Impact of donor-specific antibody with low mean fluorescence intensity on allograft outcomes in kidney transplant.

BACKGROUND: Immune-mediated rejection is the most common cause of allograft failure in kidney transplant (KT) patients. Exposure to alloantigen, including human leukocyte antigen (HLA), results in the production of donor-specific antibodies (DSA). There are limited data about low levels of mean fluorescence intensity (MFI) DSA, especially post-transplantation. This study evaluated allograft outcomes in KT patients with low MFI DSA. METHODS: From January 2007 to December 2021, KT patients who were tested for post-transplant DSA at Ramathibodi Hospital, Bangkok, Thailand, with the DSA MFI ≤ 1000 were evaluated. These KT patients were categorized into two groups: very low DSA (VLL; MFI = 1-500) and low DSA (LL; MFI = 501-1000). All KT patients were evaluated for the primary outcomes, such as the incidence of acute rejection, serum creatinine levels at one and five years after transplantation as well as allograft and patient survivals. RESULTS: Among 36 KT patients 25 were included as those with VLL and 11 as those with LL. The LL group had significantly higher T-cell mediated allograft rejection (TCMR) than the VLL group (45% vs. 12%, P = 0.04). In addition, 10 patients, 5 in the VLL group and 5 in the LL group developed antibody-mediated allograft rejection (ABMR). Both TCMR and ABMR were confirmed by biopsy results. There was a trend toward higher MFI in KT patients with ABMR than without ABMR (P = 0.22). At 5 post-transplant years, serum creatinine, allograft and patient survivals were comparable between these two groups. Furthermore, the univariate and multivariate analyzes revealed that the LL group was a high risk for rejection. CONCLUSION: Low MFI DSA values after transplantation may be associated with a higher incidence of rejection, but this finding did not show differences in allograft and patient survival in this study's analysis.

Expanded Criteria Donor With Severe Acute Kidney Injury: Worth to Use?

BACKGROUND: Expanded criteria donors (ECDs) may present with acute kidney injury (AKI). Many transplantation centers refuse to use these kidneys because of concerns about poor transplant outcomes, resulting in a high discard rate. However, long-term results of ECDs with AKI (ECDs + AKI) have not been extensively studied. METHODS: We retrospectively compared outcomes of ECDs with ECDs + AKI. Primary outcome was 5-year allograft and patient survival rate. Secondary outcomes were allograft function, rates of delayed graft function, and allograft rejection. RESULTS: Of 743 deceased donor kidney transplant recipients, 95 ECD cases were included in this study. There were 38 patients (40%) with ECDs and 57 patients (60%) with ECDs + AKI. Mean donor creatinine was progressively higher with severity of AKI. Five-year graft and patient survival were comparable between ECDs and ECDs + AKI (80.6% vs 81.1%, P = .95 and 91.7% vs 88.7%, P = .73). Mean (SD) allograft estimated glomerular filtration rate was 36.7 (14.5) vs 40.6 (22.7) mL/min/1.73 m2 with P = .61, respectively. Multivariate analysis showed factors associated graft loss were delayed graft function (P = .01) and donor-recipient age difference ≥10 years (P = .038), not AKI status. CONCLUSIONS: Kidney transplant from ECDs + AKI has comparable allograft survival with ECDs without AKI. Use of ECDs + AKI is worthwhile and kidneys from ECDs + AKI should not be discarded. Recipient selection and perioperative care are important to optimize the use of scarce resource.

The Effect of a Booster Dose mRNA Vaccine on COVID-19 Infection in Kidney Transplant Recipients after Inactivated or Viral Vector Vaccine Immunization.

The mortality rate after novel coronavirus infection, which causes severe acute respiratory distress syndrome (SARS-CoV-2), is much higher in kidney transplant recipients (KTRs) compared to the general population. Seroconversion after vaccination is also lower, and breakthrough infection is much higher. Many studies reported seroconversion rate after a booster (third) dose of vaccine but clinical outcomes received less attention. Here, we reported the impact of an mRNA vaccine booster dose on clinical outcomes of KTRs with SARS-CoV-2 infection. A total of 183 KTRs with SARS-CoV-2 infection were identified. Of 183 KTRs, 146 KTRs had sufficient data for analysis and were included in this study. Forty-eight patients (32.9%) received zero to 1 doses of vaccine (Group 1), thirty-one (21.2%) received two doses (Group 2), and sixty-seven (45.9%) received a booster dose (Group 3). Pneumonia developed in 50%, 23%, and 10% in Group 1, 2, and 3 (p < 0.001). Hospital admission requirement was 81%, 48%, and 12% (p < 0.001). Mortality rate was 26%, 3%, and 3% (p = 0.001). A multivariate analysis showed that only diabetes adversely affects mortality while the booster dose of the vaccine significantly reduced mortality. The booster dose of the vaccine is strongly recommended in all KTRs especially those with diabetes. Our study also suggested the timing of the booster dose vaccine to be administered within 4 months after the second dose.

Benefits of Inactivated Vaccine and Viral Vector Vaccine Immunization on COVID-19 Infection in Kidney Transplant Recipients.

The coronavirus virus disease 2019 (COVID-19) pandemic has impacted the global healthcare system. In Thailand, the first and most available vaccines were inactivated and viral vector vaccines. We reported the impact of those vaccines in preventing severe disease and death in kidney transplant recipients. This retrospective study comprised 45 kidney transplant recipients with COVID-19 infection, classified by vaccination status. Outcomes of interest were death, pneumonia, and allograft dysfunction. There were 23 patients in vaccinated group and 22 patients in unvaccinated group. All baseline characteristics were similar except mean age was older in vaccinated group, 55 vs. 48 years. Total 11 patients (24%) died (13% vaccinated vs. 36% unvaccinated RR, 0.56; 95% CI, 0.29-0.83; p = 0.03). Multivariate analysis showed that vaccination significantly decrease mortality (odds ratio, 0.54; 95% CI, 0.10-0.94; p = 0.03). Pneumonia developed equally in both groups (70%). There was a trend toward less oxygen requirement as well as ventilator requirement in vaccinated group. The rate of allograft dysfunction was similar (47%). Inactivated and viral vector COVID-19 vaccines have beneficial effect on mortality reduction in kidney transplant recipients. Even partial vaccination can exert some protection against death. However, full vaccination should be encouraged to achieve better prevention.

Trough Level and Tacrolimus Variability of Early Converted Once-Daily Tacrolimus: 1-Year Follow-up Study.

INTRODUCTION: Long-term transplant outcomes are considered a crucial point for kidney transplantation. Follow-up studies in patients receiving early conversion to once-daily tacrolimus (TAC-OD) are still limited. We aimed to investigate tacrolimus trough level (Cmin), intrapatient variability of tacrolimus dose-normalized Cmin (TAC-Cmin/D), along with other outcomes between twice-daily tacrolimus (TAC-BID) and early converted TAC-OD. MATERIAL AND METHODS: This study was a single center, retrospective, cohort study. All new kidney transplant patients who received tacrolimus and presented an estimated glomerular filtration rate of more than 45 mL/min/1.73 m2 on the day of hospital discharge were included. Studied patients were divided into the standard TAC-BID and patients who were converted from TAC-BID to TAC-OD on the day of hospital discharge. We followed patients for 1 year after transplantation. RESULTS: At the first follow-up visit, Cmin of TAC-OD was significantly lower than that of TAC-BID. However, Cmin and estimated glomerular filtration rate were comparable between TAC-BID and TAC-OD throughout 1-year follow-up. TAC-OD also provided a lower intrapatient variability of TAC-Cmin/D compared with TAC-BID when observed after 6 months post transplantation (17.40% and 23.27% for TAC-OD and TAC-BID, respectively; P = .13). The renal function, as well as other adverse outcomes, was similar between 2 formulations. DISCUSSION: TAC-OD provided a similar Cmin with comparable renal function compared with TAC-BID during 1-year follow-up. In addition, TAC-OD is likely to have a benefit of a lower intrapatient variability of tacrolimus. CONCLUSION: Early conversion from TAC-BID to TAC-OD with 1:1 ratio can be used with close long-term monitoring.

Stabilization of estimated glomerular filtration rate in kidney transplantation from deceased donors with acute kidney injuries.

AIM: To evaluate and compare the outcomes of kidney transplant (KT) from deceased donors among standard criteria, acute kidney injury (AKI) and expanded criteria donors (ECDs). METHODS: This retrospective study included 111 deceased donor kidney transplant recipients (DDKT). Deceased donors were classified as standard criteria donor (SCD), AKI donor and ECD. AKI was diagnosed and classified based on change of serum Cr by acute kidney injury network (AKIN) criteria. Primary outcome was one-year estimated glomerular filtration rate (eGFR) calculated from Cr by CKD-EPI. Multivariate regression analysis was done by adjusting factors such as type of DDKT, %Panel-reactive antibodies, cold ischemic time, the presence of delayed graft function and the use of induction therapy. Significant factors that can affect the primary outcomes were then identified. RESULTS: ECD group had a significantly lower eGFR at one year (33.9 ± 17.3 mL/min) when compared with AKI group (56.6 ± 23.9) and SCD group (63.6 ± 19.9) (P < 0.001). For AKI group, one-year eGFR was also indifferent among AKIN stage 1, 2 or 3. Patients with AKIN stage 3 had progressive increase of eGFR from 49.6 ± 27.2 at discharge to 61.9 ± 29.0 mL/min at one year. From Kaplan-Meier analysis, AKI donor showed better two-year graft survival than ECD (100% vs 88.5%, P = 0.006). Interestingly, AKI group had a stable eGFR at one and two year. The two-year eGFR of AKI group was not significantly different from SCD group (56.6 ± 24.5 mL/min vs 58.6 ± 23.2 mL/min, P = 0.65). CONCLUSION: Kidney transplantations from deceased donors with variable stage of acute kidney injuries were associated with favorable two-year allograft function. The outcomes were comparable with KT from SCD. This information supports the option that deceased donors with AKI are an important source of organ for kidney transplantation even in the presence of stage 3 AKI.