C
American Journal of Transplantation 2015; 15: 287–288 Wiley Periodicals Inc.
Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13015
Letter to the Editor
Selecting Appropriate Controls for Kidney Donors—Reply To the Editor: It is not possible to randomize an individual to become a living kidney donor. Therefore, we agree with Mjøen and Holdaas that it is necessary to examine the comparability of the baseline characteristics of the donor and nondonor
groups in any study of living donor outcomes (1). We stand by the conclusion of our manuscript, which reads: ‘‘In the context of careful medical evaluation and selection, older donors should expect similar medium-term survival and risk of CVD compared to healthy members of the general population’’ (2, p. 1859).
Table 1: Nondonor groups used as comparators in recent studies of outcomes after live kidney donation
Data source Type of baseline data on nondonors
Health and National Health National Center Retirement and Nutrition Health Study for Health Statistics Study Examination Survey of Nord-Trondelag Life Tables (Reese et al) (2) (Muzaale et al) (5) (Mjøen et al) (3) (Ibrahim et al) (6) Interviews
Healthy residents of Ontario, Canada with health system records (Garg et al) (7)
Interviews and limited clinical measurements
Interviews and limited clinical measurements
N/A
Universal healthcare administrative databases
Yes Yes Yes No Yes No Yes
Yes Yes Yes Yes Yes No No
Yes Yes Yes No No No No
No No No No No No No
Yes Yes Yes Yes Yes Yes No
Yes Yes (40 kg/m2) Yes No No
Yes Yes (>30 kg/m2) No Yes No
No Yes (>30 kg/m2) Yes No No
No No No No No
Yes No No No No
Yes Yes Yes No
No No No No
Yes No No Yes
Yes
Yes Yes2 Yes2 No (but, did match on education) No
No
No
Yes
3 368 3 368
9 364 96 217
32 621 1 901
N/A 3 698
20 280 2 028
Nondonors with this condition eliminated from comparator group1 Hypertension Diabetes Cardiovascular disease Kidney disease Pulmonary disease Liver disease Psychiatric and neurologic disorders Malignancy Elevated BMI Low self-rated health Poor functional status Abnormalities on kidney imaging
Characteristic used for matching1 Demographics BMI Blood pressure Neighborhood Income Year of cohort entry (donation date for donors) Number of nondonors Number of donors
Yes Yes2 No Yes
1
Some additional characteristics used for restriction or matching are not listed in this table. When available for donors.
2
287
Reese et al
Mjøen and Holdaas (1) note that our methods included restriction of the comparison group to nondonors who, in serial interviews with the Health and Retirement Study (HRS), denied a range of relevant health conditions such as diabetes and cardiovascular disease. The HRS participants in the comparison group also needed to rate their overall health as ‘‘good,’’ ‘‘very good,’’ or ‘‘excellent.’’ These were the strategies used to create a nondonor group with a low prevalence of serious medical problems that would serve as a useful benchmark when interpreting outcomes among older live kidney donors. However, we did not have serological values, medical records or abdominal imaging to further characterize the health of the nondonors. Mjøen and Holdaas recapitulated this limitation that we acknowledged in the manuscript, namely the potential for residual confounding by unrecognized medical problems in the nondonor group (2). Mjøen and Holdaas (1) also draw attention to the separation of the donor and nondonor survival curves in our Figure 2. Yet, that separation was not significant (p ¼ 0.21) in the primary analysis (donors 55 years). A substantive conclusion about this study’s validity should not be based on this small and statistically insignificant difference in survival, which may only reflect sampling noise. In Table 1, we present a summary of donor comparison groups from recent studies that reported mortality. The table includes an important study by Mjøen et al that also relied in part on data from interviews to generate a healthy comparison group of nondonors (3). The table examines whether individuals were excluded from the nondonor groups because of medical abnormalities for which live donors are screened (4). In each case, the approach taken to assemble the nondonor group has limitations. We hope that future studies will generate new knowledge about long-term donor outcomes using comparison groups that, while likely still imperfect, represent improvements over existing work. P. P. Reese1,2, , R. D. Bloom1, H. I. Feldman1,2, A. X. Garg3, A. Mussell2, J. Shults2 and J. H. Silber4,5 1 Renal Electrolyte & Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
288
2
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 3 Division of Nephrology, Department of Medicine, University of Western Ontario, London, Ontario, Canada 4 Center for Outcomes Research, The Children’s Hospital of Philadelphia, Philadelphia, PA 5 Departments of Pediatrics and Anesthesiology & Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA Corresponding author: Peter P. Reese, peter.reese@uphs. upenn.edu
Acknowledgments This study was funded by the American Society of Transplantation.
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Mjøen G, Holdaas H. Selecting appropriate controls for kidney donors. Am J Transplant 2015; 15: 286. 2. Reese PP, Bloom RD, Feldman HI, et al. Mortality and cardiovascular disease among older live kidney donors. Am J Transplant 2014; 14: 1853–1861. 3. Mjøen G, Hallan S, Hartmann A, et al. Long-term risks for kidney donors. Kidney Int 2014; 86: 162–167. 4. Organ Procurement and Transplantation Network. Policy 172. Living Donation. Available at: http://optn.transplant.hrsa.gov/PoliciesandBylaws2/policies/pdfs/policy_172.pdf. Accessed August 5, 2014. 5. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA 2014; 311: 579– 586. 6. Ibrahim HN, Foley R, Tan L, et al. Long-term consequences of kidney donation. N Engl J Med 2009; 360: 459–469. 7. Garg AX, Meirambayeva A, Huang A, et al. Cardiovascular disease in kidney donors: Matched cohort study. BMJ 2012; 344: e1203.
Copyright of American Journal of Transplantation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
American Journal of Transplantation 2015; 15: 287–288 Wiley Periodicals Inc.
Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/ajt.13015
Letter to the Editor
Selecting Appropriate Controls for Kidney Donors—Reply To the Editor: It is not possible to randomize an individual to become a living kidney donor. Therefore, we agree with Mjøen and Holdaas that it is necessary to examine the comparability of the baseline characteristics of the donor and nondonor
groups in any study of living donor outcomes (1). We stand by the conclusion of our manuscript, which reads: ‘‘In the context of careful medical evaluation and selection, older donors should expect similar medium-term survival and risk of CVD compared to healthy members of the general population’’ (2, p. 1859).
Table 1: Nondonor groups used as comparators in recent studies of outcomes after live kidney donation
Data source Type of baseline data on nondonors
Health and National Health National Center Retirement and Nutrition Health Study for Health Statistics Study Examination Survey of Nord-Trondelag Life Tables (Reese et al) (2) (Muzaale et al) (5) (Mjøen et al) (3) (Ibrahim et al) (6) Interviews
Healthy residents of Ontario, Canada with health system records (Garg et al) (7)
Interviews and limited clinical measurements
Interviews and limited clinical measurements
N/A
Universal healthcare administrative databases
Yes Yes Yes No Yes No Yes
Yes Yes Yes Yes Yes No No
Yes Yes Yes No No No No
No No No No No No No
Yes Yes Yes Yes Yes Yes No
Yes Yes (40 kg/m2) Yes No No
Yes Yes (>30 kg/m2) No Yes No
No Yes (>30 kg/m2) Yes No No
No No No No No
Yes No No No No
Yes Yes Yes No
No No No No
Yes No No Yes
Yes
Yes Yes2 Yes2 No (but, did match on education) No
No
No
Yes
3 368 3 368
9 364 96 217
32 621 1 901
N/A 3 698
20 280 2 028
Nondonors with this condition eliminated from comparator group1 Hypertension Diabetes Cardiovascular disease Kidney disease Pulmonary disease Liver disease Psychiatric and neurologic disorders Malignancy Elevated BMI Low self-rated health Poor functional status Abnormalities on kidney imaging
Characteristic used for matching1 Demographics BMI Blood pressure Neighborhood Income Year of cohort entry (donation date for donors) Number of nondonors Number of donors
Yes Yes2 No Yes
1
Some additional characteristics used for restriction or matching are not listed in this table. When available for donors.
2
287
Reese et al
Mjøen and Holdaas (1) note that our methods included restriction of the comparison group to nondonors who, in serial interviews with the Health and Retirement Study (HRS), denied a range of relevant health conditions such as diabetes and cardiovascular disease. The HRS participants in the comparison group also needed to rate their overall health as ‘‘good,’’ ‘‘very good,’’ or ‘‘excellent.’’ These were the strategies used to create a nondonor group with a low prevalence of serious medical problems that would serve as a useful benchmark when interpreting outcomes among older live kidney donors. However, we did not have serological values, medical records or abdominal imaging to further characterize the health of the nondonors. Mjøen and Holdaas recapitulated this limitation that we acknowledged in the manuscript, namely the potential for residual confounding by unrecognized medical problems in the nondonor group (2). Mjøen and Holdaas (1) also draw attention to the separation of the donor and nondonor survival curves in our Figure 2. Yet, that separation was not significant (p ¼ 0.21) in the primary analysis (donors 55 years). A substantive conclusion about this study’s validity should not be based on this small and statistically insignificant difference in survival, which may only reflect sampling noise. In Table 1, we present a summary of donor comparison groups from recent studies that reported mortality. The table includes an important study by Mjøen et al that also relied in part on data from interviews to generate a healthy comparison group of nondonors (3). The table examines whether individuals were excluded from the nondonor groups because of medical abnormalities for which live donors are screened (4). In each case, the approach taken to assemble the nondonor group has limitations. We hope that future studies will generate new knowledge about long-term donor outcomes using comparison groups that, while likely still imperfect, represent improvements over existing work. P. P. Reese1,2, , R. D. Bloom1, H. I. Feldman1,2, A. X. Garg3, A. Mussell2, J. Shults2 and J. H. Silber4,5 1 Renal Electrolyte & Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
288
2
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 3 Division of Nephrology, Department of Medicine, University of Western Ontario, London, Ontario, Canada 4 Center for Outcomes Research, The Children’s Hospital of Philadelphia, Philadelphia, PA 5 Departments of Pediatrics and Anesthesiology & Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA Corresponding author: Peter P. Reese, peter.reese@uphs. upenn.edu
Acknowledgments This study was funded by the American Society of Transplantation.
Disclosure The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.
References 1. Mjøen G, Holdaas H. Selecting appropriate controls for kidney donors. Am J Transplant 2015; 15: 286. 2. Reese PP, Bloom RD, Feldman HI, et al. Mortality and cardiovascular disease among older live kidney donors. Am J Transplant 2014; 14: 1853–1861. 3. Mjøen G, Hallan S, Hartmann A, et al. Long-term risks for kidney donors. Kidney Int 2014; 86: 162–167. 4. Organ Procurement and Transplantation Network. Policy 172. Living Donation. Available at: http://optn.transplant.hrsa.gov/PoliciesandBylaws2/policies/pdfs/policy_172.pdf. Accessed August 5, 2014. 5. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA 2014; 311: 579– 586. 6. Ibrahim HN, Foley R, Tan L, et al. Long-term consequences of kidney donation. N Engl J Med 2009; 360: 459–469. 7. Garg AX, Meirambayeva A, Huang A, et al. Cardiovascular disease in kidney donors: Matched cohort study. BMJ 2012; 344: e1203.
Copyright of American Journal of Transplantation is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
