Sophie Girerd

Université de Lorraine

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Nicolas Girerd

Inserm

Luc Frimat

Université de Lorraine

Frédéric Jaisser

Université Paris Cité

Kévin Duarte

French Clinical Research Infrastructure Network

Alice Aarnink

Centre Hospitalier Régional et Universitaire de Nancy

Johan Schikowski

Centre Hospitalier Régional et Universitaire de Nancy

Jonatan Barrera‐Chimal

Université de Montréal

Patrick Rossignol

Université de Lorraine

Zohra Lamiral

Centre d'Investigation Clinique Pierre Drouin

Madonna Salib

Centre d'Investigation Clinique Pierre Drouin

Cooperative Institutions

Inserm

RELX Group (United States)

Centre Hospitalier Régional et Universitaire de Nancy

Université de Lorraine

French Clinical Research Infrastructure Network

Défaillance Cardiovasculaire Aiguë et Chronique

Centre d'Investigation Clinique Pierre Drouin

Université Paris Cité

Heidelberg University

Harvard University

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Arteriovenous fistula thrombosis is associated with increased all-cause and cardiovascular mortality in haemodialysis patients from the AURORA trial

Clinical Kidney Journal (2019)

Sophie Girerd Nicolas Girerd Luc Frimat Hallvard Holdaas Alan G. Jardine

The impact of arteriovenous fistula (AVF) or graft (AVG) thrombosis on mortality has been sparsely studied. This study investigated the association between AVF/AVG thrombosis and all-cause and cardiovascular mortality.The data from 2439 patients with AVF or AVG undergoing maintenance haemodialysis (HD) included in the A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events trial (AURORA) were analysed using a time-dependent Cox model. The incidence of vascular access (VA) thrombosis was a pre-specified secondary outcome.During follow-up, 278 AVF and 94 AVG thromboses were documented. VA was restored at 22 ± 64 days after thrombosis (27 patients had no restoration with subsequent permanent central catheter). In multivariable survival analysis adjusted for potential confounders, the occurrence of AVF/AVG thrombosis was associated with increased early and late all-cause mortality, with a more pronounced association with early all-cause mortality {hazard ratio [HR] < 90 days 2.70 [95% confidence interval (CI) 1.83-3.97], P < 0.001; HR > 90 days 1.47 [1.20-1.80], P < 0.001}. In addition, the occurrence of AVF thrombosis was significantly associated with higher all-cause mortality, whether VA was restored within 7 days [HR 1.34 (95% CI 1.02-1.75), P = 0.036] or later than 7 days [HR 1.81 (95% CI 1.29-2.53), P = 0.001].AVF/AVG thrombosis should be considered as a major clinical event since it is strongly associated with increased mortality in patients on maintenance HD, especially in the first 90 days after the event and when access restoration occurs >7 days after thrombosis. Clinicians should pay particular attention to the timing of VA restoration and the management of these patients during this high-risk period. The potential benefit of targeting overall patient risk with more aggressive treatment after AVF/AVG restoration should be further explored.

10.1093/ckj/sfz048

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Citations (52)

Mineralocorticoid receptor antagonists in kidney transplantation: time to consider?

Nephrology Dialysis Transplantation (2018)

Sophie Girerd Frédéric Jaisser

Although patient survival is significantly improved by kidney transplantation (KT) in comparison with dialysis, it remains significantly lower than that observed in the general population. Graft function is one of the major determinants of patient survival after KT. Mineralocorticoid receptor antagonists (MRAs) could be of particular interest in this population to improve graft function and treat or prevent cardiovascular (CV) complications. In KT, ischaemia/reperfusion injury is a major factor involved in delayed graft function, which is often associated with inferior long-term graft survival. Preclinical studies suggest that MRAs may prevent ischaemia/reperfusion-related lesions in addition to having a protective effect in preventing calcineurin inhibitor-induced nephrotoxicity. Clinical data also support the anti-proteinuric effect of MRAs in chronic kidney disease (CKD). Taken together, MRAs may hence be of particular benefit in improving short- and long-term graft function. Numerous randomized controlled trials (RCTs) have shown the efficacy of MRAs in both heart failure and resistant hypertension. As these comorbidities are frequent in kidney transplant recipients before transplantation or during follow-up, MRAs could represent a useful therapeutic option in those with mild renal function impairment. However, CKD patients are under-represented in RCTs and the CV effects of MRAs in kidney transplant recipients have yet to be specifically assessed in large-scale trials. Available evidence indicates a good safety profile for MRAs in patients with a glomerular filtration rate (GFR) >30 mL/min/1.73 m2. However, as for all patients prescribed an MRA, creatinine and potassium should also be closely monitored following MRA initiation in kidney transplant patients. Given the current evidence suggesting that MRAs prevent ischaemia/reperfusion-related lesions and calcineurin inhibitor-induced nephrotoxicity in kidney transplant recipients as well as CV events in patients at high risk of CV complications (such as those in kidney transplant recipients), trials are urgently needed to fully assess the clinical impact of MRA use in this population.

MRAS

Eplerenone

10.1093/ndt/gfy065

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Citations (11)

Un cas de vascularite à anti-MPO positifs sous Enbrel® avec des dépôts de C3 isolés

Néphrologie & Thérapeutique (2015)

Fleuria Meibody J. Champigneulle Éric Rondeau L. Guillevin Véronique Frémeaux‐Bacchi

10.1016/j.nephro.2015.07.253

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Nonepithelial mineralocorticoid receptor activation as a determinant of kidney disease

Kidney International Supplements (2022)

Toshifumi Nakamura Sophie Girerd Frédéric Jaisser Jonatan Barrera‐Chimal

Homeostasis

Knockout mouse

Mineralocorticoid

Cell type

10.1016/j.kisu.2021.11.004

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Citations (26)

Association between Long-Term Change in Arterial Stiffness and Cardiovascular Outcomes in Kidney Transplant Recipients: Insights from the TRANSARTE Study

Journal of Clinical Medicine (2022)

Madonna Salib Arnaud Simon Nicolas Girerd Anna Kearney‐Schwartz Patrick Rossignol

(1) Background: Increased arterial stiffness is associated with cardiovascular (CV) diseases in end-stage renal disease (ESRD) patients, and CV mortality remains higher in kidney transplantation (KT) recipients compared to in the general population. KT is associated with an improvement in arterial stiffness in the early post-transplant period, followed by a potential re-worsening in the late period. In a cohort of KT patients, we evaluated the associations of pulse-wave velocity (PWV) measured at different time-points (pre-transplant, and early and late post-transplant periods) with CV morbi-mortality, as well as the evolution between these measurements with CV morbi-mortality. (2) Methods: Forty KT recipients with a 10-year follow-up were included. The association of PWV with CV events was assessed with multivariable cox analysis. Backward linear regressions were conducted to identify the determinants of PWV at 1 year and those of the long-term evolution of PWV after KT (delta PWV at 1 year—latest PWV). (3) Results: The absence of arterial stiffening during the long-term follow-up after KT is associated with a lower CV outcome rate (HR for the delta PWV = 0.76 (0.58–0.98), p = 0.036). Age at KT is associated with the worsening of arterial stiffness in the late post-transplantation period (β for the delta PWV = −0.104, p = 0.031). A high PWV at 1 year was associated with a potential for recovery during follow-up (β = 0.744, p < 0.0001). (4) Conclusions: The absence of PWV worsening in the late post-transplantation period was significantly associated with a lower risk of CV events, whereas early changes in PWV were not. Finding an intervention capable of reducing long-term PWV could improve the prognosis of KT recipients.

10.3390/jcm11051410

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Which is the best predictor of de novo donor‐specific antibodies in a cohort of non‐sensitized first kidney transplantation: Antigenic, allelic, epitope, or physiochemical HLA mismatches?

Clinical Transplantation (2019)

Alexandra Delion Sophie Girerd Kévin Duarte Nicolas Girerd Johan Schikowski

Assessment of human leukocyte antigen (HLA) matching by using high-resolution allele typing and knowledge of HLA molecule structure may lead to better prediction of de novo donor-specific antibody (dnDSA) development.We conducted a single-center cohort study among 150 non-sensitized first kidney transplant recipients to compare the association between antigenic (Ag), allelic (Al), eplet (Ep), amino acid (AAMS) HLA matching and electrostatic (EMS) and hydrophobic (HMS) mismatch scores, and the development of dnDSA.After a mean follow-up time of 49.3 ± 17.7 months, 18 patients (12%) developed dnDSA. The number of HLA mismatches (MM) was significantly associated with the development of dnDSA. The optimal threshold, determined by Harrell's C-index, varied according to the method (5 MM for Ag, P = 0.006; 6 for Al, P = 0.009; 22 for Ep, P = 0.005; 42 for AAMS, P = 0.0007; 45 for EMS, P = 0.009 and 44 for HMS, P = 0.026). C-indices were similar for all matching approaches, suggesting a similar prediction of dnDSA development.In this cohort of low immunological risk transplant patients, the use of Al or Ep matching did not improve the prediction of dnDSA development in comparison with the traditional approach.

Donor-Specific Antibodies

Histocompatibility

10.1111/ctr.13508

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Citations (5)

Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014

BMC Nephrology (2018)

Sophie Girerd Johan Schikowski Nicolas Girerd Kévin Duarte Hélène Busby

In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6–8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

Immunosuppression

Nephrology

10.1186/s12882-018-1014-2

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Citations (22)

Cardiovascular Comorbidities Are the Main Predictors of Cardiac Reverse Remodeling following Kidney Transplantation

Cardiology (2020)

Masatake Kobayashi Olivier Huttin Johan Schikowski Erwan Bozec Zohra Lamiral

End-stage renal disease is associated with cardiac remodeling, which is partly reversible after kidney transplantation (KT). We aimed to determine the association of cardiovascular comorbidities or kidney-related factors with cardiac reverse remodeling after KT.We performed echocardiography in 56 patients (aged 48 ± 15 years, mean ± SD) before and 24 months after undergoing their first KT. Echocardiograms were reviewed using a standardized process with blinding for the patient characteristics and evaluation timing. Multivariable linear regression analysis was used to evaluate the association between comorbidities and changes in cardiac structure and systolic/diastolic function.Left ventricular mass index (LVMI) and diastolic parameters did not change significantly, while left ventricular ejection fraction (LVEF) increased from 63.9 to 69.6% (p = 0.046). Multivariable analysis revealed associations of histories of valvular heart disease with a smaller reduction in LVMI (β = -27.3, p = 0.04), of coronary artery disease or heart failure with a smaller increase in LVEF (β = 7.17, p = 0.02), and of diabetes mellitus with less improvement in E wave (β = -0.19, p = 0.05), e' (β = 4.15, p = 0.046), and E/e' (β = -5.00, p < 0.01).Cardiovascular comorbidities were -associated with less improvement in cardiac structure and function following KT. Our findings suggest that patients with CV comorbidities may experience limited "favorable" reverse cardiac remodeling following KT.

Ventricular remodeling

10.1159/000504381

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Citations (7)

Potassium canrenoate in brain-dead organ donors: a randomised controlled clinical trial protocol (CANREO-PMO)

BMJ Open (2023)

Lilia Belarif Sophie Girerd Frédéric Jaisser Xavier Lepage Ludovic Mercklé

Ischaemia/reperfusion injuries (IRIs) are associated with poorer survival of kidney grafts from expanded criteria donors. Preclinical studies have shown that mineralocorticoid receptor antagonists (MRAs) prevent acute and chronic post-ischaemic renal dysfunction by limiting IRI. However, data concerning the safety of MRAs in brain-dead donor patients are scarce. We seek to investigate the tolerance of MRAs on the haemodynamics in this population.

10.1136/bmjopen-2023-073831

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Citations (1)

Long-term follow-up of corticosteroid refractory acute GVHD treated with an Inolimomab-based algorithm: a single center experience

Bone Marrow Transplantation (2013)

Sophie Girerd M. Renaud Joëlle Guilhot Christine Giraud R Larchée

Refractory (planetary science)

Single Center

Immunosuppression

10.1038/bmt.2013.16

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Citations (9)