BACKGROUND:

The coronavirus disease 2019 (COVID-19) pandemic has especially affected kidney transplant (KT) recipients, who are more vulnerable than the general population because of their immunosuppressive status and added comorbidities. The purpose of this study was to determine risk factors related to infection and mortality from COVID-19 in KT recipients.

METHODS:

The study included 113 stable KT recipients who had polymerase chain reaction-confirmed COVID-19 infection between March 2020 and February 2021, from a total of 2150 KT recipients. Outcomes related to patient survival were analyzed.

RESULTS:

The mean (standard deviation) age of the patients was 56 (14) years; 62% (n = 70) were men. The median time between KT and infection was 88 months (interquartile range, 39-155 months); 90% (n = 102) were on tacrolimus therapy and 81% (n = 92) on mycophenolate mofetil. The clinical presentation was pneumonia (n = 57; 51%), fever (n = 61; 54%), cough (n = 62; 55%), dyspnea (n = 43; 38%), lymphopenia (n = 57; 50%), and gastrointestinal symptoms (n = 28; 25%). A total of 21% (n = 24) required intubation and intensive care unit admission, and 27 patients (25%) were asymptomatic. A total of 9% (n = 10) received hydroxychloroquine therapy plus azithromycin, 11% (n = 12) tocilizumab, 3.7% (n = 4) lopinavir/ritonavir, 49% (n = 55) steroids, 0.9% (n = 1) remdesivir, and 9.3% (n = 11) convalescent plasma. Immunosuppression was reduced in all symptomatic patients. Nineteen patients (17%) died. Cox univariate analysis showed that the factors significantly associated with death were patient age, presence of pneumonia or lymphopenia, and elevated C-reactive protein on admission.

CONCLUSIONS:

Mortality in KT recipients with COVID-19 is very high, more than for the general population. Risk factors are patient age, presence of pneumonia or lymphopenia, and a higher C-reactive protein level at the time of diagnosis.

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06-1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04-2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

American Transplant Congress, 30 May- 3 June 2020, Pennsylvania, USA

TTS 2018. 27th International Congress of The Transplantation Society. June 30-July 5 Madrid, Spain. Introduction Monocytes comprise a heterogeneous population divided according to the membrane expression level of their molecules. One of these populations is the CD14++CD16+, which presents proinflammatory characteristics. Our aim was to evaluate the role of this monocyte population in renal transplant recipients with borderline rejection. Material and Methods This controlled clinical trial (NCT02284464) recruited patients with a low immunological risk to randomly receive conventional triple therapy (steroids, TAC and MMF) versus steroid withdrawal three months after the protocol biopsy. We analysed 66 patients with either a normal histology or borderline rejection. In all the patients we studied pre-randomisation levels of CD14++CD16+ at the third month in peripheral blood (PB) and blood extracted from the graft by fine needle aspiration cytology (FNAP). The monocytes were analysed by flow cytometry using CD14 and CD16 monoclonal antibodies. Results Of the 66 patients, 38 (51.1±12.8 years; 68.4% men) had a normal biopsy and 28 (57.8±9.5 years; 67.9% men) had borderline rejection. The percentage of proinflammatory monocytes was similar in the PB and FNAP samples from the patients with a normal biopsy (PB: 13.2±12.9 vs FNAP:16.3±14.3%; p=0.070). However, in the group with borderline rejection the difference in the percentage of these monocytes was significantly greater in the FNAP sample compared to the PB sample (PB: 7.9±5.4 vs FNAP: 16.9±16.5%; p=0.006). No differences were seen at the time of biopsy in renal function or proteinuria (Normal: Cr=1.6±0.6 vs Borderline: 1.7±0.5 mg/dL; p=0.536 and Normal: 268.2±197.9 vs Borderline: 269.3±239.8 mg/24h; p=0.986). Conclusion These preliminary results show that patients with a diagnosis of borderline rejection in the protocol biopsy present a significant difference in CD14++CD16+ monocytes between peripheral blood and graft blood, despite having a stable renal function. This suggests recruitment of these proinflammatory monocytes. Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional-FEDER, RETICS (REDINREN RD16/0009/0006). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

18th Congress of the European Society for Organ Transplantation, 24-27 September 2017, Barcelona, Spain

18th Congress of the European Society for Organ Transplantation, 24-27 September 2017, Barcelona, Spain

American Transplant Congress, June 11-15, 2016, Boston, America.