Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07–0.56, P < 0.01). Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin‐6 (IL‐6) release. The IL‐6‐receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID‐19) . In this pandemic, kidney transplant (KT) recipients are a high‐risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID‐19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL‐6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D‐dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C‐reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004‐1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID‐19 but randomized trials are needed.

The World Health Organization has declared the SARS-CoV-2 infection (COVID-19) outbreak as a Public Health Emergency of International Concern and characterized it as a pandemic. 1,2 Since early March, 2020, the Spanish cases curve started to rise, with more than 177 000 people infected in 6 weeks. 3 The reported fatality-rate in the general population with COVID-19 admitted to a large tertiary Spanish Hospital is 20.7%, 34% in the subgroup of age 70-79 years. 4

Background COVID-19 has exposed hemodialysis patients and kidney transplant recipients to an unprecedented life-threatening infectious disease raising concerns about kidney replacement therapy (KRT) strategy during the pandemic. The present study investigated the association of type of KRT with COVID-19 severity adjusting for differences in individual characteristics. Methods Data on kidney transplant recipients and hemodialysis patients diagnosed with COVID-19 between February 1st and December 1st 2020 were retrieved from ERACODA. Cox regression models adjusted for age, sex, frailty and comorbidities were used to estimate hazard ratios (HR) for 28-day mortality risk in all patients and in the subsets who were tested because of symptoms Results In total, 1,670 patients (496 functional kidney transplant and 1,174 hemodialysis) were included. 16.9% of kidney transplant and 23.9% of hemodialysis patients died within 28 days of presentation. The unadjusted 28-day mortality risk was 33% lower in kidney transplant recipients compared with hemodialysis patients (HR: 0.67, 95%CI: 0.52-0.85). In a fully adjusted model, the risk was 78% higher in kidney transplant recipients (HR: 1.78, 95%CI: 1.22-2.61) compared with hemodialysis patients. This association was similar in patients tested because of symptoms (fully adjusted model HR: 2.00, 95%CI: 1.31-3.06). This risk was dramatically increased during the first post-transplant year. Results were similar for other endpoints (e.g. hospitalization, ICU admission, mortality beyond 28 days) and across subgroups. Conclusions Kidney transplant recipients had a greater risk of a more severe course of COVID-19 compared with hemodialysis patients; they therefore require specific infection mitigation strategies.

BackgroundCorrelation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.MethodsWe retrospectively assessed patients with transplant biopsies scored following Banff’15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (AT1R)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMRh) with and without HLA-DSA.ResultsOne-hundred eighteen patients with normal histology (n = 19), ABMRh (n = 52) or IFTA (n = 47) were studied. ABMRh patients were HLA-DSApos (n = 38, 73%) or HLA-DSAneg (n = 14, 27%). Pre-transplant HLA-DSA and AT1R-Ab were more frequent in ABMRh compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRhDSAneg cases showed non-HLA antibodies. ABMRhDSAneg and ABMRhDSApos cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRhDSApos but not with ABMRhDSAneg. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31–10.37], p = 0.013) and AT1R-Ab (OR: 5.47 [1.78–16.76], p = 0.003) were independent predictors of ABMRhDSApos.ConclusionsIn conclusion, pre-transplant AT1R-Ab is frequently found in ABMRhDSApos patients. However, AT1R-Ab, MICA-Ab, ETAR-Ab or EC-XM+ are rarely found among ABMRhDSAneg patients. Pre-transplant AT1R-Ab may act synergistically with preformed or de novo HLA-DSA to produce ABMRhDSApos but not ABMRhDSAneg. HLA epitope mismatch associates with ABMRhDSApos compared with ABMRhDSAneg, suggesting factors other than HLA are responsible for the damage.

Background. The clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in kidney transplant (KT) recipients is lower than in the general population. Methods. From April to October 2021, 481 KT recipients with COVID-19, included in the Spanish Society of Nephrology COVID-19 Registry, were analyzed. Data regarding vaccination status and vaccine type were collected, and outcomes of unvaccinated or partially vaccinated patients (n = 130) were compared with fully vaccinated patients (n = 351). Results. Clinical picture was similar and survival analysis showed no differences between groups: 21.7% of fully vaccinated patients and 20.8% of unvaccinated or partially vaccinated died ( P = 0.776). In multivariable analysis, age and pneumonia were independent risk factors for death, whereas vaccination status was not related to mortality. These results remained similar when we excluded patients with partial vaccination, as well as when we analyzed exclusively hospitalized patients. Patients vaccinated with mRNA-1273 (n = 213) showed a significantly lower mortality than those who received the BNT162b2 vaccine (n = 121) (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85; P = 0.010). Conclusions. COVID-19 severity in KT patients has remained high and has not improved despite receiving 2 doses of the mRNA vaccine. The mRNA-1273 vaccine shows higher clinical effectiveness than BNT162b2 in KT recipients with breakthrough infections. Confirmation of these data will require further research taking into account the new variants and the administration of successive vaccine doses.

Cytomegalovirus (CMV) infection constitutes a complication for kidney transplant recipients (KTR) and CMV‐specific T cells reduce the risk of viral replication in seropositive patients. CMV promotes the adaptive differentiation and expansion of an NK cell subset, hallmarked by expression of the CD94/NKG2C receptor with additional characteristic features. We previously reported an association of pretransplant NKG2C+ NK cells with a reduced incidence of CMV infection. We have strengthened the analysis in cryopreserved peripheral blood mononuclear cells from an enlarged KTR cohort (n = 145) with homogeneous immunosuppression, excluding cases at low risk of infection (ie, CMV D−R−) or receiving antiviral prophylaxis. Moreover, adaptive NKG2C+ NK cell–associated markers (ie, NKG2A, CD57, Immunoglobulin‐like transcript 2 [LIR1 or LILRB1], FcεRI γ chain, and Prolymphocytic Leukemia Zinc Finger transcription factor) as well as T lymphocyte subsets were assessed by multicolor flow cytometry. The relation of NKG2C+ NK cells with T cells specific for CMV antigens was analyzed in pretransplant patients (n = 29) and healthy controls (n = 28). Multivariate Cox regression and Kaplan‐Meier analyses supported that NKG2C+ NK cells bearing adaptive markers were specifically associated with a reduced incidence of posttransplant symptomatic CMV infection; no correlation between NKG2C+ NK cells and CMV‐specific T cells was observed. These results support that adaptive NKG2C+ NK cells contribute to control CMV infection in KTR.

The COVID-19 pandemic has led to frequent referrals to the emergency department on suspicion of this infection in maintenance hemodialysis (MHD) and kidney transplant (KT) patients. We aimed to describe their clinical features comparing confirmed and suspected non-confirmed COVID-19 cases during the Spanish epidemic peak. Confirmed COVID-19 ((+)COVID-19) corresponds to patient with positive RT-PCR SARS-CoV-2 assay. Non-confirmed COVID-19 ((−)COVID-19) corresponds to patients with negative RT-PCR. COVID-19 was suspected in 61 patients (40/803 KT (4.9%), 21/220 MHD (9.5%)). Prevalence of (+)COVID-19 was 3.2% in KT and 3.6% in MHD patients. Thirty-four (26 KT and 8 MHD) were (+)COVID-19 and 27 (14 KT and 13 MHD) (−)COVID-19. In comparison with (−)COVID-19 patients, (+)COVID-19 showed higher frequency of typical viral symptoms (cough, dyspnea, asthenia and myalgias), pneumonia (88.2% vs. 14.3%) and LDH and CRP while lower phosphate levels, need of hospital admission (100% vs. 63%), use of non-invasive mechanical ventilation (36% vs. 11%) and mortality (38% vs. 0%) (p < 0.001). Time from symptoms onset to admission was longer in patients who finally died than in survivors (8.5 vs. 3.8, p = 0.007). In KT and MHD patients, (+)COVID-19 shows more clinical severity than suspected non-confirmed cases. Prompt RT-PCR is mandatory to confirm COVID-19 diagnosis.