Remote Ischaemic PreConditioning (RIPC) in Partial Nephrectomy for the Prevention of Ischemia/Reperfusion Injury

Study Overview
=================
Brief Summary
-----------------
Remote Ischaemic PreConditioning (RIPC) is performed prior to partial nephrectomy. Postoperative calprotectin dynamics and Blood Oxygen-Level-Dependent (BOLD) MRI are used to to demonstrate the potential renoprotective effect of RIPC

Detailed Description
-----------------
Partial nephrectomy represents the gold standard in organ sparing kidney surgery. Cold ischaemia prevents major bleeding but can yet be associated with impaired kidney function due to reperfusion injury to the tubuli. Patients undergoing partial nephrectomy (any surgical technique, open, retroperitoneoscopic, transperitoneal, Da Vinci assisted) will be treated with Remote Ischaemic PreConditioning (RIPC). RIPC is delivered with a standard blood pressure cuff placed on the upper arm and another standard blood pressure cuff placed on the upper thigh. The cuffs are then simultaneously inflated to 200 mm HG and left inflated for 5 minutes, then deflated to 0 mmHG and left uninflated for 5 minutes. This cycle is repeated twice, so that the RIPC protocol takes 20 minutes in total. If the systolic blood pressure is > 185mm HG the cuffs are inflated to 15 mmHG above that level. Several studies already demonstrated the reno- and cardioprotective potential of Remote Ischaemic PreConditioning (RIPC). It was shown that urinary calprotectin can be used to monitor tubular damage after nephron sparing surgery. Postoperative calprotectin dynamics will be monitored in order to demonstrate the potential renoprotective effect of RIPC. Additionally a BOLD MRI will be performed to to visualize ischemia/reperfusion injury.

Official Title
-----------------
Remote Ischaemic PreConditioning (RIPC) in Partial Nephrectomy for the Prevention of Ischemia/Reperfusion Injury

Conditions
-----------------
Reperfusion Injury

Intervention / Treatment
-----------------
* Procedure: RIPC
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed Consent as documented by signature (Appendix Informed Consent Form) Kidney tumor (any entity, benign, malign) Partial nephrectomy (any surgical technique, open, retroperitoneoscopic, transperitoneal, Da Vinci assisted) 18 years of age Sufficient perfusion of all 4 extremities palpable distal pulses: A. radialis and A. dorsalis pedis or A.tibialis post. Exclusion Criteria: Women who are pregnant Significant peripheral arterial disease affecting upper and/or lower limbs or history of Significant renal disease (GFR <15 ml/min/1.73m2) or undergoing haemodialysis Concomitant therapy with glibenclamide or nicorandil (due to potential inference with RIPC) Urothelial cancer Acute Urinary tract infection international normalized ratio (INR) >2 (haematoma risk at cuff site)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (RIPC)<br>RIPC treatment prior to partial nephrectomy. | Procedure: RIPC<br>* RIPC is delivered with a standard blood pressure cuff placed on the upper arm and another standard blood pressure cuff placed on the upper thigh. The cuffs are then simultaneously inflated to 200 mm HG and left inflated for 5 minutes, then deflated to 0 mmHG and left uninflated for 5 minutes. This cycle is repeated twice, so that the RIPC protocol takes 20 minutes in total. If the systolic blood pressure is > 185mm HG the cuffs are inflated to 15 mmHG above that level.<br>|
| Placebo Comparator: Placebo Control<br>Placebo prior to partial nephrectomy. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker reduction | The study seeks primarily to determine the reduction of the biomarker concentration (Calprotectin and NGAL) in urine. Change in biomarkers will be measured at baseline, during 5 days after surgery and at timepoint month 3. | Baseline, 5 days and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute renal failure | The secondary objective is to demonstrate the effect/reduction acute renal failure after RIPC as compared to the control group. Number of patients with acute renal failure will be compared between both groups. Acute renal failure will be assessed in the days after surgery (acute kidney failure) | Baseline, 5 days, 3 Months | 
| Chronic renal failure | Number of patients with chronic renal failure will be compared between both groups. Chronic renal failure will be assessed in at baseline until timepoint month 3 (chronic kidney failure). | Baseline, 3 Months | 
| Tubular damage in BOLD MRT | Δ R2*-values in BOLD magnetic resonance tomography (MRT) will be compared between both groups. | Baseline, day 2 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Partial nephrectomy, RIPC, Reperfusion Injury