Immunosuppression and cancer risk in kidney transplant recipients : A retrospective cohort study
© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC..
We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:154 |
|---|---|
| Enthalten in: |
International journal of cancer - 154(2024), 12 vom: 15. Apr., Seite 2043-2053 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sapir-Pichhadze, Ruth [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Age |
|---|
| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/ijc.34875 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368353052 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368353052 | ||
| 003 | DE-627 | ||
| 005 | 20240415233209.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240213s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/ijc.34875 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1376.xml |
| 035 | |a (DE-627)NLM368353052 | ||
| 035 | |a (NLM)38345158 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sapir-Pichhadze, Ruth |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Immunosuppression and cancer risk in kidney transplant recipients |b A retrospective cohort study |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.04.2024 | ||
| 500 | |a Date Revised 15.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. | ||
| 520 | |a We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a age | |
| 650 | 4 | |a cancer | |
| 650 | 4 | |a immunosuppression | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a sex | |
| 650 | 7 | |a Tacrolimus |2 NLM | |
| 650 | 7 | |a WM0HAQ4WNM |2 NLM | |
| 650 | 7 | |a Prednisone |2 NLM | |
| 650 | 7 | |a VB0R961HZT |2 NLM | |
| 650 | 7 | |a Mycophenolic Acid |2 NLM | |
| 650 | 7 | |a HU9DX48N0T |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 700 | 1 | |a Laprise, Claudie |e verfasserin |4 aut | |
| 700 | 1 | |a Beauchamp, Marie-Eve |e verfasserin |4 aut | |
| 700 | 1 | |a Kaouache, Mohammed |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xun |e verfasserin |4 aut | |
| 700 | 1 | |a Della Vecchia, Alexia |e verfasserin |4 aut | |
| 700 | 1 | |a Azoulay, Laurent |e verfasserin |4 aut | |
| 700 | 1 | |a Franco, Eduardo L |e verfasserin |4 aut | |
| 700 | 1 | |a Abrahamowicz, Michal |e verfasserin |4 aut | |
| 700 | 1 | |a Nicolau, Belinda |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of cancer |d 1966 |g 154(2024), 12 vom: 15. Apr., Seite 2043-2053 |w (DE-627)NLM000004383 |x 1097-0215 |7 nnns |
| 773 | 1 | 8 | |g volume:154 |g year:2024 |g number:12 |g day:15 |g month:04 |g pages:2043-2053 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/ijc.34875 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 154 |j 2024 |e 12 |b 15 |c 04 |h 2043-2053 | ||