Donal J Sexton1,2, Patrick O'Kelly1, Eamonn O'Leary3, Susan Murray1, Sandra Deady3, Fergus Daly1, Jim Egan4, Diarmaid D Houlihan5, P Aiden McCormick5, Patrick G Morris6, Siona Ni Raghallaigh7, Fergal J Moloney8, James Paul O'Neill2,9, Peter J Conlon1,2. 1. Department of Nephrology and Kidney Transplantation, Beaumont Hospital Dublin, Ireland. 2. Royal College of Surgeons in Ireland, Dublin, Ireland. 3. National Cancer Registry Ireland, Cork Airport Business Park, Cork, Ireland. 4. National Lung Transplantation Center, Mater University Hospital, Dublin, Ireland. 5. National Liver Transplant Center, St Vincent's University Hospital, Dublin, Ireland. 6. Department of Oncology, Beaumont Hospital, Dublin, Ireland. 7. Department of Dermatology, Beaumont Hospital, Dublin, Ireland. 8. Department of Dermatology, Mater Misericordiae University Hospital, University College Dublin, School of Medicine, Dublin, Ireland. 9. Department of Otolaryngology-Head and Neck Surgery, Beaumont Hospital, Dublin, Ireland.
Abstract
IMPORTANCE: Existing data suggest that nonmelanoma skin cancer (NMSC) is more common in renal transplant recipients than in maintenance dialysis patients. However, whether the risk of NMSC varies as the treatment modality for end-stage kidney disease (ESKD) changes between dialysis and transplantation is not well described. OBJECTIVE: To determine whether the incidence of NMSC is attenuated during periods of graft loss with a return to dialysis in those who receive multiple kidney transplants. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of data from recipients of kidney transplants from the Irish National Kidney Transplant Service database, linked with the Irish Cancer Registry, from 1994 to 2014. All analysis took place between January 10, 2018 and March 31, 2018. Standardized incidence ratios (SIRs) were calculated for NMSC incidence in comparison with the general population using Irish census data as the denominator. Incidence of NMSC was calculated with modality of treatment for ESKD varying over time; incidence rates and rate ratios associated with dialysis intervals were calculated using Poisson regression; and disease was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for cancer diagnosis. EXPOSURES: Kidney transplantation. MAIN OUTCOMES AND MEASURES: Incidence rates per 1000 patient-years and incident rate ratios of NMSC after kidney transplant. RESULTS: Data from the records of 3821 deceased or living donor kidney transplant recipients were assessed; 2399 (62.8%) male and 1422 (37.2%) female recipients; mean (SD) age at time of first data recorded, 41.9 (16.0) years. A total of 3433 recipients were included who had a functioning transplant on January 1, 1994, or received a transplant after that date up to December 31, 2014: 3215 received 1 transplant, 522 a second kidney transplant, and 84 had 3 or more kidney transplants. Periods of treatment with a functioning transplant were associated with a higher incidence of NMSC diagnosis than periods of graft failure: adjusted incidence rate ratio (aIRR), 2.19 (95% CI, 1.56-3.07), P < .001. The aIRRs of NMSC fell from 41.7 (95% CI, 39.38-44.15) per 1000 patient-years in the first transplant to 19.29 (95% CI, 13.41-27.76) in the dialysis period following the first allograft failure. Incidence similarly rose and fell following each subsequent consecutive transplant. CONCLUSIONS AND RELEVANCE: In recipients of multiple kidney transplants, while the incidence of NMSC fell during periods defined by transplant failure, there was residual elevated risk. While ascertainment bias may have contributed to the observed trends, the stagnant incidence of invasive cancer overall highlights the need for continued cancer surveillance during graft failure.
IMPORTANCE: Existing data suggest that nonmelanoma skin cancer (NMSC) is more common in renal transplant recipients than in maintenance dialysis patients. However, whether the risk of NMSC varies as the treatment modality for end-stage kidney disease (ESKD) changes between dialysis and transplantation is not well described. OBJECTIVE: To determine whether the incidence of NMSC is attenuated during periods of graft loss with a return to dialysis in those who receive multiple kidney transplants. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of data from recipients of kidney transplants from the Irish National Kidney Transplant Service database, linked with the Irish Cancer Registry, from 1994 to 2014. All analysis took place between January 10, 2018 and March 31, 2018. Standardized incidence ratios (SIRs) were calculated for NMSC incidence in comparison with the general population using Irish census data as the denominator. Incidence of NMSC was calculated with modality of treatment for ESKD varying over time; incidence rates and rate ratios associated with dialysis intervals were calculated using Poisson regression; and disease was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for cancer diagnosis. EXPOSURES: Kidney transplantation. MAIN OUTCOMES AND MEASURES: Incidence rates per 1000 patient-years and incident rate ratios of NMSC after kidney transplant. RESULTS: Data from the records of 3821 deceased or living donor kidney transplant recipients were assessed; 2399 (62.8%) male and 1422 (37.2%) female recipients; mean (SD) age at time of first data recorded, 41.9 (16.0) years. A total of 3433 recipients were included who had a functioning transplant on January 1, 1994, or received a transplant after that date up to December 31, 2014: 3215 received 1 transplant, 522 a second kidney transplant, and 84 had 3 or more kidney transplants. Periods of treatment with a functioning transplant were associated with a higher incidence of NMSC diagnosis than periods of graft failure: adjusted incidence rate ratio (aIRR), 2.19 (95% CI, 1.56-3.07), P < .001. The aIRRs of NMSC fell from 41.7 (95% CI, 39.38-44.15) per 1000 patient-years in the first transplant to 19.29 (95% CI, 13.41-27.76) in the dialysis period following the first allograft failure. Incidence similarly rose and fell following each subsequent consecutive transplant. CONCLUSIONS AND RELEVANCE: In recipients of multiple kidney transplants, while the incidence of NMSC fell during periods defined by transplant failure, there was residual elevated risk. While ascertainment bias may have contributed to the observed trends, the stagnant incidence of invasive cancer overall highlights the need for continued cancer surveillance during graft failure.
Authors: P Maisonneuve; L Agodoa; R Gellert; J H Stewart; G Buccianti; A B Lowenfels; R A Wolfe; E Jones; A P Disney; D Briggs; M McCredie; P Boyle Journal: Lancet Date: 1999-07-10 Impact factor: 79.321
Authors: C A Harwood; D Mesher; J M McGregor; L Mitchell; M Leedham-Green; M Raftery; R Cerio; I M Leigh; P Sasieni; C M Proby Journal: Am J Transplant Date: 2012-10-16 Impact factor: 8.086
Authors: G F L Hofbauer; N R Attard; C A Harwood; J M McGregor; P Dziunycz; G Iotzova-Weiss; G Straub; R Meyer; Y Kamenisch; M Berneburg; L E French; R P Wüthrich; P Karran; A L Serra Journal: Am J Transplant Date: 2011-09-22 Impact factor: 8.086
Authors: Elizabeth L Yanik; Christina A Clarke; Jon J Snyder; Ruth M Pfeiffer; Eric A Engels Journal: J Am Soc Nephrol Date: 2015-11-12 Impact factor: 14.978
Authors: Susan L Murray; Fergus E Daly; Patrick O'Kelly; Eamonn O'Leary; Sandra Deady; James P O'Neill; Alexander Dudley; Nicholas R Rutledge; Aiden McCormick; Diarmuid D Houlihan; Yvonne Williams; Patrick G Morris; Siona Ni Raghallaigh; Fergal J Moloney; Donal J Sexton; Peter J Conlon Journal: Ren Fail Date: 2020-11 Impact factor: 2.606