Body mass index affects kidney transplant outcomes: a cohort study over 5 years using a steroid sparing protocol

Background: There is controversy regarding the suitability of high body mass index (BMI) candidates accessing the transplant waitlist. Patients and Methods: Observational study on consecutive kidney transplant recipients undergoing surgery between January 2014 and March 2016 at our centre. Patients were stratified according to BMI. Survival outcomes and graft function were analysed to In review investigate the effect of donor’s and recipient’s demographic characteristics. Results: 396 kidney transplant recipients: 260 males, mean age 51.8 ± 15.9 years, followed up for a mean time of 5.86 ± 2.29 years. Mean BMI 26.2 ± 5.1. BMI class 1 (20 ≤ BMI ≤ 24.9) n=133, class 2 (25 ≤ BMI ≤ 29.9) n= 155, class 3 (30 ≤ BMI ≤34.9) n=53, class 4 (BMI ≥ 35) n=21), class V (BMI ≤ 19.9) n=34. Patient survival was not significantly different according to the recipient’s BMI class (p=0.476); graft survival was affected (p=0.031), as well as graft function up to 2 years post-transplant and at 4 years follow up (p=0.016). At logistic regression the factors independently associated with graft loss were only donor’s age (p=0.05) and BMI class of the recipient (p=0.002). Conclusions: Obesity did not impact on patient’s survival but affected graft function and graft loss

The impact of recipient demographics on outcomes from living donor kidneys: systematic review and meta-analysis.

Background and Aims: Recipient demographics affect outcomes after kidney transplantation. The aim of this study was to assess, for kidneys retrieved from living donors, the effect of recipient sex, ethnicity, and body mass index (BMI) on delayed graft function (DGF) and one-year graft function, incidence of acute rejection (AR), and recipient and graft survivals. Methods: A systematic review and meta-analysis was performed. EMBASE and MEDLINE databases were searched using algorithms through Ovid. Web of Science collection, BIOSIS, CABI, Korean Journal database, Russian Science Citation Index, and SciELO were searched through Web of Science. Cochrane database was also searched. Risk of bias was assessed using the NHBLI tools. Data analysis was performed using Revman 5.4. Mean difference (MD) and risk ratio (RR) were used in analysis. Results: A total of 5129 studies were identified; 24 studies met the inclusion criteria and were analysed. Female recipients were found to have a significantly lower serum creatinine 1-year-post renal transplantation (MD: -0.24 mg/dL 95%CI: -0.18 to -0.29 p 30) was found to have no effect on 1-year recipient (p = 0.28) and graft survival (p = 0.93) compared to non-obese recipients although non-obese recipients had a lower rate of DGF (RR = 0.65 p < 0.01) and AR (RR = 0.81 p < 0.01) compared to obese recipients. Conclusions: Gender mismatch between male recipients and female donors has negative impact on graft survival. African ethnicity and obesity do not to influence recipient and graft survival but negatively affect DGF and AR rates

Obesity affects graft function but not graft loss in kidney transplant recipients

Background: There is an ongoing debate regarding the suitability for transplantation of the high Body Mass Index (BMI) kidney transplant recipients (KTRs). Methods: Retrospective analysis of 370 consecutive KTRs stratified according to the World Health Organisation Body Mass Index categories. As a measure of allograft function eGFR was used. Results: Mean BMI was 26.2: 148 (40%) pre-obese, 47 (12.7%) class I obese, 11 (3%) class II obese, 9 (2.4%) class III obese. A linear trend from the normal BMI group moving through the progressively higher groups was observed for male sex and younger age. Overweight and obese KTRs had higher incidence of pre-transplant diabetes (P = 0.021), but there was no difference in new-onset hyperglycemia post-transplant (P = 0.35). Obesity was not a significant risk factor for lower eGFR at 1 year follow-up, but it became at 2 and 3 years follow up. No statistical difference in Delayed Graft Function and hospital length of stay was observed. 28 patients lost their grafts, and 25 patients died during follow-up. Kaplan-Meier analysis showed no difference in all-cause allograft loss between the different BMI groups (log rank P = 0.8) in a mean follow-up of 42 months (0-58). Conclusion: Obesity affects eGFR in the long-term. The allograft survival was lower but not significant

Bilateral nephrectomy for adult polycystic kidney disease does not affect the graft function of transplant patients and does not result in sensitisation

Background. Native nephrectomy in Adult Polycystic Kidney Disease (ADPKD) patients is a major operation with controversy related to timing and indications. We present our single centre experience in transplanted patients and future candidates for transplantation. Methods. Retrospective analysis from an anonymised database of bilateral nephrectomies for ADPKD patients. Results were reported as median, range, and percentage. Differences between groups were tested using ANOVA and t-test. Surgery was performed between January 2012 and July 2018. Results. Thirty-three patients underwent bilateral native nephrectomy for APKD. 18 had a functioning kidney transplant (transplant group, 55%) while 15 patients were on dialysis (dialysis group, 45%) at the time of surgery; 8 patients of the latter group (24% of the whole cohort) were eventually transplanted. 53% were males, with median age of 55 years (27-71). Indications to surgery were the following: space (symptoms related to the size of the native kidneys or need to create space for transplantation) (59%), recurrent cyst infection (36%), haematuria (15%), pain (24%), and weight loss associated with cystic alteration on imaging (3%). In the transplant group, postoperative kidney function was not affected; haemoglobin serum levels significantly dropped in the whole cohort: 121 (82-150) g/L, versus 108 (58-154) g/L (p<0.001), with 14 patients being transfused perioperatively. Elevation of anti-HLA antibodies was noted in one female patient on dialysis, with no change in DSA levels and no rejection after transplant for all 26 transplanted patients. Median postoperative length of hospital stay was 9 days (6-71). One patient died (3%) after six months. Median follow-up for the whole cohort was 282 days (13-1834). Histopathological examination revealed incidental renal neoplasms in five cases (15%): 1 pT1a papillary renal cell carcinoma and 4 papillary adenomas. Conclusions. Native nephrectomy for ADPKD could be safely performed in case of refractory symptoms, suspect of cancer or to create space for transplantation. It does not affect graft function or DSA status of transplanted patients or the prospect of transplantation of those on the waiting list

Proposed Definitions of T Cell-Mediated Rejection and Tubulointerstitial Inflammation as Clinical Trial Endpoints in Kidney Transplantation

The diagnosis of acute T cell-mediated rejection (aTCMR) after kidney transplantation has considerable relevance for research purposes. Its definition is primarily based on tubulointerstitial inflammation and has changed little over time; aTCMR is therefore a suitable parameter for longitudinal data comparisons. In addition, because aTCMR is managed with antirejection therapies that carry additional risks, anxieties, and costs, it is a clinically meaningful endpoint for studies. This paper reviews the history and classifications of TCMR and characterizes its potential role in clinical trials: a role that largely depends on the nature of the biopsy taken (indication vs protocol), the level of inflammation observed (e.g., borderline changes vs full TCMR), concomitant chronic lesions (chronic active TCMR), and the therapeutic intervention planned. There is ongoing variability-and ambiguity-in clinical monitoring and management of TCMR. More research, to investigate the clinical relevance of borderline changes (especially in protocol biopsies) and effective therapeutic strategies that improve graft survival rates with minimal patient morbidity, is urgently required. The present paper was developed from documentation produced by the European Society for Organ Transplantation (ESOT) as part of a Broad Scientific Advice request that ESOT submitted to the European Medicines Agency for discussion in 2020. This paper proposes to move toward refined definitions of aTCMR and borderline changes to be included as primary endpoints in clinical trials of kidney transplantation.Copyright © 2022 Seron, Rabant, Becker, Roufosse, Bellini, Böhmig, Budde, Diekmann, Glotz, Hilbrands, Loupy, Oberbauer, Pengel, Schneeberger and Naesens

Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

Antibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR definition have made it difficult to compare data and evaluate associations between AMR and graft outcome. The present paper was developed following a Broad Scientific Advice request from the European Society for Organ Transplantation (ESOT) to the European Medicines Agency (EMA), which explored whether updating guidelines on clinical trial endpoints would encourage innovations in kidney transplantation research. ESOT considers that an AMR diagnosis must be based on a combination of histopathological factors and presence of donor-specific HLA antibodies in the recipient. Evidence for associations between individual features of AMR and impaired graft outcome is noted for microvascular inflammation scores ≥2 and glomerular basement membrane splitting of >10% of the entire tuft in the most severely affected glomerulus. Together, these should form the basis for AMR-related endpoints in clinical trials of kidney transplantation, although modifications and restrictions to the Banff diagnostic definition of AMR are proposed for this purpose. The EMA provided recommendations based on this Broad Scientific Advice request in December 2020; further discussion, and consensus on the restricted definition of the AMR endpoint, is required.Copyright © 2022 Roufosse, Becker, Rabant, Seron, Bellini, Böhmig, Budde, Diekmann, Glotz, Hilbrands, Loupy, Oberbauer, Pengel, Schneeberger and Naesens

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}}$ = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in $|\eta|<0.8$ and $0.3 < p_T < 20$ GeV/$c$ are compared to the expectation in pp collisions at the same $\sqrt{s_{\rm NN}}$, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor $R_{\rm AA}$. The result indicates only weak medium effects ($R_{\rm AA} \approx$ 0.7) in peripheral collisions. In central collisions, $R_{\rm AA}$ reaches a minimum of about 0.14 at $p_{\rm T}=6$-7GeV/$c$ and increases significantly at larger $p_{\rm T}$. The measured suppression of high-$p_{\rm T}$ particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98