La rhéophérèse réalisée chez les patients hémodialysés chroniques cible l'endothélium et exerce un effet anti-inflammatoire

Introduction : la rhéophérèse est une technique de plasmaphérèse de double filtration en cascade qui élimine les protéines de haut poids moléculaire afin de diminuer la viscosité du plasma. La rhéophérèse peut être réalisée chez les patients hémodialysés(HD) qui présentent une ischémie micro-circulatoire sévère, en même temps que leur séance de dialyse. Certaines études indiquent que les séances de rhéophérèse améliorent la fonction endothéliale quant aux capacités de réponse vasodilatatrice.Objectif : notre étude a évalué l'évolution des biomarqueurs inflammatoires et endothéliaux (molécules d'adhésion endothéliales circulantes, cytokines, facteurs angiogéniques et cellules endothéliales circulantes(CEC)) chez 23 patients HD traités ou non par rhéophérèse. Une valeur p ≤ 0,001 a été considérée comme statistiquement significative.Résultats : 13 patients HD traités par rhéophérèse soit pour une artériopathie périphérique sévère (N=8), soit pour une calciphylaxie (N=5) ont été analysés. 10 patients HD ont également été inclus en témoin,afin de s’affranchir des effets du circuit de dialyse. Dans ce groupe HD sans rhéophérèse, nous n’avons pas observé de modification après les séances des dosages des molécules d'adhésion endothéliales circulantes, des cytokines, des facteurs angiogéniques et des CEC. Dans le groupe HD avec rhéophérèse, les molécules d'adhésion endothéliales circulantes (sVCAM-1, sP-selectine et sE-selectine) diminuaient significativement après les séances, à l'exception de sICAM-1. Parmi les cytokines pro-inflammatoires, le TNF-α diminuaient significativement de 32,6 % [(-42,2) -(-22,5)] (p<0,0001), tandis que la cytokine anti-inflammatoire IL-10 augmentait de 674 % [306 -1299] (p<0,0001). Parmi les facteurs angiogéniques, seule l’endogline diminuait significativement. Le niveau de CEC avait tendance à augmenter de 13 [3 -33] cellules/mL à 43 [8 -140] cellules/mL (p=0,002). Nous n'avons pas observé de différence dans les valeurs des molécules d'intérêt au branchement entre la première et la dernière session de rhéophérèse.Conclusion : il s'agit de la première étude qui montre que la rhéophérèsea un effet immédiat sur la balance inflammatoire et sur les biomarqueurs endothéliaux. D'autres études sont nécessaires pour comprendre le mécanisme qui sous-tend ces observations biologiques

Rheopheresis for severe peripheral arterial disease in hemodialysis patients: A clinical series

International audienceBackground Rheopheresis is a double-filtration plasmapheresis that removes high-molecular-weight molecules from the plasma and thereby lowers blood viscosity. This treatment has been proposed in hemodialysis (HD) patients for chronic limb-threatening ischemia (CLTI), but very few studies have evaluated the usefulness of this technique. Principal Objective To assess 1-year amputation-free survival (AFS) of HD patients suffering from CLTI treated by rheopheresis. Material and Method We conducted a retrospective study of 28 consecutive HD patients treated by rheopheresis in three French dialysis centers between 1 February 2017 and 30 April 2019 in two indications resulting from CLTI, namely chronic ulceration or recent minor amputation with delayed healing. Results One-year AFS rate reached 53.6 (-19.8; +16.3)%. One-year overall survival rate reached 67.9 (-20.5; +13.1)%. Main causes of death were infections and related to palliative care implying reduction or withdrawal of regular dialysis treatment. Hypotension episodes were the main rheopheresis adverse events with a prevalence rate of 13.5%. Rheopheresis sessions significantly reduced fibrinogen, C-reactive protein, alpha 2-macroglobulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, IgM, and estimated plasma viscosity (P < .0001). Conclusion Rheopheresis may improve clinical outcomes of CLTI in HD patients. The assessment of rheopheresis effectiveness needs to be confirmed by a multicenter randomized controlled trial, such as the ongoing project in France (RHEO-PAD, NCT: 03975946)

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100 mg/m2 seems sufficient

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Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100 mg/m2 seems sufficient

International audienceHigh dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m2, instead of the usual dose of 3500mg/m2, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients

Rheopheresis Performed in Hemodialysis Patients Targets Endothelium and Has an Acute Anti-Inflammatory Effect

Background: Rheopheresis is a double-filtration plasmapheresis that removes a defined spectrum of high-molecular-weight proteins to lower plasma viscosity and improves microcirculation disorders. This technique can be performed in hemodialysis (HD) patients with severe microischemia. Interestingly, some studies showed that rheopheresis sessions improve endothelial function. Methods: Our study evaluated the inflammatory and endothelial biomarker evolution in 23 HD patients treated or not with rheopheresis. A p value ≤ 0.001 was considered statistically significant. Results: Thirteen HD patients treated by rheopheresis either for a severe peripheral arterial disease (N = 8) or calciphylaxis (N = 5) were analyzed. Ten control HD patients were also included in order to avoid any misinterpretation of the rheopheresis effects in regard to the HD circuit. In the HD group without rheopheresis, the circulating endothelial adhesion molecules, cytokines, angiogenic factor concentrations, and circulating levels were not modified. In the HD group with rheopheresis, the circulating endothelial adhesion molecules (sVCAM-1, sP-selectin, and sE-selectin) experienced a significant reduction, except sICAM-1. Among the pro-inflammatory cytokines, TNF-α was significantly reduced by 32.6% [(−42.2)–(−22.5)] (p p p = 0.002). We did not observe any difference on the pre-session values of the molecules of interest between the first rheopheresis session and the last rheopheresis session. Conclusion: Rheopheresis immediately modified the inflammation balance and the endothelial injury biomarkers. Further studies are needed to understand the mechanisms underlying these biological observations

Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has not been systematically studied, particularly in non-V30M mutations, and is not well known to nephrologists. METHODS: We conducted a retrospective study describing the kidney phenotype of all prevalent patients with ATTR mutations, with neurological or cardiac involvement or presymptomatic carriers, followed up in two university hospitals from the South of France between June 2011 and June 2021. RESULTS: A total of 103 patients were included, among whom 79 were symptomatic and 24 were presymptomatic carriers. Patients carried 21 different ATTR mutations and 54% carried the V30M mutation. After a mean follow-up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD) and 20.3% had a urinary protein:creatinine ratio ≥0.5 g/g. None of the presymptomatic carriers had CKD or proteinuria. In a multivariate analysis, late onset of symptoms (after 60 years), the V122I mutation and proteinuria were significantly associated with CKD. The median CKD-free survival in symptomatic patients was estimated at 81.0 years (interquartile range 77.1–84.9). It did not differ between V30M and non-V30M patients, but was lower in patients with the V122I mutation. The average age of the onset of CKD was 69.3 ± 13.0 years. In one 38-year-old V30M female who presented a kidney-predominant phenotype, treatment with patisiran resulted in remission of the nephrotic syndrome. CONCLUSION: CKD affects almost one-third of patients with symptomatic ATTRv. The role of ATTRv per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies

Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients

BackgroundHereditary transthyretin amyloidosis (ATTRv) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has not been systematically studied, particularly in non-V30M mutations, and is not well known to nephrologists.MethodsWe conducted a retrospective study describing the kidney phenotype of all prevalent patients with ATTR mutations, with neurological or cardiac involvement or presymptomatic carriers, followed up in two university hospitals from the South of France between June 2011 and June 2021.ResultsA total of 103 patients were included, among whom 79 were symptomatic and 24 were presymptomatic carriers. Patients carried 21 different ATTR mutations and 54% carried the V30M mutation. After a mean follow-up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD) and 20.3% had a urinary protein:creatinine ratio ≥0.5 g/g. None of the presymptomatic carriers had CKD or proteinuria. In a multivariate analysis, late onset of symptoms (after 60 years), the V122I mutation and proteinuria were significantly associated with CKD. The median CKD-free survival in symptomatic patients was estimated at 81.0 years (interquartile range 77.1–84.9). It did not differ between V30M and non-V30M patients, but was lower in patients with the V122I mutation. The average age of the onset of CKD was 69.3 ± 13.0 years. In one 38-year-old V30M female who presented a kidney-predominant phenotype, treatment with patisiran resulted in remission of the nephrotic syndrome.ConclusionCKD affects almost one-third of patients with symptomatic ATTRv. The role of ATTRv per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies

Kidney Histopathology Can Predict Kidney Function in ANCA-Associated Vasculitides with Acute Kidney Injury Treated with Plasma Exchanges

International audienceBackground Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. Methods We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). Results No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (−15.9%; 95% CI, −29.4 to −2.5) compared with the PLEX not recommended group (−4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. Conclusions PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making