Impact of COVID-19 on Kidney Transplant Outcomes: An 8-Year Study From the Czech Republic

Introduction

The Coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, had a serious impact on healthcare worldwide. The pandemic disrupted transplant programs due to logistical challenges, concerns about immunosuppression, and general overload of healthcare systems. This resulted in a decline in the number of living [1] and deceased donor transplants [2]. Kidney recipients were found to be particularly vulnerable to the effects of COVID-19 due to numerous comorbidities, compromised immune systems, and dependency on dialysis. Studies have shown that a prior SARS-CoV-2 infection increases the risk of acute rejection [3], endothelial cell injury [4], or kidney failure [5]. These hazards are further highlighted in donors after circulatory determination of death (DCDD), where the risks may be increased by the donor’s or recipient’s current SARS-CoV-2 infection. Although the pandemic is mostly over, some modifications to kidney transplantation strategies and to patient care will likely be implemented permanently [6]. The present study investigated whether the COVID-19 pandemic influenced short- and long-term outcomes of a single tertiary center kidney transplant program.

Material and Methods

RECIPIENT SELECTION AND PREOPERATIVE CARE:

Recipients are selected from the kidney transplantation waiting list based on numerous criteria (eg, AB0 blood group system, compatibility index, reactive antibodies, remaining kidney function, position on the waiting list). A surgeon and a nephrologist evaluate graft quality and suitability for the selected recipient. The team caring for the recipient and the graft is always different from the donor’s caregivers. The nephrologist decides on induction medication immunosuppression therapy based on the Kidney Disease Improving Global Outcomes (KDIGO) recommendations [9].

STATISTICAL ANALYSIS:

Numerical variables are shown as medians and interquartile ranges (IQR, lower and upper quartiles). Categorical variables are described in absolute frequencies and relative frequencies (%). Groups were compared using the Mann-Whitney test, the chi-square independence test, or Fisher’s exact test. The Kaplan-Meier method with the log-rank test was used to calculate patient and graft survival. The significance level was set to 0.05. Data were analysed in R (version 4.4.1, www.r-project.org).

Results

During the pre-COVID-19 period, 99 transplantations were performed (mean 19.8 per year), while 46 were performed during the pandemic (mean 15.3 per year). A total of 20 DCDD transplants were performed before the pandemic (mean 4.0 per year), while only 4 were performed during the pandemic (mean 1.3 per year).

The statistical analysis of donor baseline and paraclinical data is presented in Table 1. The most common cause of death was intracranial bleeding (64/138 donors, 46.4%), trauma (49/138 donors, 35.5%, mostly traffic accidents or falls from height), and sudden cardiac arrests (10/138 donors, 7.3%). The remaining causes include ischemic stroke, pulmonary embolism, acute myocardial infarction, intoxication, and hypoxia. Out of all donors, 87 (63.0%) were identified as ECD. During the pre-COVID-19 era, 70/94 ECD donors (74.5%) were harvested, whereas only 17/44 ECD donors (38.6%) were harvested during the pandemic. Notably, the proportion of DCDD donors was higher before COVID-19 (21/94 donors, 22.3%) than during the pandemic (4/44 donors, 9.0%), but the difference was not significant (P=0.100).

No statistically significant difference was found between pre-COVID-19 and COVID-19 eras in terms of pre-existing comorbidities (arterial hypertension, diabetes mellitus, ischemic heart disease, or chronic obstructive pulmonary disease). Interestingly, during the pandemic, the percentage of ECD donors was significantly lower (38.6% vs 74.5%, P<0.001), and donors had a considerably better estimated glomerular filtration rate (median 1.62 vs 1.29 ml/s/1.73 m2, P=0.038). This suggests a tendency to select more favorable donors during pandemic years.

Descriptive parameters of kidney graft recipients are shown in Table 2. In baseline parameters, no statistically significant difference was found, including the aforementioned chronic illnesses. During the pandemic, recipients had a generally shorter duration of pre-transplantation long-term hemodialysis (median 12 vs 22 months, P=0.003), and a higher percentage of pre-emptive transplantations (17.4% vs 3.0%, P=0.011). Even though the compatibility index and preoperative panel-reactive antibodies did not differ significantly (P=0.779 vs P=0.633, respectively), the induction therapy was altered considerably (P<0.001), with a higher percentage of patients receiving anti-CD25 (45.7% vs 24.2%). On the contrary, the number of patients without induction therapy plummeted (6.4% vs 46.5%).

Aside from shorter duration of transplantation procedures during the pandemic (median 105 vs 125 minutes, P<0.001), no significant differences were found between pre-pandemic and pandemic eras. The incidence of post-transplantation graft function impairments (acute rejection, delayed graft function, and primary non-function) was not significantly different between groups. All periprocedural parameters are summarized in Table 3.

Out of all 46 recipients during the pandemic, 24 patients (52.2%) received at least 1 dose of the COVID-19 vaccine – all vaccinated with Comirnaty vaccine (BioNTech Manufacturing GmbH, Germany & Pfizer Manufacturing Belgium NV, Belgium) – while the rest were unvaccinated. One patient (2.2%) received 1 dose, 12 (26.1%) received 2 doses, and the remaining 11 (23.9%) received 3 doses. At the beginning of the pandemic, vaccines were not available. In 2021 and 2022, when vaccines were generally accessible to patients, only 3 of 27 patients were unvaccinated. There was no statistically significant difference in serum creatinine concentration or estimated glomerular filtration rate at 7 days (P=0.177 and P=0.233, respectively) or 1 month (P=0.704 and P=0.893, respectively) between vaccinated and unvaccinated patients. Seven recipients (15.2%) with a history of COVID-19 were transplanted during the pandemic.

The results of Kaplan-Meier analysis for overall survival and failure-free survival (death-censored graft loss) are shown in Table 4 and depicted in Figure 1. Survival medians could not be determined due to the generally high survival probability. No statistically significant difference in overall survival (P=0.092) or failure-free survival (P=0.377) was found. To better compare pre-pandemic and pandemic survival, only 4-year survival was assessed (ie, no pandemic patients were followed for more than 4 years). Before the pandemic, 1-year survival was 96.0% (95% CI 92.2; 99.9) and 3-year survival was 90.9% (95% CI 85.4; 96.8); during the pandemic, survival was 97.8% (95% CI 93.7; 100.0) and 97.8% (95% CI 93.7; 100.0), respectively. The failure-free survival rate before the pandemic was 95.9% (95% CI 92.0; 99.9) at 1 year and 90.4% (95% CI 84.7; 96.6) at 3 years. During the pandemic, the rate was 95.6% (95% CI 89.8; 100.0) and 95.6% (95% CI 89.8; 100.0), respectively.

Discussion

LIMITATIONS:

This study is based on a single-center experience, limiting the applicability of its findings. Furthermore, when evaluating these results, regional differences in transplantation programs need to be considered. The retrospective nature of the presented data may incur unrecognized confounding.

Conclusions

The COVID-19 pandemic did not significantly affect the short- or long-term results of a single-center kidney transplantation program.