We had a blog entry on this topic a while ago, but the debate continues. A couple of high-profile papers published in 2013 and 2014 suggested that ADT could increase the risk of acute kidney injury (AKI). However, a paper this year by Cardwell et al. in the journal Prostate Cancer & Prostatic Diseases came to the opposite conclusion, asserting that “there was little evidence that gonadotropin-releasing hormone agonists were associated with marked increases in acute kidney injury.”
What is amazing to us, who follow this literature, is that a paper in the same journal with publication dates just a month apart reached the opposite conclusion. That other paper, by Sherer et al., concluded that "ADT is associated with an increased risk of AKI in patients undergoing definitive RT for prostate cancer.”
It is worth noting that neither paper cites the other. We might postulate that each paper was handled by different editors at the journal, who were unaware that they had contradictory papers in the pipeline.
So what are we, as PCa patients, supposed to make of these seemingly contradictory results? The best thing to do is to dig into the details of the papers. One may observe that the studies are built upon large retrospective data sets and the patient populations, drug treatments and measures of kidney disease are not identical. But overall, if there is a risk of AKI, the ongoing debate is a testimony to the fact that the risk, whatever it might be, is relatively small. So, for example, in the paper by Sherer et al., "at two years of follow-up, 4.6% of men receiving ADT experienced a moderate or severe AKI compared with 3.2% of those not receiving ADT". That was based on a data from 27,868 patients in the US Veterans Heath Administration database.
Another important point is that the AKI was diagnosed as a rise in serum creatinine levels, which is a blood marker of kidney function and not necessarily a measure of pending kidney failure. The increased incidence of severe AKI from 3.2 to 4.6% was not statistically significant for those veterans being treated for PCa. Most shifts in creatinine levels in the Sherer et al. study were in the mild range. The overall increased risk of AKI that they documented was from 7.9% in men who did not go on ADT to 10.5% for the men who did. That is an increase of < 3%.
What this suggests to us is that, like cardiovascular status, one should monitor serum creatinine levels in patients going on ADT. The risk of AKI, if real, is small enough that patients with healthy kidneys should not avoid ADT if they need it to control their PCa.
To read the study abstracts, see:
Cardwell et al. (2021): https://pubmed.ncbi.nlm.nih.gov/33772218/
Sherer et al. (2021): https://pubmed.ncbi.nlm.nih.gov/34811501/
References
Cardwell, C. R., O'Sullivan, J. M., Jain, S., Hicks, B. M., Devine, P. A., & McMenamin, Ú. C. (2021). Hormone therapy use and the risk of acute kidney injury in patients with prostate cancer: a population-based cohort study. Prostate cancer and prostatic diseases, 24(4), 1055–1062. https://doi.org/10.1038/s41391-021-00348-x
Sherer, M. V., Deka, R., Salans, M. A., Nelson, T. J., Sheridan, P., & Rose, B. S. (2021). Androgen deprivation therapy and acute kidney injury in patients with prostate cancer undergoing definitive radiotherapy. Prostate cancer and prostatic diseases, 10.1038/s41391-021-00415-3. Advance online publication. https://doi.org/10.1038/s41391-021-00415-3