New imaging method might assist establish kidney harm from most cancers immunotherapy

How would you summarize your examine for a lay viewers?

Immune checkpoint inhibitors (ICIs) are a category of immunotherapy which have revolutionized the therapy of most cancers. Nevertheless, they’ll trigger all kinds of autoimmune toxicities, together with immune checkpoint inhibitor-associated acute kidney harm (ICI-AKI). Differentiating ICI-AKI from acute kidney harm (AKI) because of different causes, that are widespread in most cancers sufferers, is difficult with out a kidney biopsy as a result of threat of bleeding for some sufferers. 

On this examine, we examined whether or not F¹⁸-FDG PET-CTs, a kind of nuclear imaging examine, might be used to tell apart sufferers with ICI-AKI from these with AKI from different causes. We discovered that sufferers with ICI-AKI had a lot greater ranges of radioactively-labeled glucose within the kidneys, indicating kidney irritation, in comparison with sufferers with AKI from non-ICI causes. These findings point out that this sort of radiographic scan might be a non-invasive different to kidney biopsy for diagnosing ICI-AKI. 

What information gaps does your examine assist to fill? 

Earlier analysis has demonstrated that the most typical discovering from kidney biopsies in sufferers with ICI-AKI is acute interstitial nephritis, or irritation within the kidney because of activated T-cells. To diagnose this situation in present apply, sufferers should bear a kidney biopsy. Nevertheless, sufferers could have contraindications (e.g., they might have just one kidney or they might be receiving therapy with blood thinners), stopping them from continuing safely with a kidney biopsy. Thus, non-invasive markers are vastly wanted to diagnose ICI-AKI. 

Case studies and smaller research had explored the utility of F¹⁸-FDG PET-CT scans as a non-invasive possibility for diagnosing ICI-AKI, however these research had important limitations, together with small pattern measurement, lack of clear inclusion and exclusion standards, and lack of a management group. On this examine, we sought to deal with these limitations and examine the utility of F¹⁸-FDG PET-CTs as technique to non-invasively diagnose ICI-AKI. 

How did you conduct your examine? 

Utilizing knowledge from our earlier multi-center examine of sufferers with ICI-AKI, we centered on those that had a F¹⁸-FDG PET-CT scan across the time of ICI-AKI analysis. We additionally included 2 management teams: sufferers with AKI from non-ICI etiologies and sufferers handled with ICIs who didn’t have AKI on the time of a follow-up F¹⁸-FDG PET-CT. For all three teams, sufferers have been included if that they had F¹⁸-FDG PET-CTs scans at baseline and inside 14 days of AKI onset (or, for the second management group, a follow-up scan between 90-Three hundred and sixty five days following ICI initiation). 

Nuclear radiologists reviewed the F¹⁸-FDG PET-CTs at baseline and follow-up and recorded the common radiotracer standardized uptake worth (SUV) within the renal cortices. The SUV quantifies the quantity of radioactively-labeled glucose within the kidneys, serving as a marker of the quantity of irritation and metabolic exercise occurring within the kidneys. 

We then calculated the common p.c change in SUV from baseline to follow-up for every affected person. The SUV imply elevated by a median of 57.4% from baseline to follow-up amongst sufferers with ICI-AKI, whereas it solely elevated by 8.5% amongst sufferers with AKI from non-ICI causes and was unchanged in sufferers receiving ICIs with out AKI. 

What are the implications? 

Our findings counsel that F¹⁸-FDG PET-CTs could also be a helpful take a look at for diagnosing ICI-AKI. Our hope is to supply sufferers who cannot bear a kidney biopsy safely a non-invasive testing possibility, resembling with F¹⁸-FDG PET-CTs scans, to distinguish the reason for AKI as being ICI-related vs. non-ICI-related. This has essential implications for sufferers, as a result of these with ICI-AKI are handled promptly with steroids, and their ICI remedy is often held till their AKI has recovered or at the least stabilized. 

What are the following steps? 

The following step is to validate our findings in a bigger potential examine the place we recruit sufferers who’ve AKI whereas on ICI therapy to see if F¹⁸-FDG PET-CTs can definitively differentiate ICI-AKI from AKI from non-ICI causes. 

Authorship: Along with Leaf and Gupta, Mass Common Brigham authors embrace Olivia Inexperienced-Lingren (co-first writer), Sudhir Bhimaniya (co-first writer), Aleksandra Krokmal, Heather Jacene, Sophia L. Wells, Sarah A. Kaunfer, Jessica L. Ortega, Sujal I. Shah, Michael Weintraub, Raad B. Chowdhury, Meghan E. Sise, Pedram Heidari, Meghan D. Lee, Harish Seethapathy and Kerry Reynolds. Extra authors embrace Marlies Ostermann, Sugama Chicklore, Ben Sprangers, Christophe M. Deroose, Sandra M. Herrman, Clara Garcia Carro, Michael Daring, Kevin L. Chen, Wai Lun Will Pak, Pazit Beckerman, Yael Eshet, Raymond Ok. Hsu, Miguel Hernandez Pampaloni, Arash Rashidi, Norbert Avril, Vicki Donley, Zain Mithani, Russ Kuker, Muhammad Awiwi, Mindy Wang, Heiko Schoder, Harish Seethapathy, Kerry Reynolds, Maria Jose Soler, Ala Abudayyeh and Ilya Glezerman.