Non-Coding RNA, Other Therapeutics Can Impact Acute Kidney Injury Treatment, Recovery

In an interview with Pharmacy Times, Laura Denby, PhD, kidney research United Kingdom senior fellow, senior lecturer, and principal investigator within the Centre for Cardiovascular Science at the University of Edinburgh, United Kingdom, discusses the current state of acute kidney injury (AKI) and potential therapies, non-coding RNA, and endogenous repair. Denby will be presenting at the panel “Non-Coding RNA in AKI” during ASN Kidney Week in Philadelphia, Pennsylvania (November 2, 2023, to November 5, 2023).

Pharmacy Times: How are recent advances contributing to the understanding of acute kidney injury (AKI) pathophysiology, and what therapeutic strategies are on the horizon for AKI treatment?

Laura Denby: So, I think we're in a really exciting time in kidney research, and things like the application of single-cell RNA technologies allowed us to understand an unprecedented level, the sort of granularity of data that we didn't have about how the individual cells are functioning in the pathophysiology of various diseases, including AKI. And I think with this, we've been allowed for the first time to really understand the individual cellular contribution to the pathophysiology, and from that information, what we're able to do is really consider new therapeutic targets which we possibly didn't understand before.

So obviously, I'm very interested in non-coding RNA—in particular microRNAs—and what we've done is we have done sort of population sequencing for microRNAs to understand their cellular context, and then we've integrated this with single-cell data to understand their targets and how they're changing. And these will then—hopefully—lead to a whole new branch of sort of new therapeutics for AKI.

Pharmacy Times: Can you provide insights into the approaches and developments in targeting metabolic pathways for AKI treatment?

Denby: As I said, with the greater understanding of what's occurring in the pathophysiology in the last few years, we're able to understand certain pathways that affect metabolism so we can either look at altered metabolism, we can look at changing the balance and the flux of the metabolites, therefore bringing around tubular protection. One of the things to also consider in AKI is to make sure that the tissue recovers effectively post-AKI, so 1 of the areas I think will be really interesting moving forward will be to target the repair and endogenous reparative processes in order to ensure that the kidney is as healthy as possible after a bout of [AKI].

Pharmacy Times: Where are we currently with the use of non-coding RNA in health care? How might non-coding RNA and related factors shape the direction of AKI therapy?

Denby: In terms of the non-coding RNA, we know that, for example, therapeutics targeting microRNAs have been in clinical trial and we're moving more and more of these towards clinical trial. In terms of the AKI, because we already have a sort of footprint for how we might think about translating these new therapeutics, I think if we do find 1 that's suitable within that space, then we should be able to fast track it quite quickly.

Pharmacy Times: Do you see any potential breakthroughs with the use of non-coding RNA that we can anticipate in the near future?

Denby: Well, as I said, the area that I think is most interesting is whether or not we can boost endogenous repair, and that's 1 area that we haven't really looked at. We've got some interesting non-coding RNA that seem to be very particular to that period, and then recovery, so we think if we can boost the sort of beneficial endogenous repair then that might be a really exciting breakthrough.