Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

BackgroundAn essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the role of Fas − 670A/G and Fas Ligand (FasL) − 843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients.MethodsIn 47 pediatric kidney transplant recipients and 20 healthy controls, Fas − 670A/G and FasL − 843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured.ResultsSerum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25 ± 298.64 pg/ml vs 143.17 ± 44.55 pg/ml, p = 0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70 ± 279.87 pg/ml vs 507.85 ± 342.80 pg/ml, p = 0.56). Fas − 670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. (P > 0.05 for all). FasL − 843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR (P > 0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P = 0.03). FasL − 843C/T alleles were significantly different between patients with and without AR (P = 0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR.ConclusionThis study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR.     

Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival

BackgroundThe essential function of B cell–activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood.MethodsObjective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival.ResultsPretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262 ± 2796 pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252 ± 1425 pg/ml; p < 0.0001). In addition, pretransplant BAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r = 0.2966, p = 0.0025). Patients with high pretransplant BAFF levels (≥ 2137 pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p = 0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p = 0.02), presence of anti-HLA antibodies (RR 2.5; p = 0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p = 0.003) before transplant and AMR post transplant (RR 2.5; p = 0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p = 0.03).ConclusionElevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR.     

Clinical risk factors associated with the post-transplant anemia in kidney transplant patients

BackgroundAnemia is a very common occurrence in post-renal transplant patients. Post-transplantation anemia (PTA) is associated with significant graft loss or cardiovascular morbidity. The objective of this study is to identify clinical risk factors associated with anemia after kidney transplantation.MethodsOur retrospective cohort study included a total of 570 renal transplant recipients. For the definition of anemia, we adopted “the lower limit of normal for Hgb concentration of blood” proposed by Beutler E and Waalen J [14], which has adjustments for age, gender and ethnicity. Post-transplant anemia (PTA) was defined as anemia that arose between 30 and 180 days after transplantation. Based on this definition, of the 570 renal transplant recipients, 344 patients (62.1%) experienced PTA. The patients were divided into anemic and non-anemic groups, and a total of 20 clinical factors were compared between the two groups.ResultsIn the univariate analysis, age, race, multiple transplants, delayed graft function (DGF), and use of tacrolimus, sirolimus, thymoglobulin, ganciclovir, ACE inhibitors, and ARBs were associated with PTA. In the multivariate analysis, age (> 60 years old, OR = 2.62, p = 0.001), race (OR = 2.54, p = 0.001), and use of sirolimus (OR = 2.01, p = 0.019), antiviral agents (OR = 1.96, p = 0.015), thymoglobulin (OR = 1.86, p = 0.011), and DGF (OR = 2.78, p = 0.001) remained significant.ConclusionThe current results show that undergoing a transplant at age 60 or older, use of sirolimus, antiviral agents, and thymoglobulin are independent clinical risk factors associated with PTA. In terms of ethnicity, AA, MEA, or PI is higher risk for PTA and Hispanic is significantly lower risk for PTA compared to Caucasians.     

Study of the cytokine polymorphisms in correlation to rejection and graft survival in renal allograft donors and recipients from a homogenous Saudi population

ObjectivesAllograft outcome can be improved with the discovery of risk factors that influence adverse events and may allow individualization of patients' treatment. Rejection is the main hurdle to successful transplantation and the immune response is the key effecter to rejection development. Hence, the major objective of the present study was to assess the relationship between single nucleotide polymorphisms (SNPs) in 5 cytokine genes, HLA mismatch and graft outcome in a cohort of 100 Saudi kidney transplant recipients and 100 living related donors at a single transplant center.Materials & methodsGenotyping of the following positions: TNFA (? 308 G/A), TGFB1 (codon 10 T/C, codon 25 C/G), IL-10 (? 1082 G/A, ? 819 C/T, ? 592 C/A), IL-6 (? 174 C/G), and IFNG (+ 874 T/A) were performed.ResultsThe majority of the donors whose recipients presented with either cellular or antibody mediated graft rejection (90% and 100%) respectively were found to be significantly (p = 0.0351) associated with intermediate or high IL-10 producing haplotypes, compared to those with stable grafts (58.66%). Haplotypes linked with lower IL-10 production were not detected in the donors or their recipients with antibody mediated graft rejection compared to donors with stable graft (41.33%). The distribution of donor IL-10-1082 haplotypes (GG, GA, AA) showed a statistically significant association of IL-10-1082 GA genotype (p = 0.0351) with rejection, when grouped according to patients' rejection status. No other statistically significant deviations were observed in the donors' genotypes. Analyses of cytokine polymorphisms in the recipients revealed no significant association. Multivariate logistic regression analyses showed that only HLA-DRB1 mismatch significantly influenced graft loss (p = 0.0135).ConclusionThis study demonstrates that the donor IL-10 genotypes and HLA-DRB1 mismatch are key determinants in graft outcome after renal transplantation.     

Tuberculosis Following Lung Transplantation. A 27-Year Spanish Multicenter Experience. Incidence,Presentation, Prevention and Treatment with Rifampicin

BackgroundTuberculosis (TB) represents a diagnostic and therapeutic challenge for solid organ transplant recipients, particularly after lung transplant (LT). Our aim was to determine the impact of TB in LT patients in Spain, considering prevalence, clinical presentation, prevention and therapeutic management. In addition, differences in outcome between rifampicin (RIF) versus non-RIF containing regimens were analyzed.MethodsMulticenter, observational retrospective study, including all cases of TB diagnosed in recipients after LT, in five pulmonary transplant units in Spain, between January 1990 and December 2017.ResultsAmong 2962 LT recipients, 45 cases of TB were diagnosed, resulting in a prevalence of 1.52%. Most of them (88.89%) were diagnosed during the first year posttransplantation, 86.67% with pulmonary presentation. Screening for latent TB infection (LTBI) was done in 36 of the 45 patients and LTBI was detected pretransplant in 12 (33.33%). Less than half of the patients with disease (42.22%) received rifampicin (RIF). Lower probability of TB worsening was found in RIF-containing regimens (p = 0.049), as well as longer survival (p = 0.001). RIF use was not associated with an increased risk in rejection (p = 0.99), but doses of calcineurin inhibitors (CNI) had to be raised an average of 215%.ConclusionsRisk of TB after LT was lower in our series than previously reported. TB should be searched during the first year posttransplant in patients with TB risk factors. Pulmonary presentation was predominant. More sensitive algorithms for detecting LTBI before LT are crucial. It is reasonable to use RIF-containing regimens over non-RIF regimens based on the tendency toward better outcome in our series. RIF regimen requires close monitoring of CNI trough level for 2–3 weeks, until stability is achieved.     

The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes

BackgroundNon-HLA antibodies (Abs) targeting vascular receptors are considered to have an influence on renal transplant injury. Anti-endothelin-1 type A receptor (anti-ETAR) antibodies were associated with cellular and antibody-mediated rejection and early onset of vasculopathy in heart transplant patients but their role in renal transplantation remains unclear. The aim of our study was to assess the incidence and importance of anti-ETAR antibodies and their impact on renal transplant during the first year observation.MethodsWe evaluated the presence of anti-ETAR antibodies in 116 consecutive renal transplant recipients in pre- and post-transplant screening (before and in 1st, 3rd, 6th, 12th month after transplantation). Additionally, we assessed the presence of anti-HLA antibodies. Anti-ETAR antibodies were assayed by ELISA. The diagnosis of acute rejection was based on the Banff criteria.ResultsAnti-ETAR antibodies were observed in 55 (47.4%) of the analyzed recipients before transplantation. The function of renal transplant was significantly worse in the anti-ETAR(+) group compared to the anti-ETAR(?) group during the first post-transplant year. One month after transplantation the serum creatinine in anti-ETAR (+) patients (pts) was 1.86 ± 0.8 mg/dl and 1.51 ± 0.5 in anti-ETAR(?) pts (p = 0.009). Twelve months after transplantation the difference between the groups was still observed 1.70 ± 0.7 vs. 1.40 ± 0.4 (p = 0.04).Biopsy proven acute rejection was recognized in 8/55 (14.5%) in ETAR(+) and 9/61 (14.8%) in ETAR(?) patients but cases with mild to severe intimal arteritis (v1–v3) were more often observed in patients with the presence of anti-ETAR Abs 4/55 (7.2%) comparing with 1/61 (1.6%) in anti-ETAR(?) patients. The anti-ETAR antibody levels varied at different measurement intervals during the one-year follow-up.ConclusionsThe presence of anti-ETAR antibodies is associated with a worse renal transplant function during the first 12 months after transplantation. Including anti-ETAR antibodies in the diagnostics of renal transplant recipient immune status should be considered to provide comprehensive assessment of humoral alloimmunity.     

Preemptive therapy for cytomegalovirus based on real-time measurement of viral load in liver transplant recipients

BackgroundReal-time PCR has emerged as the preferred diagnostic assay for CMV. However, its utility as a preemptive therapy tool for CMV disease and related outcomes in liver transplant recipients has not been fully defined.MethodsPatients comprised 117 consecutive liver transplant recipients who underwent CMV surveillance monitoring using real-time PCR. Preemptive therapy with valganciclovir was employed upon detection of viremia. Baseline viral load was considered high based on log values (median).ResultsCMV viremia developed in 54% (63/117) of the patients, including 77% of R−/D+, 63% of R+/D+, 43% of R+/D−, and 10% of R−/D− patients. Overall, 23% (15/63) of the patients had recurrent viremia; R− serostatus (p = 0.065) but not initial viral load correlated with recurrent viremia (p = 0.80). At 12 months post-transplant, CMV disease occurred in 0.85% (1/117) of the patients (R+/D + recipient). None (0/30) of the R−/D + patients had CMV disease. Patients with CMV viremia treated preemptively did not differ significantly from those who never developed CMV viremia with regards to bacterial or fungal infections, rejection, graft loss, mortality rate, and probability of survival at 12 months (p > 0.05 for all variables). The above outcomes also did not differ for patients with high (> 1.9 logs) vs. low viral load (< 1.9 logs) (p > 0.05 for all outcomes).ConclusionsPreemptive therapy guided by real-time PCR based monitoring led to outcomes in all patients or in those with high viral loads that were comparable to outcomes in patients who never developed viremia or had low viral loads, respectively. Late-onset CMV disease at 12 months was observed in < 1% of all patients.     

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study

IntroductionImmune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients.MethodsA multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months.ResultsTwenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225–525 ng/mL) in 14 (15.2%) patients and low (ATP < 225 ng/mL) in 78 (84.8%); no patients had a strong response (ATP ≥ 525 ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p = 0.043). Similar acute rejection rates were recorded in patients with mean ATP ≥ 225 vs. <225 ng/mL during the study period (7.1% vs. 9.1%, p = 0.81).ConclusionAlthough ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.     

Early assessment of glucose abnormalities during continuous glucose monitoring associated with lung function impairment in cystic fibrosis patients

BackgroundCystic fibrosis-related diabetes (CFRD) is correlated with a decline in lung function. Under certain circumstances, oral glucose tolerance test (OGTT) screening, used to diagnose CFRD, fails to reveal early glucose tolerance abnormalities. In this situation, continuous glucose monitoring (CGM) could be a useful tool for evaluating early abnormalities of glucose tolerance in CF patients. We aimed to study the CGM glucose profile in CF patients with normal OGTT screening results and to evaluate lung function and nutritional status according to the CGM glucose profile.MethodsWe assessed glycemic control, the CGM glucose profile, nutritional status, lung function antibiotic courses and colonization (P. aeruginosa and S. aureus) in CF patients, aged 10 years and over, with normal screening OGTT results (blood glucose at T120 min < 7.8 mmol/l). Two groups were identified according to the max CGM glucose value: Group 1 < 11 mmol/l and Group 2 ≥ 11 mmol/l.ResultsAmong the 38 patients with normal OGTT, 12 (31.6%) were in Group 2. Compared to Group 1, Group 2 patients exhibited a significant impairment in lung function: FEV₁, 68.2 ± 25.6% vs. 87.3 ± 17%, p = 0.01 and FVC, 86.1% ± 19.4% vs. 99.3% ± 13.4%, p = 0.021, as well as a higher rate of colonization by P. aeruginosa: 83.3% vs. 44%, p = 0.024. Nevertheless, there were no differences in nutritional status (BMI standard deviation score: p = 0.079; prealbumin: p = 0.364).ConclusionsCGM reveals early abnormalities of glucose tolerance that remain undiagnosed by OGTT screening and are associated with worse lung function and a higher prevalence of P. aeruginosa colonization in patients with CF.Clinical trial registration number: NCT00476281.     

Repeated human leukocyte antigen mismatches in lung re-transplantation

BackgroundThe role of HLA-sensitization in the absence of detectable DSA in lung re-transplantation is unclear. Antigens of the second donor matching the HLA typing of the first donor are considered ‘unacceptable’, by some tissue typing laboratories, especially in kidney re-transplantation.MethodsThus, we performed a retrospective analysis of all lung re-transplantations focussing on the impact of HLA-homologies between the first and the second donor (‘unacceptable’ antigens; repeated HLA mismatch) on patient and graft survival.ResultsA total of 132 lung re-transplantations were performed at our centre between 1985 and 2014, of which 120 with complete HLA data were analysed. 55.8% of the recipients received re-transplants with repeated HLA mismatched antigens whereas 43.2% of the re-transplants were transplanted without repeated HLA mismatched antigens.Postoperative survival showed no difference between re-transplant procedures with or without repeated HLA mismatches (p = 0.99). While neither homologies on the HLA-A, -B, -C, or -DR locus, nor the addition of several locus homologies (p = 0.72) had an impact on survival, unexpectedly, repeated HLA mismatching on the HLA-DQ locus was correlated with better survival. Re-transplantations with repeated HLA mismatches did not result in more development of CLAD as compared to recipients without repeated HLA mismatches (p = 0.99). Neither the number of repeated HLA mismatched antigens (p = 0.52) nor the HLA locus (HLA-A(p = 0.34), HLA-B(p = 0.97), HLA-C (p = 0.80), HLA-DR(p = 0.49) and HLA-DQ(p = 0.07)) had an impact on the development of CLAD after re-transplantation.ConclusionTransplantation with repeated HLA mismatches due to sensitization by a previous transplantation in the absence of detectable HLA-antibodies does not have a negative impact on patient or graft survival.     

Antibody response to HBV vaccination on dialysis does not correlate with the development of deNovo anti-HLA antibodies after renal transplantation

BackgroundResponse to Hepatitis B virus (HBV) vaccination can be diminished in some (50–80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to predict alloresponses.MethodsThe response to HBV vaccination on dialysis and the development of deNovo anti-HLA antibodies post-transplant was analyzed in 188 non-immunized renal transplant recipients. The response to HBV vaccination was evaluated by measuring the anti-HBs titer at time of transplantation. Anti-HLA antibodies post-transplant were monitored by serial measurements by means of Luminex. Acute rejection episodes, graft loss and renal dysfunction were assessed within a median follow-up of 5.5 years.ResultsOne hundred and forty-one patients (75%) exhibited an adequate immune response to HBV vaccination on dialysis. Vaccine responder (R) and none responder (NR) did not differ with respect to age, gender and BMI, while R spend significantly more time on dialysis before transplantation (4.58 ± 3.35 vs 3.23 ± 2.55 years, p = 0.033). More NR developed deNovo anti-HLA antibodies (27.7 vs 22.7%, p = 0.554) and donor-specific anti-HLA antibodies (23.4 vs 14.2%, p = 0.173) in comparison to R. Accordingly, the number of acute rejections was higher in NR as compared to R (36.1 vs 24.1%, p = 0.130) while graft survival was similar in both groups.ConclusionContrary to our hypothesis antibody response to HBV vaccination on dialysis does not predict the development of anti-HLA antibodies post transplant.     

Impact of Covid-19 on kidney transplant and waiting list patients: Lessons from the first wave of the pandemic

BackgroundThe first wave of the Covid-19 pandemic resulted in a drastic reduction in kidney transplantation and a profound change in transplant care in France. It is critical for kidney transplant centers to understand the behaviors, concerns and wishes of transplant recipients and waiting list candidates.MethodsFrench kidney patients were contacted to answer an online electronic survey at the end of the lockdown.ResultsAt the end of the first wave of the pandemic in France (11 May 2020), 2112 kidney transplant recipients and 487 candidates answered the survey. More candidates than recipients left their home during the lockdown, mainly for health care (80.1% vs. 69.4%; P < 0.001). More candidates than recipients reported being exposed to Covid-19 patients (2.7% vs. 1.2%; P = 0.006). Many recipients and even more candidates felt inadequately informed by their transplant center during the pandemic (19.6% vs. 54%; P < 0.001). Among candidates, 71.1% preferred to undergo transplant as soon as possible, 19.5% preferred to wait until Covid-19 had left their community, and 9.4% were not sure what to do.ConclusionsDuring the Covid-19 pandemic in France, the majority of candidates wished to receive a transplant as soon as possible without waiting until Covid-19 had left their community. Communication between kidney transplant centers and patients must be improved to better understand and serve patients’ needs.     

Immunoglobulin isotype switching of antibodies to vimentin is associated with development of transplant glomerulopathy following human renal transplantation

BackgroundImmune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development.MethodsSera were collected from 24 patients with TG (diagnosed on biopsy), 24 matched stable kidney transplant recipients (KTxRs) and 22 normal healthy subjects who did not undergo transplant. Serum vimentin Abs concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Immunoglobulin isotypes of anti-vimentin were determined using isotype-specific Abs conjugated with horseradish peroxidase. Samples were considered positive to vimentin Abs if the values were above mean + 2 × standard deviations of the levels in the healthy control subjects. Specificities of anti-vimentin for mutated citrullinated vimentin and anti-mutated citrullinated vimentin were measured by ELISA.ResultsIn this retrospective analysis of 24 KTxRs with TG, 16/24 (67%) patients with biopsy-proven TG developed Abs to vimentin (645 ± 427 ng/ml). In contrast, only 4/24 (17%) stable KTxRs had detectable Abs to vimentin (275 ± 293 ng/ml; p = 0.001). Of the patients with TG, 15/24 (63%) developed Abs to vimentin of IgG isotype (572 ± 276 ng/ml), whereas only 6/24 (25%) stable KTxRs (310 ± 288 ng/ml) had anti-vimentin of IgG isotype (p = 0.002). However, no significant difference was noted in the concentration of IgM isotype anti-vimentin between KTxRs with TG (9/24 [38%], 407 ± 401 ng/ml) and stable KTxRs (5/24 [21%], 348 ± 439 ng/ml; p = 0.631). The serum concentration of Abs specific for the mutated form of citrullinated vimentin was not significantly different between KTxRs with TG and stable KTxRs.ConclusionsPatients with biopsy-proven TG demonstrated significantly increased levels of anti-vimentin Abs of the IgG isotype compared with stable KTxRs. Anti-vimentin in stable KTxRs was primarily of IgM isotype. Therefore, the observed isotype switching of anti-vimentin from IgM to IgG isotype strongly suggests ongoing immune responses to vimentin in KTxRs diagnosed with TG. Furthermore, as opposed to patients with rheumatoid arthritis (who develop immune responses primarily to citrullinated vimentin), KTxRs diagnosed with TG developed immune responses to non-citrullinated vimentin, suggesting that modification of vimentin protein via citrullination is not required for the de novo anti-vimentin response seen in patients with TG.     

Detection of plasma cells,C4d deposits and donor-specific antibodies on sequential graft biopsies of renal transplant recipients with chronic dysfunction

BackgroundIn order to look for a relationship between humoral mechanisms of rejection and chronic allograft dysfunction, plasma cells, C4d deposits and donor-specific antibodies (DSA) were simultaneously sought on serial biopsies of kidney allograft recipients.Patients and methodsTen recipients with chronic dysfunction (G1) and 8 recipients with long-term normal graft function (G2) were included. Biopsies and serums were sampled at early graft dysfunction (T1), between 8 months and 2 years (T2) and after the third year following transplantation (T3).ResultsIn G1, plasma cells represented 12.3% (T1), 8.2% (T2) and 14.1% (T3) of mononuclear cells. The mean percentage of plasma cells was 11.6% in G1 versus 0.4% in G2 (p < 0.05). A progressive rise in C4d deposits was seen in G1, from 25% at T1 to 80% at T3. Donor-specific antibodies were identified in at least one serum sample of 60% of the patients in G1 and 12.5% of the patients in G2 (p = 0.012), whereas donor-specific antibodies were eluted from at least one biopsy of 50% of the patients in G1 and 12.5% of the patients in G2 (p = 0.03). In G1, C4d deposits were significantly associated with plasma cells (p = 0.0012) and anti-HLA Abs in serum samples and/or eluates (p = 0.026).ConclusionThis study shows that plasma cells, DSA and C4d are associated in renal transplants developing chronic rejection.     

Association of genetic polymorphisms of angiopoietin-like 4 with severity of posttransplant proteinuria in kidney allograft recipients

BackgroundProteinuria is a hallmark of glomerular injury, and persistent proteinuria is associated with graft failure in kidney transplant patients. Recently, it is known that the level of circulating angiopoietin-like 4 (ANGPTL4) is elevated in the patients with human nephrotic syndrome, in which ANGPTL4 is responsible for relieving proteinuria.PurposeThe purpose of this study is to determine effects of clinical factors and genetic polymorphism of ANGPTL4 on proteinuria after kidney transplantation.MethodsA total of 282 patients out of 400 renal transplant patients between 2008 and 2012 at St. Vincent Medical Center, CA were studied in a retrospective study design. The level of proteinuria was measured by random urine protein to creatinine ratio, and divided into two groups (Group 1: UPC < 500 mg/day, Group 2: ≥ 500 mg/day). Single nucleotide polymorphisms of ANGPTL4 genes (rs1044250, rs2278236, rs116843064, rs11672433, rs4076317) were determined by real time PCR with sequence specific primers.ResultsAmong various clinical factors, only delayed graft function, mTOR inhibitor use and fish oil use were significantly associated with posttransplant proteinuria. Statistical differences were found in genetic polymorphisms of ANGPTL4 (rs1044250, rs2278236) in regards to proteinuria among tested patients. rs1044250 (C/T, T228M, missense mutation) alleles showed multiple significant differences (Group 1 vs. Group 2: C vs. T: OR = 1.893, CI = 1.322–2.710, p < 0.001). Similar trends were found in rs2278236 (A/G) alleles with statistical significances (Group 1 vs. Group 2: A vs. G: OR = 0.620, CI = 0.443–0.867, p = 0.005). With multiple logistic regression, rs1044250 was still a significant risk factor of moderate/severe proteinuria (p = 0.021).ConclusionsThis study suggests that the presence of C allele of rs1044250 and G allele of rs2278236 in ANGPTL4 gene is associated with higher risk of moderate/severe proteinuria in renal transplant patients.     

Impact of pulmonary hypertension on survival in patients with cystic fibrosis undergoing lung transplantation: An analysis of the UNOS registry

BackgroundPulmonary hypertension (PH) is a comorbidity reported in patients with cystic fibrosis (CF) with research limited to single-center studies.MethodsTo assess the impact of PH in patients with CF who received a lung transplant (LTx), the United Network for Organ Sharing was queried from 1987 to 2012, restricting analysis to transplant patients 6–55 years old between 1/1/2005 and 7/6/2011.ResultsOf 23,951 lung transplants, 1177 met inclusion criteria with 831 having mean pulmonary artery pressure (mPAP) data available. For the entire cohort, mean age was 30.3 (SD = 9.2, range 12–55), and mean mPAP was 26.5 (SD = 7.8, range 5–66) mm Hg. A total of 470 (57%) had PH defined as mPAP ≥ 25 mm Hg. Comparing PH to non-PH groups, mean forced expiratory volume in one second (FEV₁) was 24.4 (SD = 13.8) vs. 26 (SD = 13.9) % of predicted, mean supplemental oxygen requirement at rest was 4.5 (SD = 4.1) vs. 3.7 (SD = 3.0) liters per minute, and mean lung allocation score was 49 (SD = 16) vs. 43 (SD = 12), respectively. For the PH group, median survival was 84.4 months compared to 67.1 months for the non-PH group (log-rank p-value = 0.326). The adjusted hazard ratio for PH vs. non-PH was 0.862 (95% CI: 0.653–1.138; p = 0.293), thus indicating no statistically significant effect of PH on survival.ConclusionsA high prevalence of PH was found in CF patients prior to LTx. Based on our models despite PH being prevalent, there is no strong evidence suggesting that it significantly alters the risk of death in CF patients after LTx.     

Orthopaedic injuries among electric bicycle users

IntroductionThe use of electric bicycles (E-bike) has dramatically increased. E-bikes offer convenient, environmental-friendly, and less expensive alternative to other forms of transport. However, E-bikes provide a new public health challenge in terms of safety and injury prevention.This study is the first to specifically investigate the E-bike related orthopaedic injuries, based on a national trauma registry.MethodsData from a National Trauma Registry were reviewed for patients hospitalized following E-bike related injuries. Between Jan 2014 to Dec 2015, a total of 549 patients were reviewed. Data were analyzed according to demography, type of orthopaedic injury, associated injuries and severity, injury mechanism and treatment in the operating room.ResultsA total of 360 (65%) patients sustained orthopaedic injuries, out of them 230 (63.8%) sustained limb/pelvis/spine fractures. Lower extremity fractures were more prevalent than upper extremity fractures (p < 0.001). The tibia was the most fractured bone (19.2%). Patients over the age of 50 years were at the highest risk for spine (20. 5%, p = 0.0001), pelvis (15.9%, p = 0.0001) and femoral neck (15.9%, p = 0.0172) fractures relative to other age groups. Approximately 42% of patients sustained associated injuries, with head/neck/face injuries being the most prevalent (30.3%). followed by chest (11.9%) and abdominal injury (13.3%). A collision between E-bike and a motorized vehicle was the mechanism of injury in 35% of cases. In this mechanism of injury, patients had 1.7 times the risk for associated injuries (p < 0.0001) and the risk for major trauma (ISS score ≥16) was more than the double (p = 0.03).One third of patients with orthopaedic injuries required treatment in the operating room.Treatment varied depending on the type of fracture.ConclusionsThis study provides unique information on epidemiological characteristics of orthpaedic injuries caused be E-bikes, pertinent both to medical care providers, as well as to health policy-makers allocating resources and formulating prevention strategies.     

Prognostic relevance of dynamic hyperinflation during cardiopulmonary exercise testing in adult patients with cystic fibrosis

BackgroundDynamic hyperinflation during cardiopulmonary exercise testing (CPET) in cystic fibrosis (CF) has not been well characterized, and little is known regarding its prevalence, risk factors and clinical associations.MethodsCPET data from 109 adult patients with mild-to-moderate CF was used, in this retrospective study, to characterize and determine the prevalence of dynamic hyperinflation, and evaluate its relationship with lung function and exercise tolerance, clinical symptoms, and prognosis over a two-year period.Results58% of patients responded to CPET with dynamic hyperinflation. These patients had significantly lower lung function (FEV₁ 66 ± 19 versus 79 ± 18%pred., p < 0.01) and exercise tolerance (peak oxygen uptake 28.7 ± 8.1 versus 32.9 ± 6.1 mL·kg^? 1·min^? 1, p = 0.02), and experienced greater shortness of breath at peak exercise (7 ± 3 versus 5 ± 2 Modified Borg scale, p = 0.04) compared to patients who responded without dynamic hyperinflation. Significant relationships between FEV₁, FVC, FEV₁/FVC, FEF_25–75 and dynamic hyperinflation were shown (p < 0.01; p = 0.02; p < 0.01; p < 0.01, respectively). Dynamic hyperinflation was also significantly correlated with oxygen uptake, tidal volume, work-rate and shortness of breath at peak exercise (p = 0.03; p < 0.01; p < 0.01; p = 0.04, respectively). Responding to CPET with or without dynamic hyperinflation did not significantly predict FEV₁ at 2 years beyond the FEV₁ at baseline (p = 0.06), or increase the likelihood of experiencing a pulmonary exacerbation over a two-year period (p = 0.24).ConclusionThe prevalence of dynamic hyperinflation during CPET in adult patients with mild-to-moderate CF is high, and is associated with reduced lung function and exercise tolerance, and increased exertional dyspnea. However, identifying dynamic hyperinflation during CPET had limited prognostic value for lung function and pulmonary exacerbation.     

Three-year outcomes of intracapsular femoral neck fractures fixed with sliding hip screws in adults aged under sixty-five years

IntroductionIntracapsular femoral neck fractures remain associated with high rates of post-traumatic femoral head necrosis, non-union, and revision surgery.AimOur aim was to identify factors associated with revision surgery in intracapsular femoral neck fractures treated with sliding hip screws (SHS) in adults aged <65 years.Patients and methodsConsecutive admissions were identified retrospectively from the Royal Victoria Hospital, Belfast, which was the largest volume hospital on the National Hip Fracture Database. Of 2201 hip fractures between 1st August 2008 and 31st December 2010, 97 (4%) intracapsular fractures treated with SHS in adults <65 years were followed for a mean of 2.9 years (range 0–6.6).ResultsTwenty-one (22%) hips were revised to arthroplasty. Avascular necrosis developed in 28 (29%) femoral heads. Eight (8%) fractures proceeded to non-union. Displaced fractures (p < 0.001, Fisher’s exact [FE]), posterior comminution (p = 0.049, FE), chronic respiratory disease (p = 0.006, FE) and residual distraction (p = 0.011, χ²) were associated with revision to arthroplasty. Multiple regression found displaced fractures (p = 0.006) and chronic respiratory disease (p = 0.017) significant; in the latter 4 of 6 were revised (67%), including all four patients with chronic obstructive pulmonary disease (COPD). Eleven (11%) individuals required walking aids before injury, which rose to 34 (35%) at one year (p < 0.0001, χ²). Eighty-nine (92%) individuals could walk alone outdoors before injury, but only 76 (78%) at one year (p = 0.009, χ²).ConclusionsDisplaced fractures in individuals with chronic respiratory disease should be considered high risk for revision to arthroplasty. Posterior cortex deficiency should be evaluated prior to choice of operation. Fracture biology and revascularisation play a greater role than operation timing. A significant proportion of individuals do not recovery pre-morbid mobility by one year.