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Experts highlight findings on the effect of ischemia on longitudinal renal function


“The primary thing we found was that the average kidney–and we study the ipsilateral kidney, or the kidney that was operated on–fell at the natural aging process,” says Carlos Muñoz-Lopez.

In this video, Carlos Muñoz-Lopez and Steven C. Campbell, MD, PhD, highlight the background and findings of their study, “Parenchymal volume analysis to assess longitudinal functional decline following partial nephrectomy,” for which they served as the lead and senior authors, respectively. Muñoz-Lopez is a 4th-year medical student at the Cleveland Clinic Lerner College of Medicine, and Campbell is the residency program director and a professor of surgery at Cleveland Clinic in Cleveland, Ohio.

Could you provide some background on this study?

Campbell: The objective with this study was to look at a controversial topic in the field. And that is, when we do a partial nephrectomy, we typically temporarily clamp the artery and the vein, because there's so much blood flow to the kidney that if we don't do that, there can be an increased risk of bleeding. So, traditionally, most centers will do either clamping with cold ischemia, where the kidneys packed in ice, or clamping with warm ischemia. The controversy has been that some in the field have argued that exposure to that ischemia, that timeframe where there's no blood flow, that it might predispose the kidney to progressive longitudinal decline and function. It leads the kidney vulnerable so that as the years go by, there can be progressive loss of renal function.

So, what we tried to do in this study, is we studied a large number of partial nephrectomy patients with more than 3 years follow-up, and we wanted to look at first how much progressive decline in function was there as the years went by. In this cohort, we had over 6 years of follow-up, so we had a decent amount of follow-up.We're comparing not the kidney before the partial nephrectomy, but the kidney after it's recovered from the partial nephrectomy, several months later, then what happens from that point, heading into the future. Is there a progressive decline? What is the degree of the decline? And what are the risk factors that that associate with that decline? And specifically, is exposure to ischemia really one of the major risk factors? That was the idea behind the study.

And the other thing about it is that there's not many studies at all that have looked at this issue of what happens to the kidney through the years. One of the possibilities is that the kidney might become progressively atrophic. We see that with the aging process, so even if you don't have a partial nephrectomy, each year, you tend to lose about .8 GFR units, and in 1 kidney, you lose half of that, .4. That's the natural aging process of atrophy of the kidney as we get older. The question is for patients who've had a partial nephrectomy, do they decline at that same rate? Or do they decline more rapidly? And is it related to exposure of ischemia versus other factors?

What were some of the notable findings?

Campbell: Well, let me just say one thing first is that Carlos was our main guy on this study, he did all the work of building up the database and all the analysis, so we'll have him address that one.

Muñoz-Lopez: Thank you very much, and thank you very much for the opportunity to talk to you. The primary thing we found was that the average kidney–and we study the ipsilateral kidney, or the kidney that was operated on–fell at the natural aging process. So, the functional loss after new baseline GFR is established was what was predicted by natural aging. However, patients who had significant renal comorbidity, so how we defined it in the study was patients who had treatment resistant hypertension, those are patients who have greater than 3 classes of medications that treat their blood pressure, or significant CKD, meaning greater than CKD stage 3, or insulin-dependent diabetes mellitus, those patients as a collective group fell at 3 times the natural aging process.

What we found in addition to that, because that isn't necessarily surprising, is that these patients also had increased longitudinal atrophy. When we looked at that atrophy specifically, the primary driver was the presence of these significant renal comorbidities. Warm ischemia was also a predictor of longitudinal atrophy, but it only accounted for less than 10% of the atrophic process. So, the long and short of it is that these patients, after new baseline GFR is established, it's their overall systemic diseases that are driving longitudinal functional decline, most of which is not unexpected, but certainly something that hasn't been explored in the partial nephrectomy literature prior to this study.

Campbell: So, it's mostly their comorbidities, not the fact that they got to exposed to ischemia for 20 or 30 minutes on 1 day of their life. The other thing that we found was that half of the functional decline, again the average kidney lost .4 GFR units per year, half of that was due to atrophy. The other half, other factors.

This transcription has been edited for clarity.

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