Outcomes Among Kidney Transplant Recipients With COVID-19

Worldwide, elderly people and individuals with underlying chronic conditions such as diabetes and heart, lung, and kidney disease face increased risk of serious and life-threatening complications from COVID-19. For survivors of COVID-19, there is also risk for long-term consequences, including prolonged fatigue, muscle weakness, dyspnea, sleeping problems, and anxiety and depression.

Recipients of kidney transplantation have been shown to be particularly vulnerable for the development of severe COVID-19. Results from the OpenSAFELY study in the United Kingdom reported a six times higher risk of mortality in organ transplant recipients after adjustment for age and sex, and a 3.5 times higher risk after adjustment for comorbidities. Study results identified organ transplantation as one of the strongest risk factors for COVID-19-related death.

According to Raphael Duivenvoorden, MD, PhD, and colleagues, there are few data available on the clinical, functional, and mental health outcomes among kidney transplant recipients who survive COVID-19. The researchers conducted an analysis of data from adult kidney transplant recipients in the European Renal Association COVID-19 Database who presented with COVID-19 between February 1, 2020, and January 31, 2021. Results of the analysis were reported in Transplantation [2022;106(5):1012-1023].

Detailed data were collected on patient and COVID-19-related characteristics. The Clinical Frailty Score developed by Rockwood et al was used to assess frailty; low scores (1-3) indicate that patients are fit and managing well, middle scores (4-6) indicate that patients are vulnerable to moderately frail, and higher scores (7-8) indicate patients are severely to very severely frail or terminally ill (9). Patient charts were used to identify comorbidities. Graft function outcomes and functional and mental health outcomes were collected at 3 months following initial presentation with COVID-19.

Analysis of variance for continuous variables was used to compare characteristics among groups. A Kaplan-Meier plot was created to show cumulative survival probability by hospitalization and intensive care unit (ICU) admission status. Cox proportional-hazards models were used to examine predictors of 3-month vital status (being dead or alive). In addition, the use of immunosuppressive drugs was assessed as a risk factor for 3-month vital status in a multivariable Cox proportional-hazards model adjusted for age, sex, frailty, obesity, hypertension, diabetes, heart failure, chronic lung disease, estimated glomerular filtration rate (eGFR), and time after transplantation in a stepwise manner.

The database included 1035 adult kidney transplant recipients who presented with COVID-19 between February 1, 2020, and January 31, 2021. Following application of exclusion criteria, the analysis cohort included 912 patients. Mean age was 56.7 years, 61.5% were male, and 85.3% were White.

Patients who were hospitalized were, on average, 58.7 years of age and had more comorbidities than non-hospitalized patients. In particular, obesity, hypertension, diabetes, coronary artery disease, and heart failure were more prevalent in hospitalized patients. Hospitalized patients also had higher Clinical Frailty Score and were more often being treated with a triple immunosuppression regimen compared with non-hospitalized patients.

Patients who were hospitalized more often presented with shortness of breath, fever, nausea, and vomiting. Their respiration rate was higher and oxygen saturation lower at presentation. Those who required hospital admission also had lower eGFR at presentation and had a 25% increase in creatinine compared with the pre-COVID-19 baseline value. Of the 147 patients admitted to the ICU, 72.5% (n=107) were intubated.

Three-month survival was 98.8% for patients who were not hospitalized and 84.2% for those who were hospitalized but not admitted to the ICU. In those two groups, death occurred primarily within the first 14 days after presentation. Among patients who were admitted to the ICU, 3-month survival was 49.0%, and the mortality plateaued later at around 50 days following presentation. At 3 months following initial presentation, the majority of patients were living at home and only 4.5% were still hospitalized or admitted to a nursing home.

Overall, patients who survived were younger, had a lower Clinical Frailty Score, and fewer comorbidities. Symptoms and signs of disease at presentation were less severe, particularly respiratory symptoms and markers of inflammation. In multivariate analysis, the most important predictors for survival at 3 months were age, frailty, heart failure, respiratory rate, and lymphocyte count. There was a hazard ratio pointing toward better survival for patients on dual therapy versus triple-drug immunosuppression therapy; however, the difference did not reach statistical significance. There was no association between type of immunosuppressive drug and survival.

Of the 751 patients alive at 3 months, 487 had available data for analysis of outcomes related to graft function and 450 had data available for analysis of physician-reported functional and mental health outcomes. Baseline characteristics were similar for those with complete data and those with missing data.

Of the 487 patients with data on graft function, median eGFR at presentation was 40 mL/min/1.73 m². At presentation, 21.8% had an increase in creatinine of >25% compared with their pre-COVID-19 baseline creatinine level.  Biopsy-proven acute rejection occurred in only four (0.8%) patients who survived COVID-19. Two of the four patients who experienced acute rejection developed temporary graft failure, but at 3 months all four had a functioning graft.

The need for renal replacement therapy occurred in 2.6% of all surviving patients. In the subset of surviving patients who had been admitted to the ICU, the need for renal replacement therapy was 10.6%.

Graft survival was good in patients who survived COVID-19; 97.3% had a functioning graft 3 months after presentation, with a median eGFR of 49 mL/min/1.73 m². Graft failure within 3 months of presentation occurred at similar rates in patients who were not hospitalized (0.7%) and those who were hospitalized but not admitted to the ICU (1.0%). In patients who were admitted to the ICU, five of 47 (10.7%) experienced irreversible loss of graft function within 3 months after presentation; 89.4% had a functioning graft at the 3-month follow-up.

Of the 450 patients with complete data on functional and mental health status, 83.3% reached their pre-COVID-19 functional status. The percentage of patients who reached pre-COVID-19 functional status was similar in non-hospitalized patients and hospitalized patients not admitted to the ICU (87.9% and 87.0%, respectively). Only 42.5% of patients admitted to the ICU reached their pre-COVID-19 functional status within 3 months after presentation. Pre-COVID-19 physician-reported mental health status was reached within 3 months by 94.4% of the 450 patients with available data.

Of the patients who had not yet reached their prior functional and mental health status, their treating physicians expected that 79.6% and 80.0%, respectively, would do so within the coming year.

Limitations to the study findings cited by the authors included the possibility that the database did not include all kidney transplant recipients with COVID-19 in the participating centers, lack of detailed data on in-hospital management of patients, the short follow-up period, and the high percentage of White participants.

In summary, the authors said, “Our study shows that >80% of kidney transplant recipients are alive at 3 months after presentation with COVID-19. In these survivors, acute rejection and graft failure within 3-month follow-up were rare, and most patients reached their pre-COVID-19 physician-reported functional and mental health status. ICU admission was associated with poor recovery from COVID-19.”

Takeaway Points

1. Results of an analysis of clinical, functional, and mental health outcomes in kidney transplant recipients 3 months after presenting with COVID-19.
2. For patients not hospitalized and for those hospitalized who survived to 3 months after presentation, clinical, functional, and mental health status was good.
3. For hospitalized patients admitted to the intensive care unit, recovery was less favorable.