Outcomes among Kidney Transplant Recipients Hospitalized with COVID-19

Among patients with COVID-19, reported mortality rates vary from 1% to 7.2%, reaching as high as 49% among patients with critical illness. Patients with known comorbidities, including old age, diabetes, hypertension, chronic kidney disease, morbid obesity, coronary heart disease, and chronic lung disease, are at increased risk for severe illness.

There are few data available on the infectious course of COVID-19 in solid organ transplant recipients. It is unclear whether complications associated with COVID-19 are increased in the presence of immunosuppression in that patient population. Early reports suggest that the frequency of cytokine storms, a significant cause of mortality, may be reduced in patients taking immunosuppressive drugs.

Ozgur Akin Oto, MD, and colleagues in Turkey, conducted a multicenter, retrospective study to define the clinical manifestations, course of disease, and outcomes among a large cohort of adult kidney transplant recipients with COVID-19. The study also was designed to assess the predictions of worse clinical outcomes among kidney transplant patients hospitalized with COVID-19. Results of the study were reported in BMC Nephrology [doi.org/10.1186/s12882-021-02299-w].

The primary outcomes of interest were in-hospital mortality and the need for admission to the intensive care unit (ICU). Secondary outcome was a composite of in-hospital mortality and/or ICU admission. Data were collected from 34 centers in Turkey from April 17, 2020, to June 1, 2020. The researchers reviewed data on demographic characteristics, clinical findings, laboratory parameters (hemogram, C-reactive protein, aspartate transaminase, alanine aminotransferase, lactate dehydrogenase, and ferritin) at admission and follow-up, and treatment strategies.

The diagnosis of COVID-19 was based on clinical symptoms, polymerase chain reaction (PCR) test for SARS-CoV-2 from the nasopharyngeal swab, and/or radiological findings. Patients whose first swab PCR test was negative, but with a positive repeated test, were considered to be confirmed cases. Patients whose clinical and radiological findings were consistent with COVID-19, but swab PCR tests were negative or not available, were also considered probable COVID-19 patients and were included in the study.

The final study cohort included 109 patients; of those, 63 were male and mean age was 48.4 years. The most common comorbidity was hypertension, affecting 76.4% of patients, followed by diabetes (23.4%), ischemic heart disease (17.5%), cancer (5.7%), and chronic obstructive pulmonary disease (4.8%). Previous or current smoking history was reported in 21.1% of patients.  Median time between transplantation and diagnosis of COVID-19 was 5.0 years.

Median length of stay was 9 days. A total of 46 patients (42.2%) developed acute kidney injury (AKI) and four patients (3.7%) required renal replacement therapy. Twenty-two patients (20.2%) were admitted to the ICU, and 19 (17.4%) required invasive mechanical ventilation (IMV). In non-survivors, the development of AKI, the need for IMV, and the need for RRT were significantly higher than in survivors: 71.4% vs 37.9%; P=.018; 68.4% vs 31.6%; P=.025; and 21.4% vs 1.1%; P<.001, respectively. Fourteen patients (12.8%) died and 23 (21.2%) reached the secondary outcome.

Ischemic heart disease (38.5% vs 15.3%; P=.033) and heart failure (14.3% vs 2.2%; P=.028) were higher in patients who died compared with patients who survived and those who reached the secondary outcome (31.8% vs 13.6%, P=.046; and 13.0% vs 1.2%; P=.009, respectively). Patients who died had longer length of stay: 14 days versus 8 days; P=.038).

There were no significant differences between the patients reaching the primary and secondary outcomes in terms of age, sex, transplantation duration, primary kidney disease, comorbidities (with the exception of those mentioned above), smoking history, maintenance immunosuppression, or use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

Patients who were admitted to the ICU were significantly older (≥60 years of age) (38.1% vs 14.9%; P=.016). In results of univariate analysis, there were associations between the presence of ischemic heart disease and initial serum creatinine levels and mortality. In multivariate analysis, both parameters were predictive of mortality.

Nearly all of the patients were treated with hydroxychloroquine (99.1%), the majority of patients (67%) received macrolide, oseltamivir (56.2%), glucorticoids (58.4%), and favipiravir (49.0%). A smaller subset of patients received tocilizumab (10.1%) or anakinra (3%) and lopinavir/ritonavir (10.6%), There was significant difference in mortality among tocilizumab (41.7% vs 5.7%; P<.001), glucocorticoids (85.7% vs 54%; P=.026), and favipiravir (91.7% vs 42.3%; P=.002) treatments of COVID-19.

Results of univariate analysis revealed that associations between older age (>60 years), initial serum creatinine level, ferritin, albumin level, and lymphocyte count and admission to the ICU. In multivariate analysis, the association between older age and initial serum creatinine and ICU admission remained.

In univariate analysis, older age (>60 years), baseline lymphocyte counts, and initial serum creatinine and albumin levels were predictive of the secondary outcomes. Following multivariate adjustment, older age and initial lymphocyte count remained predictive of the secondary outcome.

Limitations to the study findings cited by the authors included the retrospective design that may not have reflected the causal relationship between mortality and some of the parameters; changes in treatment algorithm during the study period that made it difficult to evaluate results; problems related to patient selection that made it difficult to evaluate treatment results; and the inclusion of PCR  negative patients as the clinical diagnosis of COVID-19.

In conclusion, the researchers said, “COVID-19 in kidney transplant recipients has a high mortality rate, especially in patients with ischemic heart disease or poor graft function. Low lymphocyte counts at admission and age >60 years increased the risk for their combined end point of death or ICU admission.”

Takeaway Points

  1. Researchers in Turkey reported results of a retrospective study designed to define the characteristics, clinical presentation, and outcomes of a multicenter adult cohort of kidney transplant recipients hospitalized with COVID-19.
  2. The cohort included 109 patients; 46 developed acute kidney injury and four required renal replacement therapy, 22 were admitted to the intensive care unit (ICU) and 19 required invasive mechanical ventilation.
  3. Fourteen of the patients died. In multivariate analysis, the presence of ischemic heart disease and initial serum creatinine levels were independent risk factors for mortality; age >60 years and initial serum creatinine levels were independent risk factors for ICU admission.