Publications by authors named "Laure Esposito"

73 Publications

Do anti-IL-6R blockers have a beneficial effect in the treatment of antibody-mediated rejection resistant to standard therapy after kidney transplantation?

Am J Transplant 2021 04 13;21(4):1641-1649. Epub 2020 Dec 13.

Department of Nephrology and Organ Transplant, CHU Toulouse Rangueil, Toulouse, France.

Antibody-mediated rejection (AMR) that resists to standard of care (SOC) therapy remains a major challenge after kidney transplantation and leads to graft failure in a majority of cases. The use of anti-IL6 receptor antibodies was suggested to treat chronic antibody-mediated rejection (cAMR) after failure of classical treatments. We treated nine patients with AMR resistant to apheresis, rituximab, and intravenous immunoglobulins, with a monthly infusion of tocilizumab and compared them with a historical cohort of 37 patients with similar clinical, immunological, and histological characteristics. The 1-year graft survival and the decline in renal function did not differ between patients who received tocilizumab and those who did not. Histological follow-up showed that despite a decrease in inflammation and tubulitis scores after tocilizumab, the course of antibody-mediated lesions and chronic glomerulopathy were similar in both groups. In our study, the addition of monthly infusions of tocilizumab did not alter the course of AMR that resist to SOC therapy. Large randomized studies are urgently needed to assess the effect of tocilizumab in this context.
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http://dx.doi.org/10.1111/ajt.16391DOI Listing
April 2021

Kidney transplantation during the COVID-19 pandemic: Potential long-term consequences of an early post-transplant infection.

Transpl Infect Dis 2020 Aug 13:e13446. Epub 2020 Aug 13.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Recently, Akalin et al. reported a 28% mortality among kidney-transplant patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Two of the 10 patients who died had been transplanted within the previous 5 weeks. During the coronavirus disease (COVID)-19 outbreak, kidney transplant programs were suspended in several countries . Although the pandemic is still ongoing, the stop of lockdown has prompted several transplant centers to restart kidney transplantation programs. It is recommended to consider that donors and recipients are screened for SARS-CoV-2 before transplantation by means of nuclear acid tests with or without chest CT scans.
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http://dx.doi.org/10.1111/tid.13446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435497PMC
August 2020

A Randomized Prospective Study Comparing Anti-T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients.

Kidney Int Rep 2020 Aug 2;5(8):1207-1217. Epub 2020 Jun 2.

Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR-BMT, University Paul Sabatier, Toulouse, France.

Background: Two prospective studies that were performed before the era of highly sensitive solid-phase assays have shown a lower incidence of acute rejection in highly sensitized kidney-transplant patients given polyclonal antibodies compared with those given anti-CD25 monoclonal antibodies.

Methods: This prospective pilot randomized French multicenter study aimed to compare anti-T-lymphocyte Ig (ATLG) ( = 32) and basiliximab ( = 27) in highly sensitized kidney-transplant patients without preformed donor-specific antibodies (pDSAs) as assessed by a Luminex Single-Antigen flow bead assay. Only patients with a calculated panel reactive antibody ≥50%, with at least 1 antibody with a mean fluorescence intensity ≥5000 and without a historical pDSA and without a pDSA on the day of transplantation were included.

Results: Treatment failure as defined by biopsy-proven acute rejection, patient lost to follow-up, graft loss, and death was observed in 18.8% (95% confidence interval [CI], 8.9%-37.1%) and 18.8% (95% CI, 8.9%-37.1%) in patients who received ATLG and 14.8% (95% CI, 5.8%-34.8%) and 28.2% (95% CI, 14.2%-51.2%) of patients who received basiliximab, respectively at 6 ( = 0.66) and 12 ( = 0.62) months post-transplantation. One T cell-mediated rejection was observed in ATLG-treated patients (3.1%). One antibody-mediated rejection due to a donor-specific antibody (DSA) occurred in basiliximab-treated patients (3.7%). Patient survival, graft survival, kidney parameters, and infection rate were similar in the 2 groups.

Conclusion: This pilot study indicates that in highly sensitized kidney-transplant patients without pDSAs, both ATLG and basiliximab can be used efficiently and safely. However, because of the lack of power, these results should be interpreted with caution.
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http://dx.doi.org/10.1016/j.ekir.2020.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403559PMC
August 2020

Specific organization for in-hospital belatacept infusion to avoid nosocomial transmission during the SARS-CoV-2 pandemic.

Am J Transplant 2020 10 15;20(10):2962-2963. Epub 2020 Jul 15.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

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http://dx.doi.org/10.1111/ajt.16074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283850PMC
October 2020

Outcomes of solid organ transplant recipients with invasive aspergillosis and other mold infections.

Transpl Infect Dis 2020 Feb 6;22(1):e13200. Epub 2019 Nov 6.

Département de Néphrologie et Transplantation d'organes, Hôpital Rangueil, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Objectives: To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients.

Methods: Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors.

Results: Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load.
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http://dx.doi.org/10.1111/tid.13200DOI Listing
February 2020

Adherence profiles in kidney transplant patients: Causes and consequences.

Patient Educ Couns 2020 01 7;103(1):189-198. Epub 2019 Aug 7.

CHU Limoges, Department of Pharmacology, Toxicology and Centre of Pharmacovigilance, F-87000 Limoges, France; INSERM, UMR-1248, F-87000 Limoges, France; FHU SUPORT, Limoges, F-87000, France.

Objective: Adherence is a dynamic phenomenon and a critical determinant of transplant patients outcome. The objective of this longitudinal study was to explore adherence in kidney transplant patients followed-up for up to three years after transplantation.

Methods: Adherence was repeatedly estimated using the Morisky-Green-Levine 4-Item Medication Adherence Scale, in two successive cohorts of 345 (EPIGREN) and 367 (EPHEGREN) kidney transplant recipients. Mixed effect modeling with latent processes and latent classes was used to describe adherence time-profiles.

Results: Two latent classes were identified. The adherent class represented 85% of the patients. Patients of the poorer-adherence class displayed a lower adherence at one month (p<10), which worsened over time. Good adherence was associated with age >50 years, fewer depression episodes (5% vs. 13%, p = 0.001) and a better mental health component of quality of life (MCS-SF36 47 ± 11 vs. 41 ± 13, p = 0.015). Survival without acute rejection episodes was longer in the adherent class (p = 0.004).

Conclusions: The risk of poor adherence in renal transplant patients can be detected as early as one month post-transplantation, using appropriate and easy tools adapted to routine monitoring.

Practice Implications: An early focus on vulnerable patients should allow putting into place actions in order to reduce the risk of poor outcome related to poor adherence.
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http://dx.doi.org/10.1016/j.pec.2019.08.002DOI Listing
January 2020

Anti-IL-2R blockers comparing with polyclonal antibodies: Higher risk of rejection without negative mid-term outcomes after ABO-incompatible kidney transplantation.

Clin Transplant 2019 10 8;33(10):e13681. Epub 2019 Sep 8.

Department of Nephrology and Organ Transplant, CHU Rangueil, Toulouse, France.

There is no recommendation regarding the type of induction therapy to use in ABO-incompatible (ABOi) kidney transplantation. The aim of this retrospective study was to compare the outcome of ABOi living donor kidney transplant (LDKT) recipients who received either polyclonal antibodies or anti-interleukin-2 receptor (IL-2R) blockers as an induction agent. All ABOi HLA-compatible patients that received a LDKT between 03/11 and 03/18 in three French transplantation center (Paris Saint-Louis, Paris Necker, and Toulouse) were included in the study. Fifty-eight patients were given polyclonal antibodies and 39 patients received anti-IL-2R blockers. We identified by a Cox proportional hazard model the use of polyclonal antibodies as a protective factor against acute rejection (HR = 0.4, 95%CI [0-0.9], P < .05). However, pathological findings on protocol biopsies at 1 year were similar in both groups, as were patient and graft survivals, renal function, and complications. We conclude that the acute rejection rate was significantly higher in patients given anti-IL-2R blockers compared to polyclonal antibodies. However, in our series, there was no negative impact on mid-term outcome.
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http://dx.doi.org/10.1111/ctr.13681DOI Listing
October 2019

Outcomes of kidney transplant recipients admitted to the intensive care unit: a retrospective study of 200 patients.

BMC Anesthesiol 2019 07 17;19(1):130. Epub 2019 Jul 17.

Département de Néphrologie et Transplantation d'organes, Unité de Réanimation, Hôpital Rangueil, Centre Hospitalier Universitaire de Toulouse, 1, avenue Jean Poulhes, 31059, Toulouse, France.

Background: Risk of over-immunosuppression or immunization may mitigate the overall and long-term renal outcomes of kidney transplant recipients (KTR) admitted to the ICU in the modern era but remain poorly described. Thus, there is an unmet need to better characterize the survival of KTR admitted to the ICU, but also the renal and immunological outcomes of survivors.

Methods: Retrospective observational study that included 200 KTR admitted between 2010 and 2016 to the ICU of a teaching hospital (median age 61 years [IQR 50.7-68]; time from transplantation 41 months [IQR 5-119]). Survival curves were compared using the Log-rank test.

Results: Mortality rates following admission to the ICU was low (26.5% at month-6), mainly related to early mortality (20% in-hospital), and predicted by the severity of the acute condition (SAPS2 score) but also by Epstein Barr Virus proliferation in the weeks preceding the admission to the ICU. Acute kidney injury (AKI) was highly prevalent (85.1%). Progression toward chronic kidney disease (CKD) was observed in 45.1% of survivors. 15.1% of survivors developed new anti-HLA antibodies (donor-specific antibodies 9.2% of cases) that may impact the long-term renal transplantation function.

Conclusions: Notwithstanding the potential biases related to the retrospective and monocentric nature of this study, our findings obtained in a large cohort of KTR suggest that survival of KTR admitted in ICU is good but in-ICU management of these patients may alter both survival and AKI to CKD transition, as well as HLA immunization. Further interventional studies, including systematic characterization of the Epstein Barr virus proliferation at the admission (i.e., a potential surrogate marker of an underlying immune paralysis and frailty) will need to address the optimal management of immunosuppressive regimen in ICU to improve survival but also renal and immunological outcomes.
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http://dx.doi.org/10.1186/s12871-019-0800-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637509PMC
July 2019

Incidence of Donor-Specific Anti-HLA Antibodies in Non-HLA-Sensitized Patients Given Tacrolimus Once or Twice Daily During the First 2 Years After Kidney Transplant.

Exp Clin Transplant 2019 06 31;17(3):313-319. Epub 2018 Dec 31.

From the Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Objectives: Antibody-mediated rejection is a main cause of long-term kidney allograft loss. Nonad-herence and tacrolimus intrapatient variability have been identified as risk factors for developing de novo donor-specific antibodies. Tacrolimus, given once daily, can improve adherence and reduce variabilities among patients. The aim of this retrospective observational study was to compare the incidences of donor-specific antibodies at 2 years posttransplant in de novo kidney transplant recipients given tacrolimus either once or twice daily.

Materials And Methods: Non-HLA sensitized de novo kidney-transplant recipients given tacrolimus either once daily (n = 82) or twice daily (n = 168), combined with mycophenolic acid with or without steroids, were included in the study. All patients were screened for anti-HLA antibodies before transplant, at 6, 12, and 24 months posttransplant, and each time the patient presented with impaired kidney function.

Results: The 2-year incidence of donor-specific antibodies was 2.8%. During the follow-up period, 6 patients (3.6%) receiving tacrolimus twice daily and one patient (1.2%) receiving tacrolimus once daily developed a donor-specific antibody (P = .43). The incidence of antibody-mediated rejection was 4.8% under tacrolimus once daily and 2.7% under tacrolimus twice daily (P = .5). Tacrolimus intrapatient variability was similar with both formulations and was not associated with development of donor-specific antibodies.

Conclusions: The use of tacrolimus-based immunosup-pression associated with mycophenolic acid was associated with a low risk of de novo donor-specific antibodies. After 2 years, the incidence of de novo donor-specific antibodies did not differ significantly between patients treated with tacrolimus once daily versus those treated with the twice-daily formulation.
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http://dx.doi.org/10.6002/ect.2018.0043DOI Listing
June 2019

Monitoring hepatitis E virus fecal shedding to optimize ribavirin treatment duration in chronically infected transplant patients.

J Hepatol 2019 01 24;70(1):206-209. Epub 2018 Oct 24.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France; Inserm UMR1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France; Université Paul Sabatier, Toulouse, France. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2018.09.011DOI Listing
January 2019

Hepatitis E virus-associated cryoglobulinemia in solid-organ-transplant recipients.

Liver Int 2018 12 14;38(12):2178-2189. Epub 2018 Jun 14.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Background & Aims: An association between hepatitis E virus (HEV) infection and cryoglobulinemia has been suggested. The aims of this study were to assess the prevalence of cryoglobulinemia during HEV infection in solid-organ-transplant (SOT) recipients, to describe its outcomes under ribavirin therapy and to evaluate its effects on kidney function and histology.

Methods: Between November 2005 and June 2016, 128 cases of HEV infection were diagnosed among SOT recipients followed in our institution. Cryoglobulinemia data obtained from 66 patients during acute-phase HEV and 51 patients during chronic-phase HEV were compared to a historical control group of 89 SOT recipients without HEV markers. Cryoglobulins were also monitored in a group of 43 patients treated by ribavirin.

Results: The prevalence of cryoglobulinemia was increased in HEV-infected SOT patients during a chronic phase (52.9%) compared to HEV-infected SOT patients at acute phase (36.4%) (P = .1) and to HEV-negative SOT patients (23.6%) (P < .001). HEV infection was identified as an independent predictive factor for cryoglobulinemia (OR 2.3, CI 95%: 1.17-4.55, P = .02). After ribavirin therapy and HEV clearance, the prevalence of cryoglobulin was significantly decreased from 53.5% to 20.9% (P = .003). Kidney function was significantly worse and proteinuria tended to be higher in chronically HEV-infected patients with cryoglobulinemia compared to those without cryoglobulinemia. Membranoproliferative glomerulonephritis was diagnosed in 2 patients, of which 1 had detectable cryoglobulinemia.

Conclusions: In conclusion, a relationship between HEV and cryoglobulin formation seems to exist. However, the clinical impact of cryoglobulinemia in SOT patients infected with HEV has to be confirmed.
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http://dx.doi.org/10.1111/liv.13894DOI Listing
December 2018

Impact of donor BK polyomavirus replication on recipient infections in living donor transplantation.

Transpl Infect Dis 2018 Aug 11;20(4):e12917. Epub 2018 Jun 11.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Background: Multiple risk factors for BK polyomavirus (BKPyV) replication after kidney transplantation have been described. Here, we investigated the impact of living donors' urinary BKPyV shedding and recipients' BKPyV antibody status pre-transplant on BKPyV replication during the first year post-transplantation.

Methods: We assessed a cohort of living kidney donors and their paired recipients (n = 121). All donors were tested before transplantation, and recipients were tested before and after transplantation for BKPyV viruria and viremia. BKPyV-specific serology was assessed in all recipients at transplantation.

Results: Ten of 121 donors (8.3%) had urinary BKPyV shedding pre-transplant, none had viremia. Overall, 33 (27.3%) recipients developed viruria after transplantation: 7 had received a kidney from a donor with BK viruria (7/10 positive donors) and 26 had received a kidney from a donor without BK viruria (26/111 negative donors; P = .0015). Fifteen (12.4%) recipients developed BK viremia after transplantation: 3 received a kidney from a donor with viruria (3/10 positive donors, 30%) and 12 received a kidney from a donor without viruria (12/111 negative donors, 11%; P = .08). One patient developed proven nephropathy. Ninety-one percent of recipients were seropositive for BKPyV. No relationship between recipients' sero-reactivity at transplantation and post-transplant BKPyV replication was observed. Pre-transplant donor urinary shedding was an independent risk factor for post-transplant BKPyV replication.

Conclusion: Screening living kidney donors for BKPyV can identify recipients at higher risk for BKPyV replication after transplantation who may benefit from intensified post-transplant screening and treatment strategies.
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http://dx.doi.org/10.1111/tid.12917DOI Listing
August 2018

High tacrolimus intra-patient variability is associated with graft rejection, and donor-specific antibodies occurrence after liver transplantation.

World J Gastroenterol 2018 Apr;24(16):1795-1802

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse 31000, France.

Aim: To investigate the role of tacrolimus intra-patient variability (IPV) in adult liver-transplant recipients.

Methods: We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and donor-specific antibodies (DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil (with or without steroids) were included.

Results: Twenty-two patients (18.5%) experienced at least one acute-rejection episode (BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI (1.14-8.24), = 0.03] or > 40% [OR = 4.16 (1.38-12.50), = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68 (1.3-10.4), =0.014]. Thirteen patients (11.2%) developed at least one DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI (1.0-1.12), = 0.006] of > 35% [OR = 4.83, 95%CI (1.39-16.72), = 0.01] and > 40% [OR = 9.73, 95%CI (2.65-35.76), = 0.001] were identified as predictors to detect DSAs. IPV did not impact on patient- or graft-survival rates during the follow-up.

Conclusion: Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a DSA after liver transplantation.
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http://dx.doi.org/10.3748/wjg.v24.i16.1795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922997PMC
April 2018

Eculizumab for Thrombotic Microangiopathy Associated with Antibody-Mediated Rejection after ABO-Incompatible Kidney Transplantation.

Case Rep Transplant 2017 28;2017:3197042. Epub 2017 Dec 28.

Department of Nephrology and Transplantation, University Hospital of Strasbourg, Strasbourg, France.

Thrombotic microangiopathy is a form of antibody-mediated rejection (ABMR): it is the main complication of ABO-incompatible (ABOi) kidney transplantation (KT). Herein, we report on two cases of ABMR with biological and histological features of thrombotic microangiopathy (TMA) that were treated by eculizumab after ABOi KT. The first patient presented with features of TMA at postoperative day (POD) 13. Because of worsening biological parameters and no recovery of kidney function, despite seven sessions of immunoadsorption, a salvage therapy of eculizumab was started on POD 23. Kidney function slightly improved during the first 4 months after transplantation. Eculizumab was stopped at month 4. However, kidney function worsened progressively, leading to dialysis at month 13 after transplantation. The second patient presented with features of TMA at POD 1. In addition to immunoadsorption therapy, eculizumab was started on POD 6. Kidney function improved. Eculizumab was stopped on POD 64 and immunoadsorption sessions were stopped on POD 102. At the last follow-up (after 9 months), eGFR was at 43 mL/min/1.73 m. Our case reports show the beneficial effect of eculizumab to treat ABMR after ABOi KT. However, it should be given early after diagnosing TMA associated with ABMR.
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http://dx.doi.org/10.1155/2017/3197042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5763091PMC
December 2017

Malignancies in hepatitis C virus-positive and -negative kidney transplant recipients: A case-controlled study.

Transpl Infect Dis 2017 Aug 26;19(4). Epub 2017 Jun 26.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Background: Malignancies and lymphoma are common complications after kidney transplantation. However, no link has been made between the incidence of malignancies and hepatitis C virus (HCV) infection in this setting. This case-controlled study compared the incidence of malignancies, including lymphoma, between kidney transplant (KT) patients with or without HCV replication.

Patients And Methods: A total of 99 HCV-positive RNA-positive KT patients were matched with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of transplantation, and were followed for 145.8±78.4 months.

Results: During the follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and 64 (32%) patients developed cancer in the HCV-negative group (P=not significant [ns]). Survival without a cancer was similar between both groups. Thirteen HCV-positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV-negative patients (P=ns). Survival without a solid cancer was similar between both groups. Three patients from the HCV-positive and 4 from the HCV-negative group developed a lymphoma. Only 2 patients from the HCV group died from hepatocellular carcinoma. Survival without a skin cancer was similar between both groups. Patient and death-censored graft survival rates were significantly lower in the HCV group.

Conclusion: The incidences and types of malignancies were similar in the HCV-positive and HCV-negative KT patients.
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http://dx.doi.org/10.1111/tid.12725DOI Listing
August 2017

Pregnancy outcomes in simultaneous pancreas and kidney transplant recipients: a national French survey study.

Transpl Int 2017 Sep 15;30(9):893-902. Epub 2017 Jun 15.

Department of Transplantation, Nephrology and Clinical Immunology, Hospices Civils de Lyon, Lyon, France.

Simultaneous pancreas and kidney transplantation (SPK) is currently the best therapeutic option for patients with type 1 diabetes and terminal renal failure. Renal transplantation restores fertility enabling women to pursue pregnancies. However, scarcity of available data on pregnancy outcomes in SPK impedes fair medical counseling. Medical files of all pregnancies that lasted ≥3 months among recipients of functional SPK performed between 1990 and 2015 in France were retrospectively analyzed. Twenty-six pregnancies in 22 SPK recipients were identified. Main maternal complications included gestational hypertension (53.8%) and infections (50%). Cesarean section was performed in 73% of cases. Overall fetal survival was 92.6% with a mean gestational age of 34.2 ± 3 weeks. Four children (16.7% of live births) had a birth weight <10th percentile. Endocrine pancreas graft function remained stable during pregnancy. An acute kidney rejection occurred in two patients, one of which resulting in graft loss. Kidney and pancreas graft survival was, respectively, 96% and 100% at 1 year postconception and did not differ from controls. Pregnancy in SPK is feasible, but patients should be informed of the risks for the fetus, the mother, and the grafts. Planning of pregnancy in SPK women is key to allow a personalized multidisciplinary monitoring, which represents the most straightforward approach to optimize outcomes.
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http://dx.doi.org/10.1111/tri.12983DOI Listing
September 2017

Impact of transplant accessibility for sensitized patients by avoiding unacceptable antigens.

Liver Transpl 2017 07;23(7):880-886

Department of Nephrology and Organ Transplantation, Centre Hospitalier Universitaire Rangueil, Toulouse, France.

Recent data have confirmed the negative impact of preformed donor-specific antibodies (pDSAs) after liver transplantation (LT). In order to reduce the risk of developing lesions associated with acute and chronic antibody-mediated rejection in LT recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding pDSAs according to several mean fluorescence intensity (MFI) titer thresholds that have been previously reported to be relevant in LT. Among the 484 included LT candidates, 99 (20.5%) presented with anti-human leukocyte antibodies (HLAs). The predictive factors for anti-HLA sensitization were a history of previous kidney transplantation (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.30-1.9; P = 0.05), a history of previous LT (OR, 1.9; 95% CI, 1.6-2.1; P = 0.01), a history of blood transfusion (OR, 2.5; 95% CI, 2.2-4.1; P = 0.01), and a history of pregnancy (OR, 2.9; 95% CI, 2.4-3.3; P = 0.04). By applying a strategy of unacceptable mismatches for recipients with an antibody (Ab) MFI of > 5000, only 35 patients were affected (7% of the cohort), but 22 of these (63%) would have been considered incompatible with >50% of the donors. Using a MFI threshold of >10,000, only 16 patients were affected (1.4% of the cohort), but half of these would have been considered incompatible with >50% of the proposed donors. Considering only those with anti-class II Ab and a MFI >5000 and >10,000, respectively, 10/14 and 4/8 patients were considered incompatible with >50% of the donors. In conclusion, avoiding pDSAs affects a small but not negligible proportion of LT candidates. However, in these sensitive patients, avoiding pDSAs has the potential to significantly reduce the donor pool and, consequently, transplant accessibility. Liver Transplantation 23 880-886 2017 AASLD.
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http://dx.doi.org/10.1002/lt.24781DOI Listing
July 2017

[Therapeutic education in the transplant patient's pathway].

Rev Infirm 2016 Dec;65(226):31-33

Département de néphrologie, dialyse et transplantation d'organes, Hôpital Rangueil, 1, avenue Jean Poulhès, 31 059 Toulouse cedex 9, France.

The success of a transplant in the long term depends to a large extent on the taking of immunosuppressant treatments and its follow-up. Therapeutic education plays an important role in the follow-up of transplant patients and in nurses' daily practice. It is integrated into the patient's pre-transplant care.
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http://dx.doi.org/10.1016/j.revinf.2016.09.011DOI Listing
December 2016

Successful Transplantation in ABO- and HLA-Incompatible Living Kidney Transplant Patients: A Report on 12 Cases.

Ther Apher Dial 2016 Oct 13;20(5):507-516. Epub 2016 Apr 13.

CHU Rangueil, Nephrology, Dialysis, Transplantation, Toulouse, France.

Few studies have assessed the outcomes of ABOi/HLAi living-kidney transplantation. We report a single-center experience of 12 ABOi/HLAi living-kidney recipients. Twenty-seven donor-specific alloantibodies (DSAs) (1-6 per patient) were found with fluorescence intensities of 1500-15 000. Desensitization was based on IVIg, two doses of rituximab (375 mg/m ), tacrolimus-based (0.2 mg/kg) immunosuppression (started on day-10 pretransplant), and 11 (6-27) pretransplant apheresis sessions (plasmapheresis, specific or semi-specific immunoadsorption). By day 0, 17 of the 27 DSAs had become undetectable. After 19 (3-51) months, patient- and graft-survival rates were 100% and 91.6%, respectively. One patient had an acute humoral rejection whereas three had a chronic antibody-mediated rejection (CAMR). At the last follow-up, kidney biopsies were nearly normal in seven cases (58.3%) and renal function was excellent except for the three cases of CAMR. Four patients had a BK virus infection. We conclude that ABOi/HLAi living-kidney transplantation is a reasonable option for highly sensitized patients.
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http://dx.doi.org/10.1111/1744-9987.12408DOI Listing
October 2016

Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

J Gastroenterol Hepatol 2017 Apr;32(4):887-893

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Background And Aim: Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known.

Method: Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination.

Results: Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03).

Conclusion: In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection.
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http://dx.doi.org/10.1111/jgh.13613DOI Listing
April 2017

Treatment of large plasma volumes using specific immunoadsorption to desensitize ABO-incompatible kidney-transplant candidates.

J Nephropathol 2016 Jul 29;5(3):90-7. Epub 2016 Jun 29.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France ; Université Toulouse III Paul Sabatier, Toulouse, France ; INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France.

Background: ABO-incompatible (ABOi) kidney-transplantation has very good long-term results, i.e. similar to those observed for living-kidney ABO-compatible transplantation. This is because patients are desensitized at pretransplant using apheresis and rituximab therapy, with tacrolimus-based immunosuppression.

Objectives: To assess the efficacy of a single, pretransplant (Day -1), specific immunoadsorption session using Glycosorb® columns (anti-A or anti-B; Glycorex Sweden) to treat large volumes of plasma (up to 18 L).

Patients And Methods: Prospective single-center study evaluating 12 consecutive patients (6 males), aged 40 (23-59) years. Incompatibilities were A into 0 (8), B into 0 (3), and AB into 0 (1). Pretransplant desensitization relied on rituximab (D-30), tacrolimus, mycophenolic acid, and steroids (all started on D-13), and a single session of specific immunoadsorption on D-1. Immunoadsorption was coupled in tandem with a hemodialysis session.

Results: Overall, 15 L (11-18) of plasma were treated per patient, i.e., 0.2 (0.11-0.36 L/kg). Isoagglutinin titers were 1/16 (1/5-1/64) before the procedure, decreasing after 6 hours to 1/5 (1/1-1/16 P = 0.008), and to 1/2 (1/1-1/8; P = 0.05) at completion of the session. The next day, i.e., the day of transplantation, there was no rebound of isoagglutinins [1/4 (1/1-1/5); P = ns]. The procedure was well tolerated with no side-effects and no significant changes in hemoglobin level, platelet counts, fibrinogen, or albumin levels.

Conclusions: For ABOi kidney-transplantation, a single, longer, specific immunoadsorption session was very efficient at 1-day pre-transplantation with no rebound. These results should be confirmed when isoagglutinin titers are higher (≥120).
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http://dx.doi.org/10.15171/jnp.2016.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961822PMC
July 2016

A 3-month course of ciprofloxacin does not prevent BK virus replication in heavily immunosuppressed kidney-transplant patients.

J Clin Virol 2016 06 12;79:61-67. Epub 2016 Apr 12.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France; Université Paul Sabatier, Toulouse, France; INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France. Electronic address:

Background: In vitro and retrospective studies of kidney-transplant patients have shown that quinolones can efficiently prevent BK virus (BKV) replication. However, in a prospective study, a 3 month-course of levofloxacin did not decrease the rate of BK viruria in kidney-transplant patients treated with standard immunosuppression.

Objectives: The aim of this study was to assess the effect of a 3-month course of ciprofloxacin prophylaxis on BKV replication in kidney-transplant patients that had received heavy immunosuppression (plasma exchange or immunoadsorption and rituximab) to achieve desensitization before undergoing HLA- and/or ABO-incompatible (ABOi) transplantation.

Study Design: Twenty-nine patients were given ciprofloxacin (500mg/d) for 3 months, starting immediately after transplantation. The results were compared with results from a previous study where patients had received a similar immunosuppression regimen without ciprofloxacin prophylaxis (n=43). Around 60% of patients had undergone a retransplantation. After transplantation, all patients were given induction therapy, tacrolimus, mycophenolic acid and steroids. BK viruria and viremia were monitored at months 1, 3, 6 and 12 post-transplantation.

Results: The rates of BK viruria, BK viremia, and BKV-associated nephropathy did not differ between patients who were given or not given ciprofloxacin prophylaxis. These rates were also identical when patients received quinolones at any time within the first year after transplantation compared to those that had not. The rate of bacterial infection was also similar in patients who had or had not received ciprofloxacin.

Conclusion: The use of quinolones seemed to not have any beneficial effect in preventing BKV replication in kidney-transplant patients receiving heavy immunosuppression.
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http://dx.doi.org/10.1016/j.jcv.2016.04.004DOI Listing
June 2016

Early post-transplant complications following ABO-incompatible kidney transplantation.

J Nephropathol 2016 Jan 30;5(1):19-27. Epub 2015 Dec 30.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France ; INSERM U563, IFR-BMT, CHU Purpan, Toulouse, France ; Université Paul Sabatier, Toulouse, France.

Background: Living-kidney transplantation is increasing because of the scarcity of kidneys from deceased donors and the increasing numbers of patients on waiting lists for a kidney transplant. Living-kidney transplantation is now associated with increased long-term patient- and allograft-survival rates.

Objectives: The purpose of this retrospective study was to identify, in a cohort of 44 ABO-incompatible (ABOi) live-kidney transplant patients, the main complications that occurred within 6 months post-transplantation, and to compare these findings with those from 44 matched ABO-compatible (ABOc) live-kidney transplant patients who were also from our center.

Patients And Methods: This single-center retrospective study assessed post-transplantation complications in 44 ABO-i versus 44 matched ABO-c patients. All patients were comparable at baseline except that ABO-i patients had greater immunological risks.

Results: During the 6-month post-transplant period, more ABO-i patients presented with postoperative bleeds, thus requiring significantly more blood transfusions. Bleeds were associated with significantly lower values of fibrinogen, platelets, prothrombin time, and hemoglobin levels. Surgical complications, patient- and graft-survival rates, and kidney-function statuses were similar between both groups at 6 months post-transplantation.

Conclusions: We conclude that impairment of hemostatic factors at pre-transplant explained the increased risk of a post-transplant bleed in ABO-i patients.
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http://dx.doi.org/10.15171/jnp.2016.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790183PMC
January 2016

Successful pregnancy after ABO-incompatible kidney transplantation.

Transpl Int 2016 Apr 29;29(4):506-7. Epub 2015 Dec 29.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

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http://dx.doi.org/10.1111/tri.12724DOI Listing
April 2016

Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia.

Transpl Int 2016 Mar 16;29(3):315-22. Epub 2015 Dec 16.

Department of Nephrology and Organ Transplantation, University Hospital, Toulouse, France.

Immunosuppression using everolimus (EVR) plus low-dose tacrolimus (Tac) is commonly used in organ transplantation. EVR has potential antiviral effects. Herein, the long-term outcomes and impacts of Tac-EVR on the BK virus are reported in ABO-incompatible kidney-transplant recipients. The initial immunosuppressive regimen combined steroids, Tac, and mycophenolic acid (MPA). At a median of 141 (34-529) days post-transplantation, seven stable ABO-incompatible kidney-transplant recipients were converted from MPA to EVR because of active BK replication, and compared with a reference group of fourteen ABO-incompatible patients receiving classical Tac plus MPA. At 1 month before conversion, at 1, 3 months after, and at last follow-up, clinical and biological parameters were monitored. The median time from conversion to the last follow-up was 784 (398-866) days. Conversion to EVR caused no change to rejection episodes or immunological status (isoagglutinin titers, anti-HLA antibodies). At last follow-up, median eGFR was similar in the Tac-MPA versus Tac-EVR group (40 [range: 14-56] vs. 54.5 ml/min/1.73 m(2) [range: 0-128], P = 0.07). The major adverse event was dyslipidemia. Interestingly, conversion from MPA to EVR decreased BK viral load in five patients. ABO-incompatible kidney-transplant recipients with an active BK virus infection may benefit from conversion to EVR.
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http://dx.doi.org/10.1111/tri.12718DOI Listing
March 2016

Calcineurin Inhibitors Downregulate HNF-1β and May Affect the Outcome of HNF1B Patients After Renal Transplantation.

Transplantation 2016 Sep;100(9):1970-8

1 Département de Néphrologie et Transplantation d'organes, Centre de reference des maladies rénales rares, Hôpital Rangueil, CHU, Toulouse, France. 2 INSERM U1048 (I2MC, équipe 12), Hôpital Rangueil, Toulouse, France. 3 Service de Néphrologie, Cliniques Universitaires Saint-Luc, Louvain, Belgique. 4 Service de Néphrologie, Médecine interne, Hôpital des Enfants, CHU, Toulouse, France. 5 Service de Néphrologie-Transplantation, Hôpital Huriez, CHRU, Lille, France. 6 Service de Néphrologie-Transplantation, Hôpital Lapeyronie, CHU, Montpellier, France. 7 Service de Néphrologie-Transplantation Pédiatrique, CHU, Hôtel-Dieu, Nantes, France. 8 Service de Néphrologie-Transplantation, Hôpital Pellegrin, CHU, Bordeaux, France. 9 University of Zürich, Institute of Physiology, Zürich Centre for Integrative Human Physiology (ZIHP), Zürich, Switzerland. 10 Service de Diabétologie, Hôpital Rangueil, CHU Toulouse, France. 11 Service de Génétique Médicale, Hôpital Purpan, CHU Toulouse, France.

Background: Patients with HNF1B mutations develop progressive chronic renal failure, diabetes mellitus (40-50%), and liver tests abnormalities (40-70%). In HNF1B patients who reach end-stage renal disease, single kidney transplantation (SKT) or combined kidney-pancreas transplantation can be considered.

Methods: A retrospective multicenter study including 18 HNF1B patients receiving SKT or kidney-pancreas transplantation, and in vitro experiments including the characterization of the HNF1B expression after calcineurin inhibitor (CNI) exposure.

Results: After SKT, 50% of the HNF1B patients develop early posttransplantation diabetes mellitus, whereas 40% experience new-onset or severe worsening of preexisting abnormalities of liver tests, including severe cholestasis. In liver biopsies, disorders of the cholangiocytes primary cilium and various degrees of bile duct paucity and dysplasia were identified. In vitro studies combining CNI exposure and siRNA-mediated inhibition of NFATc revealed that calcineurin inhibition decreases HNF1B expression in epithelial cells but independent of NFATc.

Conclusions: Because HNF1B-related disease is a heterozygous condition, CNIs used to prevent rejection may induce reduced expression of the nonmutated allele of HNF1B leading to a superimposed defect of HNF-1β transcriptional activity. Taking into account the specific risk of posttransplantation diabetes mellitus and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach.
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http://dx.doi.org/10.1097/TP.0000000000000993DOI Listing
September 2016

De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant patients.

Transpl Int 2015 Dec;28(12):1371-82

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR.
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http://dx.doi.org/10.1111/tri.12654DOI Listing
December 2015

An Early Viral Response Predicts the Virological Response to Ribavirin in Hepatitis E Virus Organ Transplant Patients.

Transplantation 2015 Oct;99(10):2124-31

1 Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France. 2 INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France. 3 Université Paul Sabatier, Toulouse, France. 4 Laboratory of Virology, CHU Purpan, Toulouse, France. 5 Department of Thoracic Surgery and Lung Transplantation, CHU Rangueil-Larrey, Toulouse, France. 6 Pediatric Hepatology, Hôpital des enfants, Toulouse, France. 7 Laboratory of Toxicology, CHU Purpan, Toulouse, France.

Background: Ribavirin is efficient at treating chronic hepatitis E virus infection in solid-organ transplant patients. However, the early kinetics of viral replication under therapy and the impact of immunosuppressant regimens on viral replication are unknown: thus, determining the aim of our study.

Methods: Thirty-five patients with a solid-organ transplant and chronic hepatitis E virus infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA concentrations were determined before treatment, at days 7, 15, and 21 and at months 1, 2, and 3 during therapy and after ribavirin cessation.

Results: A sustained virological response (SVR) occurred in 63%. Decreased viral concentration within the first week post-ribavirin therapy was an independent predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL or greater had an 88% positive predictive value. No correlation between ribavirin trough level on day 7 or at month 2 with a virological response or an SVR was observed. Before therapy, HEV RNA concentration was significantly greater in patients receiving mechanistic target of rapamycin inhibitor-based immunosuppression compared to patients given calcineurin inhibitors. The use of mycophenolic acid did not impact on the response to ribavirin.

Conclusion: An early response to ribavirin can be used to define the optimal duration of therapy in the setting of HEV infection.
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http://dx.doi.org/10.1097/TP.0000000000000850DOI Listing
October 2015

Pretransplant urinary proteome analysis does not predict development of chronic kidney disease after liver transplantation.

Liver Int 2015 Jul 20;35(7):1893-901. Epub 2015 Jan 20.

Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France.

Background & Aims: Chronic kidney disease (CKD) is a common complication after liver transplantation. Kidney biopsies cannot be easily performed before liver transplantation to predict patients at high risk for CKD. The aim of our study was to determine whether pre-, peri- and post-transplant factors, as well as peptides present in preliver transplant urine samples were associated with loss in kidney function at 6 months post-transplantation using proteome analysis.

Methods: Eighty patients who underwent a liver transplantation and that had pretransplant glomerular filtration rate (GFR) value of ≥60 mL/min/1.73 m² (MDRD) were included in the study.

Results: GFR decreased significantly after transplantation. At month 6 post-transplantation, 40 patients displayed a CKD, i.e. eGFR of <60 mL/min/1.73 m², while the other 40 patients did not. Although thousands of peptides were identified, none was significantly associated with the development of CKD at 6 months after liver transplantation. Moreover, using a urinary peptidome classifier to detect preexisting CKD, no difference was found in CKD scores between the 2 groups. After analysis of a large number of pre-, peri- and post-transplant parameters, viral hepatitis as a cause for liver transplantation was the sole independent predictive factor for CKD. No difference in peptides with differential urinary abundance between patients who received a graft for virus related liver disease vs. all other causes of liver disease was observed.

Conclusion: Urinary peptidome analysis before liver transplantation failed to identify a peptide pattern associated with the development of CKD at 6 months after liver transplantation.
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http://dx.doi.org/10.1111/liv.12763DOI Listing
July 2015

Beneficial effect of conversion to belatacept in kidney-transplant patients with a low glomerular-filtration rate.

Case Rep Transplant 2014 18;2014:190516. Epub 2014 May 18.

Department of Nephrology and Organ Transplantation, CHU Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France ; Université Paul Sabatier, 31062 Toulouse, France ; INSERM U1043, IFR-BMT, CHU Purpan, 31059 Toulouse, France.

Belatacept has been found to be efficient at preserving good kidney function in maintenance kidney-transplant patients. Herein, we report on the use of belatacept as a rescue therapy for two kidney-transplant patients presenting with severe adverse events after treatment with calcineurin inhibitors (CNIs) and mammalian target-of-rapamycin (mTOR) inhibitors. Two kidney-transplant patients developed severely impaired kidney function after receiving CNIs. The use of everolimus was associated with severe angioedema. Belatacept was then successfully used to improve kidney function in both cases, even though estimated glomerular-filtration rate before conversion was <20 mL/min. These case reports show that belatacept can be used as a rescue therapy, even if kidney function is very low in kidney-transplant patients who cannot tolerate CNIs and/or mTOR inhibitors.
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http://dx.doi.org/10.1155/2014/190516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052196PMC
June 2014