In Reply Dr Smith suggests that a cause-effect relationship between ADT and AKI is biologically improbable. Although this biological link may not be obvious, there is emerging evidence from animal models that reduction of testosterone to castration levels promotes renal dysfunction and injury, whereas testosterone repletion offers a protective effect to the kidneys.1 Furthermore, ADT leads to a depletion of estrogen,2 with estrogen shown to have a renoprotective effect in AKI models.3 Even though the relative contributions of testosterone and estrogen deficiencies on AKI models require further study, there is biological evidence that these hormones may play a role in preventing or minimizing injury to the kidneys, which could be disrupted with the use ADT. This evidence is compounded by the fact that ADT has also been associated with an increased risk of cardiovascular outcomes, which may indirectly increase the risk of AKI. The fact that this infrequent adverse event was not observed in individual randomized controlled trials is not surprising given their limited size.
Azoulay L, Benayoun S, Suissa S. Androgen Deprivation Therapy and Acute Kidney Injury—Reply. JAMA. 2013;310(21):2313-2314. doi:10.1001/jama.2013.281602