Trend of Kidney Transplant Recipients and Donor Cause of Death Before vs During the Covid-19 Pandemic

Author Information¹
Chloe Lee², Roy Shang³, Ahan Tenneti⁴
(Editor: Koizumi, Naoru⁵)

¹ All authors are listed in Alphabetical Order. 
² Battlefield High School, VA, ³ San Marino High School, CA, ⁴ Quarry Lane High School, CA, ⁵ George Mason University

Background

In 2020 and 2021, drug-related overdose death rates have dramatically increased, primarily driven by the Covid-19 pandemic and escalating use of synthetic-opioids like fentanyl. Drug overdose mortality rates in 2020 have increased significantly compared to previous years between 1999 to 2019, particularly Black, Hispanic/Latino, and American Indian/Alaska Native communities [1]. It is assumed that drug usage increased due to factors such as economic disturbance, lack of socialization, and psychological distress [2]. A study found from March 2020 to March 2021 states that drug overdose deaths rose by 29.4%, from 71,000 in 2019 to 93,000 in 2020, compared to the previous 12-month period. The increase was particularly among non-Hispanic Black individuals, who experienced a 44% rise in overdose deaths. Additionally, the study highlighted regional variations, with the highest increases observed in the Southern and Western United States. 

Organs procured from overdose death donors (ODDs) are typically finer in comparison to organs from donors who passed from long-term illnesses. A study between 2000 and 2017 analyzed deceased donors and transplant recipients at transplant centers, using data from the Scientific Registry of Transplant Recipients. Outcomes of transplanted organs from organ donors who died from drug overdoses (OODs) have been compared to the outcomes of trauma-death donors (TDDs) and medical-death donors (MDDs). They have also confirmed that they have very similar outcomes to TDDs and MDDs, revealing that ODDs should not be discarded due to infection risk and hepatitis C concerns [4].  Another study compared the lungs used in transplants from drug intoxicated donors and non-drug intoxicated donors. While drug intoxicated donors tended to be younger, there was no significant difference in post-lung transplant survival after 1, 3, and 5 years using the data between 2000 and 2024. [5].  

Objective

The objective of this study was to assess the outcomes of transplants using kidneys from donors with various causes of death before and during the pandemic. The specific interest was to identify any changes in the outcomes of transplants using kidneys from donors died from drug overdose during the pandemic given the reported change in the profile of drug overdose death victims during the pandemic.  

Methods

The analysis was performed using the UNOS dataset consisting of the various characteristics of recipients and donors involved in kidney transplants as well as characteristics of the transplants themselves, such as location and compatibility between donors and transplant recipients. Using R, the data was used to perform a descriptive statistical analysis comparing various transplant-related variables. Kaplan Meier survival curves were created to track the graft and patient survival rates for 6 causes of death. Cox regression was performed to evaluate the relative effects of variables on graft failure and patient mortality. Log-rank tests were used to determine the differences between the KM curves. A p-value of 0.05 or lower qualified as a variable with statistical significance. 

Results

Characteristics	Pre-pandemic(n = 25,548)	During pandemic(n = 37,177)	p-value
Patient Characteristics
Male, n (%)	15,418 (60.35%)	22,661 (60.95%)	0.127
Age, mean (sd)	54.12 (13.10)	53.89 (13.22)	0.051
Race, n (%)
White	9,340 (36.56%)	13,290 (35.75%)	0.038
Black	8,690 (34.01%)	12,964 (34.87%)	0.027
Hispanic	4,982 (19.50%)	7,258 (19.52%)	0.945
Asian	1,947 (7.62%)	2,864 (7.70%)	0.702
Other	589 (2.31%)	801 (2.15%)	0.207
Wait time (in days), median (IQR)	610 (927.80)	529 (887.27)	<0.001
Retransplant, n (%)	2,895 (11.33%)	4,008 (10.78%)	0.03
Diabetes at the time of TX, n (%)	9,822 (38.45%)	14,693 (39.52%)	0.007
BMI at the time of TX, mean (sd)	28.84 (5.43)	29.06 (5.45)	<0.001
Dialysis at the time of TX, n (%)	21,780 (85.25%)	31,649 (85.13%)	0.676
cPRA at the time of TX, mean (sd)	25.27 (37.11)	24.58 (36.50)	0.01
Donor Characteristics
Male, n (%)	15,632 (61.19%)	23,680 (63.70%)	<0.001
Age, mean (sd)	41.55 (13.17)	41.90 (12.80)	<0.001
Race, n (%)
White	17,705 (69.30%)	25,482 (68.54%)	0.044
African American	3,278 (12.83%)	4,987 (13.41%)	0.034
Hispanic	3,602 (14.10%)	5,250 (14.12%)	0.936
Asian	605 (2.37%)	911 (2.45%)	0.509
Other	358 (1.40%)	547 (1.47%)	0.47
Cause of death, n (%)
Drug overdose	4,291 (16.80%)	7,676 (20.65%)	<0.001
Stroke	6,459 (25.28%)	8,553.00 (23.01%)	<0.001
Blunt Injury	5,039 (19.72%)	6,740 (18.13%)	<0.001
Cardiovascular disease	4,651 (18.20%)	7,208 (19.39%)	<0.001
Natural death	1,054 (4.13%)	1,621 (4.36%)	0.153
Other	4,054 (15.87%)	5,379 (14.47%)	<0.001
KDPI, mean (sd)	0.45 (0.26)	0.46 (0.25)	<0.001
Creatinine at the time of TX, mean (sd)	1.38 (1.29)	1.40 (1.34)	0.066
Diabetes at the time of TX, n (%)	2,123 (8.38%)	3,324 (9.08%)	0.002
Hypertensive at the time of TX, n (%)	7,991 (31.59%)	11,780 (32.22%)	0.098
BMI at the time of TX, mean (sd)	28.97 (6.97)	29.35 (7.23)	<0.001
Donor after Circulatory Death, n (%)	6,652 (26.04%)	11,712 (31.50%)	<0.001
Expanded Criteria Donor, n (%)	4,029 (15.77%)	5,829 (15.68%)	0.758
Transplant Characteristics
HLA mismatch level, mean (sd)	4.12 (1.47)	4.15 (1.46)	0.052
Cold ischemic time (hrs), mean (sd)	18.22 (8.47)	19.17 (8.00)	<0.001
Locally shared, n (%)	17,537 (68.64%)	20,776 (55.88%)	<0.001
Regionally shared, n (%)	3,887 (15.21%)	7,846 (21.10%)	<0.001
Nationally shared, n (%)	4,124 (16.14%)	8,555 (23.01%)	<0.001

Our analysis compared kidney transplants before and after the COVID-19 pandemic, revealing significant shifts in both recipient and donor characteristics. During the pandemic, the number of transplant recipients increased across all racial groups, with a notable rise in patients with diabetes (39.52% vs. 38.45%) and a slight increase in average BMI (29.06 vs. 28.84). Median wait times for transplants decreased significantly (529 days vs. 610 days), while the average cPRA (antibody) level was slightly lower during the pandemic (24.58 vs. 25.27). Among donors, there was an increase in male donors (63.70% vs. 61.19%) and the average donor age (41.90 years vs. 41.55 years). The racial composition of donors shifted slightly, with a decrease in White donors and an increase in African American donors. Causes of donor death also changed, with more deaths due to drug overdoses, cardiovascular diseases, and natural causes. Cold ischemic times were slightly shorter during the pandemic (19.17 hours vs. 18.22 hours), and there was a significant increase in the proportion of nationally shared transplants (23.01% vs. 16.14%). These findings underscore the widespread impact of the COVID-19 pandemic on kidney transplant practices and outcomes.

Graft Survival by Cause of Death: Pre-pandemic 

Patient Survival by Cause of Death: Pre-pandemic 

Graft Survival by Cause of Death: During the pandemic 

Patient Survival by Cause of Death: During the pandemic 

The KM curves showed statistically significant differences in graft and patient survival rates. The order of highest to lowest survival rate, however, stayed constant before and after the pandemic, the distribution changed; pre-pandemic, there are two distinct groups consisting of three causes of death that are similar to each other but different from the other group; during the pandemic, the distributions of survival rates is much more even. Despite this, in every case, kidneys from donors who died of drug overdose resulted in the highest survival rates. 

Pre-pandemic: Graft Failure

Variable	HR	[95%	C.I.]	P-Value
Male patient	1.157	1.08	1.238	<0.001
Age	1.019	1.016	1.022	<0.001
White patient	0.9093	0.8459	0.9775	0.01
Hispanic patient	0.8317	0.7613	0.9085	<0.001
Asian patient	0.6241	0.5412	0.7196	<0.001
Re-transplantation	1.195	1.067	1.338	0.002
BMI at the time of transplant	1.014	1.008	1.021	<0.001
Cold ischemic time in hours	1.006	1.003	1.01	<0.001
Patient history of diabetes	1.261	1.181	1.346	<0.001
Dialysis at the time of transplant	1.631	1.469	1.811	<0.001
cPRA at the time of transplant	1.001	1	1.002	0.037
KDPI (the quality measure for donated kidneys)	1.889	1.615	2.21	<0.001
Donor diabetes status	1.15	1.041	1.272	0.006
Donor of circulatory death	1.103	1.029	1.183	0.006
Donor died from:
Stroke	1.194	1.074	1.328	0.001
Blunt injury	1.117	0.9993	1.25	0.051
Cardiovascular related	1.188	1.065	1.326	0.002
Natural cause	1.3	1.103	1.532	0.002
Other sudden death	1.091	0.9696	1.228	0.148

Pre-pandemic: Patient Mortality

Variable	HR	[95%	C.I.]	P-Value
Male patient	1.184	1.101	1.274	<0.001
Age	1.045	1.041	1.049	<0.001
White patient	0.7968	0.6427	0.9879	0.038
Black patient	0.7985	0.6443	0.9897	0.04
Hispanic patient	0.75	0.6007	0.9364	0.011
Asian patient	0.5486	0.4258	0.7068	<0.001
Re-transplantation	1.265	1.124	1.425	<0.001
BMI at the time of transplant	1.013	1.006	1.02	<0.001
Cold ischemic time in hours	1.004	1	1.008	0.043
Patient history of diabetes	1.48	1.375	1.593	<0.001
Dialysis at the time of transplant	1.822	1.617	2.053	<0.001
Donor age	1.006	1.003	1.009	<0.001
African American donor	1.139	1.027	1.262	0.013
Hispanic donor	1.148	1.034	1.276	0.01
Asian donor	1.295	1.044	1.607	0.019
Donor history of hypertension	1.113	1.028	1.204	0.008
Donor BMI	0.9942	0.9891	0.9993	0.026
Donor of circulatory death	1.121	1.036	1.213	0.005
Donor died from:
Stroke	1.123	0.9935	1.27	0.063
Blunt injury	1.083	0.9517	1.232	0.227
Cardiovascular related	1.172	1.033	1.33	0.014
Natural cause	1.374	1.144	1.649	<0.001
Other sudden death	1.062	0.9283	1.215	0.382

During pandemic: Graft Failure

Variable	HR	[95%	C.I.]	P-Value
Male patient	1.123	1.035	1.22	0.006
Age	1.026	1.022	1.029	<0.001
Re-transplantation	1.164	1.012	1.338	0.033
BMI at the time of transplant	1.024	1.017	1.032	<0.001
HLA Mismatch Level	1.069	1.04	1.099	<0.001
Cold ischemic time in hours	1.01	1.005	1.014	<0.001
Patient history of diabetes	1.367	1.264	1.478	<0.001
Dialysis at the time of transplant	1.568	1.387	1.774	<0.001
cPRA at the time of transplant	1.003	1.001	1.004	<0.001
Male donor	0.9187	0.8503	0.9925	0.031
African American donor	1.347	1.073	1.691	0.01
White donor	1.297	1.05	1.603	0.016
Hispanic donor	1.291	1.025	1.625	0.03
KDPI (the quality measure for donated kidneys)	1.891	1.571	2.276	<0.001
Donor of circulatory death	1.188	1.097	1.287	<0.001
Donor died from:
Stroke	1.232	1.093	1.389	<0.001
Blunt injury	1.213	1.065	1.38	0.004
Cardiovascular related	1.177	1.042	1.329	0.009
Natural cause	1.307	1.079	1.584	0.006
Other sudden death	1.104	0.9584	1.271	0.171

During pandemic: Patient Mortality

Variable	HR	[95%	C.I.]	P-Value
Male patient	1.18	1.073	1.298	<0.001
Age	1.044	1.039	1.048	<0.001
Asian patient	0.8108	0.6781	0.9696	0.022
BMI at the time of transplant	1.02	1.011	1.029	<0.001
HLA Mismatch Level	1.054	1.021	1.088	0.001
Donor history of diabetes	1.595	1.456	1.747	<0.001
Dialysis at the time of transplant	1.64	1.421	1.893	<0.001
cPRA at the time of transplant	1.004	1.003	1.006	<0.001
KDPI (the quality measure for donated kidneys)	1.601	1.3	1.972	<0.001
Donor of circulatory death	1.153	1.053	1.263	0.002
Donor died from:
Stroke	1.095	0.9551	1.256	0.193
Blunt injury	1.178	1.018	1.363	0.027
Cardiovascular related	1.115	0.9704	1.28	0.125
Natural cause	1.093	0.8652	1.38	0.457
Other sudden death	1.083	0.9237	1.269	0.327

There are multiple variables that have a significant effect on graft failure or patient mortality, but the focus is the donor’s cause of death, using drug overdose death as a reference group. In terms of the effect on graft failure, only stroke, cardiovascular, and natural deaths presented a significant difference from drug overdose pre-pandemic, and everything besides other was significant during the pandemic. In terms of the effect on patient mortality, cardio and natural presented a significant difference from drug overdose pre-pandemic, and only blunt was significant during the pandemic. In every case, kidneys donated by donors who died from drug overdose posed the lowest effect on graft failure and patient survival, both pre- and during the pandemic.

Conclusion

The COVID-19 pandemic has led to significant changes in profiles of kidney transplant recipients and donors. These changes included an increase in transplant recipients in all races, an increase in transplant recipients with diabetes, and a decrease in those on dialysis at the time of transplant. There have also been notable changes in donor profiles such as more male/older donors, an increase in white donors, and more deaths caused by drug overdoses and cardiovascular diseases. As for the graft survival rates, there has not been much of a remarkable change that occurred. The trend of higher survival rates from donors who died from drug overdose and other non-natural causes compared to those from cardiovascular and other natural causes have been the same before and after the pandemic.  

References

1. Durand CM, Bowring MG, Thomas AG, Kucirka LM, Massie AB, Cameron A, Desai NM, Sulkowski M, Segev DL. (2018). The drug overdose epidemic and deceased-donor transplantation in the United States: a national registry study. Annals of internal medicine. https://pubmed.ncbi.nlm.nih.gov/29710288/  
2. Friedman JR, Hansen H. (2022). Evaluation of Increases in Drug Overdose Mortality Rates in the US by Race and Ethnicity Before and During the COVID-19 Pandemic. https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2789697
3. Glober, N., Mohler, G., Huynh, P. et al. Impact of COVID-19 Pandemic on Drug Overdoses in Indianapolis. J Urban Health 97, 802–807 (2020). https://doi.org/10.1007/s11524-020-00484-0  
4. Lee H, Singh GK. (2023) Estimating the impact of the COVID-19 pandemic on rising trends in drug overdose mortality in the United States, 2018-2021. Annals of Epidemiology. https://www.sciencedirect.com/science/article/pii/S1047279722003003  
5. Moghtaderi, A., Zocchi, M. S., Pines, J. M., Venkat, A., & Black, B. (2023). Estimating the uncertain effect of the COVID pandemic on drug overdoses. PloS one, 18(8), e0281227. https://doi.org/10.1371/journal.pone.0281227
6. Warraich, H. J., Lu, D., Cobb, S., Cooper, L. B., DeVore, A., Patel, C. B., … & Mentz, R. J. (2018). Trends and outcomes of cardiac transplantation from donors dying of drug intoxication. American Heart Journal, 199, 92-96.https://www.sciencedirect.com/science/article/abs/pii/S0002870318300413  
7. Whited, W. M., Ising, M. S., Trivedi, J. R., Fox, M. P., & van Berkel, V. (2018). Use of drug intoxicated donors for lung transplant: impact on survival outcomes. Clinical Transplantation, 32(5), e13252.https://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.13252