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.

Years of life lost and long-term outcomes due to glomerular disease in a Southeast Asian Cohort.

Death and end-stage kidney disease (ESKD) are major outcomes of glomerular disease. (GD) The years of potential life lost (YLL) may provide additional insight into the disease burden beyond death rates. There is limited data on premature mortality in GD. In this retrospective observational cohort study, we evaluated the mortality, ESKD rates, and YLL in Thais with biopsy-proven GD. The mortality and combined outcome rates were determined by log-rank test and ESKD by using a competing risk model. YLL and premature life lost before age 60 were calculated for different GD based on the life expectancy of the Thai population. Patients with GD (n = 949) were followed for 5237 patient years. The death rate and ESKD rates (95%CI) were 4.2 (3.7-4.9) and 3.3 (2.9-3.9) per 100 patient-years, respectively. Paraprotein-related kidney disease had the highest death rate, and diabetic nephropathy had the highest ESKD rate. Despite not having the highest death rate, lupus nephritis (LN) had the highest YLL (41% of all GD) and premature loss of life before age 60. In conclusion, YLL provided a different disease burden assessment compared to mortality rates and identified LN as the major cause of premature death due to GD in a Southeast Asian cohort.

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.

GC × GC-TOFMS metabolomics analysis identifies elevated levels of plasma sugars and sugar alcohols in diabetic mellitus patients with kidney failure.

Two dimensional GC (GC × GC)-time-of-flight mass spectrometry (TOFMS) has been used to improve accurate metabolite identification in the chemical industry, but this method has not been applied as readily in biomedical research. Here, we evaluated and validated the performance of high resolution GC × GC-TOFMS against that of GC-TOFMS for metabolomics analysis of two different plasma matrices, from healthy controls (CON) and diabetes mellitus (DM) patients with kidney failure (DM with KF). We found GC × GC-TOFMS outperformed traditional GC-TOFMS in terms of separation performance and metabolite coverage. Several metabolites from both the CON and DM with KF matrices, such as carbohydrates and carbohydrate-conjugate metabolites, were exclusively detected using GC × GC-TOFMS. Additionally, we applied this method to characterize significant metabolites in the DM with KF group, with focused analysis of four metabolite groups: sugars, sugar alcohols, amino acids, and free fatty acids. Our plasma metabolomics results revealed 35 significant metabolites (12 unique and 23 concentration-dependent metabolites) in the DM with KF group, as compared with those in the CON and DM groups (N = 20 for each group). Interestingly, we determined 17 of the 35 (14/17 verified with reference standards) significant metabolites identified from both the analyses were metabolites from the sugar and sugar alcohol groups, with significantly higher concentrations in the DM with KF group than in the CON and DM groups. Enrichment analysis of these 14 metabolites also revealed that alterations in galactose metabolism and the polyol pathway are related to DM with KF. Overall, our application of GC × GC-TOFMS identified key metabolites in complex plasma matrices.

A 46-Year-Old Thai Woman with Secondary Acquired Pure Red Cell Aplasia Due to Treatment with Recombinant Erythropoietin While on Dialysis for End-Stage Renal Disease Who Recovered Following ABO-Incompatible Kidney Transplantation.

BACKGROUND Pure red cell aplasia (PRCA) is an uncommon cause of anemia in end-stage kidney disease (ESKD). It is attributed to recombinant human erythropoietin (rHuEPO) administration. Although immunosuppression is the mainstay therapy, its effectiveness varies from 30% to 70%. PRCA in ESKD has been reported to improve following kidney transplantation. CASE REPORT A 46-year-old woman with ESKD secondary to lupus nephritis was treated for uremia at our center. She developed severe anemia. Bone marrow aspiration and biopsy revealed a reduction of erythroid precursors, consistent with PRCA. Because she had no sibling's blood group matched with her, ABO-incompatible kidney transplantation was an option for treatment. She underwent a desensitization protocol consisting of rituximab 375 mg/m2, tacrolimus, mycophenolate mofetil, and prednisolone 4 weeks before surgery, in addition to 3 sessions of double-filtration plasmapheresis (DFPP) every other day followed by intravenous immunoglobulin (IVIG) and 1 session of specific immunoadsorption (Glycosorb® B column) at pre-transplant day -1. She also received low-dose rabbit anti-thymocyte globulin (rATG) (Thymoglobulin®) (total 2.0 mg/kg). Maintenance therapy included tacrolimus, mycophenolate mofetil, and prednisolone. Allograft function normalized a few days after transplantation and her Hb gradually increased. CONCLUSIONS We report a rare case of PRCA in a patient with ESKD undergoing ABO-incompatible kidney transplantation. The outcome was satisfactory, with complete correction of anemia and kidney function.

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.

Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients.

Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1-2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4-26.8), 1092.5 (606.9-1927.2), and 1740.9 (1106-3762.3) BAU/mL, and percent neutralization was 0.9 (0-9.9), 98.8 (95.9-99.5), and 99.4 (98.8-99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).

SARS-CoV-2-specific humoral and cell-mediated immune responses after immunization with inactivated COVID-19 vaccine in kidney transplant recipients (CVIM 1 study).

Immunogenicity following inactivated SARS-CoV-2 vaccination among solid organ transplant recipients has not been assessed. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals, of an inactivated whole-virus SARS-CoV-2 vaccine. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose. The median (IQR) age of KT recipients was 50 (42-54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens. The median (IQR) time since transplant was 4.5 (2-9.5) years. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1-3.7] vs. 1742.0 [747.7-3783.0] AU/ml, p < .01) as well as percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0 [0-0] vs. 71.2 [56.8-92.2]%, p < .01). However, the median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4-120] vs. 12 [0-56] T cells/106  PBMCs, p = .02) and not different from the controls. Our findings revealed weak HMI but comparable CMI responses in fully vaccinated KT recipients receiving inactivated SARS-CoV-2 vaccination compared to immunocompetent individuals (Thai Clinical Trials Registry, TCTR20210226002).