Cardiac mortality is a concern both before and after kidney transplantation, with annual rates of circulatory death of approximately 7% on dialysis1 and mortality from cardiac disease accounting for 40%–50% of deaths in the first year postkidney transplant.2 Despite reduction in the risk of cardiac mortality after transplantation compared with dialysis and improvements in risk seen in the current era, rates of circulatory death remain higher among kidney transplant recipients than in the general population, as demonstrated in this issue of Transplantation.3 Wyld et al3 performed an analysis of 16 329 kidney transplant recipients in Australian and New Zealand registry data and reported several notable findings. Consistent with previous studies, traditional risk factors including older age, male sex, longer duration of dialysis, and history of coronary artery disease were associated with an increased risk of circulatory death posttransplant. While the risk of cardiac mortality decreased dramatically over time (falling >40% from 1988 to 2013), rates of mortality were still 5 times higher than the general population. Furthermore, the standardized mortality rates were the highest among women across all age groups posttransplantation.
Recent reviews have confirmed traditional and transplant-related risk factors, as well as persistently high rates of cardiac mortality in the transplant population,4-6 but few studies have made the comparison to nontransplant cohorts in the modern era. This issue’s study by Wyld et al3 describes such a comparison and demonstrated that there is still room for improvement in the long-term care of this population related to targeted cardiac risk reduction. The authors demonstrate that the reduction in risk of cardiac mortality in transplant patients has outpaced that of the general population, but rates remain higher than their age and sex-matched counterparts despite advances in prevention and treatment. This finding supports the argument for widespread adoption of management guidelines (such as the Kidney Disease: Improving Global Outcomes group), tailoring immunosuppression regimens, and considering inclusion of these individuals in trials of new treatment options. While the unique management of transplant patients makes it important to understand cardiac risks specific to transplant patients, it is also necessary to put these risks in context, to evaluate whether deaths of cardiac origin occur at a rate that would be expected in the absence of end-stage disease. Replicating this study utilizing other data sources (eg, the Organ Procurement and Transplantation Network and National Health and Nutrition Examination Survey data in the United States and the European Renal Association–European Dialysis and Transplant Association Registry compared to the data from the European Heart Network) could be of great value to the field, to understand whether these disparate rates are universal.
Moreover, gender disparities in kidney transplantation are well-described, with women known to have longer waiting times and lower access to transplantation due to sensitization and worse posttransplant graft outcomes.7-10 However, Wyld et al3 are the first to describe gender disparities in cardiac outcomes among transplant patients compared with the general population. An important finding of this study was the persistence of a greater risk of cardiac mortality among female transplant recipients in all age groups. Alarmingly, excess cardiac mortality was highest in young women posttransplant, with 27 times the circulatory death of women the same age in the general population (compared to only 7.5 times among male transplant recipients versus their general population counterparts). The findings of Wyld et al3 suggest that female transplant recipients may not have appropriate access to cardiac care and further highlight the need for targeted cardiac risk reduction programs in this population.
The authors note an important limitation in the demographics of their study population. Given the lack of racial/ethnic diversity in this cohort, they may not have been able to appropriately assess race-related differences, and the findings may not be generalizable to other transplant populations. While this limitation underscores the potential benefit of performing this study using other national data sources, it does not decrease the value of the current analysis, which is the first to span over 3 decades and be performed in the current era of cardiac screening for transplantation and immunosuppression protocols.
Despite reductions in cardiac mortality observed over time, Wyld et al3 demonstrate that the risk of circulatory death remains higher among transplant patients compared to the general population, with rates highest in female recipients. These findings represent important opportunities for improvements in posttransplant care of all patients but particularly among women, to reduce persistent gender disparities in transplant outcomes.
1. 2006 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. 2006, Bethesda, Maryland: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases
2. Pilmore H, Dent H, Chang S, et al. Reduction in cardiovascular death after kidney transplantation. Transplantation. 2010; 89:851–857
3. Wyld MLR, De La Mata NL, Masson P, et al. Cardiac mortality in kidney transplant patients: a population-based cohort study 1988-2013 in Australia and New Zealand. Transplantation. In press
4. Devine PA, Courtney AE, Maxwell AP. Cardiovascular risk in renal transplant recipients. J Nephrol. 2019; 32:389–399
5. Neale J, Smith AC. Cardiovascular risk factors following renal transplant. World J Transplant. 2015; 5:183–195
6. Stoumpos S, Jardine AG, Mark PB. Cardiovascular morbidity and mortality after kidney transplantation. Transpl Int. 2015; 28:10–21
7. Wolfe RA, Ashby VB, Milford EL, et al. Differences in access to cadaveric renal transplantation in the United States. Am J Kidney Dis. 2000; 36:1025–1033
8. Segev DL, Kucirka LM, Oberai PC, et al. Age and comorbidities are effect modifiers of gender disparities in renal transplantation. J Am Soc Nephrol. 2009; 20:621–628
9. Redfield RR, Scalea JR, Zens TJ, et al. The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients. Nephrol Dial Transplant. 2016; 31:1746–1753
10. Melk A, Babitsch B, Borchert-Mörlins B, et al. Equally interchangeable? How sex and gender affect transplantation. Transplantation. 2019; 103:1094–1110