G. Touchard

Institut Pprime, Chasseneuil, Poitou-Charentes, France

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Publications (363)702.83 Total impact

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    ABSTRACT: Randall-type heavy chain deposition disease (HCDD) is a rare disorder characterized by glomerular and peritubular amorphous deposits of a truncated monoclonal immunoglobulin (Ig) heavy chain (HC) bearing a deletion of the first constant domain (CH1). We created a transgenic mouse model of HCDD using targeted insertion in the Ig kappa locus of a human HC extracted from a HCDD patient. Our strategy allows the efficient expression of the human HC in mouse B and plasma cells and conditional deletion of the CH1 domain reproduces the major event underlying HCDD. We show that the deletion of the CH1 domain dramatically reduced serum HC levels. Strikingly, even with very low serum level of truncated monoclonal HC, histological studies revealed typical Randall-type renal lesions that were absent in mice expressing the complete human HC. Bortezomib-based treatment resulted in a strong decrease of renal deposits. We further demonstrated that this efficient response to proteasome inhibitors mostly relies on the presence of the isolated truncated HC that sensitizes plasma cells to bortezomib through an elevated unfolded protein response (UPR). This new transgenic model of HCDD efficiently recapitulates the pathophysiological features of the disease and demonstrates that the renal damage in HCDD relies on the production of an isolated truncated HC which, in the absence of a LC partner, displays a high propensity to aggregate even at very low concentration. It also brings new insights into the efficacy of proteasome inhibitor-based therapy in this pathology. Copyright © 2015 American Society of Hematology.
    Blood 06/2015; DOI:10.1182/blood-2015-03-630277 · 10.43 Impact Factor
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    ABSTRACT: Abnormal regulation of the alternative pathway of the complement system is a well-described trigger of microangiopathy leading to atypical hemolytic uremic syndrome (aHUS). However, the involvement of complement dysregulation in distal angiopathy has not been reported in adults. We describe the clinical course of a patient with severe distal angiopathy (amputation of all fingers and toes) followed 3 years later by aHUS with end-stage renal disease. This course was attributed to a circulating monoclonal immunoglobulin A λ light chain (IgAλ) with unusual properties: it bound complement factor H (CFH) and impaired CFH-glycosaminoglycan interaction and cell-surface protection. Local complement activation with distal angiopathy and microvascular injury was suggested by deposition of IgA, C4d, and C5b-9 in limb and preglomerular arteries. We therefore postulated that the monoclonal IgAλ inhibited activity of endothelial cell-bound CFH, which led to local activation of complement, vasoconstriction (distal angiopathy), and aHUS. While the patient was dependent on dialysis and plasma exchange, treatment with the anti-C5 antibody eculizumab induced remission of distal angiopathy and aHUS. During eculizumab treatment, kidney transplantation was performed. The patient had normal kidney function at the 3-year follow-up. We suggest that the association of distal angiopathy and aHUS in this patient is clearly linked to anti-CFH properties of the monoclonal IgAλ. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 05/2015; DOI:10.1053/j.ajkd.2015.03.039 · 5.76 Impact Factor
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    ABSTRACT: Kidney diseases associated with immunoglobulin M (IgM) monoclonal gammopathy are poorly described, with few data for patient outcomes and renal response. Case series. 35 patients from 8 French departments of nephrology were retrospectively studied. Inclusion criteria were: (1) detectable serum monoclonal IgM, (2) estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m(2) and/or proteinuria with protein excretion > 0.5g/d and/or microscopic hematuria, and (3) kidney biopsy showing monoclonal immunoglobulin deposits and/or lymphomatous B-cell renal infiltration. All patients received chemotherapy, including rituximab-based regimens in 8 cases. Patients were classified into 3 groups according to renal pathology: glomerular AL amyloidosis (group 1; n=11), nonamyloid glomerulopathies (group 2; n=15, including 9 patients with membranoproliferative glomerulonephritis), and tubulointerstitial nephropathies (group 3; n=9, including cast nephropathy in 5, light-chain Fanconi syndrome in 3, and isolated tumor infiltration in 1). Posttreatment hematologic response (≥50% reduction in serum monoclonal IgM and/or free light chain level) and renal response (≥50% reduction in 24-hour proteinuria or eGFR≥30mL/min/1.73m(2) in patients with glomerular and tubulointerstitial disorders, respectively). Nephrotic syndrome was observed in 11 and 6 patients in groups 1 and 2, respectively. Patients in group 3 presented with acute kidney injury (n=7) and/or proximal tubular dysfunction (n=3). Waldenström macroglobulinemia was present in 26 patients (8, 12, and 6 in groups 1, 2, and 3, respectively). Significant lymphomatous interstitial infiltration was observed in 18 patients (4, 9, and 5 patients, respectively). Only 9 of 29 evaluable patients had systemic signs of symptomatic hematologic disease (2, 5, and 2, respectively). In groups 1, 2, and 3, respectively, hematologic response was achieved after first-line treatment in 3 of 9, 9 of 10, and 5 of 6 evaluable patients, while renal response occurred in 5 of 10, 9 of 15, and 5 of 8 evaluable patients. Retrospective study; insufficient population to establish the impact of chemotherapy. IgM monoclonal gammopathy is associated with a wide spectrum of renal manifestations, with an under-recognized frequency of tubulointerstitial disorders. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 05/2015; DOI:10.1053/j.ajkd.2015.03.035 · 5.76 Impact Factor
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    ABSTRACT: Markers of epithelial-mesenchymal transition (EMT) may identify patients at high risk of graft fibrogenesis who could benefit from early calcineurin inhibitor (CNI) withdrawal. In a randomized, open-label, 12-month trial, de novo kidney transplant patients received cyclosporine, enteric-coated mycophenolate sodium (EC-MPS) and steroids to month 3. Patients were stratified as EMT+ or EMT- based on month 3 biopsy, then randomized to start everolimus with half-dose EC-MPS (720 mg/day) and cyclosporine withdrawal (CNI-free) or continue cyclosporine with standard EC-MPS (CNI). The primary endpoint was progression of graft fibrosis (interstitial fibrosis/tubular atrophy [IF/TA] grade increase ≥1 between months 3-12) in EMT+ patients. 194 patients were randomized (96 CNI-free, 98 CNI); 153 (69 CNI-free, 84 CNI) were included in histological analyses. Fibrosis progression occurred in 46.2% (12/26) CNI-free EMT+ patients versus 51.6% (16/31) CNI EMT+ patients (p = 0.68). Biopsy-proven acute rejection (BPAR, including subclinical events) occurred in 25.0% and 5.1% of CNI-free and CNI patients, respectively (p < 0.001). In conclusion, early CNI withdrawal with everolimus initiation does not prevent interstitial fibrosis. Using this CNI-free protocol, in which everolimus exposure was relatively low and administered with half-dose EC-MPS, CNI-free patients were overwhelmingly under-immunosuppressed and experienced an increased risk of BPAR. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 03/2015; 15(5). DOI:10.1111/ajt.13132 · 6.19 Impact Factor
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    ABSTRACT: We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 02/2015; DOI:10.1111/ajt.13191 · 6.19 Impact Factor
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    ABSTRACT: Monoclonal gammopathy of renal significance (MGRS) regroups all renal disorders caused by a monoclonal immunoglobulin (MIg) secreted by a nonmalignant B-cell clone. By definition, patients with MGRS do not meet the criteria for overt multiple myeloma/B-cell proliferation, and the hematologic disorder is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). However, MGRS is associated with high morbidity due to the severity of renal and sometimes systemic lesions induced by the MIg. Early recognition is crucial, as suppression of MIg secretion by chemotherapy often improves outcomes. The spectrum of renal diseases in MGRS is wide, including old entities such as AL amyloidosis and newly described lesions, particularly proliferative glomerulonephritis with monoclonal Ig deposits and C3 glomerulopathy with monoclonal gammopathy. Kidney biopsy is indicated in most cases to determine the exact lesion associated with MGRS and evaluate its severity. Diagnosis requires integration of morphologic alterations by light microscopy, immunofluorescence (IF), electron microscopy, and in some cases by IF staining for Ig isotypes, immunoelectron microscopy, and proteomic analysis. Complete hematologic workup with serum and urine protein electrophoresis, immunofixation, and serum-free light-chain assay is required. This review addresses the pathologic and clinical features of MGRS lesions, indications of renal biopsy, and a proposed algorithm for the hematologic workup.Kidney International advance online publication, 21 January 2015; doi:10.1038/ki.2014.408.
    Kidney International 01/2015; 87(4). DOI:10.1038/ki.2014.408 · 8.52 Impact Factor
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    ABSTRACT: A 39-year-old female patient was admitted to explore chronic renal failure. Clinical history included silicone breast implants. Clinical exam was normal. Urinalysis revealed tubular proteinuria with Bence-Jones κ protein. Monoclonal Ig G κ and free monoclonal κ-light chains were revealed by serum protein immunoelectrophoresis. Bone marrow aspiration with karyotype analysis and skeletal radiologic survey were normal. Kidney biopsy revealed a peculiar pattern of proximal tubular cells with hypertrophy and clarification initially diagnosed as an osmotic nephrosis. Immunofluorescence study, including Ig light chains conjugates was normal. Immuno-electron microscopy finally revealed a crystalline light chain proximal tubulopathy κ Our case presents some peculiarities: the absence of hematologic malignancy sign and the young patient’s age. The silicone breast implants have been reported to be involved in the generation of monoclonal gammopathy.
    Human pathology 10/2014; 46(1). DOI:10.1016/j.humpath.2014.10.008 · 2.81 Impact Factor
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    ABSTRACT: Background: Genetic factors are suspected in the pathogenesis of IgA nephropathy, as well as in the course of IgA nephropathy progression towards end stage renal failure. UMOD polymorphism rs12917707 is known to associate with end stage renal failure of mixed aetiologies. Methods: We tested a large cohort of Caucasian patients for association of rs12917707 with IgA nephropathy showing a benign, stable course and with IgA nephropathy that progressed toward end stage renal failure. Results: No association was observed between either groups, and a non-significant trend was observed for more severe IgA nephropathy with the allele reported to protect against end stage renal failure of mixed aetiologies. Conclusion: We conclude that UMOD is unlikely to play a role in IgA nephropathy pathogenesis nor progression to end stage renal failure, and suggest that UMOD effects are restricted to some causes of renal disease, e.g. diabetes or hypertension.
    BMC Nephrology 08/2014; 15(1):138. DOI:10.1186/1471-2369-15-138 · 1.52 Impact Factor
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    ABSTRACT: Acute bilateral renal cortical necrosis (BRCN) has been reported following envenoming by exotic venomous snakes. Proatheris superciliaris is a rare viper with restricted distribution in east Africa. Very little information is available on envenoming by this species. We herein describe the case of a 60-year-old professional wildlife photographer who was bitten on his thumb while photographing an adult specimen of Proatheris superciliaris that he held at home in France. On admission, physical examination revealed severe hypertension and bruising with edema at the bite site. Within the following 24hours, he developed vomiting, diarrhea, acute lumbar pain and anuria. Laboratory tests showed acute kidney injury (serum creatinine 4.6 mg/dL), with thrombocytopenia, anemia and severe coagulopathy. Contrast-enhanced computed tomography scan revealed hypodense areas in the cortex of both kidneys consistent with diffuse BRCN. As no appropriate antivenom existed, only symptomatic care was given to the patient. Coagulation tests returned to normal within 48hours. The patient was placed on chronic hemodialysis, until he underwent successful kidney transplantation 18 months later. In developed countries, severe complications provoked by snakebites tend to be more frequent with the number of trendy exotic pets. Acute kidney injury, including BRCN, is a classic complication of viper bites. The present case of end-stage renal failure related to diffuse BRCN illustrates the potentially devastating effects of envenoming by Proatheris superciliaris. Clinicians in developed countries should be informed about renal disorders and other potentially fatal complications of venomous snake bites and seek urgent expert advice for optimizing clinical management. Education and coaching of envenomed patients and exotic snake owners is mandatory to prevent dramatic accidents.
    Toxicon 04/2014; DOI:10.1016/j.toxicon.2014.03.008 · 2.58 Impact Factor
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    ABSTRACT: Different associations between single nucleotide polymorphisms (SNPs) in cellular target, metabolism enzymes or transport proteins, and biopsy-proven acute rejection (BPAR) or adverse events have been reported in transplant patients receiving mycophenolate mofetil. This work aimed to study these in patients on enteric-coated mycophenolate sodium (EC-MPS). The study included 189 renal transplant patients from the DOMINOS trial. Fifteen SNPs in IMPDH2, IMPDH1, ABCC2, SLCO1B3, UGT1A8, UGT1A9, UGT2B7, CYP2C8, HUS1, and IL12A were genotyped in all patients. Associations between SNPs and the first event of BPAR or diarrhea were investigated using multivariate logistic regressions. Associations between SNPs and leukopenia or anemia at nine different visits between days 0 and 190 after transplantation were studied using time-dependent Cox proportional hazards regression models. Multivariate analyses showed that the CYP2C8 rs11572076 wild-type genotype was associated significantly with a lower risk of leukopenia [GG vs. GA: hazard ratio (95% confidence interval) 0.14 (0.03, 0.59), P=0.00783]. Higher EC-MPS doses and the UGT2B7 c.-840 G>A variant allele were associated with an increased risk of anemia [EC-MPS per unit dose increase: 1.004 (1.003, 1.005), P<0.0001; UGT2B7 GA vs. AA: 1.65 (1.12, 2.43), P=0.01043; GG vs. AA: 1.88 (1.23, 2.88), P=0.00343]. However, no significant association was found between any of the SNPs studied and diarrhea or BPAR. Two pharmacogenetic associations reported previously with mycophenolate mofetil were found in a population of 189 renal transplant patients treated with EC-MPS.
    Pharmacogenetics and Genomics 03/2014; DOI:10.1097/FPC.0000000000000045 · 3.45 Impact Factor
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    ABSTRACT: Renal involvement in light chain (LC) deposition disease (LCDD) is typically characterized by nodular glomerulosclerosis and nephrotic range proteinuria. Rare cases of LCDD without glomerular symptoms have been reported, but clinical and pathological characteristics of this entity remain poorly described. This multi-centre retrospective study included 14 patients with biopsy-proven renal LCDD and proteinuria <0.5 g/day at diagnosis. Baseline median serum creatinine was 281 (136-594) μmol/L, with a glomerular filtration rate of 20 (6-48) mL/min/1.73 m(2). A serum monoclonal immunoglobulin was detected in 12 cases and LC proteinuria only in 7, always of kappa isotype. Monoclonal gammopathy of undetermined significance/indolent multiple myeloma (MM) was diagnosed in nine cases, symptomatic MM in three cases. Hypertension was almost constant (10 of 14). Immunofluorescence studies of kidney biopsies showed linear kappa LC deposition along tubular basement membranes in all cases, with linear glomerular and vascular LC deposits in 11 and 10 patients, respectively. By light microscopy, tubulo-interstitial lesions were prominent in all patients and focal nodular glomerulosclerosis was only observed in two cases. Identification of LCDD led to initiation of chemotherapy in 12 cases. After a median follow-up of 25.5 months, five patients died and four progressed to end-stage renal disease. Renal response occurred in five of the eight patients who achieved sustained haematological response. LCDD can cause severe renal dysfunction, despite the absence of glomerular symptoms. Early identification of the disease and introduction of a chemotherapy targeting the underlying plasma cell disorder may preserve long-term renal prognosis.
    Nephrology Dialysis Transplantation 03/2014; 29(10). DOI:10.1093/ndt/gfu045 · 3.49 Impact Factor
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    ABSTRACT: The endogenous molecules high mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been identified as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. We analysed serum and urinary HMGB1 and IL-33 levels, all determined by enzyme-linked immunosorbent assay, in a cohort of 26 deceased renal transplant recipients. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to those before treatment. Moreover, both serum and urinary IL-33 (but not HMGB1) increase was positively correlated with cold ischemia time, from 30 min to 3 days post-transplantation. In vitro, human umbilical vein endothelial cells subjected to hypoxia conditions released both HMGB-1 and IL-33, while only the latter was further increased upon subsequent re-oxygenation. Finally, we postulate that leukocytes from renal recipient patients are targeted by both HMGB1 and IL-33, as suggested by increased transcription of their respective receptors (TLR2/4 and ST2L) shortly after transplantation. Consistent with this view, we found that iNKT cells, an innate-like T cell subset involved in IRI and targeted by IL-33 but not by HMGB1 was activated 1 hour post-transplantation. Altogether, these results are in keeping with a potential role of IL-33 as an innate-immune mediator during kidney IRI in humans.
    PLoS ONE 02/2014; 9(2):e88742. DOI:10.1371/journal.pone.0088742 · 3.53 Impact Factor
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    ABSTRACT: In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA) induction, enteric-coated mycophenolate sodium (EC-MPS: 2160 mg/day to week 6, 1440 mg/day thereafter), and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal). The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR) graft loss, death, or loss to follow-up) occurred in 21.4% (95% CI 11.8-31.0%) of steroid avoidance patients and 16.4% (95% CI 7.1-25.7%) of steroid withdrawal patients by month 36 (P = 0.46). BPAR had occurred in 20.0% and 11.5%, respectively (P = 0.19). The incidence of adverse events with a suspected relation to steroids during months 6-36 was 22.9% versus 37.1% (P = 0.062). By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months.
    Journal of Transplantation 01/2014; 2014:171898. DOI:10.1155/2014/171898
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    ABSTRACT: Acute bilateral renal cortical necrosis (BRCN) has been reported following envenoming by exotic venomous snakes. Proatheris superciliaris is a rare viper with restricted distribution in east Africa. Very little information is available on envenoming by this species. We herein describe the case of a 60-year-old professional wildlife photographer who was bitten on his thumb while photographing an adult specimen of Proatheris superciliaris that he held at home in France. On admission, physical examination revealed severe hypertension and bruising with edema at the bite site. Within the following 24hours, he developed vomiting, diarrhea, acute lumbar pain and anuria. Laboratory tests showed acute kidney injury (serum creatinine 4.6 mg/dL), with thrombocytopenia, anemia and severe coagulopathy. Contrast-enhanced computed tomography scan revealed hypodense areas in the cortex of both kidneys consistent with diffuse BRCN. As no appropriate antivenom existed, only symptomatic care was given to the patient. Coagulation tests returned to normal within 48hours. The patient was placed on chronic hemodialysis, until he underwent successful kidney transplantation 18 months later. In developed countries, severe complications provoked by snakebites tend to be more frequent with the number of trendy exotic pets. Acute kidney injury, including BRCN, is a classic complication of viper bites. The present case of end-stage renal failure related to diffuse BRCN illustrates the potentially devastating effects of envenoming by Proatheris superciliaris. Clinicians in developed countries should be informed about renal disorders and other potentially fatal complications of venomous snake bites and seek urgent expert advice for optimizing clinical management. Education and coaching of envenomed patients and exotic snake owners is mandatory to prevent dramatic accidents.
    Toxicon 01/2014; · 2.58 Impact Factor
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    ABSTRACT: In this ancillary study of the CONCEPT trial, we studied the role of CsA withdrawal at 3 months (3M) post-transplant on the intensity of epithelial phenotypic changes (EPC, an early marker for kidney fibrogenesis) on the 12M surveillance biopsy. Although conversion from CsA to Sirolimus (SRL) at 3M was reported to have improved mean graft function at 12M, it did not reduce the score of EPC (1.73±1.15 in the SRL group vs 1.87±1 in the CsA group, p=0.61). Acute rejection, which had occurred twice more frequently in SRL converted patients included here, was associated with 12M EPC. Interestingly, we observed that the patients durably exposed to CsA and who developed 12M EPC had a significant progression of blood pulse pressure (pp) from 1 to 6M post-transplantation (Δpp=+12.3mmHg, p=0.0035). pp at 4, 6 and 9M and pp progression from 1 to 6M were significantly associated with the development of EPC at 12M in renal grafts. Logistic regression analysis revealed that a high 6M pp (≥60 mmHg) was an independent risk factor for 12M EPC with an odds ratio of 2.25 per additional 10mm Hg pp (95%CI: 1.14-4.4, p=0.02) after adjustment with recipient's and donor's age, acute rejection incidence and immunosuppressive regimen. A post hoc analysis of the data collected in the whole population CONCEPT study revealed that pp was significantly higher at 6 months in patients maintained on CsA, and that at this time point pp correlated negatively with GFR at 1 year. This article is protected by copyright. All rights reserved.
    Transplant International 11/2013; 27(4). DOI:10.1111/tri.12253 · 3.16 Impact Factor
  • Néphrologie & Thérapeutique 11/2013; 9(6):451. DOI:10.1016/j.nephro.2013.03.002 · 0.55 Impact Factor
  • Néphrologie & Thérapeutique 09/2013; 9(5):321. DOI:10.1016/j.nephro.2013.07.008 · 0.55 Impact Factor
  • Néphrologie & Thérapeutique 09/2013; 9(5):330. DOI:10.1016/j.nephro.2013.07.033 · 0.55 Impact Factor
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    ABSTRACT: BACKGROUND: Fibrillary glomerulonephritis (GN) is a rare disorder with poor renal prognosis. Therapeutic strategies, particularly the use of immunosuppressive drugs, are debated. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 27 adults with fibrillary GN referred to 15 nephrology departments in France between 1990 and 2011 were included. All patients were given renin-angiotensin system blockers and 13 received immunosuppressive therapy, including rituximab (7 patients) and cyclophosphamide (3 patients). OUTCOMES & MEASUREMENTS: Clinical and histologic features of patients and kidney disease outcome. Renal response was defined as a >50% decrease in 24-hour proteinuria with <15% decline in estimated glomerular filtration rate (eGFR). RESULTS: All patients presented with proteinuria, associated with nephrotic syndrome (41%), hematuria (73%), and hypertension (70%). Baseline median eGFR was 49 mL/min/1.73 m(2). Eight patients had a history of autoimmune disease and none had evidence of hematologic malignancy during follow-up. Light microscopic studies showed mesangial GN (70%), predominant pattern of membranous GN (19%), or membranoproliferative GN (11%). By immunofluorescence, immunoglobulin G (IgG) deposits (IgG4, 15/15; IgG1, 9/15) were polyclonal in 25 cases. Serum IgG subclass distribution was normal in the 6 patients tested. After a median 46-month follow-up, renal response occurred in 6 of 13 patients who received immunosuppressive therapy with rituximab (5 patients) or cyclophosphamide (1 patient). Of these, 5 had a mesangial or membranous light microscopic pattern, and median eGFR before therapy was 76 mL/min/1.73 m(2). In contrast, chronic kidney disease progressed in 12 of 14 patients who were not given immunosuppressive therapy, 10 of whom reached end-stage renal disease. LIMITATIONS: Number of patients, retrospective study, use of multiple immunosuppressive regimens. CONCLUSIONS: The therapeutic approach in fibrillary GN remains challenging. The place of immunosuppressive therapy, particularly anti-B-cell agents, needs to be assessed in larger collaborative studies.
    American Journal of Kidney Diseases 06/2013; 62(4). DOI:10.1053/j.ajkd.2013.03.031 · 5.76 Impact Factor
  • Guy Touchard, Frank Bridoux
    American Journal of Kidney Diseases 04/2013; 61(4):644. DOI:10.1053/j.ajkd.2013.01.014 · 5.76 Impact Factor

Publication Stats

3k Citations
702.83 Total Impact Points

Institutions

  • 2015
    • Institut Pprime
      Chasseneuil, Poitou-Charentes, France
  • 1981–2014
    • Université de Poitiers
      Poitiers, Poitou-Charentes, France
  • 2012
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1989–2012
    • Centre Hospitalier Universitaire de Poitiers
      Poitiers, Poitou-Charentes, France
  • 2005–2009
    • Ecole Nationale Supérieure de Mécanique et d'Aérotechnique
      • Laboratory of Aerodynamics Research (LEA)
      Chasseneuil, Poitou-Charentes, France
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 1982–2008
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2004
    • University of Buenos Aires
      • Faculty of Engineering
      Buenos Aires, Buenos Aires F.D., Argentina
  • 2002
    • Instituto Tecnológico de Celaya
      Celaya, Guanajuato, Mexico
    • The American Institute of Aeronautics and Astronautics
      Reston, Virginia, United States
  • 2000
    • Max Planck Institute of Biophysics
      Frankfurt, Hesse, Germany
  • 1999
    • Centre Hospitalier Universitaire de Limoges
      Limages, Limousin, France
  • 1997–1999
    • McMaster University
      • Department of Engineering Physics
      Hamilton, Ontario, Canada
  • 1988–1998
    • Aichi Institute of Technology
      Okazaki, Aichi, Japan