Remote Ischemic Preconditioning Living Donor Renal Transplant Protocol
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 19 - Any |
| Updated: | 2/22/2019 |
| Start Date: | July 2, 2014 |
| End Date: | December 30, 2020 |
In this study, patients undergoing live donor kidney transplantation will be allocated to the
control group or remote ischemic preconditioning group (RIPC). RIPC is the utilization of
short periods of ischemia to provide protection of the myocardium or other organ (i.e.
kidney) from a subsequent ischemic event. Before allograft implantation, RIPC will be
accomplished in the recipient and donor by inducing intermittent extremity ischemia through
intermittent inflation of an extremity tourniquet three times for five-minute intervals with
five minutes of deflation between inflation periods. The monitored clinical end points will
include total urine output following kidney reperfusion over five days, plasma creatinine
declination over five days, initiation of dialysis, and development of graft injury.
Magnitude of graft injury is the primary endpoint and will be measured using biochemical
markers, such as, plasma and urinary concentration of neutrophil gelatinase associated
lipocalin (NGAL), IL-18, and KIM-1. The sample size calculation is based on a projected
difference of NGAL levels between the two study arms. Hall et al reported a mean NGAL level
of 49 mg/mL (SD = 37 mg/mL) for a group of patients that had immediate graph function and a
mean NGAL level of 248 mg/mL in a group of patients with slow graft function. (which Hall
reference is this) Based on these data, a conservative estimate of a mean difference between
study groups will be considered 35 mg/mL NGAL. Using these assumptions, an alpha level of
0.05 and 80% power, a sample size of n= 19 per study group will be calculated. By rejecting
our null hypothesis, RIPC may serve as a safe, cost-effective protective strategy to prevent
allograft injury in the clinical setting of live donor kidney transplantation.
control group or remote ischemic preconditioning group (RIPC). RIPC is the utilization of
short periods of ischemia to provide protection of the myocardium or other organ (i.e.
kidney) from a subsequent ischemic event. Before allograft implantation, RIPC will be
accomplished in the recipient and donor by inducing intermittent extremity ischemia through
intermittent inflation of an extremity tourniquet three times for five-minute intervals with
five minutes of deflation between inflation periods. The monitored clinical end points will
include total urine output following kidney reperfusion over five days, plasma creatinine
declination over five days, initiation of dialysis, and development of graft injury.
Magnitude of graft injury is the primary endpoint and will be measured using biochemical
markers, such as, plasma and urinary concentration of neutrophil gelatinase associated
lipocalin (NGAL), IL-18, and KIM-1. The sample size calculation is based on a projected
difference of NGAL levels between the two study arms. Hall et al reported a mean NGAL level
of 49 mg/mL (SD = 37 mg/mL) for a group of patients that had immediate graph function and a
mean NGAL level of 248 mg/mL in a group of patients with slow graft function. (which Hall
reference is this) Based on these data, a conservative estimate of a mean difference between
study groups will be considered 35 mg/mL NGAL. Using these assumptions, an alpha level of
0.05 and 80% power, a sample size of n= 19 per study group will be calculated. By rejecting
our null hypothesis, RIPC may serve as a safe, cost-effective protective strategy to prevent
allograft injury in the clinical setting of live donor kidney transplantation.
All female patients of childbearing age that qualify for this study will receive a urinary
pregnancy test prior to enrollment. Application of a tourniquet will occur after induction of
anesthesia and intubation with minimal possibility of causing discomfort as the patient will
be anesthetized. The tourniquet will be applied preferably to a leg but an arm will be used
if a leg is unavailable. The tourniquet will be inflated for three 5 minute intervals over a
30 minute period of time using the Zimmer A.T.S. 2000 Tourniquet System. Patients will be
randomly allocated to one of two groups. The experimental group will have the tourniquet
inflated on the leg or arm to 200 mmHg. The control group will have the tourniquet inflated
on the leg or arm to only 20 mmHg. An audible timer will be used to help alert investigators
that the tourniquet is in need of deflation after each 5-minute interval. The tourniquet will
be removed after the needed 30 minutes of inflation/deflation to prevent inadvertent
inflation of the tourniquet. Blood and Urine specimens will be labeled with patient name and
medical record number. Urine samples will be taken in the operating room and at 6,12,24,48
hours postoperatively to test for urinary biomarkers at the O'Brien Clinical Research Center.
Blood samples for calculation of serum blood urea nitrogen and creatinine will be
collected/processed/distributed/stored according to current UAB main laboratory guidelines as
this test is routinely ordered on renal transplant patients. Urinary biomarker laboratory
testing samples will be obtained by a bedside nurse placed in a routine urine sample
container and a co-investigator will then bring samples to the laboratory where the samples
will be tested for NGAL, KIM-1, and IL-18. Blood samples will be taken daily for the first 5
days. A blood sample will be taken from the patient at 1 month to determine the serum blood
urea nitrogen level and the creatinine level. The degree of allograft injury will be assessed
by the levels of urinary biomarkers NGAL, IL-18, and KIM-1. Incidence of allograft or
transplanted kidney primary malfunction will be based on urine output during the first three
days after transplantation, the one month serum creatinine concentration, one month estimated
glomerular filtration rate calculated according to diet modification. Additional secondary
endpoints include 90-day mortality, length of ICU stay, and length of hospital stay. There is
a low probability of tourniquet postoperative pain secondary to time of tourniquet inflation
being both intermittent and for a short period of time. Inconvenience includes phone
discussions with researchers/coordinators and preoperative discussions addressing risks and
benefits of the study. Tourniquets will not be placed on extremities with preexisting
arteriovenous fistulas or grafts utilized for hemodialysis. In addition, tourniquets will be
placed after oscillometric blood pressure cuff placement for intraoperative
anesthesia/surgical monitoring to provide adequate patient blood pressure assessment. The
tourniquet will not be placed on the same extremity as the oscillometric blood pressure cuff.
The primary investigator or a co-investigator will be present during times of tourniquet
inflation. The patient will be assessed for complications immediately after tourniquet
removal, in the PACU, and in the ICU/or step down unit. Finally, patient complication
assessment will occur on the transplant floor after effects of anesthesia have completely
resolved within 24 hours of tourniquet application. The extremity will also be assessed for
injury at the 1-month follow up visit.
pregnancy test prior to enrollment. Application of a tourniquet will occur after induction of
anesthesia and intubation with minimal possibility of causing discomfort as the patient will
be anesthetized. The tourniquet will be applied preferably to a leg but an arm will be used
if a leg is unavailable. The tourniquet will be inflated for three 5 minute intervals over a
30 minute period of time using the Zimmer A.T.S. 2000 Tourniquet System. Patients will be
randomly allocated to one of two groups. The experimental group will have the tourniquet
inflated on the leg or arm to 200 mmHg. The control group will have the tourniquet inflated
on the leg or arm to only 20 mmHg. An audible timer will be used to help alert investigators
that the tourniquet is in need of deflation after each 5-minute interval. The tourniquet will
be removed after the needed 30 minutes of inflation/deflation to prevent inadvertent
inflation of the tourniquet. Blood and Urine specimens will be labeled with patient name and
medical record number. Urine samples will be taken in the operating room and at 6,12,24,48
hours postoperatively to test for urinary biomarkers at the O'Brien Clinical Research Center.
Blood samples for calculation of serum blood urea nitrogen and creatinine will be
collected/processed/distributed/stored according to current UAB main laboratory guidelines as
this test is routinely ordered on renal transplant patients. Urinary biomarker laboratory
testing samples will be obtained by a bedside nurse placed in a routine urine sample
container and a co-investigator will then bring samples to the laboratory where the samples
will be tested for NGAL, KIM-1, and IL-18. Blood samples will be taken daily for the first 5
days. A blood sample will be taken from the patient at 1 month to determine the serum blood
urea nitrogen level and the creatinine level. The degree of allograft injury will be assessed
by the levels of urinary biomarkers NGAL, IL-18, and KIM-1. Incidence of allograft or
transplanted kidney primary malfunction will be based on urine output during the first three
days after transplantation, the one month serum creatinine concentration, one month estimated
glomerular filtration rate calculated according to diet modification. Additional secondary
endpoints include 90-day mortality, length of ICU stay, and length of hospital stay. There is
a low probability of tourniquet postoperative pain secondary to time of tourniquet inflation
being both intermittent and for a short period of time. Inconvenience includes phone
discussions with researchers/coordinators and preoperative discussions addressing risks and
benefits of the study. Tourniquets will not be placed on extremities with preexisting
arteriovenous fistulas or grafts utilized for hemodialysis. In addition, tourniquets will be
placed after oscillometric blood pressure cuff placement for intraoperative
anesthesia/surgical monitoring to provide adequate patient blood pressure assessment. The
tourniquet will not be placed on the same extremity as the oscillometric blood pressure cuff.
The primary investigator or a co-investigator will be present during times of tourniquet
inflation. The patient will be assessed for complications immediately after tourniquet
removal, in the PACU, and in the ICU/or step down unit. Finally, patient complication
assessment will occur on the transplant floor after effects of anesthesia have completely
resolved within 24 hours of tourniquet application. The extremity will also be assessed for
injury at the 1-month follow up visit.
Inclusion Criteria:
- > OR = 19 years of age receiving a living donor renal transplant and their donors
Exclusion Criteria:
- < 19 years of age
- No safe extremity to place tourniquet
- Patients with previous muscle, vascular, or nerve injury to an extremity,
- Patients with only one available extremity that has an arteriovenous fistula
- Patients who are hemodialysis dependent who have not received hemodialysis in the past
4 days
- Paraplegic/quadriplegic patients
- Active pathologic cutaneous lesions on extremities
- Patients with a history of tourniquet pain or CRPS
- Pregnant patients
We found this trial at
1
site
Birmingham, Alabama 35249
Principal Investigator: Mali Mathru, MD
Phone: 205-934-0045
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