Incidence of De Novo Post-Transplant Malignancies in Thai Adult Kidney Transplant Recipients: A Single-Center, Population-Controlled, Retrospective Cohort Study at the Highest Volume Kidney Transplant Center in Thailand.

Kidney transplant recipients (KTRs) are at increased risk of developing de novo post-transplant malignancies (PTMs), with regional differences in types with excess risk compared to the general population. A single-center, population-controlled, retrospective cohort study was conducted at a tertiary care center in Thailand among all adults who underwent their first kidney transplant from 1986 to 2018. Standardized incidence ratios (SIRs) of malignancy by age, sex, and place of residence were obtained using data from the National Cancer Registry of Thailand as population control. There were 2,024 KTRs [mean age, 42.4 years (SD 11.4); female patients, 38.6%] during 16,495 person-years at risk. Of these, 125 patients (6.2%) developed 133 de novo PTMs. The SIR for all PTMs was 3.85 (95% CI 3.22, 4.56), and for pooled solid and hematologic PTMs, it was 3.32 (95% CI 2.73, 3.99). Urothelial malignancies had the largest excess risk, especially in women [female SIR 114.7 (95% CI 66.8, 183.6); male SIR 17.5 (95% CI 8.72, 31.2)]. The next two most common cancers were non-Hodgkin's lymphoma and skin cancer [SIR 20.3 (95% CI 13.6, 29.1) and 24.7 (95% CI 15.3-37.8), respectively]. Future studies are needed to identify the risk factors and assess the need for systematic screening among PTMs with excess risk in KTRs.

The current therapeutic approach for anaemia after kidney transplant.

PURPOSE OF REVIEW: Anaemia after kidney transplantation is a common finding with no uniform management guideline. Most approaches are derived from the chronic kidney disease (CKD) population. Recent advances for the treatment of anaemia in patients with CKD/End stage renal disease include hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHi), a novel class of oral erythropoietin-stimulating agents (ESAs). We present relevant studies of HIF-PHi in the transplant population and its implications on the management of posttransplant anaemia. RECENT FINDINGS: Data on HIF-PHi use in the kidney transplant population are promising. Limited data demonstrate a significant increase in haemoglobin, with a comparable safety profile to epoetin. Reported adverse effects include overcorrection and low iron stores. SUMMARY: Current therapeutic approaches to anaemia in the kidney transplant population is mostly derived from the CKD population. More studies are needed on HIF-Phi, a novel class of ESAs that has thus far demonstrated promise in the kidney transplant population.

Utility of the Interferon-Gamma Enzyme-Linked Immunosorbent Spot Assay to Predict Risk of Cytomegalovirus Infection in Kidney Transplant Recipients.

Non-specific interferon-gamma (IFN-γ) enzyme-linked immunosorbent (ELISpot) responses after solid organ transplant (SOT) and their relationship with cytomegalovirus (CMV) reactivation have hardly been investigated. Adult kidney transplant (KT) recipients underwent measurement of IFN-γ-producing T cells using the ELISpot assay before and 1 month after transplantation. Data for CMV infection episodes were collected. Risk factors for post-transplant CMV infection, based on IFN-γ responses, were analyzed using a Cox proportional hazards model. A total of 93 KT recipients were enrolled in the study and 84 evaluable participants remained at 1 month post KT. Thirty-three (39%) recipients developed subsequent CMV infection within 6 months post-transplant. At 1-month post-transplant, IFN-γ-producing T cells with <250 spot-forming units (SFUs)/2.5 × 105 peripheral blood mononuclear cells (PBMCs) were significantly associated with CMV infection (HR 3.1, 95% CI 1.4-7.1, p = 0.007). On multivariable analysis, posttransplant IFN-γ-producing T cells with <250 SFUs/2.5 × 105 PBMCs remained independently associated with CMV infection (HR 3.1, 95% CI 1.2-7.8, p = 0.019). Conclusions: KT recipients with low IFN-γ-producing T cells measured by the ELISpot assay are more likely to develop CMV infection after transplantation. Therefore, measurement of nonspecific cell-mediated immunity ELISpot responses could potentially stratify recipients at risk of CMV infection (Thai Clinical Trials Registry, TCTR20210216004).

Enhancing healthcare quality and outcomes for peritoneal dialysis patients in Thailand: An evaluation of key performance indicators and PDOPPS cohort representativeness.

AIM: To assess whether the peritoneal dialysis (PD) centres included in the Peritoneal Dialysis Outcomes and Practise Patterns Study (PDOPPS) in Thailand are representative of other PD centres in the country, based on 8 key performance indicators (KPIs 1-8). METHODS: A retrospective analysis was conducted comparing PD-related clinical outcomes between PD centres included in the PDOPPS (the PDOPPS group) and those not included (the non-PDOPPS group) from January 2018 to December 2019. Logistic regression analysis was used to identify predictors associated with achieving the target KPIs. RESULTS: Of 181 PD centres, 22 (12%) were included in the PDOPPS. PD centres in the PDOPPS group were larger and tended to serve more PD patients than those in the non-PDOPPS group. However, the process and outcome KPIs (KPIs 1-8) were comparable between the 2 groups. Large hospitals (≥120 beds), providing care to ≥100 PD cases and having experience for >10 years were independent predictors of achieving the peritonitis rate target of <0.5 episodes/year. Most PD centres in Thailand showed weaknesses in off-target haemoglobin levels and culture-negative peritonitis rate. CONCLUSIONS: The PD centres included in Thai PDOPPS were found to be representative of other PD centres in Thailand in terms of clinical outcomes. Thus, Thai PDOPPS findings may apply to the broader PD population in Thailand.

Role of highly sensitive nucleic acid amplification testing for plasma cytomegalovirus DNA load in diagnosis of cytomegalovirus gastrointestinal disease among kidney transplant recipients.

BACKGROUND: High plasma cytomegalovirus (CMV) DNA load is generally associated with CMV tissue-invasive disease in solid organ transplant recipients. However, some tissue-invasive diseases, especially CMV gastrointestinal (GI) disease, have undetectable to very low plasma CMV DNA loads. Highly sensitive nucleic acid amplification testing (NAAT) has been increasingly used to quantify low-level CMV DNA loads. Our primary objective was to investigate the epidemiology of CMV GI disease and evaluate the validity of plasma CMV NAAT for the diagnosis of CMV GI disease in kidney transplant (KT) recipients. METHODS: We conducted a retrospective study of all KT recipients who developed CMV GI disease from January 2016 to December 2018. Plasma CMV DNA load was measured using real-time PCR. The cut-off value of plasma CMV DNA load for diagnosing and risk factors of CMV GI disease were analyzed. RESULTS: A total 17 (3.4%) cases of CMV GI disease occurred in 494 KT recipients. Fifteen (88%) patients had CMV D + /R + serostatus. Fourteen (82%) patients developed CMV GI disease within 6 months after KT. Plasma CMV DNA loads were detectable in all (100%) patients with a median load 11,102 (IQR 2,935-107,160) IU/ml. A plasma CMV DNA load of 4,063 IU/ml was established as al cut-off for diagnosing CMV GI disease (AUC 0.74, sensitivity 76.5%, specificity 70%, PPV 68, NPV 78). In multivariate analysis, prolonged cold ischemic time (HR 1.14, 95% CI 1.05-1.23, P = .002) and CMV D + /R - serostatus (HR 9.31, 95% CI 2.12-40.74, P = .003) were associated with CMV GI disease. CONCLUSIONS: Using highly sensitive NAAT could potentially assist in the diagnosis of CMV GI disease in a CMV D + /R + serostatus setting. KT recipients with CMV seromismatch and prolonged cold ischemic time are at higher risk of CMV GI disease.

Absolute lymphocyte count and human adenovirus-specific T-cell immune restoration of human adenovirus infection after kidney transplantation.

INTRODUCTION: Human adenovirus (HAdV) infection can cause substantial morbidity in kidney transplant (KT) recipients. Cell-mediated immunity plays an important role in controlling HAdV infection after KT. METHODS: We prospectively (January 2015 to June 2018) investigated the absolute lymphocyte count (ALC) and interferon-γ-producing CD4+ and CD8 + T cells at diagnosis and at viral clearance by an intracellular cytokine assay after stimulating with HAdV whole lysate, hexon, and penton proteins. HAdV infection was defined as the presence of HAdV DNA load in plasma or clinical specimens measured by the polymerase chain reaction assay. RESULTS: Eighteen adult KT recipients were diagnosed with HAdV infection at a median of 16 months (interquartile range [IQR], 2-39) after KT. The majority (94%) had HAdV-associated hemorrhagic cystitis. The median ALC at viral clearance was significantly higher compared with diagnosis (2257 cells/mm3 [IQR, 1544-3078] vs 1001 cells/mm3 [IQR, 641-1385]; P < 0.001). Eleven patients underwent measurement of the HAdV-specific T-cell response. The median numbers of CD4+ and CD8+ T cells at viral clearance were significantly higher compared with diagnosis (448 cells/mm3 [IQR, 248-651] vs 215 cells/mm3 [IQR, 159-272], P = 0.02; and 623 cells/mm3 [IQR, 242-772] vs 235 cells/mm3 [IQR, 129-266], P < 0.01), respectively. The median percentages of penton-specific CD4+ and hexon-specific CD8+ T cells at viral clearance were significantly higher compared with diagnosis (0.012% vs 0%, P = 0.03%; and 0.136% vs 0.016%, P = 0.003, respectively). CONCLUSIONS: Our findings suggest a trend of ALC and HAdV-specific T-cell immune restoration in KT recipients who achieve successful HAdV clearance.

BK Polyomavirus-specific T cell immune responses in kidney transplant recipients diagnosed with BK Polyomavirus-associated nephropathy.

BACKGROUND: Adjustment of immunosuppression is the main therapy for BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) after kidney transplantation (KT). Studies of BKPyV-specific T cell immune response are scarce. Here, we investigated BKPyV-specific T cell immunity in KT recipients diagnosed with BKPyVAN. METHODS: All adult KT recipients with BKPyVAN diagnosed at our institution from January 2017 to April 2018 were included. Laboratory-developed intracellular cytokine assays measuring the percentage of IFN-γ-producing CD4+ and CD8+ T cells, after stimulation with large-T antigen (LT) and viral capsid protein 1 (VP1), were performed both at the time of diagnosis and after adjustment of immunosuppression. RESULTS: We included 12 KT recipients diagnosed with BKPyVAN (7 proven, 4 presumptive, and 1 possible). Those with presumptive BKPyVAN had a median plasma BKPyV DNA load of 5.9 log10 copies/ml (interquartile range [IQR]: 4.9-6.1). Adjusted dosing of mycophenolic acid and tacrolimus with (86%) or without (14%) adjunctive therapies were implemented after diagnosis. There was a significantly higher median percentage of IFN-γ-producing CD4+ T cells to LT at a median of 3 (IQR: 1-4) months after adjustment of immunosuppression compared with at the time of diagnosis (0.004 vs. 0.015; p = 0.047). However, the difference between the median percentage of IFN-γ-producing CD4+ T cells to VP1 and CD8+ T cells to LT and VP1 did not reach statistical significance. Four (33%) patients achieved plasma BKPyV DNA clearance, and the remaining eight (67%) patients had persistent BKPyV DNAemia. Although eight (67%) patients developed allograft dysfunction, none required hemodialysis. CONCLUSIONS: We observed a marginal trend of BKPyV-specific CD4+ T cell recovery after adjustment of immunosuppression in KT recipients diagnosed with BKPyVAN. A further study would be benefited to confirm and better assess BKPyV-specific immune response after KT.

Impact of POR and CYP3A5 Polymorphisms on Trough Concentration to Dose Ratio of Tacrolimus in the Early Post-operative Period Following Kidney Transplantation.

BACKGROUND: Tacrolimus, a critical dose drug, is widely used in transplantation. Knowing the contribution of genetic factors, which significantly influence tacrolimus variability, is beneficial in the personalization of its starting dose. The significant impact of CYP3A5*3 polymorphisms on tacrolimus exposure has been reported. Conflicting results of the additional influence of POR*28 polymorphisms on tacrolimus pharmacokinetic interindividual variability have been observed among different populations. The objective of this study was to explore the interaction between POR*28 and CYP3A5*3 polymorphisms and their main effects on tacrolimus trough concentration to dose ratios on day 7 after kidney transplantation. METHODS: Two hundred sixteen adult kidney transplant recipients participated in this retrospective study. All participants received a twice daily tacrolimus regimen. Blood samples and data were collected on day 7 after transplantation. A 2-way analysis of covariance was performed. Tested covariates were age, hemoglobin, serum albumin, and prednisolone dose. RESULTS: A 2 × 2 analysis of covariance revealed that the interaction between CYP3A5 polymorphisms (CYP3A5 expresser and CYP3A5 nonexpresser) and POR polymorphisms (POR*28 carrier and POR*28 noncarrier) was not significant (F(1, 209) = 2.473, P = 0.117, (Equation is included in full-text article.)= 0.012). The predicted main effect of CYP3A5 and POR polymorphisms was significant (F(1, 209) = 105.565, P < 0.001, (Equation is included in full-text article.)= 0.336 and F(1, 209) = 4.007, P = 0.047, (Equation is included in full-text article.)= 0.019, respectively). Hemoglobin, age, and steroid dose influenced log C0/dose of tacrolimus (F(1, 209) = 20.612, P < 0.001, (Equation is included in full-text article.)= 0.090; F(1, 209) = 14.360, P < 0.001, (Equation is included in full-text article.)= 0.064; and F(1, 209) = 5.512, P = 0.020, (Equation is included in full-text article.)= 0.026, respectively). CONCLUSIONS: After adjusting for the influences of hemoglobin, age, and prednisolone dose, significant impacts of the CYP3A5 and POR polymorphisms on tacrolimus exposure were found. The effect of POR*28 and CYP3A5*3 polymorphisms during the very early period after kidney transplantation is independent of each other.

Hyperparathyroidism and increased fractional excretion of phosphate predict allograft loss in long-term kidney transplant recipients.

BACKGROUND: After kidney transplantation, fibroblast growth factor-23 (FGF-23) normally returns to baseline within 1 year whereas hyperparathyroidism persists in most kidney transplant (KT) recipients. As a result, serum phosphate remains relatively low in association with increased serum calcium and urinary phosphate excretion when compared to chronic kidney disease patients. The relationship between mineral metabolism and outcomes in long-term KT recipients has not been extensively studied. This study investigated whether the alteration in mineral metabolism influenced graft survival in long-term KT recipients. METHODS: This study included 273 KT recipients after 1 year of transplantation. Mineral parameters were obtained at the time of enrolment and patients were followed prospectively for an average of 71 months. RESULTS: Graft loss (death-censored) occurred in 41 (15%) patients. In univariate analysis, deceased donor transplantation, decreased serum albumin and estimated glomerular filtration rate, increased serum phosphate, parathyroid hormone (PTH), FGF-23 and fractional excretion of phosphate (FePi) predicted future allograft loss. After adjustments for cardiovascular disease risk factors, donor type, dialysis vintage, serum albumin and allograft function, only increased PTH and FePi remained associated with the outcome. Relationships between increased serum phosphate and FGF-23 with graft survival were lost after adjustments. Adjusted survival curves revealed the association between PTH > 90 pg/mL and FePi > 20% with worse graft survival. CONCLUSIONS: Hyperparathyroidism and increased FePi predicted allograft loss in long-term KT recipients.

Prevalence and Risk Factors of Peripheral Arterial Disease Among Thai Dialysis Patients.

Objective: To identify the prevalence and risk factors of peripheral arterial disease (PAD) in dialysis patients covering both hemodialysis and peritoneal dialysis. Material and Method: All consecutive cases of stable dialysis patients in Ramathibodi hospital from September 2013 to December 2013 were surveyed. Patients were classified as having PAD if they had ankle-brachial blood pressure index (ABI) values of ≤0.9 or >1.4. We also measured toe-brachial blood pressure index (TBI) and TBI ≤0.6 was classified as abnormal TBI. Data were analyzed to identify the prevalence and risk factors of PAD. Results: Among these 269 stable dialysis patients, the mean age was 48.8±15.1 years and 56.9% were male. The mean dialysis vintage was 52.6±41.8 months. The prevalence of PAD was 11.5% and the prevalence of abnormal TBI was 29.7%. Multivariate regression analysis found that increased body mass index (BMI), history of coronary artery disease (CAD), and increased pulse pressure were associated with PAD. Conclusion: The prevalence of PAD among long-term stable dialysis patients in Thailand was around one-tenth. The prevalence of abnormal TBI was higher than those of abnormal ABI criteria. Factors associated with PAD were increased BMI, history of CAD, and increased pulse pressure.

Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation.

PURPOSE: The purpose of this study is to determine the impacts of CYP3A5 polymorphism on tacrolimus concentration and the proportion of patients within a target therapeutic range during the first week after transplantation together with the 3-month acute rejection rate in kidney transplant patients receiving a minimized tacrolimus regimen. METHODS: A total of 164 patients participated in the study. All received oral tacrolimus twice daily starting on the day of surgery with the target pre-dose (trough) concentration of 4-8 ng/ml for prevention of allograft rejection. Cytochrome P450 (CYP) 3A5 genotypes were determined. The patients were divided into CYP3A5 expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (homozygous CYP3A5*3). Whole blood tacrolimus concentrations on days 3 and 7 posttransplantation and the incidence of biopsy-proven acute rejection (BPAR) at 3-month posttransplantation were compared between groups. RESULTS: On day 3, the median (IQR) dose-and-weight-normalized trough concentration in expressers and nonexpressers were 54.61 (31.98, 78.87) and 91.80 (57.60, 130.20) ng/ml per mg/kg/day, respectively (p < 0.001). Although only 47 and 42% of expressers and nonexpressers were within the target range on day 3, approximately 60% of both groups were within the target range on day 7. Proportions of BPAR among expressers and nonexpressers were 6.0 and 7.4 %, respectively (p = 0.723). The median (IQR) times to the first rejection in CYP3A5 expressers and nonexpressers were 32 (12, 68) and 15 (12, 37) days, respectively (p = 0.410). CONCLUSIONS: Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP3A5 polymorphism on BPAR was not observed in this study.

Transient Elastography in End-Stage Renal Disease Patients on Hemodialysis: The Effect of Net Fluid Withdrawal.

BACKGROUND/AIMS: The impact of volume status on liver stiffness measurement (LSM) as measured by transient elastography (TE) as in end-stage renal disease (ESRD) was unclear. We evaluated LSM before and after hemodialysis (HD) and identified the associated factors if the difference of LSM existed. METHODS: A cross-sectional study was conducted in ESRD patients on regular HD. Subjects underwent TE and bioelectrical impedance before and after HD. RESULTS: Thirty-six patients were enrolled. Mean (SD) net fluid withdrawal volume (NFWV) per session was 2.55 (0.9) l. Median (range) pre- and post-HD LSMs were 5.38 (2.8-25.7) and 5.4 (2.8-26) kPa, respectively (p = 0.712). Mean differences of pre- and post-HD LSMs correlated with NFWV (r = 0.49, 95% CI 0.19-0.71, p = 0.002). CONCLUSION: In ESRD on regular HD, LSM is not affected by HD. TE can be done before or after HD with similar results. However, fluid excess at pre-HD can cause inaccurately high LSM.

Association of soluble human leukocyte antigen-G with acute tubular necrosis in kidney transplant recipients.

BACKGROUND: Human leukocyte antigen (HLA)-G is a nonclassical HLA class I molecule that displays strong immune-inhibitory properties and has been associated with allograft acceptance. However, there are conflicting data on the correlation of soluble HLA-G (sHLA-G) and acute rejection and no data on the correlation with acute tubular necrosis in kidney transplantation. OBJECTIVE: To evaluate the association of sHLA-G level in early post-transplant period and allograft rejection/ and acute tubular necrosis (ATN) in kidney transplant recipients. METHODS: The sera procured before transplantation and serially on day 3 and day 7 after transplantation from 76 kidney transplant recipients were analyzed for the level of sHLA-G by enzyme-linked immunosorbent assay. RESULTS: The levels of sHLA-G from three serial sera did not differ between patients with acute rejection and patients without rejection. However, the sHLA-G levels on day 3 post-transplant and day 7 post-transplant in patients with ATN were significantly higher than that in patients without ATN (16.3 vs 9.85 U/ml, p = 0.018, for day 3 post-transplant and 12.47 vs 5.42 U/ml, p = 0.044, for day 7 post-transplant). In addition, the ROC analysis of sHLA-G for identifying patients with ATN showed that the area under curve was 0.67 (95% confidence interval 0.54-0.80). CONCLUSIONS: There was no significant difference for sHLA-G levels between patients with acute rejection and without rejection. Interestingly, high levels of sHLA-G in day 3 and day 7 after transplantation were associated with acute tubular necrosis. Our findings raise the question whether the increased levels of sHLA-G in patients with acute tubular necrosis after transplantation might be a result of ischemia and reperfusion injury.

Low hip bone mineral density predicts mortality in maintenance hemodialysis patients: a five-year follow-up study.

BACKGROUND: Bone loss is common among hemodialysis patients and contributes to mortality. The association between bone loss and vascular calcification may explain the increased mortality risk. Studies on the association between decreased bone mass and mortality in maintenance hemodialysis patients are limited. METHODS: Eighty-three hemodialysis patients underwent bone mineral density (BMD) and coronary artery calcification (CAC) measurements. The relationship between BMD and mortality was analyzed after a 5-year follow-up period. RESULTS: Eighty percent of the patients had reduced hip BMD. In univariate Cox regression analyses, age, cardiovascular disease, dyslipidemia, increased CAC score, increased comorbidity score and decreased hip BMD were associated with mortality. Low hip BMD remained independently associated with mortality after adjustments for cardiovascular risk factors, comorbidity score and CAC score. Patients with BMD in the lowest tertile had the worst survival. CONCLUSION: Low hip BMD predicted mortality in maintenance hemodialysis patients independent of CAC.

Vascular calcification in long-term kidney transplantation.

AIM: Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. METHODS: The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. RESULTS: The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. CONCLUSIONS: Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.

Impact of HLA Eplet Mismatch on De Novo Donor Specific Antibody Formation After Kidney Transplantation.

BACKGROUND: HLA eplet mismatching is an alternative approach to assess the risk of developing de novo donor-specific antibodies (dnDSA) in kidney transplantation. This strategy may offer more precise risk stratification than conventional approaches. This study aimed to find the association between HLA eplet mismatches and dnDSA formation in Thai kidney transplant recipients. METHODS: A retrospective cohort study of kidney transplant recipients transplanted between 2000 and 2021 at Ramathibodi Hospital was performed. Recipients with pretransplant panel reactive antibody >0% or without DSA testing post-transplant were excluded. One hundred fifty recipients were included in the final study. High-resolution HLA typing was imputed by the HaploStat application. HLA eplet mismatch analysis was conducted using HLAMatchmaker. The association between the number of eplet mismatches and the risk of dnDSA formation was assessed by Cox regression analysis. RESULTS: Of 150 recipients, 43 were dnDSA-positive, and 107 were dnDSA-negative patients. Compared with the dnDSA-negative group, patients with class II dnDSA had significantly more HLA-DR/DQ antibody (Ab)-verified eplet mismatches (6 [IQR 4-8] vs 4 [IQR 1-7], P = .045). The receiver operating characteristics analysis showed that the HLA-DQ Ab-verified eplet mismatches ≥2 were the best predictive of HLA class II dnDSA development. The number of HLA-DQ Ab-verified eplet mismatches ≥2 had the highest hazard rate of HLA class II dnDSA occurrence (adjusted HR, 3.74; 95%CI, 1.24-11.24, P = .019). CONCLUSIONS: HLA-DQ Ab-verified eplet mismatches are significantly associated with class II dnDSA development. Our data supports the utility of HLA eplet mismatching for donor-recipient risk assessment.

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.

SARS-CoV-2-Specific Antibodies, B Cell and T Cell Immune Responses after ChAdOx1 nCoV-19 Vaccination in Solid Organ Transplant Recipients.

BACKGROUND: Immunization against SARS-CoV-2 is essential for vulnerable solid organ transplant (SOT) recipients who are at risk of infection. However, there are concerns about suboptimal immunogenicity, especially in humoral immunity (HMI), and limited exploration of cell-mediated immune (CMI) responses. The primary objective of this study was to assess the immunogenicity of ChAdOx1 nCoV-19 vaccination in SOT recipients. The secondary endpoint was to evaluate factors that affect immunogenicity and adverse events (AEs) following immunization in SOT recipients. METHODS: All adult SOT recipients who received the two-dose ChAdOx1 nCoV-19 vaccine at a 12-week interval underwent measurements of HMI by evaluating anti-receptor-binding domain (RBD) IgG levels and CMI by investigating SARS-CoV-2-specific T cell and B cell responses before and after complete vaccination, around 2-4 weeks post-vaccination, and compared to controls. AEs were monitored in all participants. RESULTS: The study included 63 SOT recipients: 44 kidney recipients, 16 liver recipients, and 3 heart transplant recipients, along with 11 immunocompetent controls. Among SOT recipients, 36% were female, and the median (IQR) age was 52 (42-61). The median (IQR) time since transplant was 55 (28-123) months. After the second dose, the median (IQR) anti-RBD antibody levels were significantly lower in SOT recipients compared to those in the control group (8.3 [0.4-46.0] vs. 272.2 [178.1-551.6] BAU/mL, p < 0.01). This resulted in a seroconversion rate (anti-RBD antibody > 7.1 BAU/mL) of 51% among SOT recipients and 100% among controls (p = 0.008). Receiving the vaccine beyond one year post-transplant significantly affected seroconversion (OR 9.04, 95% CI 1.04-78.56, p = 0.046), and low-dose mycophenolic acid marginally affected seroconversion (OR 2.67, 95% CI 0.89-7.96, p = 0.079). RBD-specific B cell responses were also significantly lower compared to those in the control group (0 [0-4] vs. 10 [6-22] SFUs/106 PBMCs, p = 0.001). Similarly, S1- and SNMO-specific T cell responses were significantly lower compared to those in the control group (48 [16-128] vs. 216 [132-356] SFUs/106 PBMCs, p = 0.004 and 20 [4-48] vs. 92 [72-320] SFUs/106 PBMCs, p = 0.004). AEs were generally mild and spontaneously resolved. CONCLUSIONS: SOT recipients who received the full two-dose ChAdOx1 nCoV-19 vaccine demonstrated significantly diminished HMI and CMI responses compared to immunocompetent individuals. Consideration should be given to administering additional vaccine doses or optimizing immunosuppressant regimens during vaccination (Thai Clinical Trial Registry: TCTR20210523002).

Nutritional Content of Popular Menu Items from Online Food Delivery Applications in Bangkok, Thailand: Are They Healthy?

The rise in online food delivery (OFD) applications has increased access to a myriad of ready-to-eat options, which may lead to unhealthier food choices. Our objective was to assess the nutritional profile of popular menu items available through OFD applications in Bangkok, Thailand. We selected the top 40 popular menu items from three of the most commonly used OFD applications in 2021. Each menu item was collected from the top 15 restaurants in Bangkok for a total of 600 items. Nutritional contents were analysed by a professional food laboratory in Bangkok. Descriptive statistics were employed to describe the nutritional content of each menu item, including energy, fat, sodium, and sugar content. We also compared nutritional content to the World Health Organization's recommended daily intake values. The majority of menu items were considered unhealthy, with 23 of the 25 ready-to-eat menu items containing more than the recommended sodium intake for adults. Eighty percent of all sweets contained approximately 1.5 times more sugar than the daily recommendation. Displaying nutrition facts in the OFD applications for menu items and providing consumers with filters for healthier options are required to reduce overconsumption and improve consumer food choice.

Clinical and immunological characteristics for BK polyomavirus-associated nephropathy after kidney transplantation.

INTRODUCTION: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) can cause a significant risk of allograft impairment after kidney transplantation (KT). Intact BKPyV-specific immunity is associated with viral containment. This study investigated BKPyV-specific immunological factors among KT recipients. METHODS: This prospective study in a single transplant center from January 2019 to August 2019 assessed associations between clinical and immunological characteristics, with a focus on BKPyV-cell-specific immunity and BKPyVAN, among KT recipients aged ≥15 years. The numbers of interferon-gamma (IFN-γ)-producing CD4+  T, CD8+  T, natural killer (NK), and natural killer T (NKT) cells were measured after stimulation with large T antigen and viral capsid protein 1 (VP1). RESULTS: In total, 100 KT recipients were included (mean age ± SD, 42 ± 11 years); 35% of the recipients were female patients, and 70% had received induction immunosuppressive therapy. The 1-year cumulative incidence of high-level BKPyV DNAuria (possible BKPyVAN) and (presumptive BKPyVAN) was 18%. Among 40 patients with immunological factor data, pre-KT %NK cells (hazard ratio [HR], 1.258; 95% confidence interval [CI], 1.077-1.469; p = .004) and %VP1-specific NK cells (HR, 1.209; 95% CI, 1.055-1.386; p = .006) were factors independently associated with possible and presumptive BKPyVAN. KT recipients with possible and presumptive BKPyVAN were more likely to exhibit significant mean coefficients of %NK, %VP1-specific NK, and %NKT cells at 1 month after KT than before KT (all p < .05). CONCLUSION: Individuals with nonspecific and VP1-specific NK cells before KT and increasing numbers of these cells after KT may be at risk for high-level BKPyV DNAuria and presumptive BKPyVAN. Further studies are needed to determine the utility of BKPyV-specific innate immune surveillance in predicting the occurrence of BKPyVAN.