The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation.
OBJECTIVE
Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time.


METHODS
We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis.


RESULTS
Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation.


CONCLUSIONS
Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.
Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel. shelly_licht@yahoo.com.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. shelly_licht@yahoo.com.
Shelly
S
Lichtenberg
Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Organ Transplantation, Rabin Medical Center, Petah Tikva, Israel.
Ruth
R
Rahamimov
Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Hefziba
H
Green
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|The Pulmonary Institute, Rabin Medical Center, Petah Tikva, Israel.
Benjamin D
BD
Fox
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Department of Organ Transplantation, Rabin Medical Center, Petah Tikva, Israel.
Eytan
E
Mor
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Uzi
U
Gafter
Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Avry
A
Chagnac
Department of Nephrology and Hypertension, Rabin Medical Center, Petah Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Benaya
B
Rozen-Zvi
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology*; D016017:Odds Ratio; D016559:Tacrolimus / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016559:Tacrolimus
Immunosuppressive drugs; Malignancy; Tacrolimus; Transplantation