Results from the Radical Nephroureterectomy Outcomes (RaNeO) Registry - Clara Cerrato

June 1, 2023

In a cross-institutional study investigating the impact of nephroureterectomy on renal function, urologist Clara Cerrato and her international team analyzed data from 576 patients across 17 tertiary centers. They discovered factors such as age, hydronephrosis, and postoperative day one acute kidney injury were independently associated with the estimated glomerular filtration rate (eGFR) variation. Surprisingly, older patients and those with preoperative hydronephrosis had more favorable eGFR variations, while those with acute kidney injuries postoperatively experienced the most significant eGFR decline. These insights have potential clinical implications for patient care, allowing physicians to predict which patients are likely to see significant decreases in renal function postoperatively. Identifying such patients could guide more effective treatment strategies and perioperative care, including possible considerations for nephron-sparing surgeries or adjustments in chemotherapy regimens. Future research will focus on prospective studies and developing a nomogram to enhance patient stratification and counseling.


Clara Cerrato, MD, Università degli studi di Verona, Verona, Italy

Sam S. Chang, M.D., M.B.A. Patricia and Rodes Hart Endowed Chair of Urologic Surgery Professor Department of Urology at Vanderbilt University Medical Center

Read the Full Video Transcript

Sam Chang: Hello everyone. My name is Sam Chang. I'm a urologist in Nashville, Tennessee at Vanderbilt University. And we have an international guest today. This is Clara Cerrato, who is an MD at the University of Verona in Italy. And she and her colleagues have actually put together a multi-institutional effort to look at the impact of nephroureterectomy on renal function. And so we're going to turn it over to Clara to talk about how this group has come together and what they found and how they put their data together. So dear Clara, thank you so much for joining us and we look forward to your presentation.

Clara Cerrato: Good morning to everybody. Thank you for your invitation and for this opportunity. So this was the work that we presented at the EAU in Amsterdam this year. So basically the aim of our study was to investigate the frequency and the predictors of renal function drug variation after radical nephroureterectomy for upper tract urothelial carcinoma.

We were able to retrospectively analyze data coming from 17 tertiary centers. We collaborated with an Austrian center as well. So they were not just Italian centers. And we evaluated the renal function variation at postoperative day one, six and 12 months follow-up, and the relative differences between the same time points. Regarding the analysis, we used linear mix model to evaluate the effect of the clinical factors and eGFR decline and their interaction with follow-up. So we were able to recruit about 576 patients. The median age was about 72 years old.

We classified about 40% of the population as older, since they were more than 75 years old. And about 60% of patients instead as younger, since they were less than 75 years old. At the new univariate model, we found that elderly patients had an early favorable eGFR variation with respect to the younger one. And those who experienced the preoperatory hydronephrosis had an early favorable eGFR variation as well. While the radical nephroureterectomy had a detrimental effect on those patients who had postoperative day one acute kidney injury. And patients who develop the postoperative day one acute kidney injury actually did not have preoperatory hydronephrosis.

So when we performed a multi-variable analysis, we found that age, hydronephrosis and postoperative day one acute kidney injury were factors that were independently associated with the eGFR variation. And during follow-up that was about with a median value of about 25 months, we found that the eGFR recovery was more pronounced in those who experienced post-operative day one acute kidney injury, that the elderly recovery was lower with respect to the ones of the younger patient. And that eGFR generally had a positive trend during follow-up. This was probably because of the contralateral kidney adaptation.

So the conclusion of our study were that the eGFR change magnitude varied according to age, hydronephrosis, and postoperative day one acute kidney injury. And that elderly patients usually had a smaller eGFR change after the surgical procedure with respect to the younger, but that younger patient usually could recover better during follow-up and in the long run.

Sam Chang: Fantastic. That's important work as we counsel our older patients, our patients with hydronephrosis in terms of their changes immediately after surgery. It may not put them at high, high risk that they need to be, "It's okay, there may be some recovery." So when you look back and look at the hundreds of patients that you looked at, were there certain things that you thought that might make a difference, but didn't really make a difference? So for instance, I would think that people who have less favorable renal function before surgery would be more likely to have bad problems down the line, or I don't know, what did you find with those that had already some renal insufficiency?

Clara Cerrato: I think that the major implications under a clinical perspective are to find some characteristics that could define patients that are going to decrease a lot their eGFR post operatively. Because if you know how the trend of the kidney function of our patient is going after the surgery, then you can better address them for adjuvant, or neoadjuvant chemotherapy.

We know that these patient have a very low survival with respect to other kind of cancers and that chemotherapy can really make an impact on their survival. So if we are able to predict that in those settings like older patients, patients that may not have an hydronephrosis, may have a longer recovery or of the eGFR variation, then you can maybe address those patient to a neoadjuvant regiment, so that they can have an higher survival expectancy with respect to now. And I think that one of the major points is that knowing that the postoperative day one acute kidney injury may have such an impact in the first postoperative time, in the first postoperative period of these patients may give us a chance to better treat these patients even in the taking care during the pre operatory and the peri operatory period.

Even with the ICU team, for example, nephrologist, we can even just think about the blood pressure variation, kidney hyperperfusion, or the nephrotoxic drug and agents that we may avoid to decrease the risk of acute kidney injury in the first period so that those patients maybe could have a better eGFR variation and then get access to adjuvant regimen. And conversely, if we know the patients that have a decrease in the eGFR variation, or a decrease in the eGFR function in the postoperative period, we may even address them to nephron sparing surgeries when, of course, oncologically feasible and safe. But I think that we could really make an impact on this kind of population of patient.

Sam Chang: Yeah, I mean your point about I think urologic surgeons, we under utilize and probably underemphasize just as you said, the perioperative care of the kidney function; hydration, blood pressure control, both hypo and hyper, involving nephrology early. I think that is really important, especially I think now in the population that you've defined that may be more at risk for more of the eGFR variation down the line. I think that's a really important take home point. So where are you going to go next with your, you've now built this multi-institutional team or help bring it together. Are you guys going to start looking at things prospectively or interventions you take to help preserve renal function? Where do you go next?

Clara Cerrato: Yeah, I think that two major parts, maybe one starting something prospective. So trying to understand if in a prospective view if those factors really make an impact. And the other part may be finding a nomogram to understand better our population and to better stratify patients so that you can even counsel them in the better way possible. So that you face your patient and you can tell them, "Okay, that's fine. This is their situation, you know that you have those risks. And if you incurring those risks then maybe you could have these kind of survival like these. and others." So you may have more opportunities, more comparable opportunities for your patient as well.

Sam Chang: Right.

Clara Cerrato: So I hope that we will go in this two, in this...

Sam Chang: Making it in the prospective manner then to basically just as you say, impact positively either protect, or at the same time, I think importantly also be able to say upfront that, "You're better off probably getting say neoadjuvant," just as you said to, "... because afterwards you're not going to be able to get anything systemic despite everything we do." So I think right now we just guess. We have an idea. But understanding those factors that really make a difference. And just as you said, if you can prospectively show that, and prove that, and then help actually protect those kidneys or protect that kidney function, that's even better.

Well, I mean, kudos to your excellent work. The presentation at the EAU got a lot of press, and so we wanted to make sure to invite you and go over all the work and all that you and your group have been able to accomplish. So we look forward to actually future things and future exciting research from you, and all the multi-institution collaboration that you've brought together. So, thank you very much.

Clara Cerrato: Thank you. Thank you very much for your time, for your invitation and your great words.

Sam Chang: Absolutely.