Investigating a Novel Modifiable Factor Affecting Renal Function After Partial Nephrectomy: Cortical Renorrhaphy

Purpose: To evaluate a never before studied modifiable factor affecting renal function after
partial nephrectomy: the suture closure of the renal cortex after tumor removal
(renorrhaphy).

Background:

There is increasing interest in preserving renal function when removing renal tumors. This is
partly due to studies that link chronic kidney disease with cardiovascular events and overall
survival. There is an approximate loss of 10% overall renal function after partial
nephrectomy along with a loss of 15% of the volume in the operated kidney. Studies point to 3
factors leading to this loss in renal function after partial nephrectomy: 1) Poor
preoperative renal function, 2) Ischemia time (clamping the renal blood vessels to decrease
bleeding during surgery, and 3) Loss in renal volume from the surgery.

The only factor that is considered modifiable is ischemia time, especially when over
20-25-minutes in duration. Modern techniques now aid in keeping the ischemia time below the
25-minute cutoff. Leading experts from institutions such as the Cleveland Clinic, The
University of Southern California, and The Mayo Clinic have concluded that the most important
factor in preserving renal function, renal volume loss, is not modifiable.

Specific Aims: Our question is: if we are removing non-functional tissue (tumor) then why is
there a loss in renal volume (15%) and function (10%)? We hypothesize that by omitting one
particular step during surgery, sewing closed the defect caused by tumor removal, we will be
able to improve renal volume loss and function (RENORRHAPHY CLIP
http://youtu.be/NXOtUHdigj4). Indiana University is in a unique position to study this
hypothesis as two of our surgeons have routinely omitted closing the defect left after tumor
removal (NO RENORRHAPHY CLIP http://youtu.be/ZisMjrm85s8).

In a recently accepted abstract, we discovered that omitting the cortical closure (n=28)
resulted in a 0.8% loss in glomerular filtration rate while using the closure resulted in a
7.3% loss (p=0.03). Following this discovery a 3D modeling project was performed to isolate
the volume loss in operated kidneys using pre- and postoperative CT scans (not yet
published). In this study, we discovered a 15% volume loss with cortical closure (n=38)
compared to only a 5% loss without closure (n=20, p < 0.001).

Bias and confounders cannot completely be removed from our retrospective data making it hard
to believe that others will consider our hypothesis without a randomized controlled trial
(RCT). We propose a RCT for robotic partial nephrectomy (20 stitch closure vs. 20 no stitch
closure) with the primary outcome being volume change in the affected kidney.

3.0 INCLUSION/EXCLUSION CRITERIA

3.1 Inclusion criteria:

- ≥ 18 years of age.

- Must provide written informed consent

- Presence of cT1 renal mass by diagnostic CT assessment.

- Scheduled for partial nephrectomy of renal mass.

- Expected survival of at least 3 months.

- ECOG ≤ 1.

- Negative serum/urine pregnancy test within 24 hours for females of child bearing age
prior to surgery

- Recovered from toxicity of any prior therapy to grade 1 or better

- If biopsy of mass has been done, pathology must be consistent with RCC.

3.2 Exclusion criteria:

- Solitary kidney

- Multiple or bilateral renal masses when more than one mass is operated on at the same
time or within 4-months of each other.

- Hepatic or renal toxicity (GFR <30) greater than or equal to Grade 2 (using CTCAE
version 4 standard definitions)

- Bleeding diathesis or inability to hold anticoagulation for surgery

- Participation in another investigational trial concurrently or within 30 days

- Significant acute or chronic medical, neurologic, or psychiatric illness in the
subject that, in the judgment of the Principal Investigator, could compromise subject
safety, limit the subject's ability to complete the study, and/or compromise the
objectives of the study.