Protective Effect of BCG and Neutrophil-to-Lymphocyte Ratio on Latent Tuberculosis in End Stage Renal Disease.

INTRODUCTION: Bacillus Calmette-Guérin (BCG) vaccination has been reported to be protective against latent tuberculosis infection (LTBI) in the general population. The aim of this study was to investigate the protective effect of BCG vaccination against LTBI in adult patients with end-stage renal disease (ESRD) and renal transplants. METHODS: Patients aged ≥ 20 years with ESRD who received hemodialysis (HD), peritoneal dialysis (PD) or kidney transplant were enrolled from January 2012 to December 2019 at a medical center and a regional hemodialysis center. Patients with active tuberculosis (TB), previously treated TB, active immunosuppressant therapy or human immunodeficiency virus infection were excluded. LTBI status was determined by QuantiFERON-TB Gold In-tube (QFT-GIT). RESULTS: After the exclusion of indeterminate results of QFT-GIT, 517 participants were enrolled and 97 (18.8%) were identified as having LTBI. Participants with LTBI were older (55.1 ± 11.4 vs. 48.5 ± 14.6 years, p < 0.001) and had a significantly higher proportion receiving HD than those without LTBI (70.1% vs. 56.7%, p = 0.001). The percentage with BCG scars was higher in the non-LTBI group than in the LTBI group (94.8% vs. 81.4%, p < 0.001), whereas the neutrophil-to-lymphocyte ratio (NLR) (≥ 2.68) was significantly higher in the LTBI group (62.8% vs. 45.5%, p = 0.02). By multivariate logistic regression analysis, presence of BCG scar and high NLR were independent protective factors against LTBI [adjusted OR: 0.19 (0.063-0.58, p = 0.001) and 0.50 (0.28-0.89, p = 0.02)]. CONCLUSION: The prevalence of LTBI was as high as 18.8% in patients with end-stage kidney disease or kidney transplant. BCG vaccination and high NLR might have protective effects against LTBI in patients with renal failure or transplant.

Protective Effect of Vaccine Doses and Antibody Titers Against SARS-CoV-2 Infection in Kidney Transplant Recipients.

Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324-0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311-0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800-0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995-1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient.

Long-term durability of sustained virologic response for hepatitis C virus infection in solid organ transplant recipients receiving direct-acting antivirals.

Data are limited regarding the long-term durability of sustained virologic response (SVR) in solid organ transplant recipients who achieve SVR12 with direct-acting antivirals (DAAs) for hepatitis C virus (HCV). We reported the virologic outcomes in 42 recipients who received DAAs for acute or chronic HCV infection after heart, liver, and kidney transplantation. After achieving SVR12, all recipients received HCV RNA surveys at SVR24, and biannually until the last visit. If HCV viremia was detected during the follow-up period, direct sequencing and phylogenetic analysis were performed to confirm late relapse or reinfection. Sixteen (38.1%), 11 (26.2%), and 15 (35.7%) patients underwent heart, liver and, kidney transplantation. Thirty-eight (90.5%) received sofosbuvir (SOF)-based DAAs. No recipients had late relapse or reinfection after a median (range) of post-SVR12 follow-up 4.0 (1.0-6.0) years. We demonstrate that the durability of SVR in solid organ transplant recipients is excellent once SVR12 is achieved with DAAs.

Outbreak investigation in a COVID-19 designated hospital: The combination of phylogenetic analysis and field epidemiology study suggesting airborne transmission.

BACKGROUND: Healthcare-associated COVID-19 infections caused by SARS-CoV-2 have increased morbidity and mortality. Hospitals and skilled nursing facilities (SNFs) have been challenged by infection control and management. METHODS: This case study presents an outbreak investigation in a COVID-19-designated hospital and a hospital-based SNF. Real-time polymerase chain reaction (PCR) and other studies were performed on samples obtained from SNF residents, hospital patients, and healthcare workers (HCWs). The results of the laboratory tests and field epidemiological data were analyzed. Genome sequencing and phylogenetic analysis of SARS-CoV-2 were performed to identify the associations between cases. The tracer gas was released and recorded by a thermal imaging camera to investigate the spatial relations within clusters. RESULTS: During the outbreak, 29 COVID-19 infections in 3 clusters were identified through hospital-wide, risk-guided, and symptom-driven PCR tests. This included 12 HCWs, 5 patients, and 12 SNF residents who had been hospitalized for at least 14 days. Serology tests did not identify any cases among the PCR-negative individuals. The phylogenetic analysis revealed that viral strains from the 3 clusters shared a common mutation of G3994T and were phylogenetically related, which suggested that this outbreak had a common source rather than multiple introductions from the community. Linked cases exhibited vertical spatial distribution, and the sulfur hexafluoride release test confirmed a potential airborne transmission. CONCLUSIONS: This report addressed the advantage of a multi-disciplinary team in outbreak investigation. Identifying an airborne transmission within an outbreak highlighted the importance of regular maintenance of ventilation systems.

Immunogenicity and safety of two-dose SARS-CoV-2 vaccination via different platforms in kidney transplantation recipients.

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.

Survey of factors associated with the willingness toward living kidney donation.

BACKGROUND: Living donor kidney transplantation (LDKT) is an important organ resource, especially in countries with low deceased donation rates. Strategies for expanding access to transplantation should be developed by identifying the modifiable factors. In this study, we evaluated these factors in the relatives of patients from both medical centers and dialysis clinics using questionnaires. METHODS: The questionnaires were anonymous and confidential. We collected questionnaires from previous donors, relatives of patients on the waitlist in the medical center, and relatives of dialysis patients in three nephrology clinics. The study groups were divided into three categories: donor group (n = 68), willing group (n = 43), and non-donor group (n = 65). RESULTS: Respondents in the clinics had lower cognition and willingness towards LDKT than those in the medical center. More knowledge of LDKT, better relationship with patients, more familial support, and female gender were positively related to donation. The non-donor group tended to want to maintain an intact body for the afterlife. There was no significant difference in age, educational degree, average monthly income, and medical compliance among the three groups. CONCLUSION: More efforts need to be made in dialysis clinics, where general nephrologists are important for the outreach of information. In addition, dealing with religious ambivalence and reestablishing cultural mindsets with health education programs are important issues in a non-Christian country.

Different methods of detaching adherent cells and their effects on the cell surface expression of Fas receptor and Fas ligand.

In cell culture environment, some cells adhere firmly to the culture plates and may be vulnerable to cell detachment during passage. Therefore, it is important to harvest cells with a proper detaching method to maintain the viability of cells after detachment. Trypsinization is frequently used for cellular dissociation and detachment. However, most surface proteins and the extracellular matrix are degraded by enzymatic digestion. A mild cell detachment buffer, accutase, is recommended for the replacement of trypsin to dissociate adherent cells and thereby avoid cellular damage. In this study, we demonstrated that use of accutase for cellular detachment may compromise some surface proteins. Compared with ethylenediaminetetraacetic acid (EDTA)-based nonenzymatic cell dissociation buffers, accutase was associated with significant decreases in the surface Fas ligands and Fas receptors. Moreover, we found that accutase may be able to cleave surface Fas ligands into pieces. Our results also illustrated that surface proteins required 20 h to recover after accutase treatment. We demonstrated that using accutase to dissociate adherent cells compromised the expression of Fas ligands and Fas receptors on the cell surface. These findings indicate that it is important to choose suitable cell detachment buffers and allow cells to recover after detachment before experiments.

Effects of perioperative dexmedetomidine infusion on renal function and microcirculation in kidney transplant recipients: a randomised controlled trial.

OBJECTIVE: Ischemia-reperfusion injury affects postoperative transplanted kidney function in kidney transplant recipients. Dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation, but its propensity to cause bradycardia and hypotension may adversely affect microcirculation. This study investigated the effect of dexmedetomidine on postoperative renal function and sublingual microcirculation in kidney recipients. METHODS: The enrolled kidney transplant recipients were randomly allocated to the control group or dexmedetomidine group. After anaesthesia induction, patients in the dexmedetomidine group received dexmedetomidine infusion until 2 h after surgery. Sublingual microcirculation was recorded using an incident dark-field video microscope and analysed. The primary outcomes were the creatinine level on a postoperative day 2 and total vessel density at 2 h after surgery. RESULTS: A total of 60 kidney recipients were analysed, and the creatinine levels on postoperative day 2 were significantly lower in the dexmedetomidine group than in the control group (1.5 (1.1-2.4) vs. 2.2 (1.7-3.0) mg/dL, median difference -0.6 (95% CI, -0.7 to -0.5) mg/dL, p = .018). On a postoperative day 7, the creatinine levels did not differ significantly between the two groups. Total vessel density at 2 h after surgery did not differ significantly between the two groups. CONCLUSION: We found that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine infusion, but total vessel density was not significantly different between the intervention and control groups. Key messagesIschemia-reperfusion injury affects postoperative transplanted kidney function, and dexmedetomidine was reported to attenuate ischemia-reperfusion injury and improve microcirculation in other clinical conditions.This study showed that early postoperative renal function was better in kidney transplant recipients receiving dexmedetomidine.Dexmedetomidine's side effect of bradycardia and hypotension may affect microcirculation, our results revealed that the perioperative sublingual microcirculation did not differ significantly in kidney transplant recipients receiving dexmedetomidine.

Importance of the creation of a short musculofascial tunnel in peritoneal dialysis catheter placement.

BACKGROUND: Peritoneal dialysis (PD) catheter migration impedes the efficacy of dialysis. Therefore, several techniques involving additional sutures or incisions have been proposed to maintain catheter position in the pelvis. AIM: To evaluate the efficacy of creating a short musculofascial tunnel beneath the anterior sheath of the rectus abdominis during PD catheter implantation. METHODS: Patients who underwent PD catheter implantation between 2015 and 2019 were included in this retrospective study. The patients were divided into two groups based on the procedure performed: Patients who underwent catheter implantation without a musculofascial tunnel before 2017 and those who underwent the procedure with a tunnel after 2017. We recorded patient characteristics and catheter complications over a two-year follow-up period. In addition, postoperative plain abdominal radiographs were reviewed to determine the catheter angle in the event of migration. RESULTS: The no-tunnel and tunnel groups included 115 and 107 patients, respectively. Compared to the no-tunnel group, the tunnel group showed lesser catheter angle deviation toward the pelvis (15.51 ± 11.30 vs 25.00 ± 23.08, P = 0.0002) immediately after the operation, and a smaller range of migration within 2 years postoperatively (13.48 ± 10.71 vs 44.34 ± 41.29, P < 0.0001). Four events of catheter dysfunction due to migration were observed in the no-tunnel group, and none occurred in the tunnel group. There was no difference in the two-year catheter function survival rate between the two groups (88.90% vs 84.79%, P = 0.3799). CONCLUSION: The musculofascial tunnel helps maintain catheter position in the pelvis and reduces migration, thus preventing catheter dysfunction.

Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment.

BACKGROUND: Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment-induced sustained virologic response (SVR) in patients on haemodialysis. AIMS: To assess the risk of HCV reinfection among patients on haemodialysis with treatment-induced SVR. METHODS: Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct-acting antiviral (DAA)-based treatment received follow-up at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12 . The low-risk general population who achieved SVR12 and who underwent the same post-SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person-years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups. RESULTS: We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post-SVR12 follow-up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 also achieved SVR24 . The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09-0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10-0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44-4.38, P = 0.57). CONCLUSIONS: The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low-risk general population. HCV microelimination in this special population is feasible once universal screening and scaled-up treatment are implemented.

Dynamics of cellular immune responses in recipients of renal allografts positive for hepatitis B surface antigen.

BACKGROUND/PURPOSE: Hepatitis B surface antigen (HBsAg)-positive renal transplantation recipients must take lifelong immunosuppressants and nucleotide analogues (NAs). We investigated the cellular immune responses of HBsAg-positive renal transplantation recipients taking immunosuppressants and NAs. METHODS: Blood samples were collected from HBsAg-positive individuals with end-stage renal disease on the transplant waiting list (Group 1) and renal transplantation recipients taking immunosuppressants and NAs (Group 2) or immunosuppressants without NAs (Group 3). Hepatitis B virus (HBV)-specific pentamers were used to quantify circulating HBV-specific CD8+ T cells. RESULTS: Groups 2 and 3 had higher cellular immune responses, as indicated by significantly lower regulatory T (Treg)/CD8+ T cell ratios than Group 1. With undetectable viral loads under both immunosuppressant and NAs, the CD8+ T cell and HBV-specific CD8+ T cell frequencies were similar in Group 2 and Group 1. Patients in Group 3 did not use NAs and had an elevated viral load and higher HBV-specific CD8+ T cell and IFN-γ-producing HBV-specific CD8+ T cell frequencies, but lower a frequency of programmed death-1 (PD-1)+ HBV-specific CD8+ T cells than the other groups. Increased viral replication in Group 3 resulted in significantly higher CD8+ T cell and IFN-γ-producing CD8+ T cell frequencies than Group 1. CONCLUSION: Immunosuppressant therapy increases viral replication in HBsAg-positive renal transplant recipients due to disabling or dysregulation of virus-specific CD8+ T cells. The higher cellular immune responses due to lower Treg/CD8+ T cell ratios in HBsAg-positive renal transplant recipients may be one of the reasons to induce liver pathology because of uncontrolled viral replication.

The role of S100A9 in the interaction between pancreatic ductal adenocarcinoma cells and stromal cells.

BACKGROUND: A major feature of the microenvironment in pancreatic ductal adenocarcinoma (PDAC) is the significant amount of extracellular matrix produced by pancreatic stellate cells (PSCs), which have been reported to enhance the invasiveness of pancreatic cancer cells and negatively impact the prognosis. METHODS: We analyzed the data from two publicly available microarray datasets deposited in the Gene Expression Omnibus and found candidate genes that were differentially expressed in PDAC cells with metastatic potential and PDAC cells cocultured with PSCs. We studied the interaction between PDAC cells and PSCs in vitro and verified our finding with the survival data of patients with PDAC from the website of The Human Protein Atlas. RESULTS: We found that PSCs stimulated PDAC cells to secrete S100A9, which attracted circulatory monocytes into cancer tissue and enhanced the expression of programmed death-ligand 1 (PD-L1) on macrophages. When analyzing the correlation of S100A9 and PD-L1 expression with the clinical outcomes of patients with PDAC, we ascertained that high expression of S100A9 and PD-L1 was associated with poor survival in patients with PDAC. CONCLUSIONS: PSCs stimulated PDAC cells to secrete S100A9, which acts as a chemoattractant to attract circulatory monocytes into cancer microenvironment and induces expression of PD-L1 on macrophages. High expression of S100A9 and PD-L1 was associated with worse overall survival in a cohort of patients with PDAC.

Unmet Care Needs and Related Factors of Spouses of Liver or Kidney Transplant Recipients.

This study aimed to (1) explore the unmet care needs of spouses of liver or kidney transplant recipients, (2) compare the unmet care needs, depression, and anxiety levels of transplant recipients and their spouses, and (3) identify factors related to spouses' unmet care needs. A cross-sectional study was conducted using purposive sampling from transplant outpatient departments at a medical center. Ninety-one liver or kidney transplant recipient-spouse dyads were recruited. Most unmet needs for dyads were involved in the psychological needs and health system and service needs domains. Spouses had significantly higher unmet needs, anxiety, and depression than recipients did. The significant factors related to the spouses' unmet needs included being male, having higher anxiety, and whose partners had higher unmet needs. Health care professionals must attend to the needs of both recipients and spouses. Providing disease-specific information and resources to spouses who potentially had higher unmet needs is strongly suggested.

Care Needs for Organ Transplant Recipients Scale: Development and psychometric testing.

BACKGROUND: Needs assessment can determine how large the gap is between needs and available services; however, no tools are available to assess the unmet needs of renal transplant recipients. OBJECTIVES: The aim of this study was to develop the Care Needs for Organ Transplant Recipients Scale (CNOTRS) and examine its psychometric properties. DESIGN: A cross-sectional design for instrument development and psychometric testing. PARTICIPANTS: In total, 217 renal transplant recipients were recruited through convenience sampling. METHODS: An initial 36-item CNOTRS was developed after a comprehensive literature review. After the CNOTRS was tested through content validity and face validity, the factor structure was explored using exploratory factor analysis (EFA). Convergent validity was examined using Pearson's correlation between the CNOTRS and Hospital Anxiety and Depression Scale (HADS). Known-group validity was tested by comparing CNOTRS scores of patients grouped based on whether they had experienced complications or rejection. RESULTS: Twenty-eight items with three factors (namely daily care and social interaction needs, psychological needs, and health system and service needs) were identified in EFA by parallel analysis and Velicer's MAP test. The psychological needs domain had a stronger positive correlation with the HADS than the other two domains. The known-group validity was supported as a significant association between complications or rejection occurrence and unmet needs. The Cronbach's α of the CNOTRS was 0.94. CONCLUSIONS: The CNOTRS demonstrated satisfactory reliability and validity to assess the care needs for renal transplant recipients and can assist health care professionals to tailor more personalised care for their individual needs.

Two-year protocol biopsy after kidney transplantation in clinically stable recipients - a retrospective study.

The idea of protocol biopsy is to detect subclinical pathologies, including rejection, recurrent disease, or infection for early intervention and adjustment of immunosuppressants. Nevertheless, it is not adopted by most clinicians because of its low yield rate and uncertain long-term benefits. This retrospective study evaluated the impact of protocol biopsy on renal function and allograft survival. A two-year protocol biopsy was proposed for 190 stable patients; 68 of them accepted [protocol biopsy (PB) group], while 122 did not [nonprotocol biopsy (NPB) group]. The rejection diagnosis was made in 13 patients by protocol biopsy, and 11 of them had borderline rejection. In the following 5 years, graft survival was better in the PB group than in the NPB group (P = 0.0143). A total of 4 and 17 patients in the PB and NPB groups, respectively, had rejection events proven by indication biopsy. Renal function was better preserved in the PB group than in the NPB group (P = 0.0107) for patients with rejection events. Nevertheless, the survival benefit disappeared by a longer follow-up period (12-year, P = 0.2886). In conclusion, 2-year protocol biopsy detects subclinical pathological changes in rejection and preserves renal function by early intervention so as to prolong graft survival within 5 years.

Latent Tuberculosis Infection Increases in Kidney Transplantation Recipients Compared With Transplantation Candidates: A Neglected Perspective in Tuberculosis Control.

BACKGROUND: The prevalence and incidence of latent tuberculosis infection (LTBI) in patients with kidney transplantation remain unclear. METHODS: In this prospective study, we enrolled kidney transplantation candidates (KTCs) and recipients (KTRs) from 2014 to 2018. We defined LTBI as a positive result of QuantiFERON-TB Gold In-tube (QFT). We analyzed the predictors for LTBI acquisition and followed up on QFT assay test for 2 years among those initially without LTBI. RESULTS: Of 425 patients enrolled, 305 (71.8%) patients belonged to the KTC group and 120 (28.2%) to the KTR group. The initial QFT showed positive results in 32 (10.5%) and 24 (20.0%) patients in the KTC and KTR groups, respectively (P = .009). The QFT response value in patients with LTBI was higher in the KTR group than in the KTC group (1.85 vs 1.06 IU/mL, P = .046). Multivariate logistic regression showed that old age, absence of bacillus Calmette-Guérin (BCG) scar, presence of donor-specific antibody, and KTR group were independent factors for positive LTBI. For participants with initial negative QFT, positive QFT conversion within a 2-year follow-up was higher after kidney transplantation (20%) than in KTCs (5.5%) (P = .034). CONCLUSIONS: This study is the first cohort to follow up LTBI status in patients with kidney transplantation and shows its higher prevalence and incidence in KTRs. It indicates that surveillance of LTBI after renal transplantation is important. In addition to status of kidney transplantation, old age, no BCG vaccination, and positive donor-specific antibody are also positive predictors for LTBI.

Telbivudine for renal transplant recipients with chronic hepatitis B infection: a randomized controlled trial with early termination.

BACKGROUND: The aim of this study was to analyze changes in renal function in HBsAg-positive renal transplant recipients receiving lamivudine who did or did not switch to telbivudine. METHODS: In this prospective randomized clinical trial (RCT), HBsAg-positive renal transplant recipients who had received lamivudine prophylaxis for at least 6 months were 1:2 randomized to receive either lamivudine or telbivudine for another 24 months. Renal function was evaluated by creatinine level and estimated glomerular filtration rate (eGFR) at the time of randomization (baseline), 6, 12, 18, and 24 months respectively. RESULTS: This RCT was prematurely terminated after recruiting only 17 patients due to a high incidence (61.5%; 8/13) of clinical myalgia in the telbivudine group. Cox's proportional hazards model revealed that there was no independent predictor of myalgia. Based on intention-to-treat and per protocol analyses using generalized estimating equations, the patients in the randomized telbivudine group had a significantly increased eGFR and the patients in the lamivudine group had a significantly decreased eGFR at the end of follow-up compared to the values at study enrollment. However, there was no significant difference between the lamivudine and telbivudine groups. CONCLUSIONS: The renal protective effect of telbivudine for HBsAg positive renal transplant recipients was uncertain for high incidence of myalgia and only patients who were on telbivudine for 24 months had renal function maintenance.

Prognostic factors for renal transplant graft survival in a retrospective cohort of 1000 cases: The role of desensitization therapy.

BACKGROUND: To review the results of renal transplantation after promulgation of the Human Organ Transplant Act in Taiwan in 1987, we conducted a retrospective study in the first 1000 cases performed in our hospital. Prognostic factors for graft survival were assessed with emphasis on the impact of donor-specific antibody (DSA). METHODS: Between January 1988 and April 2014, there were 1000 cases of renal transplantation performed in our hospital. Excluding 30 patients of ABO-incompatible transplantation, we reviewed 970 cases of ABO-compatible renal transplantation to analyze the prognostic factors for graft survival. The patients were grouped according to the dates of operations before (the Early group: 503 cases) and after (the Late group: 467 cases) the introduction of detection and desensitization of alloantibody in our hospital in 2004. RESULTS: The overall 5-year graft survival rate were 82.6%, which was significantly lower in the Early group (79.2%) than the Late group (86.3%) (p = 0.0012). The 1-year rejection-free survival was significantly lower in the Early group (78.3%) than the Late group (91.2%) (p = 0.0165). The difference between the two groups became insignificant when the time of observation extended beyond 12 months. In a multivariate regression model, we identified significant factors for poor graft survival, including HLA mismatches, delayed graft function with or without recovery, and antibody-mediate rejection (AMR). CONCLUSION: HLA mismatches, delayed graft function with or without recovery, and AMR were significant factors for poor graft survival. Detection and desensitization of DSA currently might be inadequate to improve the long-term outcome of renal transplantation.

Endothelial chimerism and vascular sequestration protect pancreatic islet grafts from antibody-mediated rejection.

Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models. Live imaging revealed that DSAs were sequestrated in the circulation of the recipients and failed to reach the endocrine cells of grafted islets. We used murine heart transplantation models to confirm that endothelial cells were the only accessible targets for DSAs, which induced the development of typical microvascular lesions in allogeneic transplants. In contrast, the vasculature of DSA-exposed allogeneic islet grafts was devoid of lesions because sprouting of recipient capillaries reestablished blood flow in grafted islets. Thus, we conclude that endothelial chimerism combined with vascular sequestration of DSAs protects islet grafts from humoral rejection. The reduced immunoglobulin concentrations in the interstitial tissue, confirmed in patients, may have important implications for biotherapies such as vaccines and monoclonal antibodies.

An observational study of microcirculation in dialysis patients and kidney transplant recipients.

BACKGROUND: Microcirculatory dysfunction contributes to acute and chronic kidney diseases. To the best of our knowledge, no study has compared differences in microcirculation among healthy volunteers, dialysis patients and kidney transplant recipients. MATERIALS AND METHODS: Sublingual microcirculation was examined using sidestream dark field imaging and was compared among 90 healthy volunteers, 40 dialysis patients and 40 kidney transplant recipients. The gender effect on microcirculation and the correlations among the microcirculation parameters, age, body mass index, heart rate and blood pressure were analysed. RESULTS: Total small vessel density, perfused small vessel density and the proportion of perfused small vessels were lower in the dialysis patients than in the healthy volunteers and kidney transplant recipients [total small vessel density; healthy volunteers vs. dialysis patients vs. kidney transplant recipients, 25·2 (2·3) vs. 22·8 (2·6) vs. 24·2 (2·9) mm/mm2 , P < 0·001]. Systolic blood pressure showed a weak negative correlation with the microvascular flow index scores in the healthy volunteers. By contrast, systolic blood pressure, diastolic blood pressure and mean arterial pressure showed weak positive correlations with proportion of perfused small vessels and the microvascular flow index scores in the dialysis patients. CONCLUSIONS: Microcirculatory dysfunction is noted in dialysis patients, and this alteration is ameliorated in KT recipients. The positive correlation between blood pressure and microcirculation in dialysis patients suggests that additional studies should investigate the optimal goal of blood pressure management for dialysis patients.