Search Results (13)

Background: Psychological impacts of the coronavirus disease 2019 (COVID-19) pandemic on individuals with chronic medical conditions remain understudied. Chronic kidney disease (CKD) is one of the chronic conditions associated with an increased risk of severe COVID-19 outcomes. The aim of this study was to define the psychological burden of individuals with CKD during the COVID-19 pandemic. Methods: In this cross-sectional study, 219 individuals with CKD were recruited from the Nephrology Outpatient Unit at the University Hospital Essen, Germany, and completed anonymous surveys incorporating validated psychological assessment tools for generalized anxiety (GAD-7) and depressive symptoms (PHQ-2), along with self-generated items addressing COVID-19-specific concerns and behavioral changes. These participants were propensity score matched with controls from the general German population. Results: Individuals with CKD exhibited lower levels of generalized anxiety and depressive symptoms compared to the general population. However, they reported significantly greater risk perceptions regarding the likelihood of experiencing symptoms, a severe disease course, and death from COVID-19. COVID-19-related fear and associated behavioral changes were more frequently reported among CKD patients. Adherent and dysfunctional safety behaviors predominated among the CKD cohort. Conclusions: This study underscores psychological challenges faced by individuals with CKD during the COVID-19 pandemic. The increased risk perceptions and fears of severe disease and mortality from COVID-19 emphasize the need for mental health interventions aimed at improving coping strategies alongside physical health management in this vulnerable population. Full article

Background/Objectives: Our previous retrospective single-center cohort study found, at 3-year follow-up, a trend toward low tacrolimus trough levels and an increased risk of de novo donor-specific anti-HLA antibodies (DSAs) and of antibody-mediated rejection (ABMR) in CYP3A5-expressing patients. Determining CYP3A5-expression status immediately after renal transplant would allow early genotype-based dosage adjustment of tacrolimus and might prevent the occurrence of de novo DSAs and ABMR, improving transplant outcome. Methods: 160 renal allograft recipients who underwent renal transplant at the University Hospital Essen between May 2019 and May 2022 were genotyped for the CYP3A5 rs776746 polymorphism within the first two weeks after transplant, and genotype-based dose adjustment of tacrolimus was performed for the follow-up of 2 years. Results: CYP3A5 expression was detected in 33 (21%) of the 160 patients. Tacrolimus trough levels were similar in CYP3A5 expressers and nonexpressers over the entire 2-year follow-up period. However, we observed a trend toward slightly higher tacrolimus trough levels in CYP3A5 expressers, who, as expected, required tacrolimus dosages twice as high as did nonexpressers during follow-up. Calcineurin inhibitor (CNI) nephrotoxicity-free survival rates were comparable between CYP3A5 expressers and nonexpressers (p = 0.49). Rejection-free survival rates (p = 0.89), de novo anti-HLA antibody-free survival rates (p = 0.57) and de novo DSA-free survival rates (p = 0.61) did not differ between the two groups. Conclusions: Early detection of CYP3A5-expression status and resultant genotype-based adjustment of tacrolimus dosage after renal transplant protected patients from transplant rejection and de novo DSA formation and was not associated with increased incidence of CNI toxicity among CYP3A5 expressers. Full article

TIMP-2 and IGFBP7 have been identified and validated for the early detection of renal injury in critically ill patients, but data on recovery of allograft function after kidney transplantation (KTx) are scarce. In a prospective observational multicenter cohort study of renal transplant recipients, urinary [TIMP-2] × [IGFBP7] was evaluated daily from day 1 to 7 after KTx. Different stages of early graft function were defined: immediate graft function (IGF) (decrease ≥ 10% in serum creatinine (s-crea) within 24 h post KTx); slow graft function (SGF) (decrease in s-crea < 10% within 24 h post KTx); and delayed graft function (DGF) (any dialysis needed within the first week after KTx). A total of 186 patients were analyzed. [TIMP-2] × [IGFBP7] was significantly elevated as early as day 1 in patients with DGF compared to SGF and IGF. ROC analysis of [TIMP-2] × [IGFBP7] at day 1 post-transplant for event “Non-DGF” revealed a cut-off value of 0.9 (ng/mL)²/1000 with a sensitivity of 87% and a specificity of 71%. The positive predictive value for non-DGF was 93%. [TIMP-2] × [IGFBP7] measured at day 1 after KTx can predict early recovery of transplant function and is therefore a valuable biomarker for clinical decision making. Full article

Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants. Full article

In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. Cellular responses were analyzed by interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpot assays. Neutralizing antibody titers were assessed against SARS-CoV-2 D614G (wild type) and the variants alpha, delta, and omicron by a cell culture-based neutralization assay. Humoral immunity was also determined by a competitive fluorescence assay, using 11 different variants of SARS-CoV-2. Antibody ratios were measured by ELISA. KTX patients showed significantly lower SARS-CoV-2-specific IFN-γ responses after booster vaccination than healthy controls. However, SARS-CoV-2-specific IL-2 responses were comparable to the T cell responses of healthy controls. Cell culture-based neutralizing antibody titers were 1.3-fold higher in healthy controls for D614G, alpha, and delta, and 7.8-fold higher for omicron (p < 0.01). Healthy controls had approximately 2-fold higher concentrations of potential neutralizing antibodies against all 11 variants than KTX patients. However, more than 60% of the KTX patients displayed antibodies to variants of SARS-CoV-2. Thus, KTX patients should be partly protected, due to neutralizing antibodies to variants of SARS-CoV-2 or by cross-reactive T cells, especially those producing IL-2. Full article

Solid organ transplant recipients have an up to ninefold higher risk of varicella–zoster virus (VZV) reactivation than the general population. Due to lifelong immunosuppressive therapy, vaccination against VZV may be less effective in kidney transplant (KTX) recipients. In the current study, twelve female and 17 male KTX recipients were vaccinated twice with the adjuvanted, recombinant zoster vaccine Shingrix™, which contains the VZV glycoprotein E (gE). Cellular immunity against various VZV antigens was analyzed with interferon-gamma ELISpot. We observed the strongest vaccination-induced changes after stimulation with a gE peptide pool. One month after the second vaccination, median responses were 8.0-fold higher than the responses prior to vaccination (p = 0.0006) and 4.8-fold higher than responses after the first vaccination (p = 0.0007). After the second vaccination, we observed an at least twofold increase in ELISpot responses towards gE peptides in 22 out of 29 patients (76%). Male sex, good kidney function, early time point after transplantation, and treatment with tacrolimus or mycophenolate were correlated significantly with higher VZV-specific cellular immunity, whereas diabetes mellitus was correlated with impaired responses. Thus, our data indicate that vaccination with Shingrix™ significantly augmented cellular, VZV gE-specific immunity in KTX recipients, which was dependent on several covariates. Full article

Several polymorphisms within Fc receptors (FCR) have been described, some of which correlate with allograft function. In the current study, we determined three Fcγ receptor and five Fcα receptor dimorphisms in 47 kidney transplant recipients who had been vaccinated against Streptococcus pneumoniae. We analyzed if FCR genotypes correlated with pneumococcal antibodies and their serotype-specific opsonophagocytic function, tested prior to and at months 1 and 12 post-vaccination. In parallel, we assessed antibodies against HLA and MICA and determined kidney function. We observed that IgG2 antibodies against pneumococci at months 1 and 12 after vaccination and IgA antibodies at month 1 differed significantly between the carriers of the three genotypes of FCGR3A rs396991 (V158F, p = 0.02; 0.04 and 0.009, respectively). Moreover, the genotype of FCGR3A correlated with serotype-specific opsonophagocytic function, reaching statistical significance (p < 0.05) at month 1 for 9/13 serotypes and at month 12 for 6/13 serotypes. Heterozygotes for FCGR3A had the lowest antibody response after pneumococcal vaccination. On the contrary, heterozygotes tended to have more antibodies against HLA class I and impaired kidney function. Taken together, our current data indicate that heterozygosity for FCGR3A may be unfavorable in kidney transplant recipients. Full article

In organ transplant recipients, the rate of invasive pneumococcal diseases is 25 times greater than in the general population. Vaccination against S. pneumoniae is recommended in this cohort because it reduces the incidence of this severe form of pneumococcal infection. Previous studies indicate that transplant recipients can produce specific antibodies after pneumococcal vaccination. However, it remains unclear if vaccination also induces specific cellular immunity. In the current study on 38 kidney transplant recipients, we established an interferon-γ ELISpot assay that can detect serotype-specific cellular responses against S. pneumoniae. The results indicate that sequential vaccination with the conjugated vaccine Prevenar 13 and the polysaccharide vaccine Pneumovax 23 led to an increase of serotype-specific cellular immunity. We observed the strongest responses against the serotypes 9N and 14, which are both components of Pneumovax 23. Cellular responses against S. pneumoniae correlated positively with specific IgG antibodies (r = 0.32, p = 0.12). In conclusion, this is the first report indicating that kidney transplant recipients can mount specific cellular responses after pneumococcal vaccination. The ELISpot we established will allow for further investigations. These could help to define, for example, factors influencing specific cellular immunity in immunocompromised cohorts or the duration of cellular immunity after vaccination. Full article

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the greatest medical challenge. Although crucial to the future management of the pandemic, the factors affecting the persistence of long-term SARS-CoV-2 immunity are not well understood. Therefore, we determined the extent of important correlates of SARS-CoV-2 specific protection in 200 unvaccinated convalescents after COVID-19. To investigate the effective memory response against the virus, SARS-CoV-2 specific T cell and humoral immunity (including virus-neutralizing antibodies) was determined over a period of one to eleven months. SARS-CoV-2 specific immune responses were present in 90% of individual patients. Notably, immunosuppressed patients did not have long-term SARS-CoV-2 specific T cell immunity. In our cohort, the severity of the initial illness influenced SARS-CoV-2 specific T cell immune responses and patients’ humoral immune responses to Spike (S) protein over the long-term, whereas the patients’ age influenced Membrane (M) protein-specific T cell responses. Thus, our study not only demonstrated the long-term persistence of SARS-CoV-2 specific immunity, it also determined COVID-19 severity and patient age as significant factors affecting long-term immunity. Full article

Chronic kidney disease may alter antiviral T cell immunity. In the current study, we assessed in 63 patients prior to kidney transplantation how humoral and cellular immunity against cytomegalovirus (CMV) correlated using an interferon (IFN)-γ ELISpot (T-Track^® CMV, Mikrogen, Neuried, Germany). The cohort comprised 24 patients with negative and 39 with positive CMV IgG. Whereas none of the patients with negative CMV IgG showed detectable responses to the T-Track^® CMV, 26 out of 39 patients with positive CMV IgG had positive ELISpot responses. The median response to CMV pp65 in the CMV seronegative group was 0 spot forming units (SFU) per 200,000 PBMC (range 0–1) and in the seropositive group 43 SFU (range 0–750). Thus, 13 out of 39 patients with positive CMV serostatus (33%) had undetectable T cell immunity and may be at an increased risk of CMV reactivation. CMV pp65-specific ELISpot responses were 29.3-fold higher in seropositive patients with vs. without dialysis and 5.6-fold higher in patients with vs. without immunosuppressive therapy, but patients with dialysis and immunosuppressive therapy showed, as expected, lower responses to phytohemagglutinin, the positive control. This finding may be caused by (subclinical) CMV-DNAemia and a “booster” of CMV-specific T cells. Full article

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has a major impact on transplant recipients, with mortality rates up to 20%. Therefore, the effect of established messenger RNA (mRNA)-based SARS-CoV-2 vaccines have to be evaluated for solid organ transplant patients (SOT) since they are known to have poor responses after vaccination. We investigated the SARS-CoV-2 immune response via SARS-CoV-2 IgG detection in 23 renal transplant recipients after two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 following the standard protocol. The antibody response was evaluated once with an anti-SARS-CoV-2 IgG CLIA 15.8 +/− 3.0 days after the second dose. As a control, SARS-CoV-2 IgG was determined in 23 healthcare workers (HCW) and compared to the patient cohort. Only 5 of 23 (22%) renal transplant recipients were tested positive for SARS-CoV-2 IgG antibodies after the second dose of vaccine. In contrast, all 23 (100%) HCWs were tested positive for antibodies after the second dose. Thus, the humoral response of renal transplant recipients after two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech, Kronach, Germany) is impaired and significantly lower compared to healthy controls (22% vs. 100%; p = 0.0001). Individual vaccination strategies might be beneficial in these vulnerable patients. Full article

mRNA-based SARS-CoV-2 vaccines offer a preventive strategy against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections that is of interest in the care of patients on hemodialysis (HDP). We measured humoral immune responses in 72 HDP after standard vaccination with two doses of the mRNA-based SARS-CoV-2 vaccine BNT162b2 (Pfizer-BioNTech). Antibody responses were evaluated with an anti-SARS-CoV-2 IgG ChemiLuminescent ImmunoAssay (CLIA) two weeks after the second dose. In addition, SARS-CoV-2 IgG was determined in a control of 16 healthy healthcare workers (HCW). The control group of HCW has shown a strong antibody response with a median (MD (Q1; Q3)) antibody titer of 800.0 AU/mL (520.5; 800.0). In comparison to HCW, HDP under 60 years of age responded equally (597.0 AU/mL (410.5; 800.0), p = 0.051). However, the antibody responses of the HDP negatively correlated with age (r² = 0.2954 p < 0.0001), leading to significantly lower antibody titers in HDP over 60 years (280.0 AU/mL (45.7; 477.0), p < 0.0001). To thoroughly understand the immunogenicity of the new mRNA-based vaccines in HDP, longitudinal data on the effectiveness and durability of antibody responses are needed. Modifications of immunization schedules should be considered in HDP with low or without antibody responsiveness after standard vaccination to boost immune reactivity and prolong protective effects in these vulnerable patients. Full article

Human leukocyte antigen (HLA)-E is important for the regulation of anti-viral immunity. BK polyomavirus (BKPyV) reactivation after kidney transplant is a serious complication that can result in BKPyV-associated nephropathy (PyVAN) and subsequent allograft loss. To elucidate whether HLA-E polymorphisms influence BKPyV replication and nephropathy, we determined the HLA-E genotype of 278 living donor and recipient pairs. A total of 44 recipients suffered from BKPyV replication, and 11 of these developed PyVAN. Homozygosity of the recipients for the HLA-E*01:01 genotype was associated with the protection against PyVAN after transplant (p = 0.025, OR 0.09, CI [95%] 0.83–4.89). Considering the time course of the occurrence of nephropathy, recipients with PyVAN were more likely to carry the HLA-E*01:03 allelic variant than those without PyVAN (Kaplan–Meier analysis p = 0.03; OR = 4.25; CI (95%) 1.11–16.23). Our findings suggest that a predisposition based on a defined HLA-E genotype is associated with an increased susceptibility to develop PyVAN. Thus, assessing HLA-E polymorphisms may enable physicians to identify patients being at an increased risk of this viral complication. Full article