Nicolette G. Payne, MD, on genetic testing in patients with nephrolithiasis

In this video, Nicolette G. Payne, MD, describes the background and notable findings from the recent Urology paper, “The Use of Genetic Testing in Nephrolithiasis Evaluation: A Retrospective Review from a Multidisciplinary Kidney Stone Clinic.” Payne is a urology resident at Mayo Clinic in Phoenix, Arizona.

Transcription:

Please describe the background for this study.

Recent studies have suggested that there may be a monogenic genetic cause for nephrolithiasis, and the rates of nephrolithiasis in the United States are rising. Up to 10% of adults in the US have nephrolithiasis, and so there's a lot of literature to look into. What are the causes of kidney stones? How can we better treat these? And a lot of causes of kidney stones have come up; of course, dietary factors, geographical factors, and then, of course, there's this whole component of what could be some genetic or hereditary causes. In the literature, about 7% to 11% of adult stone formers have an underlying genetic cause, and it's even higher in the pediatric population - up to about 17% - and there's been over 40 genes that have been identified that can predispose people to nephrolithiasis. With that information, we sought to describe the genetic and clinical characteristics for patients undergoing genetic testing at our institution that were referred to genetics from our multidisciplinary stone clinic.

What were some of the notable findings? Were any of them surprising to you and your coauthors?

I think when we were doing this study, we were hoping to compare patients who had a variant identified with a known pathogenic association, compare those to patients who were identified with a variant of unknown significance, and then to compare those to people who did not have a variant identified. And of course, our hope was that we would find some statistical differences between these groups, both in their clinical factors and in their stone parameters, such as the type of stone they produced, or how frequently they were getting stones, or if they had a stone before the age of 18, or if they had surgery for stones. And so our hope or thought was that we would see some differences between the groups. For example, we might see that those who had a variant with a known pathogenic cause, maybe they had more frequent stone events, or they had a stone event before the age of 18. And I think maybe a surprising finding was that we didn't find any differences between the groups. But the reason for that, most likely, is that our sample size was pretty small. We had 825 patients evaluated in our stone clinic from 2018 to 2022, which was the time parameter for our study. 50 of those patients, which is only about 6%, were ultimately referred to the genetics clinic. And then of those patients, 33 ultimately decided to undergo testing. Of the 33, 19 were found to have a variant, and of those, 9 of those patients had a variant with a known pathogenic association, and 10 had a variant of unknown significance. And so we were working with a pretty small sample size. Only 33 of those patients had genetic testing, and then only 19 of those had a variant identified, whether that was a variant of known pathogenic association or unknown. And unfortunately, with statistics, that gives us a very underpowered study, and so we couldn't really find any significant associations. So in that sense, it wasn't surprising that we didn't find differences among the groups. I think one other interesting finding was that cystinuria is the most common monogenic cause of nephrolithiasis, and in our cohort, we only had 1 patient who had cystinuria. And so when I was presenting this study at a lot of different meetings, that was a common question I got was, why don't you think you guys had more patients with cystinuria? I think the answer to that question lies in the fact that we do a lot of 24-hour urine studies in our clinic. That's when a patient provides a sample of urine for either 24 or 48 hours, it's sent to the lab for analysis, and it gives us a lot of amazing information that can help us counsel patients on dietary factors and metabolic factors. And based on those results, a lot of times, if you have an educated person interpreting those results, you can already diagnose with a pretty high confidence cystinuria, or have suspicion for something like a distal renal tubular acidosis and things like that. And so our stone clinic is full of such educated people who really understand the pathophysiology of stone disease that we think that probably we had already identified patients with cystinuria, or patients came from another center and were referred to our clinic and had already had the diagnosis of cystinuria. So those patients then weren't asked to go get genetic testing, because we either already had high suspicion for it, or they were already given the diagnosis at another institution.

This transcription was edited for clarity.