Outcomes among Kidney Transplant Recipients with COVID-19

COVID-19, caused by SARS-CoV-2, is primarily pulmonary, but it is now well recognized that there is significant involvement of other organs, including the kidneys and the heart, during the course of the illness. Due to immunosuppression requirements and underlying comorbidities, kidney transplant recipients are thought to be at higher risk of acquiring COVID-19 and developing severe disease requiring hospitalization.

There are few data available that compare outcomes among kidney transplant recipients with COVID-19 with those of patients receiving dialysis and waitlisted for transplant. Mysore Phanish, MBBS, MD, FRCP, PhD, and colleagues conducted a systematic review and meta-analysis describing 23 kidney transplant recipients who tested positive for SARS-CoV-2 infection from two tertiary care renal centers in the South London Renal Transplant Network, United Kingdom, including follow-up on five patients described in an earlier report. In addition, the researchers conducted a review and meta-analysis on 15 published studies on COVID-19 in kidney transplant recipients to examine case fatality-acute kidney injury (AKI) ratios in kidney transplant recipients hospitalized with COVID-19. Results were reported in Kidney International Reports [2021;6:574-585].

Data on all kidney transplant recipients who tested positive for COVID-19 during the first wave of the pandemic in the United Kingdom  (March 1, 2020, to June 30, 2020) were collected. Patients were followed until October 15, 2020. COVID-19 was diagnosed via the nasopharyngeal swab polymerase chain reaction test. Data included demographics, clinical and laboratory parameters, and outcomes. The researchers also collected data on dialysis patients, including those on dialysis and those on the transplant waiting list.

Of 1494 kidney transplant recipients under follow-up care in the two renal centers, 23 tested positive for COVID-19 (1.5% of the total transplant cohort). Four were managed at home and 19 required hospitalization. Median age was 62 years, compared with a median age of 51 years in the total transplant cohort. Six of the 23 patients with COVID-19 were female, six (26%) were Black, nine (39.1%) were White, four (21.7%) were South Asian, one was East Asian, one was Hispanic, and two were other race/ethnicity.  Among the overall transplant cohort, 7.7% were Black, 73.8% were White, and 15.4% were South Asian. Twenty-two of the 23 patients had hypertension, two had a history of cancer, eight had diabetes, and one had HIV.

Of the 19 hospitalized patients, median age was 64 years. Median follow-up period was 183 days (range, 169-199 days). Median transplant vintage (from transplant date to date of positive swab) was 1686 days (range, 47-12,054 days). Three of the 23 patients with COVID-19 (two hospitalized and one managed at home) were within 3 months of receipt of transplant (53 days, 56 days, and 47 days), three were between 3 and 12 months since their transplant, and the remaining patients were >12 months post-transplant. None of the patients who died had their transplant within the previous 6 months.

All patients had received basiliximab induction, 15 (including four managed at home) were on dual maintenance immunosuppression, and eight were on triple immunosuppression. Two of the 19 hospitalized patients had received their transplant in February 2020.

All of the 19 hospitalized patients were managed with immunosuppression reduction, and antiproliferative agents (mycophenolate mofetil/azathioprine) were stopped on admission. In mild to moderate cases (n=11), tacrolimus dose was reduced; tacrolimus was stopped in severe cases where there was progressive clinical and radiologic deterioration (n=8). In three cases, prednisolone dose was unchanged; in 13 cases, it was increased.

Some of the patients were recruited into the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial. As part of the trial protocol, two patients received hydroxychloroquine and one received dexamethasone. Two patients received tocilizumab. Of the patients managed at home, one had his mycophenolate mofetil dose reduced by 50% and then increased back to the baseline dose after 2 weeks; the remaining three patients were managed with no change to their immunosuppression regimen.

By 2 weeks post-discharge, all patients who had tacrolimus dose reduced had the dose progressively increased to levels in a therapeutic range (5-8 ng/mL). If patients were well and fever-free and had no other symptoms of COIVD-19 for at least 3 days and had normal C-reactive protein level, mycophenolate mofetil was reintroduced at 2 to 3 weeks post-discharge.

The only variables significantly different in patients who died compared with those who survived to discharge were age, admission to the intensive care unit, and type of respiratory support required. Patients who died were significantly older (59.1 vs 70.5 years; P=.01) and required more respiratory support (P=.004). The two group (survivors vs died) were similar in comorbidities, peak ferritin levels, C-reactive protein, baseline lymphocyte count, or lowest lymphocyte count during hospitalization.

Six of the 19 hospitalized patients died. Of the total cohort of transplant recipients (1494), the six who died represent 0.4% of the total cohort. Of the 14 patients on dual immunosuppression, 12 survived (85.7%); of the nine patients on triple immunosuppression, five survived (55.6%). Thirteen of the 19 hospitalized patients developed AKI.

In comparisons of kidney transplant recipients with cohorts of patients on dialysis and those on the transplant waitlist, 123 of 1278 patients on hemodialysis tested positive for COVID-19 (1.5% vs 9.6%; P<.001), 12 of 253 waitlisted patients tested positive (1.5% vs 4.7%; P=.002), and eight of 170 patients on peritoneal dialysis tested positive (1.5% vs 4.7%; P=.01).

The researchers conducted a meta-analysis of 15 published studies and the data from the current analysis to determine a pooled estimate of case fatality ratio (among hospitalized patients) and AKI in kidney transplant patients who tested positive for COVID-19. A total of 871 hospitalized patients were included. The pooled case fatality ratio was 24% (95% confidence interval [CI], 19%-28%). The AKI proportion in 10 studies was 50% (95% CI, 45%-56%). There was some evidence against no heterogeneity between studies (P=.02).

In summary, the researchers said, “From our large cohort of transplant patients, a small proportion got COVID-19, with the proportion of infection significantly lower than that of waitlisted patients and those on dialysis. The overall case fatality ratio (26%) was comparable to that of the dialysis cohort and patients on waitlist. Thirty-one percent required intubation and ventilation, of whom 50% died. Within our entire cohort, a significantly lower proportion of transplant patients died of COVID-19 compared with hemodialysis and peritoneal dialysis patients. The case fatality ratio of hospitalized transplant patients with COVID-19 was 31.57%.

“Older age and severity of disease was associated with mortality. We observed a high proportion of AKI (68%), but the majority recovered. Meta-analysis of 16 studies including ours revealed pooled case fatality ratio of 24% for hospitalized patients, pooled AKI proportion of 50%, and pooled proportion of severe AKI of 16% to 18%. We have successfully restarted our transplant program with defined donor and recipient criteria to minimize the risk and optimize the outcomes.”

Takeaway Points

1. Researchers reported results of an analysis of outcomes among kidney transplant patients who tested positive for COVID-19 during the early phase of the pandemic.
2. Twenty-three of 1494 kidney transplant recipients tested positive for COVID-19, compared with 123/1278 hemodialysis patients and 12/253 waitlisted patients.
3. Of 19 patients who required hospitalization, six died and 13 developed AKI. Patients who died were older and required more ventilatory support compared with patients who survived.