the committee assigned to the grading of the scientific internship Prof. dr. G. ter Horst I would do my utmost best to try to go through all the steps regarding the scientific internship. In order to do so, I decided to take on an additional protocol regarding the effects of Sildenafil on acute ischemic kidney damage, under the supervision of Dra. N. Bobadilla. Therefore, this report is the combination of both protocols, which, in my opinion share, the common nominator “prevention of kidney damage” weather done by way of cooling or by way of the prophylactic administration of the 5-phosphodiesterase inhibitor Sildenafil. End-stage renal failure is a worldwide problem, which increases mortality and morbidity, as well as social costs. The kidney-transplantation greatly increases the chances of a normal life for the patient with end-stage renal failure, because it relieves him of the need for and risks of dialysis. The most effective way of transplanting a kidney is from a living, heart-beating donor, an option most patient don’t have. Therefore most kidney’s transplanted today are from a deceased, heart-beating donor. During the process of harvesting and transplantation of this kidney, the organ is subjected to various ways of damaging stress from which ischemia is widely considered one of the most important. Cooling decreases the process of ischemia by lowering the metabolism, and the prophylactic administration of Sildenafil is believed to decrease the damage done to the kidney by the ischemia and the subsequent reperfusion, by ways of preventing vasoconstriction and the fall in the renal blood-flow, leukocyte activation and direct vasodilatory effects. For this purpose we included twenty-one male Wistar rats which were divided in 2 control groups and 2 groups that received bilaterally induced kidney ischemia. The rats in one of these 2 groups received a single dose of Sildenafil 90 min before the procedure, and important clinical parameters were measured 24 hrs after the ischemic period. Significant differences were found between the groups in the levels of proteinuria as well as the kidney-damage marker Hsp72. In the other variables no significant levels of difference between groups could be achieved, although we saw a tendency towards the protective effects of Sildenafil on the development of kidney damage after a period of ischemia and reperfusion. More rats and different ischemia times as well as different doses of Sildenafil are needed to evaluate the usefulness of Sildenafil as a prophylactic treatment, to prevent acute kidney injury.

Item Type: Thesis (Thesis)
Supervisor name: Faculty tutor: and Son, Prof. dr. W.J. van
Supervisor name: Tutor: and Vilatoba Chapa Dr. M. and Bobadilla, Dr. N. and Research Tutor: and Sánchez Cedillo, Dr. I. Aczel and Rodriguez Romo, Dr. Roxanna and Instituto Nacional de Ciencias Médicas y Nutrición (INCMN) and Universidad Nacional Autónoma de México
Faculty: Medical Sciences
Date Deposited: 25 Jun 2020 10:59
Last Modified: 25 Jun 2020 10:59
URI: https://umcg.studenttheses.ub.rug.nl/id/eprint/1927

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