Kidney Transplant Patient Deaths With COVID-19

The risk of death among kidney transplant patients infected with COVID-19 is so high that at least one transplant center in New York City has stopped offering kidney transplantation until it is safer to do so.

APRIL 30, 2020 -- The risk of death among kidney transplant patients infected with COVID-19 is so high that at least one transplant center in New York City has stopped offering kidney transplantation until it is safer to do so.

Enver Akalin, MD, medical director, kidney and pancreas transplant program, Montefiore Medical Center in New York City, and colleagues detail the trajectory of a small group of their own COVID-19-infected kidney transplant patients in a letter published online April 24 in the New England Journal of Medicine.

Of 36 patients assessed between March 16 and April 1, 2020, 10 have died, leading them to temporarily halt their program.

"Our results show a very high early mortality among kidney-transplant recipients with COVID-19 — 28% at 3 weeks as compared with the reported 1% to 5% mortality among patients with COVID-19 in the general population, who have undergone testing in the United States," say Akalin and colleagues.

This mortality rate is also much higher than the reported 8% to 15% mortality rate among patients with COVID-19 older than age 70 years, they add.

Akalin told Medscape Medical News: "Over 80% of patients in the Montefiore hospital are COVID-19 patients, and if more than 80% of your hospital is full of COVID-positive patients, how can you find a safe place to do transplantation?"

"So we stopped our kidney transplantation program 5 weeks ago because we have dialysis, so to delay transplantation a few months until the pandemic is cleared is not going to hurt the patient," he explained.

Almost 80% Admitted to Hospital, 40% Received Mechanical Ventilation

The median age of the group of transplant patients at the Montefiore hospital was 60 years and approximately 80% were black or Hispanic. Some 75% of patients had received a deceased donor kidney. Almost all of them had hypertension and over two thirds had diabetes.

"Twenty-eight [of the 36] patients (78%) were admitted to the hospital," Akalin detailed.

The most common initial symptom was fever, present in 58% of the group, and diarrhea was observed in 22%. However, almost all patients (96%) had radiographic findings consistent with viral pneumonia.

Eleven of the 28 patients admitted to hospital (39%) were so severely ill that they required mechanical ventilation.

Eight patients (22%) were stable enough to be monitored at home, although two of these patients ultimately died.

At a median follow-up of 21 days, 10 of the 36 patients had died, including seven of the 11 patients who required intubation (64%).

"However, with 2 additional weeks of follow-up, the remaining four [intubated] patients are still alive," Akalin noted.

The two outpatients who died were both recent kidney transplant recipients "who had received antithymocyte globulin within the previous 5 weeks," the authors note.

Antithymocyte globulin decreases all T-cell subsets for many weeks, and with no T-lymphocytes, "patients can't mount an immune response to clear the virus," Akalin explained.

Initial Treatment: Stop Mycophenolate, Trials of Other Drugs

In terms of immunosuppressive therapy, on presentation with COVID-19, 97% of the kidney transplant patients were receiving tacrolimus, 94% prednisone, and 86% were taking mycophenolate mofetil or mycophenolic acid.

Akalin said they "decrease the mycophenolate dose by half or withdraw drug altogether" in the setting of any infection requiring hospital admission, including COVID-19, because transplant patients would never be able to clear the infection with such heavy immunosuppression.

In their 28 hospitalized patients, the dose of mycophenolate was reduced in 14% of the group and was stopped altogether in the remainder of the patients.

Moreover, when the New York team first started tracking their COVID-19-infected transplant patients, there was speculation that the antimalaria drug hydroxychloroquine might help patients recover more quickly, so almost all of their hospitalized patients were treated with that drug.

But since a French study found no difference in outcomes between patients treated with hydroxychloroquine or not, they no longer use it, nor do they use azithromycin, which initially they also felt might benefit COVID-19 recovery in these patients, Akalin explained.

Intriguingly, however, they did treat two patients with the interleukin-6 (IL-6) inhibitor tocilizumab (Actemra, Roche), while six others received the CCR5 inhibitor leronlimab (CytoDyn), both of which blunt high IL-6 levels characteristic of the cytokine storm that can occur in patients with moderate and severe COVID-19.

Before and after laboratory results indicated that leronlimab markedly reduced elevated IL-6 levels in five patients with high pretreatment levels, Akalin noted.

Moreover, while only eight patients in total received tocilizumab or leronlimab, all of these patients were all among the group who received mechanical ventilation and the mortality rate was 50% in this small group, lower than that seen among intubated patients with COVID-19 in the general population, he noted.

Don't Halt All Kidney Transplants...Nor Any Others

Akalin told Medscape Medical News that their policy to put kidney transplantation on hold until the pandemic is under control does not necessarily apply to other regions of the country where COVID-19 is not as prevalent as it is in New York City.

"With very careful selection of recipients and donors, and very careful precautions taken during hospitalization, you could do the transplantation," he suggested.

However, providers still need to be aware that the nasopharyngeal swabs used to test patients for COVID-19 are only about 70% accurate, so even if all possible deceased donor candidates are tested, "you may still miss some who are positive," he cautioned.

Furthermore, if the deceased donor does test positive for COVID-19, there is always a potential for transmission of COVID-19 to the waiting recipient, so it is too risky to use kidneys from these donors, he believes.

"This policy is just for kidney transplant patients," he emphasized.

The same policy "does not apply in heart, lung, or liver transplantation because heart, lung, and liver transplantation is life-saving and if these patients don't get [a donor organ] soon, they will die within a few months."

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References
Sources: N Engl J Med. Published online. Letter

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