Mehdi Maanaoui

Centre Hospitalier Régional Universitaire de Lille · Nephrology Service

The growing disparity between the demand for transplants and the available donor supply, coupled with an aging donor population and increasing prevalence of chronic diseases, highlights the urgent need for the development of platforms enabling reconditioning, repair, and regeneration of deceased donor organs. This necessitates the ability to preser...

Background Efficacy and safety of belatacept have not been specifically reported for kidney transplantations from donors after circulatory death. Methods In this retrospective multicenter paired kidney study, we compared the outcome of kidney transplantations with a belatacept-based to a calcineurin inhibitor (CNI)-based immunosuppression. We incl...

Although their efficacy has been well-established in Oncology, the use of platinum salts remains limited due to the occurrence of acute kidney injury (AKI). Caffeine has been suggested as a potential pathophysiological actor of platinum-salt-induced AKI, through its hemodynamic effects. This work aims to study the association between caffeine consu...

Background The benefit of extracorporeal photopheresis on the course of kidney transplant rejection is unknown. The aim of our study was to investigate the variations in transcriptomics on graft biopsies when extracorporeal photopheresis was used to treat chronic humoral rejection after kidney transplantation. Methods We retrospectively analyzed t...

Type 2 diabetes (T2D) is a common comorbidity in kidney transplant recipients, representing a significant proportion of the candidate pool. Post-kidney transplantation management of T2D remains challenging, leading to inferior long-term outcomes compared to non-diabetic recipients. This study aimed to assess the association between Homeostatic Mode...

In islet transplantation (ITx), primary graft function (PGF) or beta cell function measured early after last infusion is closely associated with long term clinical outcomes. We investigated the association between PGF and 5 year insulin independence rate in ITx and pancreas transplantation (PTx) recipients. This retrospective multicenter study incl...

Background Despite the increasing number of biomarker studies published in the transplant literature over the past 20 years, demonstrations of their clinical benefit and their implementation in routine clinical practice are lacking. We hypothesized that suboptimal design, data, methodology and reporting might contribute to this phenomenon. Methods...

Given the risk of rejection, the presence of preformed donor specific antibodies (DSA) contraindicates transplantation in most allocation systems. However, HLA-Cw and -DP DSA escape this censorship. We performed a multicentric observational study, in which the objective was to determinate risk factors of acute antibody-mediated rejection (aABMR) in...

Although thrombotic thrombocytopenic purpura frequently affects women of childbearing age, there is no clear recommendation for the management of subsequent pregnancies in women with established thrombotic thrombocytopenic purpura. This single-center, retrospective, observational study included all women with hereditary thrombotic thrombocytopenic...

We describe the case of a 66-year-old woman treated with tyrosine kinase inhibitor Lenvatinib for thyroid carcinoma who had persistent proteinuria above 2 g/24 h despite maximal dose of angiotensin-converting enzyme inhibitor. We initiated a treatment with SGLT2 inhibitor Dapagliflozin. Three months after Dapagliflozin initiation, her proteinuria d...

Background and Aims The great phenotypic heterogeneity in the presentation of kidney diseases makes the diagnostic strategy all the more complex in the elderly. While kidney biopsy should play a pivotal role, its non-negligible risk of bleeding complications (2-5% in the general population) justifies a certain reluctance to its application in the e...

Background and Aims Islet transplantation is associated with a benefit on glycaemic control compared to optimized insulin therapy in recent clinical trials. However, there is a lack of evidence concerning the long-term impact of islet transplantation on type 1 diabetic kidney transplant recipients’ prognosis. Method Every type 1 diabetic recipient...

Background and Aims Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high allograft recurrence. However, recent advances in biotherapies, especially anti-IL-1 treatments, may have improved patients’ outcome in the transplantation setting. Method We conducted a retrospective...

Unlabelled: Severe or repeated hypoglycemia events may favor memory complaints in type 1 diabetes (T1D). Pancreatic islet transplantation (IT) is an alternative option to exogenous insulin therapy in case of labile T1D, implying a maintenance immunosuppression regimen based on sirolimus or mycophenolate, associated with tacrolimus, that may also h...

The ability to preserve metabolically active kidneys ex vivo for multiple days may permit reconditioning, repair and regeneration of deceased donor kidneys. However, the kidneys high metabolic demand limits its functional preservation. Current approaches focus on normothermic machine perfusion (NMP) at 37°C or hypothermic machine perfusion (HMP) at...

The complement system plays a key role in the pathophysiology of kidney thrombotic microangiopathies (TMA), as illustrated by atypical hemolytic uremic syndrome. But complement abnormalities are not the only drivers of TMA lesions. Among other potential pathophysiological actors, we hypothesized that alteration of heparan sulfate (HS) in the endoth...

Background: Allogeneic islet transplantation is a validated therapy in type 1 diabetes; however, there is decline of transplanted islet graft function over time and the mechanisms underlying this decline are unclear. We evaluated the distinct association between primary graft function (PGF) and 5-year islet transplantation outcomes. Methods: In...

Introduction L’insuffisance rénale aiguë du donneur (IRAd) est un facteur de risque de perte de greffon lorsque la créatinine de base est définie par une rétro-estimation pour un débit de filtration glomérulaire à 75 mL/min/1,73 m² selon l’équation MDRD. Bien que l’IRAd soit associée à une moins bonne survie du greffon, cela ne constitue pas une ju...

Islet transplantation is a unique paradigm in organ transplantation, since multiple donors are required to achieve complete insulin-independence. Preformed or de novo Donor Specific Antibodies (DSA) may target one or several donor islets, which adds complexity to the analysis of their impact. Adult patients with type 1 diabetes transplanted with pa...

Points essentiels La transplantation rénale concerne des patients pouvant être fragiles, comorbides et à risque de morbidité voire de mortalité en post-greffe. La recherche et l’identification de facteurs de risque de complications en post-transplantation peuvent aboutir à la mise en contre-indication à la greffe soit définitive, soit temporaire. A...

BACKGROUND AND AIMS The complement system plays a key role in the pathophysiology of renal thrombotic microangiopathies (TMA), as illustrated by atypical hemolytic uremic syndrome (HUS) characterized by a high rate of mutations in complement proteins. However, complement abnormalities are not fully sufficient to drive to TMA lesions. Among other su...

The association between blood transfusion and the occurrence of de novo HLA donor specific antibodies (DSA) after kidney transplantation remains controversial. In this single-center observational study, we examined the association between early blood transfusion, i.e. before 1-month post-transplantation, and the risk of DSA occurrence, using Lumine...

The pharmacokinetic variability of tacrolimus can be partly explained by CYP3A5 activity. Our objective was to evaluate a tacrolimus sparing policy on renal graft outcome according to CYP3A5 6986A>G genetic polymorphism. This retrospective study included 1114 recipients with a median follow-up of 6.3 years. Genotyping of the 6986A>G allelic variant...

Introduction Le complément joue un rôle clef dans la physiopathologie des microangiopathies thrombotiques (MAT), comme l’illustre le syndrome hémolytique et urémique atypique. De pénétrance variable, les anomalies de régulation du complément ne sont cependant que des facteurs de susceptibilité, sous-entendant d’autres acteurs. Parmi eux, le glycoca...

Solid organ transplantation is marked by accelerated aging and inexorable fibrosis. It is crucial to promote strategies to attenuate, or to reverse, damage before organ failure. Hence, the objective of this article is to provide insight into strategies, which aim to regenerate or rejuvenate the transplanted organs. Cell therapy with mesenchymal str...

Rationale & Objective While deceased donor acute kidney injury (AKI) frequently leads to kidney discards, its impact on long-term graft survival in kidney transplant recipients remains unclear. We investigated the association between deceased donor AKI assessed using back-estimation of baseline serum creatinine (Scr) and graft survival. Study Desi...

As the use of elderly kidney donors for transplantation is increasing with time, there is a need to understand which factors impact on their prognosis. No data exist on the impact of an impaired renal function (IRF) in such population. 116 kidney recipients from deceased kidney donors over 70 years were included from 2005 to 2015 in a single-center...

Primary focal and segmental glomerulosclerosis (pFSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, eight months after early pFSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure...

The association between acute graft pyelonephritis (AGPN) and graft failure in kidney transplant recipients (KTR) remains controversial. In this single‐center observational study, we aimed to assess the incidence of AGPN as a time‐dependent post‐transplantation event. We also examined the association between the diagnosis of AGPN and graft outcomes...

A correction to this paper has been published: https://doi.org/10.1007/s40620-021-01038-6

Résumé Afin de pallier le déficit en organes, la transplantation à partir de donneurs très âgés, notamment de plus de 70 ans, est de plus en plus fréquente. Comparativement aux États-Unis, où ces greffons représentent 5 % de la population des donneurs, la France se démarque par une utilisation croissante de ces reins, jusqu’à dépasser 20 %. Cependa...

Introduction Le Syndrome Hémolytique et Urémique (SHU) atypique est associé dans 50–60 % des cas à des anomalies de la voie alterne du complément (VAC). De pénétrance variable, les mutations identifiées ne sont cependant que des facteurs de susceptibilité, sous-entendant d’autres acteurs. Parmi eux, le glycocalyx endothélial, dont les héparanes sul...

Background and Aims Acute kidney injury (AKI) during organ procurement represents an important cause of discarded kidneys. In the context of organ shortage, the evaluation of such grafts is needed in order to enlarge the donor pool. Although many studies showed an increased risk of delayed graft function when donors present with AKI, long-term impa...

Background and Aims Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy still nowadays associated with a high risk of death. Standards of care included at first the association of plasmatic exchanges, Rituximab and steroids. The emergence of Caplacizumab, a nanobody targeting the A1 receptor of Von Willebrand Factor...

Background and Aims In patients with type 1 diabetes and end-stage renal disease, kidney transplantation improves both quality of life and survival. When simultaneous kidney-pancreas transplantation appears too invasive, or after failure of the pancreatic graft, an islet after kidney transplantation (IAK) may be considered to restore a stable endoc...

Background and Aims Caplacizumab, a bivalent Nanobody, targets the A1 domain of von Willebrand Factor, inhibiting the interaction between ultra-large vWF and platelets in the treament of Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Results of the Phase 3 HERCULES study confirm that treatment with caplacizumab reduces the time to platelet co...

HHV‐6A can be inherited and chromosomally integrated (iciHHV‐6A), and donor to recipient transmission has been reported in solid‐organ transplantation. However, when HHV‐6A reactivation happens after transplantation, the source of HHV‐6A is often not evident and its pathogenicity remains unclear. Here, we present an exhaustive case of donor‐to‐reci...

Abstract Caveolin-1 is a protein (encoded by the CAV1 gene) supposedly harboring a protective effect against fibrosis. CAV1 rs4730751 single nucleotide polymorphism (SNP) AA genotype was initially associated with lower graft survival compared to non-AA. However, subsequent studies could not find the same effect. CAV1 rs4730751 SNP was investigated...

Introduction Reference intervals (RIs) for complement assays in EDTA plasma samples have not previously been published. The objectives of the present study were to validate and/or determine RIs for classical pathway (CP50) activity and C3c, C4 and C1 inhibitor protein (C1INH) assays and to assess the need for age-specific RIs in EDTA plasma. Mater...

Introduction L’évérolimus est un inhibiteur de la voie des mtor utilisé en transplantation rénale comme traitement antirejet. Son utilisation semble associée à un état biologique procoagulant. L’objectif de ce travail est d’évaluer l’impact de l’utilisation d’évérolimus sur la survenue de maladie thrombo-embolique veineuse (MTEV) dans la population...

Purpose Cisplatin-induced acute kidney injury (CIA) is a serious adverse event that affects 20–40% of exposed patients, despite any implemented precaution to avoid it. The aim of this work was therefore to identify a relevant nephroprotective method for CIA. Methods We searched Pubmed, Embase, and Web of Science from 1 January 1978 to 1 June 2018,...

We read with interest the article by Reischig et al. 1, dealing with the risk of BK polyomavirus viremia (BKv) and nephropathy (PVAN) related to cytomegalovirus (CMV) prevention strategies. This study combined two randomized studies2,3 which compared prophylactic valgancyclovir versus high‐dose valacyclovir and preemptive valgancyclovir versus high...

Eculizumab therapy has greatly enhanced the prognosis of uncontrolled complement activation-related diseases such as paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome (aHUS), and C3 glomerulopathies (C3G). Therapeutic monitoring by eculizumab concentration measurement is not widely available, and efficacy assessment is mostly...

Background: Tacrolimus exhibits pharmacokinetics variability partly explained by CYP3A5 activity. In contrast to *3/*3 genotype, those carrying at least one CYP3A5*1 allele exhibit higher enzyme activity leading to lower Tac trough blood level despite higher daily dose. In this study, we aimed to evaluate the impact of CYP3A5 polymorphism on renal...

The bioengineering of a replacement kidney has been proposed as an approach to address the growing shortage of donor kidneys for the treatment of chronic kidney disease. One approach being investigated is the recellularization of kidney scaffolds. In this study, we present several key advances towards successful re‐endothelialization of whole kidne...

Introduction L’utilisation de reins issus de donneurs âgés est une option intéressante pour accroître le pool d’organes. L’objectif de l’étude est d’évaluer le pronostic des transplantés rénaux de donneurs cadavériques de plus de 70 ans. Patients/Matériels et méthodes Les greffes rénales de donneurs cadavériques de plus de 70 ans ont été incluses...

Objectif : L’insuffisance rénale aiguë (IRA) liée au cisplatine est un effet indésirable grave, qui touche 30 à 40% des patients traités. A ce jour, aucune méthode de prévention n’a fait preuve d’une efficacité indiscutable. Néanmoins, le magnésium semble jouer un rôle néphroprotecteur par le biais de son action sur le récepteur tubulaire OCT2 (Org...

Senescence phenotype of endothelial cells (ECs) has pathophysiological consequences, such as decreased regeneration capacity, pro-atherogenic tendency and dysregulated vessel tune. We find that netrin 4 (NTN4), recognized in neural and vascular development, is highly expressed by mature ECs. Remarkably, little is known about its role in vascular bi...

Rationale BRAF and MEK inhibitors have significantly improved the prognosis of metastatic melanoma, by inhibiting both the mitogen-activated protein kinase (MAP-kinase) pathway. They are associated with infrequent adverse kidney events. Most of these are related to the use of BRAF inhibitors and involve interstitial nephritis with acute tubular nec...