Mortality Among Solid Organ Waitlist Candidates During COVID-19 in the United States

Jonathan Miller; Andrew Wey; Donald Musgrove; Yoon Son Ahn; Allyson Hart; Bertram L. Kasiske; Ryutaro Hirose; Ajay K. Israni; Jon J. Snyder

Disclosures

American Journal of Transplantation. 2021;21(6):2262-2268. 

In This Article

Discussion

Waitlist mortality rates were notably higher at the outset of the COVID-19 national emergency among kidney waitlist candidates but not other solid organ transplant candidates. The differences in kidney waitlist mortality rates varied geographically, with dramatically higher rates in the New York City DSA. The relative waitlist mortality rate for African Americans compared with White kidney candidates was higher after COVID-19 than before. The differences in waitlist mortality rates across categories of MELD attenuated in the months after the pandemic began, though the COVID-19 pandemic coincided with the beginning of the liver acuity circle allocation policy—an alternate possible explanation for changed in waitlist mortality rates at higher MELD scores.

Waitlist mortality rates have historically been lower for kidney candidates than for candidates for other solid organs.[9] However, the largest number of candidates are listed for kidney transplant, and kidney candidates have the longest waiting times.[9] Thus, a higher hazard of waitlist mortality among kidney candidates can represent a substantial number of additional deaths, especially if the higher waitlist mortality is sustained over a long period.

Among the many possible causes of the increased mortality rates among kidney waitlist candidates, a few warrant additional discussion. One hypothesis is that the mortality rate increased due to delayed transplants. We estimated the differences in the cause-specific hazard of waitlist mortality before and after COVID-19. The cause-specific hazard does not mathematically or inherently depend on changes in the transplant rate, although residual confounding could still cause a relationship between waitlist mortality and transplant rates. A second hypothesis is that the mortality rate increased due to deaths from COVID-19 directly or as the result of delayed medical care due to fear of infection. A limitation of the SRTR database is that individual-level cause of death is significantly missing, preventing firm conclusions about which of these hypotheses is better supported. Inference about the impact of the pandemic on the United States transplant system will be improved if individual level data about COVID incidence and mortality becomes available for transplant waiting list candidates. However, analysis by the US Renal Data System (USRDS) found that hospitalizations due to COVID-19 showed peaks in April and July—consistent with the peaks in waitlist mortality found in this study, and giving support to the hypothesis of direct increases in mortality due to COVID-19.[10] In the USRDS analysis, in-home peritoneal dialysis was protective against COVID-19 as compared to in-center hemodialysis. The USRDS also found that non-COVID hospitalizations were decreased compared to the same months in 2017–2019, giving support to the hypothesis of increases in mortality due to delayed medical care.[10] Additionally, evidence of increased overall mortality among kidney candidates in the United Kingdom[2] and the substantial increase in waitlist mortality in New York City, New Jersey, and Michigan—early COVID-19 hotspots in the United States—suggests that COVID-19 increased the waitlist mortality rate of kidney candidates, although, the relative contribution of the specific mechanisms (i.e., COVID-19 infection or delayed care) remains unknown.

Understanding the reasons for higher waitlist mortality among kidney candidates than candidates for other solid organs will require continued study. Analysis of the United Kingdom registry found that risk of developing COVID-19 was higher for kidney candidates than for kidney recipients.[2] Social distancing may have been more challenging for kidney transplant candidates undergoing in-center dialysis. Future studies of candidate health behaviors or candidate health care system interactions (e.g., dialysis for kidney candidates vs. pretransplant hospitalization for other solid organ candidates) may provide insight on why only kidney transplant candidates had a higher waitlist mortality rate.

Geographic differences in waitlist mortality were notable for kidney candidates, suggesting that PSRs should be modified in the short term to address changes in outcomes driven by the COVID-19 pandemic rather than by clinical care at transplant programs. As a temporary measure, PSRs released in January 2021 censored follow-up of transplant candidates on March 12, 2020, which should remove most of the risk of confounding due to COVID-19 in the early part of the pandemic from the waitlist mortality evaluations.

However, PSRs cannot indefinitely censor follow-up on March 12, 2020. As part of the COVID-19 evaluation, SRTR continues to investigate approaches to handling COVID-19 in PSRs. For example, the waitlist mortality models could adjust for the COVID-19 incidence in the transplant program's region. If this approach removes the DSA-level variability in waitlist mortality for kidney candidates, it is a viable approach for integrating candidate follow-up after the emergence of COVID-19. Alternatively, COVID-19 may become endemic throughout the United States and equally affect transplant programs. At this point, the DSA-level variability in waitlist mortality before and after COVID-19 would likely attenuate and normal follow-up could resume, possibly with the need to carve out data from March 13, 2020 to the date at which geographic variability is reduced.

The trend of higher waitlist mortality among African American kidney candidates after than before COVID-19 should be monitored. COVID-19 has already widened health disparities between African Americans and Whites.[11] Ongoing monitoring will be important in identifying widening health disparities in specific parts of the health system due to COVID-19 (e.g., waitlist mortality of kidney candidates). Differences in mortality by MELD scores deserve more investigation, especially with respect to the nearly concurrent implementation of acuity circles. A limitation of this study was that there were currently too few mortality events to model subgroup differences for pancreas, lung and heart candidates. SRTR evaluation will continue to analyze possible subgroup differences during the course of the COVID-19 pandemic.

Preliminary time trends show that waitlist mortality among kidney candidates has remained high, and the SRTR continues to analyze whether the geographic variability in waitlist mortality remains high. Future analyses should continue to monitor waitlist mortality rates in solid organ transplant candidates and look for approaches to reduce geographic variation. This is critical for the return of the PSRs to normal reporting cohorts. While a limitation of the SRTR data is the lack of consistent cause-of-death data for transplant candidates and recipients, estimating geographic correlations of COVID-19 incidence with changes in waitlist mortality is being investigated as SRTR continues analyzing the impact of COVID-19.

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