Which Patients Will Progress to Kidney Failure After Surgery?

Anya Romanowski, MS, RD

Disclosures

April 28, 2017

Background

Medscape interviewed Ketan K. Badani, MD, vice-chair of the department of urology at Mount Sinai Health System and director of the Comprehensive Kidney Cancer Program in New York. He leads a multispecialty clinical program for kidney cancer patients that includes surgery, nephrology, interventional radiology, and complementary medicine.

Image courtesy of Ketan K. Badani, MD

Dr Badani has developed a new surgical technique to treat kidney tumors in patients. In addition, he is investigating the use of stem cells to regenerate kidney tissue and is examining whether biomarkers from a patient's urine and tumor cells can predict future kidney health after surgery.

Medscape: According to the American Cancer Society, the rate of kidney cancer has been on the rise since the 1990s and is among the 10 most common cancers in both men and women. What has led to this increased incidence?

Dr Badani: Why and how you get kidney cancer is the million-dollar question. I think there are two aspects to it. One, there is the unknown biological factors on why kidney cancer arises. We know it's a gene mutation for the most common types of kidney cancer; some are hereditary, but most diagnosed kidney cancers are not.

The other factor that has increased the rate is incidental screening and imaging (abdominal CT, ultrasound, MRI) that people are getting for other reasons. Commonly, someone has abdominal or some other type of pain, and they go to the emergency department or to their primary doctor, who orders a scan to see what's going on, and the scan picks up the kidney mass. Now, the kidney mass has nothing to do with the symptoms. Abdominal pain is rarely related to a small kidney tumor, but you find it and it's called an "incidental renal mass."

Multispecialty Kidney Cancer Program

Medscape: Can you describe the multispecialty clinical program for cancer patients that you developed and currently lead at Mount Sinai Health System? In addition, can you elaborate on what you are tracking and monitoring when treating patients?

Dr Badani: In a multispecialty program for kidney cancer, several different types of doctors will help in the process of treating a patient. The most important is the surgical oncologist or the urologist, because most kidney tumors found incidentally are curable by removal alone. Therefore, doing a procedure to take out the mass is essentially the cure.

Image courtesy of Ketan K. Badani, MD

Some patients have tumors that are more aggressive or not found as early, and then you need a medical oncologist on the team to talk about more systemic treatments. The problem with kidney cancer is that it doesn't respond to traditional chemotherapies and radiation. We now have a very interesting field of research where we are looking at targeted and personalized therapies (vaccines, immunotherapies) that are specific to the patient's kidney cancer. We can treat them with these drugs and be effective in treatment.

Our hands are tied when it comes to metastatic kidney cancer. The medical oncology team and I are doing some research to look at how we can personalize the treatment for the patients who have more advanced kidney cancer.

Another important piece of the comprehensive program is lifestyle factors, and we have a dedicated program in complementary and holistic medicine. It's not just about controlling hypertension, diabetes, and cholesterol and smoking cessation, which are all factors that lead to kidney damage. It's also about diet, nutrition supplements, and exercise that a patient can do. Many patients treated for kidney cancer are interested in making lifestyle changes to protect their remaining kidney. I think it is a very important and timely part of our program.

The 'FAST' Surgical Procedure

Medscape: You are a recognized world leader in minimally invasive robotic kidney cancer surgery and in urology, and you developed a new robotic partial nephrectomy technique to treat kidney tumors (the "FAST" procedure). Can you describe this procedure?

Dr Badani: Yes, absolutely. The whole balance of treating a small kidney tumor (meaning a tumor that is contained to the kidney) is to try to just remove the tumor and save the normal part of the kidney. In a partial nephrectomy, we remove the tumor, which is usually very well encapsulated, and we save the healthy part of the kidney, which will continue to function. Not everybody is a candidate for partial nephrectomy, but as we develop these techniques, and this particular technique, we can actually offer partial nephrectomy to even patients who have the most complex or large tumors in their kidneys. There is strong evidence that overall survival of patients undergoing partial nephrectomy for kidney cancer is superior to that in patients undergoing total nephrectomy.

The technique I've developed has minimized the ischemia time (the time that the kidney is without blood flow). Our ischemia time is well under the goal of 25-30 minutes; our average is at 12 minutes.

When you are removing a kidney tumor, two aspects contribute to a decrease in kidney function. One aspect is how much of the kidney you remove. The more kidney you remove, the more function you lose.

The second aspect, probably the most important factor, is that you have to stop the blood flow to the kidney (temporarily) in order to perform the operation, because if you just cut it, it bleeds. The kidney is a blood filter. You have to put a clamp on the blood flow to stop it, and the goal is for the kidney to be without blood flow for under 30 minutes. The kidney will not have long-term damage, but every minute counts. So 25 is better than 30, 20 is better than 25, and so on.

The technique I've developed has minimized the ischemia time (the time that the kidney is without blood flow). Our ischemia time is well under the goal of 25-30 minutes; our average is at 12 minutes.

The balancing act of minimizing the ischemia time and preserving as much of the normal kidney as possible are the goals of the technique. That's why we've developed it, and that's what we're doing to continue to improve outcomes for patients. We've taught this technique to hundreds of doctors, who have started performing robotic partial nephrectomies across the globe.

This is a robotic technique, which means we are able to do this minimally invasive procedure through holes in the abdomen and not have to make a cut to do that. All of the advantages I just described (low ischemia time, maximally preserving the kidney and still being able to remove the tumor in its entirety) are all technological advancements to the robotic platform.

Using Amniotic Cells to Regenerate Kidney Tissue

Medscape: Can you discuss the current trial you are conducting using amniotic cells to regenerate kidney tissue in patients who underwent surgery to treat their cancer? It is my understanding is that you are also collecting some of the kidney tumor tissues to conduct more research.

Dr Badani: We are conducting two distinct trials that are separate from each other, and they are both significant and haven't been done before.

The first one is the amniotic stem cell study that you alluded to. The kidney doesn't regenerate on its own, so when you cut out a part of the kidney, as I was describing earlier, you lose that and it doesn't come back later.

We are starting a randomized trial looking at using amniotic cells to regenerate and prevent continued damage to the kidney in patients undergoing partial nephrectomy. There is some good evidence that these types of stem cells will actually help the kidney regenerate, but they haven't been tested in a patient trial during this procedure. So this is the first of its kind study to do that.

All of my patients who are having the surgery are eligible for this trial, and we will have two arms. One is the control arm, where we don't use the amniotic stem cells, and the other arm is for the patients in whom we do. Over the ensuing 6 months to 1 year, we're going to see whether we are able to regenerate some of kidney using amniotic cells, or at least prevent further loss of the kidney from all the suturing and reconstruction that is required during partial nephrectomy.

Medscape: Is the patient enrollment in this trial only occurring at Mount Sinai?

Dr Badani: Yes. Because it's a pilot study, enrollment is this trial is only at Mount Sinai. So patients would have to come here, but then they can be enrolled in the study. With promising preliminary results, we hope to do a multicenter trial including several centers across the country.

Harvesting Tissue of Tumor Cells to Guide Treatment

Dr Badani: In the second trial (which is different from the amniotic cell trial), we're harvesting tissues from the kidney tumors of every patient whom I treat, and we keep them in the lab to test medications against it.

So if a patient were to develop metastatic disease in the future—thankfully, most don't, but some have very aggressive types of kidney cancer—we actually have a model where we can test different types of drugs to see which one is most effective for that particular patient, and we can personalize their treatment.

Now, this is all under protocol, so we have to enroll the patients into the trial and get their permission to harvest the tissue of the tumor cells. Once we do that, we will have the ability to test different drugs in the future to see which ones are the most effective, and they may differ from one patient to another. That is going to be the future, I think, of how we treat advanced kidney cancer.

Examining Urine Biomarkers to Predict Kidney Failure

Medscape: You mentioned that you are conducting another trial looking at biomarkers to help predict future kidney health in patients who underwent surgery to treat their cancer. Can you describe this trial?

Dr Badani: In our other big clinical trial, we are looking at markers from the urine to see which patients are likely to end up with kidney failure after partial or total nephrectomy. It doesn't happen very often, but some patients have unhealthy kidneys to begin with and will continue to have a significant decline in function even if you save the kidney. So, we are conducting a trial looking at proteins in the urine to come up with an algorithm that will tell us which patients are at risk. Obviously, these are important things to know going into an operation, if you can predict who will have kidney failure after.

Again, it's a small percentage of patients; most who have surgery for kidney cancer do find that kidney function is essentially restored back to normal. But there is a subset of patients whose kidneys are just not healthy to begin with, and then we'd be able to predict who those patients are. We are coming up with a urine-based test to do this, and that's actually very important. Nephrologists are very interested in this because they want to know who is at risk for going into potential kidney failure or will have a significant decline in kidney function after partial nephrectomy. So this is another study that the patients who are being treated at Mount Sinai can be enrolled in.

Medscape: Are there any current trends that you see in following up with these patients? Are you finding kidney failure to occur more commonly in men or women? What patients appear to be at more at risk?

Dr Badani: We are very early into the trial, so I obviously don't have any data that have been evaluated yet. Clinically, what we know is that patients who have kidney dysfunction, long-standing hypertension, diabetes, and obesity are at higher risk. Anyone who has kidney dysfunction obviously is at a deficit compared with someone who has normal kidney function. And there is a little bit of a slant toward men compared with women, although it's very small. However, there are always patients who don't fit the mold and have kidney problems that you can't detect. You don't find out until you do something to their kidney, such as perform surgery.

It's interesting that the signature of the kidney is imprinted in the protein biomarker cells in the urine that contain the DNA. We just need to figure out how to interpret the DNA, because that can tell us who is at risk. There are definitely signs. There are proteins that the kidney excretes that indicate people who are at risk for kidney damage; we can pick that up. Right now, we're trying to figure out which of those proteins are important.

Screening Patients for Kidney Cancer

Medscape: That would certainly have strong implications in screening patients in the future. Are there any additional advances in screening patients for kidney cancer that you'd like to share with us or with other nephrologists?

Dr Badani: I think what needs to be done that currently is lacking, is finding a better way to screen patients for kidney cancer. Right now, you are potentially diagnosed if you have symptoms, such as blood in the urine. Or, you feel a lump or a mass in the side of your abdomen. The kidney tumor would have to be fairly progressed to have those symptoms, and most are found incidentally. You have to have a scan, an ultrasound or an MRI—some kind of radiographic test to detect this, and obviously we're not going around scanning everyone to check for this.

We don't have a screening test, and we don't have a blood test or a urine test or some way of knowing, like we have for other cancers. We have mammography for breast cancer, prostate-specific antigen for prostate (despite all the controversy that goes with it), and colonoscopy for colon cancer. I think more than anything else, a kidney cancer screening test would be extremely beneficial to the population. We're working on trying to come up with that by looking at some of these urine markers and protein markers, but this is a goal much bigger than the scope of a single clinical trial. It has to be a national effort.

Medscape: Better methods of screening patients are certainly needed, especially with the incidence of kidney cancer on the rise.

Dr Badani: It's a little bit of a scary phenomenon, because all my of my patients say the same thing: "If I didn't get that scan, how would I know I had this?" The answer is, you wouldn't. You don't know; you wouldn't have known until it's progressed or too late.

Medscape: As far as symptoms that patients may experience that may be indicative of kidney cancer, is there anything specific that you could recommend to physicians, aside from testing patients' blood and urine at annual check-ups?

Dr Badani: I think the most important thing to check when the patient has their annual check-up is whether there is blood and protein in the urine. A urine test would detect that. Nephrologists are very in tune with the protein piece, but if you don't have blood and protein in the urine, there's really essentially nothing else to do. I think that's a reasonably clean bill of health from a kidney standpoint.

You can detect microscopic blood in the urine (microscopic hematuria), but you won't know you have it unless you test for it. When you have your annual check-up, it's worth having the test, but not everyone gets one.

Medscape: This sounds similar to the approach used by a gastroenterologist finding a polyp in a patient undergoing a routine colonoscopy exam. After removing the polyp and examining the tissue, they may discover that the patient has microscopic colitis.

Dr Badani: Absolutely, and that's a microscopic test that the doctor's office would do. And if you actually see blood in your stool or urine, then you absolutely have to get checked out.

Medscape: Are there any other studies in the field that you find promising you would like to discuss today? As far as the clinical pearls or takeaways, do have any that you'd like to share with the other surgeons or nephrologists?

Dr Badani: I think the three trials we talked about are probably the most important ones we're doing. The other piece I would like to mention is that I have a consortium of various prominent institutions that do robotic partial nephrectomy based on the techniques I described. They are in various regions of the country (New York, Midwest, Southeast, West Coast), and we're tracking all of the data across the country to see how we can continue to improve the current standard of care. If a nephrologist has a patient who has a kidney tumor, they should refer them to someone at institutions who is very experienced in treating these tumors.

My ultimate goal here is to create Centers of Excellence that are all able to do the same level of surgery via protecting the kidney with lower ischemia time, maximizing the amount of kidney we preserve, and then from any of these trials that end up showing a positive result, we can implement standardized procedures. Thus, the patients will benefit in every region in the country. Obviously, having a center and place such as ours is terrific (we are in a big city, and we have a huge patient population that we take care of), but that's not servicing the rest of the country. The whole country has to be able to benefit from this.

We're working on that too—tracking the outcomes at all of the places that are a part of this consortium.

Disclosure: Ketan K. Badani, has disclosed the following relevant financial relationships:
Received financial support for research projects from: Medtronic, Inc.; Genomic Health, Inc.

Follow Anya Romanowski on Twitter: @Anya13

Follow Medscape Nephrology on Twitter for more nephrology news: @MedscapeKidney

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