Publications by authors named "Melanie Hanoy"

12 Publications

  • Page 1 of 1

T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic.

Am J Transplant 2021 02 6;21(2):854-863. Epub 2020 Nov 6.

Department of Nephrology, Transplantation and hemodialysis, Rouen University Hospital, Rouen, France.

Immunosuppressed organ-transplanted patients are considered at risk for severe forms of COVID-19. Moreover, exaggerated innate and adaptive immune responses might be involved in severe progression of the disease. However, no data on the immune response to SARS-CoV-2 in transplanted patients are currently available. Here, we report the first assessment of antibody and T cell responses to SARS-CoV-2 in 11 kidney-transplanted patients recovered from RT-PCR-confirmed (n = 5) or initially suspected (n = 6) COVID-19. After reduction of immunosuppressive therapy, RT-PCR-confirmed COVID-19 transplant patients were able to mount vigorous antiviral T cell and antibody responses, as efficiently as two nontherapeutically immunosuppressed COVID-19 patients on hemodialysis. By contrast, six RT-PCR-negative patients displayed no antibody response. Among them, three showed very low numbers of SARS-CoV-2-reactive T cells, whereas no T cell response was detected in the other three, potentially ruling out COVID-19 diagnosis. Low levels of T cell reactivity to SARS-CoV-2 were also detected in seronegative healthy controls without known exposure to the virus. These results suggest that during COVID-19, monitoring both T cell and serological immunity might be helpful for the differential diagnosis of COVID-19 but are also needed to evaluate a potential role of antiviral T cells in the development of severe forms of the disease.
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http://dx.doi.org/10.1111/ajt.16348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675512PMC
February 2021

Ipilimumab-induced renal granulomatous arteritis: a case report.

BMC Nephrol 2019 10 11;20(1):366. Epub 2019 Oct 11.

Nephrology department, Rouen University Hospital, 147 avenue du Maréchal Juin 76230 Bois Guillaume, Rouen, France.

Background: Immune Checkpoint Inhibitors (ICPIs) are promising new drugs in treatment of advanced tumours targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein-1 (PD1) or its ligand (PDL-1). Ipilimumab is a monoclonal antibody targeting the CTLA-4 receptor used in treatment of metastatic melanoma. By increasing activity of the immune system, ICPIs lead to immune-related adverse events, such as dermatitis, colitis or hepatitis. ICPIs-related kidney adverse events are rare and acute tubulointerstitial nephritis with or without granuloma have mainly been reported.

Case Presentation: We report a case of acute kidney injury in a patient with melanoma treated by ipilimumab. Kidney biopsy revealed acute interlobular and juxtaglomerular granulomatous arteritis, which has not yet been reported in patients treated by ICPIs. Kidney function partially recovered after ipilimumab discontinuation and oral prednisone. Unfortunately, the patient died a few months later from progression of his melanoma.

Conclusion: This case highlights a new mechanism of acute kidney injury related to ICPIs and supports the interest of kidney biopsy in case of ICPIs related acute renal failure.
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http://dx.doi.org/10.1186/s12882-019-1552-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788031PMC
October 2019

Prescribing the dose of dialysis

Nephrol Ther 2019 04;15 Suppl 1:S101-S107

Service de néphrologie hémodialyse, centre hospitalier universitaire de Rouen, 147, avenue du Maréchal-Juin, 76230 Rouen cedex, France.

The concept of dose of dialysis is relatively recent. It evaluates the adequacy of extrarenal clearance, in order to provide the best chances of survival to chronic dialysis patients. Although it presents drawbacks, urea Kt/V is recognized as the most clinically relevant indicator. It can be easily calculated online thanks to the equipment of the dialysis monitors with ionic dialysance. The target of balanced Kt/V is greater than 1.2, provided the minimal Kt dialysis dose is received. To reach these targets, it is necessary to use dialysers of large surface, with high urea mass transfer coefficient. The blood pump flow must be high and dialysate flow rate sufficient. With the advent of online hemodiafiltration, a dose of convective dialysis was imposed. To achieve these convective targets, large surface dialysers with high hydraulic permeability must be used, with a high beta 2 microglobulin screening coefficient and low albumin loss. Prescribing the dose of dialysis is essential in an optimal quality-of-care based approach.
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http://dx.doi.org/10.1016/j.nephro.2019.03.001DOI Listing
April 2019

Clinical Value of Natriuretic Peptides in Predicting Time to Dialysis in Stage 4 and 5 Chronic Kidney Disease Patients.

PLoS One 2016 22;11(8):e0159914. Epub 2016 Aug 22.

Service de Néphrologie, CHU Hôpitaux de Rouen, Rouen, France.

Background: Anticipating the time to renal replacement therapy (RRT) in chronic kidney disease (CKD) patients is an important but challenging issue. Natriuretic peptides are biomarkers of ventricular dysfunction related to poor outcome in CKD. We comparatively investigated the value of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as prognostic markers for the risk of RRT in stage 4 and 5 CKD patients, and in foretelling all-cause mortality and major cardiovascular events within a 5-year follow-up period.

Methods: Baseline plasma BNP (Triage, Biosite) and NT-proBNP (Elecsys, Roche) were measured at inclusion. Forty-three patients were followed-up during 5 years. Kaplan-Meier analysis, with log-rank testing and hazard ratios (HR), were calculated to evaluate survival without RRT, cardiovascular events or mortality. The independent prognostic value of the biomarkers was estimated in separate Cox multivariate analysis, including estimated glomerular filtration rate (eGFR), creatininemia and comorbidities.

Results: During the first 12-month follow-up period, 16 patients started RRT. NT-proBNP concentration was higher in patients who reached endpoint (3221 ng/L vs 777 ng/L, p = 0.02). NT-proBNP concentration > 1345 ng/L proved significant predictive value on survival analysis for cardiovascular events (p = 0.04) and dialysis within 60 months follow-up (p = 0.008). BNP concentration > 140 ng/L was an independent predictor of RRT after 12 months follow-up (p<0.005), and of significant predictive value for initiation of dialysis within 60 months follow-up.

Conclusions: Our results indicate a prognostic value for BNP and NT-proBNP in predicting RRT in stage 4 and 5 CKD patients, regarding both short- and long-term periods. NT-proBNP also proved a value in predicting cardiovascular events. Natriuretic peptides could be useful predictive biomarkers for therapeutic guidance in CKD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159914PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993513PMC
July 2017

[Extracellular hydration status and residual urinary sodium excretion in chronic hemodialysis patients: a cross-sectional multicenter study].

Nephrol Ther 2014 Apr 4;10(2):94-100. Epub 2014 Feb 4.

Service de néphrologie, centre hospitalier universitaire de Caen, hôpital Clémenceau, boulevard Georges-Clémenceau, CS 30001, 14033 Caen cedex 9, France. Electronic address:

Background: In dialysis patients, a misevaluation of dry weight may lead to an increased morbidity and mortality. The aim of this cross-sectional multicenter study was to evaluate the association between residual urinary sodium excretion and extracellular volume status in chronically treated hemodialysis patients.

Patients And Methods: Dry weight was determined clinically and by whole-body bioimpedance spectroscopy (Body Composition Monitor, Fresenius Medical Care) prior to a mid-week session in 40 chronic hemodialysis patients with significant residual diuresis (more than 250 mL per day) and receiving treatment in four dialysis centers. Regarding their hydration status assessed by the Body Composition Monitor and in comparison to a healthy reference population, patients were assigned to 1 of the 3 categories: overhydrated, normohydrated and dehydrated. Urine output, urinary sodium excretion and residual renal function were measured for all patients within 30 days before dry weight assessment.

Results: The median post-HD session FO was of-0.40 L (IQR: from-1.95 to+0.90) and the median residual urinary sodium excretion was of 64 mmol/L (IQR: 46-79). Among these patients, 16 were normohydated, 16 were dehydrated and 8 were overhydrated. There was a linear relationship between the hydration status after HD session and the urinary sodium excretion (estimate: 5.6±1.5; p<0.001). Compared with normohydrated patients, overhydrated patients had a higher residual urinary sodium excretion (estimate: 26±10; p<0.01).

Conclusion: In this study, urinary sodium excretion is associated with the hydration status evaluated by whole-body bioimpedance spectroscopy.
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http://dx.doi.org/10.1016/j.nephro.2013.11.004DOI Listing
April 2014

High-efficiency on-line haemodiafiltration improves conduit artery endothelial function compared with high-flux haemodialysis in end-stage renal disease patients.

Nephrol Dial Transplant 2014 Feb 13;29(2):414-22. Epub 2013 Nov 13.

Department of Pharmacology, Rouen University Hospital, Rouen, France.

Background: Middle molecular weight uraemic toxins are considered to play an important role in vascular dysfunction and cardiovascular outcomes in end-stage renal disease (ESRD) patients. Recent dialysis techniques based on convection, specifically high-efficiency on-line haemodiafiltration (HDF), enhance the removal of middle molecular weight toxins and reduce all-cause mortality in haemodialysis (HD) patients. However, the mechanisms of these improved outcomes remain to be established.

Methods: This prospective study randomly assigned 42 ESRD patients to switch from high-flux HD to high-efficiency on-line HDF (n=22) or to continue HD (n=20). Brachial artery endothelium-dependent flow-mediated dilatation, central pulse pressure, carotid artery intima-media thickness (IMT), internal diastolic diameter and distensibility and circulating markers of uraemia, inflammation and oxidative stress were blindly assessed before and after a 4-month follow-up.

Results: Brachial flow-mediated dilatation and carotid artery distensibility increased significantly in the HDF group compared with HD, while carotid IMT and diameter remained similar. HDF decreased predialysis levels of the uraemic toxins β2-microglobulin, phosphate and blood TNFα mRNA expression. Oxidative stress markers were not different between the HD and HDF groups. Blood mRNA expression of protein kinase C β2, an endothelial NO-synthase (eNOS) inhibitor, decreased significantly with HDF.

Conclusions: High-efficiency on-line HDF prevents the endothelial dysfunction and stiffening of the conduit arteries in ESRD patients compared with high-flux HD. HDF decreases uraemic toxins, vascular inflammation, and is associated with subsequent improvement in eNOS functionality. These results suggest that reduced endothelial dysfunction may be an intermediate mechanism explaining the beneficial outcomes associated with HDF.
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http://dx.doi.org/10.1093/ndt/gft448DOI Listing
February 2014

Stenosis complicating vascular access for hemodialysis: indications for treatment.

J Vasc Access 2014 Mar-Apr;15(2):76-82. Epub 2013 Nov 4.

1 Department of Clinical and Molecular Medicine, Sapienza University of Rome, Nephrology Unit, Sant'Andrea Hospital, Rome - Italy.

The aim of the multidisciplinary team committed to the care of vascular access (VA) for hemodialysis is to prolong as much as possible the functional patency of the access. Stenosis is definitely the most frequent complication of arteriovenous VA. Whereas the best surveillance strategy is still a matter of debate, some evidence is now available about treatment indication and options. The available body of evidence on the best strategy facing this complication of VA is reviewed.
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http://dx.doi.org/10.5301/jva.5000194DOI Listing
January 2015

Monitoring of hemodialysis quality-of-care indicators: why is it important?

BMC Nephrol 2013 May 24;14:109. Epub 2013 May 24.

Nephrology department, Rouen University Hospital, 1 Avenue de Germont, 76031 Rouen Cedex, Rouen, France.

Background: Meeting specific guideline targets is associated with improved survival rates and reduced hospitalizations in the dialysis population. This prospective work evaluated the adequacy of hemodialysis quality indicators in an in-center hemodialysis population with severe comorbidities, and assessed whether clinical practice could impact intermediate outcomes.

Methods: All the chronic hemodialysis patients treated in Rouen University Hospital hemodialysis Unit between January 2009 and April 2010 were included in this observational study. Every quarter, mean levels and prevalence of conformity were collected for the following indicators: anemia, dialysis dose, serum calcium and phosphorus, PTH, 25OH-vitamin D, albumin, serum bicarbonate, LDL-cholesterol, serum β2-microglobulin, systolic and diastolic blood pressure, intradialytic hypotension and vascular access. Conformity of quality-of-care indicators was determined according to targets defined by international guidelines, whenever available.

Results: Altogether, 124 patients were included in the study. Thirty-three patients were evaluated during the entire follow-up period. An improvement in the percentage of conformity was observed for hemoglobin, dialysis dose, phosphates, PTH, serum bicarbonate and β2-microglobulin in the global population. Failure to improve conformity rates for several indicators, including serum albumin, was found, possibly depending on patients' comorbidities rather than on quality of care.

Conclusion: Overall, this study shows that following quality-of-care indicators can improve clinical practice by identifying center-specific weaknesses, prompting the establishment of corrective measures. Finally, we suggest that the definition and targets of some indicators, especially hypertension and LDL-cholesterol, be reviewed, since evidence of their association with mortality is not demonstrated.
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http://dx.doi.org/10.1186/1471-2369-14-109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701507PMC
May 2013

Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor.

J Am Soc Nephrol 2012 Dec 2;23(12):1949-54. Epub 2012 Nov 2.

Institut National de la Santé et de la Recherche Médicale UMR_S 702, Paris, France.

Up to 80% of patients with idiopathic membranous nephropathy have non-complement-fixing IgG4 autoantibodies to the phospholipase A2 receptor (PLA2R). Membranous nephropathy recurs in approximately 40% of patients after kidney transplantation, but the mechanism is unknown. Here, we describe a patient with recurrent membranous nephropathy 13 days after kidney transplantation whose graft biopsy specimen showed granular staining for C3, C5b-9, C1q, and IgG3κ; electron microscopy revealed subepithelial nonorganized deposits. A search for hematologic disorders was negative. Retrospective evaluation of a biopsy sample from the native kidney revealed a similar pattern: monotypic IgG3κ deposits together with C3, C1q, and C5b-9. Glomerular deposits contained PLA2R in both the graft and the native kidney, suggesting that the recurrence was the result of circulating anti-PLA2R antibodies binding to PLA2R antigen expressed on donor podocytes. Confocal analysis of anti-PLA2R and antihuman IgG3 showed co-localization, and the patient had IgG3κ-restricted circulating anti-PLA2R antibodies. Treatment with rituximab stabilized both proteinuria and serum creatinine, and circulating anti-PLA2R became undetectable. In summary, this case of recurrent membranous nephropathy in a graft suggests that circulating monoclonal anti-PLA2R IgG3κ caused the disease and activated complement by the classic pathway.
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http://dx.doi.org/10.1681/ASN.2012060577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507371PMC
December 2012

Nephroangiosclerosis in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: is NOTCH3 mutation the common culprit?

Am J Kidney Dis 2008 Aug 24;52(2):340-5. Epub 2008 Jun 24.

Nephrology Department, Rouen University Hospital, Rouen, France.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a systemic arterial disease characterized by impairment of vascular smooth muscle cell structure and function related to NOTCH3 mutations. Pathological findings include pathognomonic granular osmiophilic material (GOM) deposition with nonspecific hyalinization within the artery wall in a variety of tissues. The main clinical presentation is iterative strokes in young adults despite the lack of cardiovascular risk factors, leading to early dementia. Although arteriosclerosis and GOM have been found in kidneys from patients with CADASIL, kidney disease has been described only once up to now, in association with immunoglobulin A nephropathy. We report the case of a 61-year-old patient with a medical history of CADASIL and recent mild hypertension. His mother also showed neuropsychiatric symptoms and end-stage renal disease of unknown cause. The patient had a chronic kidney disease defined by means of estimated glomerular filtration rate using the 4-variable Modification of Diet in Renal Disease Study equation of 58 mL/min/1.73 m(2) associated with mild proteinuria and intermittent microscopic hematuria. Renal histological analysis showed severe arteriosclerosis and mild interstitial fibrosis. Glomeruli did not show mesangial immunoglobulin A deposition or focal segmental proliferation. Electron microscopic analysis showed typical GOM deposition in the vicinity of altered vascular smooth muscle cells in interlobular and juxtaglomerular arteries. The nephroangiosclerosis-like lesions were unusually severe in contrast to the recent mild hypertension. The presence of GOM strongly suggests that renal lesions were related to the NOTCH3 mutation. Here, we describe the first case of familial occurrence of kidney disease with decreased kidney function in the absence of coexisting nephropathy in patients with CADASIL. We discuss the role of NOTCH3 mutation in the pathogenesis of nephroangiosclerosis through functional impairment of renal microcirculation or primary Notch3-related vascular disease.
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http://dx.doi.org/10.1053/j.ajkd.2008.04.017DOI Listing
August 2008

Haemodialysis catheterization via type II persistent left superior vena cava.

NDT Plus 2008 Apr 19;1(2):100-102. Epub 2007 Dec 19.

Department of Nephrology and Haemodialysis, Rouen University Hospital, Rouen, F-76031, France.

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http://dx.doi.org/10.1093/ndtplus/sfm031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375280PMC
April 2008