key: cord-0973869-mj47qb88
authors: AKAGUN, TULIN; TOMAR, OZDEM KAVRAZ; USTA, MURAT; BAYLAN, SULEYMAN
title: COVID-19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A SINGLE CENTER EXPERIENCE
date: 2022-04-11
journal: Transplant Proc
DOI: 10.1016/j.transproceed.2022.04.014
sha: 3cc66d88418a8e8fd9d75fe29061c0009ae7f976
doc_id: 973869
cord_uid: mj47qb88

Background: Kidney transplant recipients appear to be at particularly high risk for critical COVID-19 illness due to chronic immunosupression and coexisting conditions. The aim of this study is to present the clinical characteristics and outcomes in our kidney transplant recipients who were hospitalized due to COVID-19 infection in our hospital. Methods: In our retrospective, observational study COVID-19 PCR positive 31 patients who were hospitalized with COVID-19 pnumoniae and were evaluated with demographics, laboratory data, treatment and outcome. The prognostic nutritional index (PNI), which is calculated using the serum albumin concentration and total lymphocytic count were also evaluated. The baseline immunosuppresive therapy of patients at the time of admission and the treatments they received during their hospitalization were recorded. All patients were treated with favipiravir. Results: Of 31 renal transplant patients with COVID-19 pneumoniae; 20 were male; mean age 52.7±13.4. A total of 9/31 (29%) patients dead. All patients were treated with favipiravir for 5 days; laboratory tests were recorded before and after treatment. Mean PNI of the patients who survived was higher than patients who were exitus. Conclusions: The 9 patients who died, had lower PNI and higher NLR (Neutrophil/Lymphocyte Ratio), creatinine, LDH, ferritin and CRP levels. Hospitalized kidney transplant recipients with COVID-19 have higher rates of mortality. PNI exhibited good predictive performance and may be a useful clinical marker that can be used for estimating survival in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) (1) . Kidney transplant recipients appear to be at particularly high risk for critical COVID-19 illness due to chronic immunosuppression and coexisting conditions (2) . The clinical presentation of COVID-19 in kidney transplant recipients may be different from general population with a higher rate of severe disease, complications including renal failure and mortality (1) .

The aim of this study is to present the clinical characteristics and outcomes in our kidney transplant recipients who were hospitalized due to COVID-19 infection in our hospital.

In our retrospective, observational study COVID-19 PCR positive 31 patients who were hospitalized with COVID-19 pnumoniae (between March-September 2020) and were evaluated with demographics, laboratory data, treatment and outcome. The prognostic nutritional index (PNI), which is calculated using the serum albumin concentration and total lymphocytic count were also evaluated. The baseline immunosuppresive therapy of patients at the time of admission and the treatments they received during their hospitalization were recorded.

Statistical analyzes were performed with MedCalc (MedCalc Software Ltd, Ostend, Belgium).

After investigating the conformity of continuous variables to normal distribution with the Shapiro-Wilk test, variables with Gaussian distribution were shown as mean±SD, while variables with non-gaussian distribution were shown as median (25th percentile-75th percentile). Paired-samples T-test or Wilcoxon signed-rank tests were used to compare dependent group means/medians. Mann-Whitney U test was used for independent group comparisons. Pearson's chi-square test or Yates' correction was used to compare group frequencies. The diagnostic tools of the clinical and laboratory parameters were evaluated by Receiver Operating Characteristics (ROC) analysis. Sensitivity, specifity, positive predictive values, negative predictive values and Youden's index (J) were determined with contingency tables for the associated criterions. Statistical significance was evaluated at the p< 0.05 (two-tailed) level.

Of 31 renal transplant patients with COVID-19 pneumoniae; 20 were male; mean age 52.7±13.4.

A total of 9/31 (29%) patients dead. The patients who survived were younger. Anti-metabolite drug (mycophenolate mofetil or mycopenolat sodium) was discontinued in all patients. Calcineurin inhibitors (cyclosporine or tacrolimus) were discontinued in 7 patients whose clinical condition deteriorated.

Favipiravir, the recommended drug by the Turkish Ministry of Health, was uniformly supplied to all patients. Favipiravir treatment was initiated with 2 loading doses of 1600 mg each on day 1, followed by 600 mg twice Daily for 5-10 days. Steroids were either continued at the maintenance dose or converted to intravenous dexamethasone/methylprednisolone depending on the disease severity. Intravenous steroid treatment was applied to 16 patients. Tocilizumab and convalescent plasma were also used in patients with progressive disease despite favipiravir treatment. Low-molecular-weight heparin was administered to all patients. Laboratory tests were recorded before and after treatment. Baseline immunosupression and treatments given for COVID-19 patients are shown in Table- 1.

The clinical and laboratory parameters of patients at the time of hospital admission are shown in Table- 2. Mean PNI of the patients who survived was higher than patients who were exitus. In the exitus patient group: lenght of hospital stay was longer (p=0.033), Neutrophil /Lymphocyte Ratio (NLR) (p=0.078), creatinine (p=0.033) and CRP (p=0.105) were higher; hemoglobin (p<0.001) and albumine (p=0.047) were lower. The clinical parameters of patients after treatment are shown in Table- 3. Mean PNI of the patients who survived was higher than patients who were exitus. Lymphocyte and hemoglobin were lower in patients who were exitus. NLR, CRP, Creatinine, LDH, and ferritin results were higher in patients who were exitus.

The diagnostic evaluations of PNI and hemoglobin before and after treatment were shown in Table- 4. The determined AUCs (Area Under Curve) of PNI and hemoglobin were higher before and after treatment. The optimal decision thresolds for sensitivity and specifity were lower after treatment for PNI and hemoglobin (≤35.6 and ≤11.9 g/dL, respectively).

Mortality was 32%-36% among patients in COVID-19 positive renal transplant patients (3, 4) .

Mortality was 29% (9/31) in our patient group. Similar to our result, Akalın et al. found 28% mortality in kidney transplant patients (5) . The clinical outcomes for the transplant patients were poor with 25% mortality mainly due to complications from pneumonia (6) . The mortality rate of the previous study from Turkey was 11.1% (7). This difference is might be attributable to the heterogeneity of included patients, differences in medical treatment level and medical resources. Although it did not reach statistical significance in our study, exitus patients were older.

The prognostic nutrional index (PNI), which is calculated from the serum albumin concentration and total lymphocyte count in peripheral blood, is an index that reflects chronic inflammation, immune system and nutritional status and indicates prognostic significance in different patients (8) . PNI had been described as a simple and objective indicator of adverse outcomes not only chronic conditions but also in acute illnesses, including acute coronary syndrome, acute heart failure and stroke (9) . In our study, mean PNI of the patients who survived was higher than patients who were exitus. [PNI=10xserum albumin (g/dL)+0.005xtotal lymphocyte count]. A low prognostic nutritional index was significantly associated with postoperative complications and survival in patients undergoing cardiovascular surgery (10) .

Similarly, in another study PNI values ≤ 34 were associated with a two-fold higher risk of overall mortality and three-fold higher risk of in hospital mortality in elderly patients hospitalized for acute heart failure (11) . In our study, we found the mean PNI value of 27.8 in the patient group who died. In another study with a larger number of COVID-19 patients (n=450), mortality was found to be 17.3% (78/450).

Comparison of baseline charactersistics showed non-survivors had higher age (p<0.001) and lower PNI (p<0.001) (12) . Although it did not reach statistical significance in our study, PNI values were found to be lower in the non-survivor group at tha time hospital admission. This may be due to smaller number of our patient group.

laboratory examination. It is used in the diagnosis, treatment and prognosis evaluation of pneumonia (13) .

In addition, NLR constitutes a novel prognostic marker for oncologic, cardiovascular and infectious diseases. Based on this, studies investigating the prognostic value of NLR in COVID-19 infection were conducted (14, 15, 16) . In a study by Busbus et al. NLR=3 presented a significant association with mortality (14) . In another study, the critical value of initial NLR and peak NLR (7.28 and 27.55 respectively) in prognosicate of intubation was prognostic factor for COVID-19 patients' death (15) .

Although it was higher in the exitus group baseline NLR values did not reach statistical significance in our study. NLR value was found to be statistically significantly higher in the exitus group after the treatment (NLR 4.40 vs 26.54 (p<0.0001). In another study, elevated age and NLR were found to be independent biomarkers for indicating poor clinical outcomes (16) . In the study of Liu et al, it was predicted that critical illness could develop in patients aged≥50 and having NLR≥3.13 (17) . Similar to our results, Peçanha-Pietrobom et al. found that patients with deteriorating clinical courses presented elevated and similar NLRs during first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21) (18) .

We found that non-survivors had higher level of white blood cell (WBC), neutrophil, lactate dehydrogenase (LDH), urea, serum creatinine, C-reactive protein (CRP) and ferritin. Whereas the level of lymphocyte, albumin and hemoglobin was significantly lower in non-survivors. Similar to our results, Wang et al. reported similar biochemical test results in patients with COVID-19 pneumonia (12) . In another study, lower lymphocytes and eGFR whereas higher CRP results were found in non-survivor kidney transplant patients (19) . In addition, in a study in which the data of 10 kidney transplant patients were presented, the ferritin values of the patients were found to be between 101-2871 ng/mL. Ferritin levels were found to be higher in 3 patients who died (20) . In our study, ferritin level was found to be significantly higher in non-survivor patient group.

There are studies conducted with the treatment of COVID-19 in kidney transplant recipients (21, 22, 23) . Cismaru et al. reported the overall mortality rate 33,3% in kidney transplant patients receiving favipiravir treatment (23) . Similarly, the mortality rate in our patient group was 29%. The efficacy of favipiravir treatment is still unclear (22, 23) . The small sample size and retrospective nature are the major limitations of this study.

In conclusion, The 9 patients who died, had lower PNI and higher NLR (Neutrophil/Lymphocyte Ratio), creatinine, LDH, ferritin and CRP levels. Hospitalized kidney transplant recipients with COVID-19 have higher rates of mortality. PNI exhibited good predictive performance and may be a useful clinical marker that can be used for estimating survival in COVID-19 patients. Further studies are required to confirm these findings and evaluate the efficacy of PNI for predicting prognosis. Withdrawal of antimetabolite 22 9 Withdrawal of CSA/FK 0 7

Tocilizumab 2 0

Convalescent plasma 1 1 

Kidney Transplantation in the times of COVID-19:Literature Review

A single center observational study of clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-Cov2 pneumonia

Covıd-19 and kidney transplantation: Results from the TANGO International Transplant Consotium

When a nephrology ward becomes a COVID-19 ward: the Cremona experience

Covid-19 and kidney transplantation

Early experience with COVID-19 in kidney transplantation

Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey

Systemic immune-inflammation index, based on platelet counts and neutrophil-lymphocyte ratio, is useful for predicting prognosis in small cell lung cancer

Prognostic nutrional index predicts acute kidney injury and mortality of patients in the coronary care unit

Clnical significance of prognostic nutritional index in patients undergoing cardiovascular surgery

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The prognostic nutritional index is associated with mortality of COVID-19 patients in Wuhan

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Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage

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