Impact of immunosuppressive regimens on antibody response after COVID-19 vaccination among Thai kidney transplant recipients

Background: The lower humoral immunity response after the COVID-19 vaccine in kidney transplant recipients (KTR) has been reported in several studies. However, there are few studies on the efficacy of the ChAdOx1 nCoV-19 (AstraZeneca) vaccine compared between various immunosuppressive regimens. Methods: We conducted a prospective cohort study at Siriraj Hospital, Bangkok, Thailand. Adult KTRs who received two doses of the ChAdOx1 nCoV-19 vaccine at intervals of 3 months were enrolled. Anti-SARS-COV-2 S-RBD-IgG antibody (anti-RBD) was assessed at the one month after the second dose and considered positive if the level ≥50 AU/mL or 7 BAU/mL. The primary outcome was the seropositivity of anti-RBD. The association between type, dose, and level of immunosuppressive regimen and anti-RBD seropositivity was analyzed. Results: Between October 2021 and January 2022, 139 KTRs with a median time of 55 months (IQR, 29–102 months), were enrolled. The mean age was 49.1 ± 11.3 years and 64.7 % were men. Seroconversion of anti-RBD was found in 72 patients (51.8 %). The seropositive rate was significantly higher in KTR who received tacrolimus (TAC)/everolimus (EVR)/prednisolone (CS) immunosuppression than EVR/mycophenolic acid (MPA)/CS and TAC/MPA/CS, respectively (95 % vs. 65 % vs. 34 %; p < 0.001). The MPA-containing regimen is associated with an inferior humoral response (OR 0.02, 95%CI 0.01–0.16; p < 0.001). In contrast, KTRs who received EVR had the highest immunogenic response (OR 12.97, 95%CI 4.69–35.84; p < 0.001). During the 11-month follow-up period, COVID-19 pneumonia occurred in 3 KTR in the seronegative group and none in the seropositive group. Conclusion: The anti-RBD response after ChAdOx1 nCoV-19 vaccination was revealed in 51.8 % of the KTR. KTRs who received the TAC/EVR/CS regimen had the highest immune response after vaccination, relatively comparable to the general population. The immunosuppressive regimen should be considered for a further vaccine dose in KTR

Variations in de novo donor-specific antibody development among HLA-DQ mismatches in kidney transplant recipients

BACKGROUND: HLA-DQ antibodies are the most prevalent de novo donor-specific antibodies (dnDSAs) after kidney transplantation (KT). The immunogenicity and impact of each HLA-DQ mismatch on graft outcomes can vary considerably. METHODS: This retrospective cohort study investigated the prevalence and risk factors for dnDSA development in patients who underwent KT at Siriraj Hospital between 2006 and 2020 and had HLA-DQB1 mismatches. Our center employed a protocol for post-KT dnDSA surveillance. The impact of dnDSAs on late rejection and graft survival was evaluated. RESULTS: In our cohort of 491 KT recipients, 59 (12.02%) developed dnDSAs to HLA-DQB1 at a median time of 4.2 years after KT. The risk of dnDSA occurrence was significantly higher among recipients with HLA-DQ7 mismatch (HR: 2.8; 95% CI: 1.21–6.52; P = 0.017) and HLA-DQ9 mismatch (HR: 2.63; 95% CI: 1.11–6.27; P = 0.028). Recipients who developed dnDSAs were younger (P = 0.009), had higher rates of medication nonadherence (P = 0.031), had pre-KT panel reactive antibody levels above 20% (P = 0.044), and received non-tacrolimus immunosuppression (P &lt; 0.001) compared to those without. Recipients who developed dnDSAs to HLA-DQ exhibited a significantly higher incidence of late graft rejection (HR: 7.76; 95% CI: 5–12.03; P &lt; 0.0001) and inferior death-censored graft survival than those without dnDSAs (log rank P &lt; 0.001). CONCLUSION: The patients with HLA-DQ7 and HLA-DQ9 mismatches exhibit the highest risk of developing dnDSAs. Individualized immunosuppression adjustment and kidney allocation based on specific HLA-DQ mismatch may enhance long-term graft survival

Impact of acute kidney injury and renal recovery status in deceased donor to kidney transplant outcome: results from the Thai national transplant registry

Abstract The influence of acute kidney injury (AKI) and renal recovery in deceased donor (DD) on long-term kidney transplant (KT) outcome has not previously been elucidated in large registry study. Our retrospective cohort study included all DDKT performed in Thailand between 2001 and 2018. Donor data was reviewed case by case. AKI was diagnosed according to the KDIGO criteria. Renal recovery was defined if DD had an improvement in AKI to the normal or lower stage. All outcomes were determined until the end of 2020. This study enrolled 4234 KT recipients from 2198 DD. The KDIGO staging of AKI was as follows: stage 1 for 710 donors (32.3%), stage 2 for 490 donors (22.3%) and stage 3 for 342 donors (15.6%). AKI was partial and complete recovery in 265 (17.2%) and 287 (18.6%) before procurement, respectively. Persistent AKI was revealed in 1906 KT of 990 (45%) DD. The ongoing AKI in DD significantly increases the risk of DGF development in the adjusted model (HR 1.69; 95% CI 1.44–1.99; p < 0.001). KT from DD with AKI and partial/complete recovery was associated with a lower risk of transplant loss (log-rank P = 0.04) and recipient mortality (log-rank P = 0.042) than ongoing AKI. KT from a donor with ongoing stage 3 AKI was associated with a higher risk of all-cause graft loss (HR 1.8; 95% CI 1.12–2.88; p = 0.02) and mortality (HR 2.19; 95% CI 1.09–4.41; p = 0.03) than stage 3 AKI with renal recovery. Persistent AKI, but not recovered AKI, significantly increases the risk of DGF. Utilizing kidneys from donors with improving AKI is generally safe. KT from donors with persistent AKI stage 3 results in a higher risk of transplant failure and recipient mortality. Therefore, meticulous pretransplant evaluation of such kidneys and intensive surveillance after KT is recommended