Association between Use of Hydrochlorothiazide and Risk of Keratinocyte Cancers in Kidney Transplant Recipients

Background and objectives Keratinocyte cancers, which primarily comprise squamous cell carcinomas and basal cell carcinomas, represent a major concern and potential risk for kidney transplant recipients. Hydrochlorothiazide, a diuretic widely used to treat hypertension, has been implicated in skin photosensitivity reaction. Recent studies conducted in the general population have found that hydrochlorothiazide use is associated with a higher risk of keratinocyte cancer, especially squamous cell carcinomas. High-risk groups, however, including transplant recipients were excluded fromthese. Our aimwas to investigatewhether hydrochlorothiazide usewas associated with keratinocyte cancer in kidney transplant recipients on immunosuppressive therapy. Design, setting, participants, & measurements In a single-center cohort of kidney (n=2155), combined kidney-pancreas (n=282), and pancreas (n=59) transplant recipients from the Donnees Informatisees VAlidees Transplantation (DIVAT) database transplanted between 2000 and 2017 in Nantes, France, we evaluated the association between hydrochlorothiazide exposure and keratinocyte cancers. Multivariable cause-specific, time varying Cox models were used to estimate the relationshipbetween hydrochlorothiazide exposure andthe hazard of squamous cell carcinoma andbasal cell carcinoma, with hydrochlorothiazide designated as the time-dependent variable. ResultsAmong the participants, 279 of 2496 (11%) were exposed to hydrochlorothiazide after the transplantation. Cumulative incidence rates of keratinocyte cancer by 10 and 15 years were 7% and 9% for squamous cell carcinomas, respectively, and8% and11% for basal cell carcinomas, respectively. We founda relationshipbetween exposure to hydrochlorothiazide and the risk of squamous cell carcinomas (hazard ratio, 2.04; 95% confidence interval, 1.27 to 3.28). In contrast, we found no association between hydrochlorothiazide exposure and basal cell carcinomas (hazard ratio, 0.63; 95% confidence interval, 0.35 to 1.15). Conclusions In a single-center cohort of kidney, combined kidney-pancreas, and pancreas transplant recipients, exposure to hydrochlorothiazide was associated with a two-fold higher risk of squamous cell carcinoma and no higher risk of basal cell carcinoma.