Publications by authors named "Dominique Chauveau"

99 Publications

Role of C5 inhibition in Idiopathic Inflammatory Myopathies and Scleroderma Renal Crisis-Induced Thrombotic Microangiopathies.

Kidney Int Rep 2021 Apr 29;6(4):1015-1021. Epub 2021 Jan 29.

Département de Néphrologie et transplantation d'Organes-Unité de Réanimation, Centre de référence des maladies rénales rares, Centre Hospitalier Universitaire, Institut National de la Santé et de la Recherche Médicale U1048 (Institut des Maladies Métaboliques et Cardiovasculaires), Toulouse, France.

Introduction: Connective tissue diseases, including systemic sclerosis and idiopathic inflammatory myopathies (IIMs), are a very rare cause of thrombotic microangiopathies (TMAs). Whether dysregulation of the complement pathways underlies these secondary forms of TMA and may be targeted by complement blocking agents remains elusive.

Methods: Kidney pathology and outcomes of 18 critically ill patients with TMA related to inflammatory myopathy flare-up (IIM, =7) or scleroderma renal crisis (SRC, =11; biopsy =9) are assessed.

Results: IIM-TMA is characterized by acute thrombotic lesions only, whereas SRC-TMA patients also harbored chronic vascular lesions and more interstitial fibrosis. C5b9 deposits, a marker of complement component 5 (C5) cleavage, were observed in the 2 subgroups at the junction of media and intima of arterioles, colocalizing with subendothelial edema. Thus, kidney biopsy distinguished between acute and chronic renal phenotypes that may help to individualize treatment. Treatment of IIM-TMA patients with combined full-code organ support, corticosteroids, B-cell depletion, and complement C5 blocking led to 1-year survival of 72%, compared with 19% in historical cohorts. Treatment of SRC-TMA was more heterogenous and relied on conversion enzyme inhibitor only or with eculizumab (=6) and immunosuppressor (=5). One-year survival of SRC-TMA patients was 52%, a result similar to historical cohorts. Eculizumab was followed by a rapid dramatic improvement of TMA in all the treated patients.

Conclusion: C5 blocking may reverse hematologic abnormalities in IIM- and SRC-TMA, and adding an early and aggressive immunosuppressive regimen may improve the survival of IIM-TMA. Underlying chronic vascular and interstitial lesions mitigate renal response in SRC-TMA.
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http://dx.doi.org/10.1016/j.ekir.2021.01.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071645PMC
April 2021

Kidney Involvement in Patients With Chronic Myelomonocytic Leukemia or BCR-ABL-Negative Myeloproliferative Neoplasms.

Kidney Int Rep 2021 Mar 14;6(3):737-745. Epub 2020 Dec 14.

Centre Hospitalier Universitaire de Toulouse, Département de Néphrologie et Transplantation d'Organes, Centre de reference des Maladies rénales rares, Toulouse, France.

Introduction: The identification of specific molecular signatures and the development of new targeted drugs have changed the paradigm of onco-nephrology, now allowing a multiscale approach of kidney involvement related to hematologic malignancies relying on combined hematologic and molecular assessments. In this study, we aimed to refine the spectrum of kidney disorders associated with chronic myelomonocytic leukemia (CMML) or BCR-ABL-negative myeloproliferative neoplasms (MPNs), 2 very rare conditions scarcely described.

Methods: Case series. Patients with myeloid neoplasms who were referred to Toulouse University Hospital Nephrology Unit and were diagnosed with acute kidney injury (AKI), chronic kidney disease (CKD), or urine abnormalities were retrospectively included.

Results: Eighteen patients (males =13, CMML =8, essential thrombocytosis [ET] =7, polycythemia vera [PV] =1, and myelofibrosis =2) developed kidney disease 7.7±2 years after the diagnosis of the malignancy. Twelve patients had AKI at presentation. Eight patients had glomerular presentation (high-range proteinuria 33%, microscopic hematuria 56%). Kidney biopsy (=14) showed various patterns, including pauci-immune glomerulosclerosis (=5), extramedullary hematopoiesis (=6), or tubular atrophy and interstitial fibrosis with polymorphic inflammation (=8). Immunostaining of CD61 confirmed the infiltration of megakaryocytes within glomeruli or interstitium in 5 of 8 patients. Other pictures of glomerulopathy were identified in 3 patients (IgA nephropathy =2, AA amyloidosis =1). Massive kidney infiltration by CMML was identified in 1 patient. After a mean follow-up of 24±6 months, malignancy was considered as stable in 11 patients (61%), but 22% of patients had progressed to end-stage renal failure. The remaining had persistently reduced kidney function. No correlation between the malignancy and the renal presentation and outcomes could be identified.

Conclusions: Kidney complications of CMML/MPN are heterogenous, and kidney biopsy may help to identify new molecular targets to prevent the development of kidney fibrosis.
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http://dx.doi.org/10.1016/j.ekir.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938079PMC
March 2021

Administration of the High-Density Lipoprotein Mimetic CER-001 for Inherited Lecithin-Cholesterol Acyltransferase Deficiency.

Ann Intern Med 2021 Mar 2. Epub 2021 Mar 2.

Institut National de la Science et de la Recherche Médicale, INSERM U1297-Institut des Maladies Métaboliques et Cardiovasculaires, and Université Paul Sabatier-Toulouse III, Toulouse, France.

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http://dx.doi.org/10.7326/L20-1300DOI Listing
March 2021

Mass spectrometry-based proteomic analysis of parathyroid adenomas reveals PTH as a new human hormone-derived amyloid fibril protein.

Amyloid 2021 Feb 13:1-5. Epub 2021 Feb 13.

Laboratoire de Génétique Moléculaire, Fédération de Génétique, Hôpital Necker-Enfants Malades, APHP.CUP, Université de Paris, Paris, France.

Background: Congo red-positive material was described in normal and diseased parathyroids (adenoma and hyperplasia) 50 years ago. However, the incidence and the clinical significance of such observation are unknown, and the causal fibril protein has never been convincingly demonstrated.

Methods: We conducted the present study including an exceptional case report accompanied with a retrospective study of 105 parathyroid adenomas. We used histopathological, immunohistochemical, ultrastructural, mass spectrometry-based proteomic analysis of parathyroid adenoma tissue samples, and genetic analysis.

Results: We describe a 57-year-old man with mild hypercalcemia and elevated parathyroid hormone (PTH) level for whom histopathological analysis revealed a parathyroid adenoma associated with nodular typical amyloid deposits. Tandem mass spectrometry after laser microdissection (LMD-MS) of amyloid adenoma identified PTH as the fibril protein, and no germline mutation in the gene was detected. Congo red-positive PTH-deposits were further observed in 6.6% of the parathyroid adenomas analyzed, and were associated with complete/incomplete or absent universal amyloid signature, but with fibrillar morphology at ultrastructural level.

Conclusions: Inappropriate PTH production leads to progressive disease-amyloid aggregation of PTH in a subset of parathyroid adenomas, providing new insights into the pathophysiology of this condition and adding PTH to the list of amyloid protein derived from hormones.
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http://dx.doi.org/10.1080/13506129.2021.1885023DOI Listing
February 2021

Treatment and long-term outcome in primary nephrogenic diabetes insipidus.

Nephrol Dial Transplant 2020 Dec 26. Epub 2020 Dec 26.

Department of Paediatrics, Division of Nephrology, Erciyes University Faculty of Medicine, Kayseri,Turkey.

Background: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome.

Methods: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form.

Results: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients.

Conclusion: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.
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http://dx.doi.org/10.1093/ndt/gfaa243DOI Listing
December 2020

Plasma exchange and thrombotic microangiopathies: From pathophysiology to clinical practice.

Transfus Apher Sci 2020 Dec 19;59(6):102990. Epub 2020 Nov 19.

Département de Néphrologie et Transplantation d'Organes, Centre Hospitalier Universitaire de Toulouse, Toulouse, France. Electronic address:

Thrombotic microangiopathy (TMA) brings together many diseases that have a commonality in the apparition of mechanical hemolysis with consuming thrombopenia. In all cases, these diseases can be life threatening, thereby justifying the implementation of treatment as an emergency. First-line treatment represents plasma exchange. This treatment has proven efficiency in improving the vital patient's and functional prognosis. However, the administration methods of plasma exchange can be redefined in light of the understanding of the pathophysiology of TMA. The aim of this review is to try to define, from pathophysiology, the place of plasma exchanges in the modern therapeutic arsenal of TMA.
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http://dx.doi.org/10.1016/j.transci.2020.102990DOI Listing
December 2020

genetic variations and myeloma cast nephropathy.

Clin Kidney J 2019 Oct 15;12(5):639-640. Epub 2019 Jun 15.

Département de Néphrologie et Transplantation d'organes, Centre de référence des maladies rénales rares, Hôpital Rangueil, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

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http://dx.doi.org/10.1093/ckj/sfz071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768300PMC
October 2019

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Blood 2019 12;134(24):2209-2217

Service d'Hématologie, AP-HP.6, Paris, France; and.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.
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http://dx.doi.org/10.1182/blood.2019000748DOI Listing
December 2019

The factor VIII:C/VWF:Ag ratio as a useful tool to predict relapse in patients with acquired haemophilia A: A retrospective cohort study.

Haemophilia 2019 May 2;25(3):527-534. Epub 2019 May 2.

Laboratoire d'Hématologie, CHU de Toulouse, France.

Introduction: Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of autoantibodies against coagulation factor VIII (FVIII). The mortality rate remains high. International recommendations define complete remission as undetectable inhibitor (<0.6 Bethesda Units [BU]) and normal FVIII activity (FVIII:C) that persists after immunosuppressive therapy stopped. For patients achieving remission, the risk of relapse reaches 20%. The risk factors for this relapse are not well known.

Aim: In this study, we examined the accuracy of the FVIII/W ratio (FVIII:C/von Willebrand Factor Antigen (VWF:Ag) ratio) to predict relapse in 64 consecutive patients with AHA.

Results: In this cohort, all patients had a very low FVIII/W ratio at the time of diagnosis, and this value progressively increased in the first weeks of immunosuppressive treatment. In our study, 9/55 (14%) did not achieve complete remission. Twenty-seven patients were followed long enough (more than a year) to show that in the 22 patients who did not relapse, the FVIII/W ratio remained durably normalized. By contrast, in the five patients who relapsed during follow-up, we noted either no normalization of the FVIII/W ratio, or a secondary decrease to an abnormal value of <0.7 after initial normalization. In all patients who relapsed, the ratio was the first abnormal biological result to be observed, always preceding changes in the activated partial thromboplastin time (aPTT), FVIII:C and anti-FVIII reappearance.

Conclusion: These data suggest that the FVIII/W ratio could be considered a sensitive biological marker to predict recovery and/or relapse in AHA.
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http://dx.doi.org/10.1111/hae.13752DOI Listing
May 2019

Outcomes of Older Patients (≥60 years) with New-Onset Idiopathic Nephrotic Syndrome Receiving Immunosuppressive Regimen: A Multicentre Study of 116 Patients.

J Clin Med 2019 Mar 2;8(3). Epub 2019 Mar 2.

Département de Néphrologie et Transplantation d'Organes, Centre de Référence des Maladies Rénales Rares, Centre Hospitalier Universitaire de Toulouse, 31000 Toulouse, France.

Because of its rarity, renal presentation and outcomes of idiopathic nephrotic syndrome (INS; minimal changes disease or focal and segmental glomerulosclerosis) has poorly been described in elderly patients, precluding an individualized therapy procedure. Whether immunosuppressive regimens formerly designed in children and young adults are safe and efficient in elderly remains elusive. In a large multicentric retrospective study that included 116 patients with INS and onset ≥ 60 years of age, we showed that cumulative incidence of renal response was 95% after frontline therapy, with an age-dependent median time-to-response (60 days before 70 years of age at the onset vs. 120 days after; = 0.03). Cumulative incidence of relapse was 90% at 7 years, with relapse occurring continuously over time. After a median follow-up of 34 months (IQR (12; 57)), 7 patients had died (6%) and 5 reached end-stage renal disease. Complications were highly prevalent: diabetes mellitus (23.3%), hypertension (24.1%), infection requiring hospitalization (21.6%) and acute kidney injury (9.5%). Thus, in older patients with INS and receiving steroids, renal response is delayed and relapse is the rule. Alternative immunosuppressive regimens, including B-cells depleting agents as frontline therapy, should be tested in this subset of patients to improve the mid- to long-term outcomes.
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http://dx.doi.org/10.3390/jcm8030298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463053PMC
March 2019

The Effectiveness of Topical Cerium Nitrate-Silver Sulfadiazine Application on Overall Outcome in Patients with Calciphylaxis.

Dermatology 2019 3;235(2):120-129. Epub 2019 Jan 3.

Department of Nephrology and Organ Transplantation, Center for Rare Renal Disease, University Hospital of Toulouse, Toulouse, France,

Background: Calciphylaxis (CPX) is a rare and life-threatening disease characterized by vascular calcification and development of painful and necrotizing skin lesions with a challenging management. Mechanisms of CPX are complex and include an imbalance between vascular calcification promoters and inhibitors, and frequently vitamin K deficiency.

Objectives: To describe the various presentations and identify predictive factors of death in patients with CPX.

Methods: In this multicenter retrospective study, we included 71 CPX patients followed in South-West France (n = 26) and in French Polynesia (n = 45), and who all received sodium thiosulfate (25 g thrice weekly for a median of 61 days).

Results: Characteristics at presentation significantly differed between metropolitan and Polynesian French patients. Polynesians were less frequently on regular dialysis at the onset of CPX, had a higher incidence of diabetes mellitus and obesity, more disturbances of calcium-phosphorus metabolism, and received vitamin K antagonists less frequently than patients from South-West France. Despite intensive management, the 1-year mortality rate was 66% and median time to death was 200 days (IQR, 40; 514). The number of body areas involved (i.e., three: OR 2.70 [1.09; 6.65], p = 0.031; four: OR 8.79 [1.54; 50.29], p = 0.015) was the only predictive factor for death, whereas application of topical cerium nitrate-silver sulfadiazine was protective (OR 0.44 [0.20; 0.99], p = 0.046). Surgical debridement, hyperbaric oxygenation therapy, and geographical origin were not associated with overall outcomes.

Conclusions: Cerium nitrate may lead to vascular decalcification and chelation of reactive oxygen species, and prevent infection. Cerium nitrate-silver sulfadiazine was associated with better outcomes and should be tested in a prospective comparative trial in CPX patients.
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http://dx.doi.org/10.1159/000493975DOI Listing
June 2019

Identification of genetic causes for sporadic steroid-resistant nephrotic syndrome in adults.

Kidney Int 2018 11;94(5):1013-1022

Inserm U1163, Imagine Institute, Paris Descartes University, Paris, France; Adult Nephrology & Transplantation, Centre de référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte, Necker Hospital, Paris, France. Electronic address:

Monogenic forms of Steroid-Resistant Nephrotic Syndrome (SRNS) have been widely characterized, but genetic screening paradigms preferentially address congenital, infantile onset, and familial cases. Our aim was to characterize the distribution of disease-causing gene mutations in adults with sporadic SRNS or focal segmental glomerulosclerosis (FSGS). We selected adult patients with non-syndromic, biopsy-proven FSGS or SRNS in the absence of known family history. Strict clinical criteria included lack of response to glucocorticoids and cyclosporine, and no recurrence after kidney transplantation. Mutations in SRNS genes were detected using a targeted gene panel. Sixteen of 135 tested participants (11.8%) carried pathogenic mutations in monogenic SRNS genes, and 14 others (10.4%) carried two APOL1 high-risk alleles. Autosomal recessive disease was diagnosed in 5 participants, autosomal dominant disease in 9, and X-linked disease in 2. Four participants carried a de novo heterozygous mutation. Among the 16 participants with identified mutations in monogenic SNRS genes, 7 (43.7%) had type IV collagen mutations. Mutations in monogenic SNRS genes were identified primarily in participants with proteinuria onset before 25 years of age, while the age at disease onset was variable in those with APOL1 high-risk genotype. Mean age at diagnosis was lower and renal survival was worse in participants with identified mutations in SNRS genes than in those without mutations. We found a significant rate of pathogenic mutations in adults with SRNS, with Type IV collagen mutations being the most frequent. These findings may have immediate impact on clinical practice.
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http://dx.doi.org/10.1016/j.kint.2018.07.024DOI Listing
November 2018

Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura.

Blood 2018 11 10;132(20):2143-2153. Epub 2018 Sep 10.

Centre de Référence des Microangiopathies Thrombotiques, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.

Preemptive rituximab infusions prevent relapses in immune thrombotic thrombocytopenic purpura (iTTP) by maintaining normal ADAMTS13 activity. However, the long-term outcome of these patients and the potential adverse events of this strategy need to be determined. We report the long-term outcome of 92 patients with iTTP in clinical remission who received preemptive rituximab after identification of severe ADAMTS13 deficiency (activity <10%) during the follow-up. Thirty-seven patients had >1 iTTP episode, and the median cumulative relapse incidence before preemptive rituximab was 0.33 episode per year (interquartile range [IQR], 0.23-0.66). After preemptive rituximab, the median cumulative relapse incidence in the whole population decreased to 0 episodes per year (IQR, 0-1.32; < .001). After preemptive rituximab, ADAMTS13 activity recovery was sustained in 34 patients (37%) during a follow-up of 31.5 months (IQR, 18-65), and severe ADAMTS13 deficiency recurred in 45 patients (49%) after the initial improvement. ADAMTS13 activity usually improved with additional courses of preemptive rituximab. In 13 patients (14%), ADAMTS13 activity remained undetectable after the first rituximab course, but retreatment was efficient in 6 of 10 cases. In total, 14 patients (15%) clinically relapsed, and 19 patients (20.7%) experienced benign adverse effects. Preemptive rituximab treatment was associated with a change in ADAMTS13 conformation in respondent patients. Finally, in the group of 23 historical patients with iTTP and persistently undetectable ADAMTS13 activity, 74% clinically relapsed after a 7-year follow-up (IQR, 5-11). In conclusion, persistently undetectable ADAMTS13 activity in iTTP during remission is associated with a higher relapse rate. Preemptive rituximab reduces clinical relapses by maintaining a detectable ADAMTS13 activity with an advantageous risk-benefit balance.
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http://dx.doi.org/10.1182/blood-2018-04-840090DOI Listing
November 2018

Zoster after Cyclophosphamide for Systemic Lupus Erythematosus or Vasculitis: Incidence, Risk Factors, and Effect of Antiviral Prophylaxis.

J Rheumatol 2018 11 15;45(11):1541-1548. Epub 2018 Jul 15.

From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.

Objective: To assess the incidence and the risk factors for zoster in patients exposed to intravenous cyclophosphamide (CYC) for systemic vasculitis or systemic lupus erythematosus (SLE), as well as the protective effect of prophylaxis by valacyclovir (VCV).

Methods: This retrospective study included all adults treated by intravenous CYC for SLE or systemic vasculitis between 2011 and 2015 at Toulouse University Hospital, France. Zoster occurrence was recorded using medical chart review, laboratory data, and patient interviews. Univariate Cox models were computed to assess the risk factors for zoster and the protective effect of prophylaxis by VCV.

Results: The cohort consisted of 110 patients (81 systemic vasculitis and 29 SLE). During a mean followup of 3.4 years after CYC initiation, 10 cases of zoster occurred, leading to an overall incidence of 27.9/1000 patient-years (95% CI 15.2-50.6); it was 59.4/1000 patients (95% CI 27.5-123.6) during the year after CYC initiation. Four patients experienced persistent postherpetic neuralgia. Probable risk factors were lymphopenia < 500/l at CYC initiation (HR 5.11, 95% CI 0.94-27.93) and female sex (HR 4.36, 95% CI 0.51-37.31). The incidence was higher in patients with SLE (HR as compared with systemic vasculitis patients = 2.68, 95% CI 0.54-13.26). None of the 19 patients exposed to VCV during the followup developed zoster.

Conclusion: The incidence of zoster is high in systemic vasculitis and in patients with SLE exposed to intravenous CYC. CYC may favor postherpetic neuralgia. Prophylaxis by VCV should be considered, particularly in cases of lymphopenia < 500/l at CYC initiation and during the year after.
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http://dx.doi.org/10.3899/jrheum.180310DOI Listing
November 2018

Risk of thrombosis with anti-phospholipid syndrome in systemic lupus erythematosus treated with thrombopoietin-receptor agonists.

Rheumatology (Oxford) 2018 Aug;57(8):1432-1438

Internal Medicine, French Referral Centre for Adult Immune Cytopenia, Henri Mondor Hospital, AP-HP, UPEC University, Créteil, France.

Objectives: The use of thrombopoietin-receptor agonists (TPO-RAs) has increased as a second-line therapy in ITP, but the efficacy and safety of such drugs has not been evaluated in SLE-associated ITP.

Methods: This was a multicentre retrospective cohort study from 2009 to 2016. Participating centres (n = 11) were secondary- or tertiary-care hospitals belonging to the French national network for adult ITP.

Results: We included 18 patients with SLE-ITP treated with TPO-RAs; 10 (55%) had aPL, 5 (27%) showing definite APS. Except for one patient, all (94%) achieved response with TPO-RAs overall. After a median follow-up of 14.7 months with TPO-RAs, four arterial thrombosis events (including one catastrophic APS) occurred in four patients. Two venous thrombosis events occurred in a patient without APS or aPLs.

Conclusion: Our results suggest that aPLs should be systematically screened before TPO-RA initiation in patients with SLE. With aPL positivity, alternative therapy should be discussed (if possible), especially in patients with definite APS or suboptimal adherence to anti-coagulation therapy.
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http://dx.doi.org/10.1093/rheumatology/key119DOI Listing
August 2018

Bendamustine plus rituximab for indolent B-cell lymphoma of renal significance.

Am J Hematol 2018 03 6;93(3):356-362. Epub 2017 Dec 6.

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

Treatment of indolent B-cell non-Hodgkin lymphomas (iNHL) of renal significance is challenging given the need for deep and prolonged hematological response to restore and control renal function overtime, yet to be balanced with the risk of adverse drug-related events. This prospective single-center study included 20 patients with iNHL of renal significance (tubulointerstitial presentation [n = 8], glomerulopathy with or without monoclonal Ig deposits [n = 12]) who received a steroid-sparing regimen of rituximab plus bendamustine (BR), with either no or <1 month of steroid intake (as a first line therapy in 80%). Seventeen patients (85%) achieved a complete (CHR, n = 12) or a partial (PHR, n = 5) hematological response. Nine out of the 12 patients (75%) with iNHL-related glomerulopathy had a complete (CRR) or a partial (PRR) renal response. Among the six patients with glomerulopathy and CHR, five had a CRR (83%) compared to 1/6 (17%) that did not reach CHR. eGFR increased from 38 to 58 mL/min/1.73 m , and returned to baseline in five patients. Among the eight patients with a tubulointerstitial presentation, six (75%) had a renal response (5 CRR), and eGFR increased from 29 to 48 mL/min/1.73 m . One patient with a PHR had a renal relapse. Mortality rate was 10% at 12 months. The BR regimen was well tolerated overall. Thus, despite severe renal disease at presentation, a relapsing iNHL in 20% of patients and several comorbidities, the BR regimen was efficient and safe in our series. It should be further assessed as a first line therapy for patients with iNHL of renal significance.
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http://dx.doi.org/10.1002/ajh.24984DOI Listing
March 2018

Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.

Pediatr Nephrol 2018 03 23;33(3):473-483. Epub 2017 Oct 23.

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

Background: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease.

Methods: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort.

Results: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing.

Conclusions: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance.
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http://dx.doi.org/10.1007/s00467-017-3819-9DOI Listing
March 2018

Incidence and outcome of lupus nephritis in French Polynesia
.

Clin Nephrol 2018 Jan;89 (2018)(1):41-49

Objective: Outcomes of systemic lupus erythematosus (SLE) and lupus nephritis (LN) are highly heterogeneous among some populations because of interactions between genetic, epigenetic, environmental, and socioeconomic factors. A better characterization of social and ethnic disparities in mixed populations may thus help to develop individualized treatment regimens.

Materials And Methods: Retrospective observational study including all patients with LN diagnosed between January 1993 and January 2014 in the only Nephrology Department of French Polynesia.

Results: The annual incidence of SLE and LN in French Polynesia was 3.6 and 0.96 per 100,000, respectively. Among the 45 patients with biopsy-proven LN (pediatric onset, 26.7%), LN occurred during the first SLE flare-up in 68.8%. At presentation, median eGFR was 72 mL/min/1.73m2 (31 - 105), 32 patients had class-III/IV active glomerulonephritis (GN), and 10 had pure or mixed class-V GN. During the follow-up, 5 patients died (11.1%) and 2 reached end-stage renal disease (4.4%). Cumulative incidences of complete and partial renal responses were 31.1% and 40% at 12 months. Complete renal response (CR) was only predicted by renal presentation (lack of leukocyturia, low proteinuria). Among the 36 patients with renal response, 18 relapsed. Maintenance treatment (mycophenolate mofetil) and place of residence (Windward Islands as compared to remote islands) were the only factors that protected from relapse.

Conclusion: Renal presentation was the main predictive factor for a renal response whereas geographical residence and maintenance-treatment regimen were predictive of LN relapses in patients from French Polynesia, an area characterized by a specific genetic background and including several isolated islands that have limited access to healthcare.
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http://dx.doi.org/10.5414/CN109194DOI Listing
January 2018

Hepatocyte Nuclear Factor-1 Controls Mitochondrial Respiration in Renal Tubular Cells.

J Am Soc Nephrol 2017 Nov 24;28(11):3205-3217. Epub 2017 Jul 24.

Institut National de la Santé et de la Recherche Médicale, U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France;

AKI is a frequent condition that involves renal microcirculation impairment, infiltration of inflammatory cells with local production of proinflammatory cytokines, and subsequent epithelial disorders and mitochondrial dysfunction. Peroxisome proliferator-activated receptor coactivator 1- (PPARGC1A), a coactivator of the transcription factor PPAR- that controls mitochondrial biogenesis and function, has a pivotal role in the early dysfunction of the proximal tubule and the subsequent renal repair. Here, we evaluated the potential role of hepatocyte nuclear factor-1 (HNF-1) in regulating PPARGC1A expression in AKI. In mice, endotoxin injection to induce AKI also induced early and transient inflammation and PPARGC1A inhibition, which overlapped with downregulation of the HNF-1 transcriptional network. , exposure of proximal tubule cells to the inflammatory cytokines IFN- and TNF- led to inhibition of HNF-1 transcriptional activity. Moreover, inhibition of HNF-1 significantly reduced PPARGC1A expression and altered mitochondrial morphology and respiration in proximal tubule cells. Chromatin immunoprecipitation assays and PCR analysis confirmed HNF-1 binding to the promoter in mouse kidneys. We also demonstrated downregulation of renal expression in a patient with an germinal mutation. Thus, we propose that HNF-1 links extracellular inflammatory signals to mitochondrial dysfunction during AKI partly PPARGC1A signaling. Our findings further strengthen the view of -related nephropathy as a mitochondrial disorder in adulthood.
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http://dx.doi.org/10.1681/ASN.2016050508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661272PMC
November 2017

Alternative complement pathway hemolytic assays reveal incomplete complement blockade in patients treated with eculizumab.

Clin Immunol 2017 10 21;183:1-7. Epub 2017 Jun 21.

Laboratoire d'Immunologie, CHU de Toulouse, Hôpital Rangueil, Toulouse, France; Laboratoire d'Immunogénétique Moléculaire, Université Paul Sabatier, Toulouse 3, Toulouse, France. Electronic address:

Eculizumab is a monoclonal anti-C5 antibody used in the treatment of atypical hemolytic uremic syndrome (aHUS). We monitored complement inhibition in 16 eculizumab-treated patients suffering from HUS or transplant rejection (not aHUS patients). Blood samples were obtained one to four weeks after the last eculizumab injection. We observed that eculizumab efficiently blocked the terminal pathway (TP) through classical pathway (CP) activation measured by kinetic hemolytic assay (HA) (<10%) but incompletely blocked the TP through alternative pathway (AP) activation measured by rabbit (APH50>23%) or chicken erythrocytes HA (AP100>15%). Conversely, functional ELISA revealed a complete blockade of TP through AP activation in all patients (<10%). C5a and sC5b9 levels were not correlated with residual APH50 or AP100. Similar results were obtained after in vitro addition of increasing amounts of eculizumab to a control serum (in vitro APH50>60% and AP100>20%). We also showed that ELISA was less sensitive than HA.
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http://dx.doi.org/10.1016/j.clim.2017.06.007DOI Listing
October 2017

Diagnostic score for the detection of cardiac amyloidosis in patients with left ventricular hypertrophy and impact on prognosis.

Amyloid 2017 Jun 29;24(2):101-109. Epub 2017 May 29.

a Department of Cardiology , University Hospital of Rangueil , Toulouse , France.

Background: Among diagnosis associated with left ventricular hypertrophy (LVH), cardiac amyloidosis (CA) is a progressive disease with poor prognosis. Early noninvasive identification is of growing clinical importance. The objective of our study was to integrate clinical, biologic, electrocardiographic and echocardiographic parameters to build a diagnostic score in patients with LVH.

Methods And Results: One hundred and fourteen patients with LVH underwent a cardiac magnetic resonance (CMR) and a Tc-hydroxymethylene-diphosphonate scintigraphy (Tc-HMDP) allowing to discriminate three groups of diagnoses: CA (n = 50 including 31, 18 and 1 ATTR, AL and AA amyloidosis), hypertrophic cardiomyopathy (n = 19) and unspecific cardiomyopathy (n = 45). Seven continuous variables associated with CA (systolic arterial pressure <130 mmHg; PR duration >200 ms; Sokolow index <12 mV; diastolic left ventricular posterior thickness >13 mm; E/Ea ratio >10; global longitudinal strain > -12% and sum of basal longitudinal strain > -47%) were selected and dichotomized according to the best cutoff value to build the diagnostic score, which was validated in an independent cohort of 34 patients with LVH from aortic stenosis. The area under the ROC curve for the diagnosis of CA using the score was 0.933 (95%CI 0.889-0.978). The best cut off value for the score was 3 leading to a sensitivity of 90% and specificity of 81%. Area under the ROC curve for the score was 0.932 in the validation cohort. A diagnostic score >3 was associated with a poorest prognosis.

Conclusion: An integrated evaluation of 6 diagnostic factors including arterial blood pressure, ECG and echocardiographic parameters to build a diagnostic score is a simple and easily method to discriminate the 3 main CA in patients with LVH.
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http://dx.doi.org/10.1080/13506129.2017.1333956DOI Listing
June 2017

Predictive features of chronic kidney disease in atypical haemolytic uremic syndrome.

PLoS One 2017 18;12(5):e0177894. Epub 2017 May 18.

Centre de Reference des Microangiopathies Thrombotiques, Hôpital Saint Antoine, AP-HP, Paris, France.

Chronic kidney disease (CKD) is a frequent and serious complication of atypical haemolytic uremic syndrome (aHUS). We aimed to develop a simple accurate model to predict the risk of renal dysfunction in aHUS based on clinical and biological features available at hospital admission. Renal function at 1-year follow-up, based on an estimated glomerular filtration rate < 60mL/min/1.73m2 as assessed by the Modification of Diet in Renal Disease equation, was used as an indicator of significant CKD. Prospectively collected data from a cohort of 156 aHUS patients who did not receive eculizumab were used to identify predictors of CKD. Covariates associated with renal impairment were identified by multivariate analysis. The model performance was assessed and a scoring system for clinical practice was constructed from the regression coefficient. Multivariate analyses identified three predictors of CKD: a high serum creatinine level, a high mean arterial pressure and a mildly decreased platelet count. The prognostic model had a good discriminative ability (area under the curve = .84). The scoring system ranged from 0 to 5, with corresponding risks of CKD ranging from 18% to 100%. This model accurately predicts development of 1-year CKD in patients with aHUS using clinical and biological features available on admission. After further validation, this model may assist in clinical decision making.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177894PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436831PMC
September 2017

Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.

Am J Hematol 2017 Apr 21;92(4):381-387. Epub 2017 Feb 21.

Service de Médecine Interne, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France.

Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.
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http://dx.doi.org/10.1002/ajh.24665DOI Listing
April 2017

The clinicopathologic characteristics of kidney diseases related to monotypic IgA deposits.

Kidney Int 2017 03 6;91(3):720-728. Epub 2017 Jan 6.

Department of Nephrology, CHU Poitiers, Centre de référence maladies rares amylose AL et autres maladies par dépôts d'immunoglobulines monoclonales, Poitiers, France; Department of Immunology, National Center for Scientific Research, Joint Research Unit 7276, University of Limoges, Centre de référence maladies rares amylose AL et autres maladies par dépôts d'immunoglobulines monoclonales, Limoges, France.

Monoclonal gammopathy of renal significance (MGRS) regroups renal disorders caused by a monoclonal immunoglobulin without overt hematological malignancy. MGRS includes tubular disorders, glomerular disorders with organized deposits, and glomerular disorders with non-organized deposits, such as proliferative glomerulonephritis with monoclonal IgG deposits. Since glomerular involvement related to monotypic IgA deposits is poorly described we performed retrospective analysis and defined clinico-biological characteristics, renal pathology, and outcome in 19 referred patients. This analysis allowed distinction between 2 types of glomerulopathies, α-heavy chain deposition disease (5 patients) and glomerulonephritis with monotypic IgA deposits (14 patients) suggestive of IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits in 12 cases. Clinicopathologic characteristics of α-heavy chain deposition disease resemble those of the γ-heavy chain disease, except for a higher frequency of extra-capillary proliferation and extra-renal involvement. IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits should be differentiated from diseases with polytypic IgA deposits, given distinct clinical, histological, and pathophysiological features. Similarly to IgG-proliferative glomerulonephritis with monoclonal immunoglobulin deposits, overt hematological malignancy was infrequent, but sensitive serum and bone marrow studies revealed a subtle plasma cell proliferation in most patients with IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Anti-myeloma agents appeared to favorably influence renal prognosis. Thus, potential progression towards symptomatic IgA multiple myeloma suggests that careful hematological follow-up is mandatory. This series expands the spectrum of renal disease in MGRS.
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http://dx.doi.org/10.1016/j.kint.2016.10.026DOI Listing
March 2017

Asymptomatic circulating T-cell clone cause renal polymorphic inflammatory fibrosis.

Clin Exp Nephrol 2017 Oct 26;21(5):781-786. Epub 2016 Dec 26.

Département de Néphrologie et Transplantation d'organes et Centre de référence des maladies rénales rares, CHU Rangueil, Toulouse, France.

Background: Renal complications of non-Hodgkin lymphoma encompass a wide spectrum of monoclonal Ig-related pathologies. Clonal circulating T cells can also be associated with non-renal autoimmune disorders induced by overproduction of specific patterns of cytokines or unbalanced lymphocytes sub-populations.

Methods: Immunophenotyping of circulating T cells and TCR gene restriction analysis using Biomed-2 protocol. NF-κB staining and mRNA quantification of inflammatory genes in HK-2 epithelial renal cells exposed to supernatants of peripheral blood mononuclear cells with clonal T-cell population.

Results: Here, we could identify a persistent clonal T-cell population, only characterized by in-depth immunophenotyping of circulating lymphocytes and using multiplex PCR analysis of TCR gene rearrangements, in two patients with polymorphic inflammatory renal fibrosis of unknown origin. Using an in vitro approach, we could demonstrate that peripheral blood mononuclear cells including the clonal population can trigger a phenotype switch of epithelial renal cells from a quiescent state to a pro-inflammatory state characterized by NF-κB nuclear translocation and overexpression of inflammatory cytokine or chemokine.

Conclusion: These preliminary data suggest that circulating T-cell clones may directly activate epithelial renal cells or promote a T-/B-cell population with autoimmune reactive properties against kidney cells, which, in the absence of overt renal lymphoma infiltration, lead to the subsequent inflammatory renal fibrotic phenotype.
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http://dx.doi.org/10.1007/s10157-016-1373-6DOI Listing
October 2017

Pilot study for left ventricular imaging phenotype of patients over 65 years old with heart failure and preserved ejection fraction: the high prevalence of amyloid cardiomyopathy.

Int J Cardiovasc Imaging 2016 Sep 30;32(9):1403-1413. Epub 2016 May 30.

Department of Cardiology, University Hospital of Rangueil, 1, avenue Jean Poulhès, TSA 50032, 31059, Toulouse Cedex 9, France.

This study sought to phenotype patients over 65 years old with heart failure and preserved ejection fraction (HFpEF) using clinical available comprehensive cardiovascular imaging modalities. Forty-nine patients with HFpEF and without coronary artery disease underwent clinical evaluation, electrocardiography, echocardiography, cardiac magnetic resonance (CMR) and Tc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy (Tc-DPD). The mean population age was 76 ± 8 years. Most of the patients (53 %) were NYHA class II. Mean NT-Pro-NBNP level was 1961 ± 2372 pg/ml. CMR exhibited a hypertrophic cardiomyopathy or infiltrative pattern in 3 (6 %) and 15 (31 %) patients, respectively. In the latter subgroup, Tc-DPD was suggestive of transthyretin-related cardiac amyloidosis for nine (18 %) patients, while AL amyloidosis was proven in five patients (10 %) by extracardiac (n = 3, 6 %) or endomyocardial (n = 2, 4 %) biopsies-one patient declined tissue biopsy. Compared to patients with unspecified cardiomyopathy (n = 31), patients with amyloid cardiomyopathy (n = 15 or n = 14/proven) had less hypertension, lower systolic blood pressure and higher NT-pro BNP level. Their electrocardiogram showed lowest QRS voltage and longer QRS duration. Left ventricular (LV) pattern was characterized by a more pronounced LV hypertrophy, a smaller ejection fraction and a decrease of global longitudinal strain associated with an increase of longitudinal strain apical-to-basal ratio. In patients over 65 years, HFpEF is a heterogeneous syndrome with at least a 29 % prevalence of amyloid cardiomyopathy. Combined CMR and Tc-DPD are helpful imaging tools for accurate phenotyping of patients amenable to histopathological diagnosis or genetic testing, and should be considered for proper management of this population. Further longitudinal investigations are needed to better clarify these preliminary results.
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http://dx.doi.org/10.1007/s10554-016-0915-zDOI Listing
September 2016

Improvement of Microstomia in Scleroderma after Carbon Dioxide Laser Treatment.

Case Rep Dermatol 2016 May-Aug;8(2):142-50. Epub 2016 May 24.

Department of Dermatology, Paul Sabatier University, Toulouse, France.

Limited mouth opening (LMO) is a frequent complication of systemic sclerosis (SS). Its management is complex and there are limited treatment options. We report four patients with SS and severe LMO [interincisal distance (IID) <30 mm] treated with pulsed carbon dioxide (CO2) laser. Pulsed CO2 laser treatment of the white lips was performed after all patients had signed a written informed consent in the absence of alternative treatment. Treatment was carried out under locoregional anaesthesia using a Sharplan 30C CO2 laser in the Silk Touch® resurfacing mode. One to three laser sessions were performed at intervals of 8-12 months between sessions. Assessments were performed at 3 and 12 months with measurement of the IID using a ruler, calculation of the Mouth Handicap in Systemic Sclerosis (MHISS) scale and global evaluation by the patients. Adverse events were also reported. In all four patients, an improvement in IID occurred 3 months after the first session with a mean gain of +5 mm (range: 2-7). At 12 months, a mean gain of +8.5 mm (range: 7-10) in IID was observed. The MHISS score decreased by a mean of •14 (range: 11-17). All patients showed improvement of lip flexibility or mouth opening, allowing better phonation and mastication and easier dental care. Adverse effects were transient erythema and/or dyschromia. CO2 laser appears to be effective and well tolerated in the improvement of LMO in SS.
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http://dx.doi.org/10.1159/000445821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924459PMC
July 2016

Short- and long-term outcomes of AL amyloidosis patients admitted into intensive care units.

Br J Haematol 2016 09 12;174(6):868-75. Epub 2016 Jun 12.

Département de Néphrologie et Transplantation d'organes, Centre de référence des maladies rénales rares, CHU de Toulouse, Toulouse, France.

Amyloidosis is a rare and threatening condition that may require intensive care because of amyloid deposit-related organ dysfunction or therapy-related adverse events. Although new multiple myeloma drugs have dramatically improved outcomes in AL amyloidosis, the outcomes of AL patients admitted into intensive care units (ICUs) remain largely unknown. Admission has been often restricted to patients with low Mayo Clinic staging and/or with a complete or very good immunological response at admission. In a retrospective multicentre cohort of 66 adult AL (n = 52) or AA (n = 14) amyloidosis patients, with similar causes of admission to an ICU, the 28-d and 6-month survival rates of AA patients were significantly higher compared to AL patients (93% vs. 60%, P = 0·03; 71% vs. 45%, P = 0·02, respectively). In AL patients, the simplified Index of Gravity Score (IGS2) was the only independent predictive factor for death by day 28, whereas the Mayo-Clinic classification stage had no influence. In Cox's multivariate regression model, only cardiac arrest and on-going chemotherapy at ICU admission significantly predicted death at 6 months. Short-term outcomes of AL patients admitted into an ICU were mainly related to the severity of the acute medical condition, whereas on-going chemotherapy for active amyloidosis impacted on long-term outcomes.
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http://dx.doi.org/10.1111/bjh.14135DOI Listing
September 2016

Outcomes of patients with Goodpasture syndrome: A nationwide cohort-based study from the French Society of Hemapheresis.

J Autoimmun 2016 09 4;73:24-9. Epub 2016 Jun 4.

CHU de Toulouse, Département de Néphrologie et Transplantation d'Organes, Centre de Référence des maladies rénales rares, Hôpital Rangueil, Université Paul Sabatier - Toulouse III, Toulouse, France; INSERM U1048 (équipe 12), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France. Electronic address:

The overall and renal outcomes of patients with Goodpasture syndrome (GS), a rare autoimmune disorder characterized by circulating anti-GBM antibodies and rapidly progressive glomerulonephritis and/or pulmonary hemorrhage, have mostly been reported in small-sized cohorts or by aggregating patients receiving a variety of therapies that include aggressive (i.e., combined plasma exchanges, corticosteroids, and cyclophosphamide) and less aggressive (i.e., either plasma exchanges or immunosuppressive drugs, or no treatment). To address the prognosis of GS patients with relatively homogeneous management including plasma exchanges, we conducted a multicenter retrospective study on GS patients included in the registry of the French Society of Hemapheresis. 122 patients were included (kidney alone (n = 28), lung alone (n = 5), or combined involvement (n = 89)). All 122 patients received plasma exchanges (median number of sessions: 13 [9-17]), either alone (n = 8) or associated with combined corticosteroids and oral or IV cyclophosphamide (n = 101) or with corticosteroids alone (n = 12) or cyclophosphamide alone (n = 2). One-year survival was 86.9%. 7/16 patients died from severe infection. In multivariate analyses (Cox's regression model), being aged <60 years, and number of plasma exchanges were correlated to overall survival. The use of alternative immunosuppressive drugs (because of refractory or relapsing GS) was correlated to mortality at one year. Superiority of oral cyclophosphamide compared to intravenous intake was close to significant. Using a logistic regression model, renal survival in patients alive at 1 year was only predicted by serum creatinine <500 μmol/L at presentation. This large series describes the predictive factors for overall and renal survival of GS patients treated by plasma exchanges. Interventional studies that compare oral and intravenous cyclophosphamide, as well as testing new immunosuppressive therapies, are warranted.
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http://dx.doi.org/10.1016/j.jaut.2016.05.015DOI Listing
September 2016