Remote Ischemic Conditioning in Renal Transplantation - Effect on Immediate and Extended Kidney Graft Function

About 25% of renal transplantations from deceased donors are complicated by
delayed graft function (DGF). DGF increases the risk of rejection and shortens
graft survival, thus implying heavy costs to the affected individuals as well
as on society.

DGF is caused by ischemia and reperfusion injury (IR-injury) of the renal
tissue. Remote ischemic conditioning (rIC) is a technique where repetitive,
short term ischemia is induced in one tissue, e.g. an arm or a leg, leading to
systemic protection against ischemia elsewhere in the body. Clinical studies
have shown, that rIC following acute myocardial infarction and before
revascularisation, reduces the myocardial damage. The Aarhus group has used
rIC in a porcine kidney transplantation model involving brain dead donors and
showed that rIC improved renal graft perfusion and glomerular filtration rate
(GFR).

The purpose of the CONTEXT study is to investigate whether rIC can improve
immediate and long term renal graft function after transplantation from
deceased donors.
The initial rate of decline in plasma creatinine and the need for dialysis post
transplantation, delayed graft function (DGF) constitute the primary endpoint .
The method for describing the rate of creatinine decline has been established
in corporation with a statistician and is based on data from earlier
transplanted patients. The goal is a rate of decline of 30% more in the rIC
group, a goal considered clinically relevant. With a power of 0.8 a total of
200 patients are needed.

Investigate wether rIC, a simple, non-invasive procedure which could be easily
implemented in clinical care, can improve immediate and long term kidney graft
function after transplantation from deceased donors

investigator initiated, randomised double-blinded, interventional study

rIC is performed on the opposite thigh of graft placement by four cycles of 5
min ischemia induced by a tourniquet inflated to 250 mmHg. Each cycle is
separated by 5 min of free blood flow. The sham procedure consists of a
pressure of 20 mmHg blocked by a pean on the tube connecting to the tourniquet.

The tourniquet placed on the contrallateral leg in order to induce the rIC is
used in other circumstances, mainly at orthopedic operations, and it is
designed to create bloodless field by inflating it to 250-300 mmHg. With a
prolonged usage over 1-2 hours with constant ischemia, light skin damages can
occur if the skin was folded under a wrongly applied tourniquet. In the rIC
protocol the tourniquet is inflated to 250 mmHG for 5 minutes and than deflated
for 5 minutes. This cycle will be repeated four times. No risks are assessed
for the patient by rIC, since the procedure is short and interrupted by free
flow of blood.
The rIC intervention is not associated with any discomfort for the patient who
is anaesthetised during the procedure.
Two routine biopsy*s during the procedure are taken according to standard
institutional guidelines and are a routine procedure during kidney
transplantation in our hospital. A piece of this material will be used for
analysis. . A biopsy has a small risk of bleeding, as do all biopsies. When so
occur it will be sutured by the surgeon according to standard institutional
guidelines. Taking of biopsies do not have negative consequences on kidney
function
Blood and urine samples at the ward are taken together with standard samples
whenever possible, and are not expected to give further risks or discomfort.
The extra blood samples during operation are taken from the arterial line
placed in the arteria radialis according to standard institutional guidelines.
The total volume of bloodsamples taken is 134 ml. Urine samples are taken from
the catheter bag and are non invasive.
GFR measurement at 3 months and one year followup are standard of care