Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Poly(ADP-ribose) Polymerase Inhibitors

Cystatins

Kidney function will be assessed by serum creatinine, serum cystatin C, and urine creatinine clearance calculation for patients who opt-in to 24 hour urine collection.

These laboratory measures will be completed by patients at the following time points:

* Timepoint A: Baseline (prior to PARP inhibitor initiation, at the time of standard of care clinical testing)
* Timepoint B: On-treatment (within 3-9 weeks of PARP inhibitor initiation, at the time of standard of care clinical testing)
* Timepoint C: Post-treatment (within 4 weeks of PARP inhibitor discontinuation, only for those patients with clinically significant changes in GFR based on serum creatinine, cystatin C, or 24 hour urinalysis at Timepoint B

Kidney Function Test

Payal Shah, MD

The purpose of this study is to observe whether PARP inhibitors have an effect on serum creatinine level, and whether this reflects a change in creatinine secretion or a true change in kidney function.

PARPi medications interact with transporters along the renal tubules involved in the secretion of creatinine and an increase in serum creatinine is often observed in patients treated with these agents; however, it is not known whether PARP inhibitors are associated with an actual change in the glomerular filtration rate, or if the observed elevations of serum creatinine are a result of a drug effect on creatinine secretion unrelated to changes in kidney function. The investigators therefore propose a prospective observational study to examine the incidence of elevation in serum creatinine from baseline levels in patients initiated on PARP inhibitors and compare the estimated glomerular filtration rate based on creatinine to that from alternative tests.

The primary purposes of this study are to:

* Assess the incidence of increase in serum creatinine in patients with a solid-organ cancer on treatment with a PARP inhibitor.
* To compare the estimated glomerular filtration rate based on serum creatinine with that of alternative biomarkers to assess whether changes in serum creatinine reflect changes in kidney function or creatinine secretion.
* To examine the persistence or resolution of creatinine increase and/or GFR decrease noted after discontinuation of PARPi

Kidney function will be assessed by serum creatinine, serum cystatin C, and urine creatinine clearance calculation for patients who opt-in to 24 hour urine collection.

Effect of PARP Inhibitors on Glomerular Filtration Rate

Change in eGFR from baselineto on-treatment by ≥20% as measured using either cystatin C or 24h urine collection

The percentage of patients who experience a eGFR reduction of ≥30%, and/or

University of Pennsylvania

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Coagulants

Central Nervous System Depressants

Other Dietary Supplements

Hemostatics

Benzocaine

Tannic Acid

Cortical renorrhaphy is performed after partial nephrectomy using a running barbed suture on MH (36mm) needle. Polymer locking clips are used to maintain tension. A base layer running stitch is performed prior to the cortical renorrhaphy.

The suture closure of the renal cortex after tumor removal is omitted. A base layer running stitch only is performed for hemostasis and urine leak prevention.

Non-renorrhaphy

After tumor resection the patient will have both a deep and cortical layer reconstruction

Renorrhaphy

Chandru P Sundaram, MD

Clinton D Bahler, MD

Preserving kidney function during removal of a kidney tumor is becoming increasingly important as rates of chronic kidney disease increase. A novel modifiable factor (suture closure of the defect caused by tumor removal) was discovered on retrospective studies to account for nearly two-thirds of the 15% volume loss commonly seen in operated kidneys. We hypothesize that a randomized controlled surgical trial will show that omitting the suture closure both preserves renal function and will not lead to unreasonable postoperative complications.

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.

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

% loss in renal volume (cm3) of the operated kidney (post-operative CT at 4 mo vs. - pre-operative CT) using Phillips IntelliSpace portal semi-automated segmentation algorithm.

Operative and postoperative complications (urine leak, bleeds) through the 4month follow-up

This is a "change" outcome measure. Pre and post-partial nephrectomy on the day of surgery Doppler/US arterial resistive index changes are recorded.

Postoperative surgeon survey evaluating comfort with surgery-Likert scale questionnaire

Assess the volume loss predicted by a preoperative scoring system. The preoperative volume loss prediction will be compared to the 4month volume loss calculation based on CT scans.

% eGFR loss from pre to postoperative (4mo) followup

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of PARP Inhibitors on Glomerular Filtration Rate	NCT04367467	Solid Tumor Ovarian Cancer Breast Cancer	Kidney Function...	18 Years -	University of Pennsylvania
Effect of PARP Inhibitors on Glomerular Filtration Rate	NCT04367467	Solid Tumor Ovarian Cancer Breast Cancer	Kidney Function...	18 Years -	University of Pennsylvania
Effect of PARP Inhibitors on Glomerular Filtration Rate	NCT04367467	Solid Tumor Ovarian Cancer Breast Cancer	Kidney Function...	18 Years -	University of Pennsylvania
Investigating a Novel Modifiable Factor Affecting Renal Function After Partial Nephrectomy: Cortical Renorrhaphy	NCT02131376	Renal Cell Carc...	Non-renorrhaphy Renorrhaphy	18 Years -	Indiana University

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