Search

Aims: High glycemic variability (GV) is the major indication for islet transplantation (IT) in patients with type 1 diabetes (T1D). The actual criteria used to assess graft function do not consider GV improvement. Our study aimed to describe GV indices' evolution in T1D patients who benefited from IT during the TRIMECO trial and to evaluate if thresholds might be defined to diagnose IT success. Methods: We collected data from 29 patients of the TRIMECO trial, a clinical trial (NCT01148680) comparing the metabolic efficacy of IT with intensive insulin therapy. Based on CGM data, we analyzed mean glucose level and four GV indices (standard deviation, coefficient of variation, MAGE and GVP) before (M0) and 6 months (M6) after IT. Results: Each GV index decreased significantly between M0 and M6: SD 53.9 mg/dL [44.6–61.5] versus 20.1 mg/dL [13.5–24.3]; CV 35.2% [30.6–37.7] versus 17.3% [12.0–20.5]; MAGE 134.9 mg/dl [111.2–155.8] versus 51.9 mg/dL [32.4–62.4]; GVP 35.3% [24.9–47.2] versus 12.2% [6.2–18.8] (p ≤ 0.0001). Thresholds diagnosing IT success at 6 months post-transplant were an SD at 22.76 mg/dL (sensibility 88.89%, specificity 80.00%), a CV at 17.47% (sensibility 88.89%, specificity 70.00%), a MAGE at 54.81 mg/dL (sensibility 88.89%, specificity 80.00%) and a GVP at 12.27% (sensibility 88.89%, specificity 70.00%). Conclusions: This study confirms a positive impact of IT on GV. The proposed thresholds allow an easy evaluation of IT success using only CGM data and may be a clinical tool for the follow-up of transplanted patients. [ABSTRACT FROM AUTHOR]

Background: The 2 main objectives regarding living kidney transplant are to provide optimal graft function and to ensure the safety of donation. Our study hypothesized that the glomerular filtration rate of a single kidney (skGFR), when transplanted, might predict graft function and that the skGFR of the remaining kidney could predict donor functional gain., Methods: A prospective monocentric study was conducted at Grenoble-Alpes University Hospital. Twenty couples of donors and recipients were included. Dimercaptosuccinic acid renal scintigraphy and 51 Cr-ethylene-diamine tetra-acetic acid clearance were evaluated predonation to calculate skGFR. All patients had renal function according to 51 Cr-ethylene-diamine tetra-acetic acid clearance at 1 year post transplant to assess graft function and donor functional gain. All donors had normal renal function predonation., Results: At 1 year post transplant, median glomerular filtration rate of the graft was 50 mL/min/1.73 m 2 (range, 46-56 mL/min/1.73 m 2 ) and donor median glomerular filtration rate was 59 mL/min/1.73 m 2 (range, 55-74 mL/min/1.73 m 2 ). Median functional gain was 20 mL/min/1.73 m 2 (range, 12-22 mL/min/1.73 m 2 ). No statistical correlation was found between skGFR of the transplanted kidney and graft function at 1 year (R 2  = 0.096, P = .7). For the donor, functional gain was not associated with predonation skGFR of the remaining kidney (R 2  = 0.17, P = .5). A statistical difference was found between donor functional gain (18 [SD, 10] mL/min) and recipient gain (delta between skGFR before and after transplant, 7 [SD, 16] mL/min; P = .02)., Conclusion: Predonation skGFR of the transplanted kidney had no influence on renal allograft function at 1 year post transplant. Similarly, there was no association between measured skGFR of the remaining kidney and donor functional gain at 1 year., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

For more than 10 years, nephrologists in the Grenoble-region have sought advice from the Ethical Concertation Unit in Nephrology with regards to whether to stop or continue dialysis for patients under palliative care. This process deserves a multidisciplinary debate between health professionals and qualified non-health professionals. Thus, we organized a qualitative research protocol in three parts (medical, philosophical, judicial) to explore this issue. Our study aimed to assess the impact of Ethical Concertation Unit in Nephrology's discussions regarding perception, knowledge, and judicial and ethical considerations. The practical repercussions of decision-making within medical practice, its impacts on the patient and his/her family, as well as associated-health professionals, was assessed. To achieve this, two questionnaires and an interview were organized by three Ethical Concertation Unit in Nephrology-leaders to review the viewpoints of the 22 permanent Ethical Concertation Unit in Nephrology members that had participated in 10 Ethical Concertation Unit in Nephrology sessions between 2015 and 2016 to discuss 21 case-reports. Only 13 persons (4 physicians, 6 nurses, 3 non-health professionals) agreed to respond to the questionnaires, and six physicians agreed to participate in an interview. Overall, it was found that most affected patients' physicians agreed with the multidisciplinary discussion, which included judicial and ethical perspectives, and felt reassured with regards to Ethical Concertation Unit in Nephrology's final decision. However, our study showed that Ethical Concertation Unit in Nephrology's functioning could be improved by promoting its existence more widely, by making these decisions earlier within clinical situations, to make Ethical Concertation Unit in Nephrology more accessible to health workers, to make reports easier to understand, to re-examine a posteriori some clinical situations, and to broaden the scope of multidisciplinary skills., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: This study aimed to identify transplantation characteristics and biomarkers that predict outcomes for kidney transplant (KT) patients from donors after circulatory death (DCDs)., Methods: Consecutive patients receiving a KT from a DCD in our center between 2014 and 2016 were included; the reference population was recipients with a living donor KT. The urinary tubular injury biomarker-to-creatinine ratio and serum lactate dehydrogenase (LDH) were measured at post-transplant days 1 and 3. The primary outcome was the occurrence of delayed graft function (DGF). Descriptive and receiver operating characteristic analyses were performed., Results: Forty-one patients were included in the analysis: 15 (36.59%) DCD KTs (9 of which suffered from DGF) and 26 (63.41%) living donor KTs. For the primary endpoint, neutrophil gelatinase-associated lipocalin, N-acetyl-beta-D-glucosaminidase, urinary tubular injury biomarker-to-creatinine ratio, and LDH areas under the curve were 1 and 0.96 (95% confidence interval: 0.84-1.0), 1 and 0.92 (95% confidence interval: 0.73-1.0), respectively. Among the transplant characteristics, only the 30-minute resistive index on the perfusion machine was significantly higher in DCD KTs with DGF vs those without DGF (0.26 mm Hg/mL/min [0.20; 0.32] vs 0.14 mm Hg/mL/min [0.12; 0.16], P = .05). Median 3-month creatinine clearance among DGF DCD KTs was 49 mL/min/1.73 m 2 [IQR: 42; 65] and 65 mL/min/1.73 m 2 [IQR: 62; 66] among DCD KTs without DGF (P = .22)., Conclusion: In the DCD KT population, clinical and biological markers were identified that provided predictive tools for DGF. Thus, systematic measurement of these biomarkers, particularly LDH, could improve the management of kidney graft recipients' immunosuppressive therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Immune-checkpoint inhibitors have been approved for first and second line treatments of metastatic non-small cell lung cancer based on the results of several phase III trials. Patients with organ transplantation were excluded from these studies because checkpoint inhibitors could activate allo-reactive T cells leading to acute graft rejection., Case Report: A 71-year-old Caucasian-male was diagnosed with stage IV pulmonary adenocarcinoma with multiple metastases, without molecular alteration and negative PD-L1 status. He had a left kidney transplant, and his immunosuppressive regimen consisted of sirolimus and mycophenolate mofetil. After failure of two therapeutic lines (carboplatin-paclitaxel and erlotinib) a multidisciplinary oncology meeting with the nephrologist started third line treatment with nivolumab 3mg/kg every 15 days, with no modification of the immunosuppressive treatment. The patient received a total of 14 injections of nivolumab with stable disease but treatment was discontinued due to acute rejection of the transplanted kidney 6 months later, without need for dialysis. The patient died of a chylothorax related to progression of the tumour 12 months after initiation of nivolumab., Conclusion: Immune checkpoint inhibitors are a potential treatment for solid organ transplant patients despite the risk of graft rejection., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: Chronic antibody-mediated rejection is the main cause of late kidney graft loss. The presence of donor-specific antibodies in the serum is the main criterion for this diagnosis. Single antigen Luminex assays can identify donor-specific antibodies, and semiquantitative estimates of antibodies can be assessed using mean fluorescence intensity. Recent data have shown that patients whose donor-specific antibodies fix C3d have worse clinical outcomes, implying that C3d-specific Luminex assays may provide useful prognostic data., Materials and Methods: We compared C3d donor-specific antibodies with standard immunoglobulin G donor-specific antibody mean fluorescence intensities in a cohort of patients with de novo class II donor-specific antibodies and analyzed subsequent graft survival. The included kidney graft recipients received transplants between 2005 and 2015 and had developed de novo class II donor-specific antibodies. Serum was tested using the standard single antigen Luminex technique and the C3d-fixing antibody-detection system (Immucor, Herentals, Belgium)., Results: In our patient cohort, 41/924 patients (4.4%) developed class II donor-specific antibodies, and 65 serum samples were analyzed (at baseline and follow-up). Among these samples, 43 (66%) were negative for C3d donor-specific antibodies. A mean fluorescence intensity threshold of 9000 in the single antigen Luminex assay discerned all negative (from positive) C3d donor-specific antibodies, even when all single-bead results were taken into account. Sixteen patients (39%) had poor outcomes (ie, either creatinine levels had doubled or they had lost their graft) over the median follow-up of 5 years. C3d results were significantly associated with graft survival (P = .04). We found a strong correlation between C3d-fixing antibody positivity and mean fluorescence intensity strength in the setting of de novo class II donor-specific antibodies., Conclusions: These results further reinforce the paradigm that the higher the mean fluorescence intensity, the more complement activation occurs. Routine C3d testing is thus unnecessary in this setting.

Background: Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients., Methods: In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11 000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified β-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed., Findings: Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified β-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p<0·0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90·5 mL/min (IQR 76·6-94·0) to 71·8 mL/min (59·0-89·0) was observed in islet recipients who had not previously received a kidney graft and from 63·0 mL/min (55·0-71·0) to 57·0 mL/min (45·5-65·1) in islet recipients who had previously received a kidney graft., Interpretation: For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients., Funding: Programme Hospitalier de Recherche Clinique grant from the French Government., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: In the presence of severe aorto-iliac calcification, aortic bypass surgery can be mandatory to allow kidney transplantation. The aim of our study was to evaluate the safety and outcomes of this strategy among asymptomatic patients., Materials and Methods: We retrospectively reviewed the files of all patients that had undergone vascular bypass surgery prior to kidney transplantation between November 2004 and March 2016. All patients undergoing aortic bypass surgery prior to kidney transplantation without any vascular-related symptoms were included., Results: Twenty-one asymptomatic patients were included. Ten patients (48%) have not received a kidney transplant. Four patients died before kidney transplantation, including 2 deaths related to the bypass surgery (9.5%). Early post-operative morbidity involved 11 cases. Eleven patients (52%) were transplanted. Transplanted patients were significantly younger (median age 60 [56-61] vs 67 [60-72] years, P = .04) at the time of bypass and were less frequently treated for coronary heart disease (9% vs 50%, P = .06)., Conclusion: Aortic bypass surgery performed prior to kidney transplantation among asymptomatic patients has significant mortality and morbidity rates. When transplantation is possible, the results are satisfying. Larger studies are required to define the selection criteria, such as age and coronary heart disease., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In kidney transplantation, conversion to mammalian target of rapamycin (mTOR) inhibitors may avoid calcineurin inhibitor (CNI) nephrotoxicity, but its impact on post-transplant allo-immunization remains largely unexplored. This retrospective cohort study analyzed the emergence of donor-specific antibodies (DSA) in kidney transplant recipients relative to their immunosuppressive therapy. Among 270 recipients without pretransplant immunization who were screened regularly for de novo DSA, 56 were converted to mTOR inhibitors after CNI withdrawal. DSA emergence was increased in patients who were converted to mTOR inhibitors (HR 2.4; 95% CI 1.06-5.41, P = 0.036). DSA were mainly directed against donor HLA-DQB1 antigens. The presence of one or two DQ mismatches was a major risk factor for DQ DSA (HR 5.32; 95% CI 1.58-17.89 and HR 10.43; 95% CI 2.29-47.56, respectively; P < 0.01). Rejection episodes were more likely in patients converted to mTOR inhibitors, but this difference did not reach significance (16% vs. 7.9%, P = 0.185). Concerning graft function, no significant change was observed one year after conversion (P = 0.31). In conclusion, conversion to mTOR inhibitors may increase the risk of developing class II DSA, especially in the presence of DQ mismatches: this strategy may favor chronic antibody-mediated rejection and thus reduce graft survival., (© 2014 Steunstichting ESOT.)

Background: Kidney transplant Chronic Allograft Dysfunction (CAD), a major cause of long-term graft failure, is currently diagnosed at a late and irreversible stage by graft biopsies. Our goal was to identify predictive urinary biomarkers of CAD before renal lesions appeared by analysis of the urine proteomic profile. METHODS/METHODS: Twenty-nine urinary samples withdrawn three months post-transplant were analyzed by SELDI-TOF technology. CAD development was evaluated by serum creatinine level and confirmed by allograft biopsy one year after transplantation. Comparison of protein profile of both groups revealed 18 biomarkers predictive of CAD occurrence., Results: The biomarker demonstrating the highest diagnostic performance was a protein of 8860 Da that predicted CAD with a sensitivity of 93% and a specificity of 65%. Moreover combination of these biomarkers in two multivariate analyses improved the diagnostic potential of CAD. Relevance of these individual biomarkers and a decisional algorithm constituted of 3 proteins was confirmed in an independent cohort of patients with undetermined CAD status one year post-transplant., Conclusions: These non invasive biomarkers, detected as soon as three months post-grafting, allowed identification of patients who would develop CAD as late as 4 years after graft. Systematic measurement of these biomarkers would greatly improve the management of immunosuppressive therapy of kidney grafted patients.

Although immunosuppressive therapy after organ transplantation is paramount for long-term outcomes, patients do not comply with their immunosuppressive treatment as much as might be expected. In this observational study, patients having undergone a kidney or liver transplantation were enrolled. Adherence was evaluated by patients using the compliance evaluation test and by physicians using a visual analogic scale. A linear regression was performed to identify determinants of adherence. Less patients having undergone kidney transplantation (27%) described themselves as good compliers than liver transplanted patients (40%). Discrepancy was noted between the physician and patient assessments. Rates of good adherence were significantly different depending on gender, age at transplantation, retransplantation, and time elapsed since transplantation, in at least one of the groups evaluated (whole cohort, kidney liver transplantation groups). In all three groups, adherence decreased with the number of immunosuppressants prescribed. In the whole cohort, the rate of good adherence was significantly higher in patients taking lower number of immunosuppressive drugs (45% for 1 vs. 24% for 3 immunosuppressants; p = 0.02). In this study, which is the first study of this scale in France, we confirmed that adherence with immunosuppressant treatment was low and that simpler treatment regimens may favor adherence., (© 2012 John Wiley & Sons A/S.)

Background: Data in kidney transplant recipients regarding elimination of calcineurin inhibitor (CNI) therapy from a de novo regimen based on low CNI exposure and an mTOR inhibitor are sparse, and restricted to CNI elimination within the first six months post-transplant., Material/methods: In a 12-month, randomized, multicenter, open-label study, kidney transplant patients who had received everolimus, low-exposure cyclosporine and corticosteroids from transplantation to month 12 (with proteinuria <1 g/24 h at month 12) were randomized to convert from cyclosporine to mycophenolate sodium 720 mg/day with increased everolimus exposure (6-10 ng/mL [CNI-free group], n=15) or continue unchanged (everolimus 3-8 ng/mL [CNI group], n=15)., Results: Median (range) baseline mGFR was 54 (21-87) mL/min and 37 (range 18-69) mL/min (p=0.053) in the CNI-free and CNI groups, respectively, compared to 56 (18-126) mL/min and 32 (12-63) mL/min at month 12 (p=0.007). The between-group difference in change in mGFR from baseline to month 12 post-conversion (the primary endpoint) was -14.4 mL/min (95% CI -29.3 to 0.6 mL/min, p=0.059 [least squares mean]). Changes in serum creatinine and estimated GFR to month 12 were significantly in favor of CNI-free patients. One CNI patient experienced biopsy-proven acute rejection. Study drug was discontinued due to adverse events in one CNI-free patient (7%) and three CNI-treated patients (20.0%)., Conclusions: Elimination of CNI from a de novo regimen of everolimus with low-exposure CNI at one year post-transplant maintained efficacy and led to a non-significant but clinically relevant improvement in renal function, although patients numbers were low (n=30). Findings from this small study require confirmation in a larger controlled trial.