Search

Antibody production by plasma cells and generation of long-term memory B-cells are positively regulated by Tfh cells and negatively regulated by Tfr cells in germinal centers. However, the precise role of Tfr cells in controlling antibody production is still unclear. We have previously shown that Tfh and Tfr cells both express IL-1R1, while only Tfr cells express the IL-1R2 decoy and IL-1Ra antagonist receptors. To study the role of these receptors in the regulation of the B cell response by Tfh and/or Tfr cells, we generated mice with knockout of IL-1 receptors in Tfh and/or Tfr cells and measured antibody production and cell activation upon immunization. We showed that IL-1β concentration is increased in the draining lymph node after immunization. Antigen-specific antibody levels and cell activation phenotypes indicated that IL-1β can activate both Tfh and Tfr cells through IL-1R1 stimulation. Surprisingly, IL-1R2 and IL-1Ra expression on Tfr cells does not block IL-1 activation of Tfh cells, but rather prevents IL-1/IL-1R1-mediated early activation of Tfr cells. IL-1Rs similarly regulate antibody response against autoantigens and its related pathophysiology in an experimental lupus model. Altogether, these results show that IL-1R1 inhibitory receptors expressed by Tfr cells prevent their own activation and suppressive function, thus licensing IL-1-mediated activation of Tfh cells after immunization.One Sentence SummaryFunctional knockout of IL-1 agonist (R1) and antagonist (R2 and Ra) receptors reveals that IL-1-R2 and -Ra on Tfr cells prevent their own early activation to license the expansion and activation of Tfh cells after immunization.

International audience; Exostosin (EXT) 1 and EXT2 proteins are recently discovered major components of the subepithelial deposits in a subset of patients with membranous nephropathy (MN).1,2 Although the detection of EXT1/2 seems to be a distinctive feature of MN related to systemic lupus erythematosus (SLE),1 the exact frequency of EXT-positive, SLE-associated MN (SLE-MN) and its potential clinical significance are not well determined.Here, we retrospectively evaluated 86 consecutive patients with biopsy-proven pure class 5 SLE-MN diagnosed between January 2010 and December 2018 in 2 nephropathology centers (La Pitié Salpêtrière and Tenon hospitals) in Paris, France; mixed classes (3 + 5 and 4 + 5 of the 2003 ISN/Renal Pathology Society classification)3 were excluded.

Resume Introduction La peau est l’organe le plus frequemment atteint par la maladie des emboles de cristaux de cholesterol (MECC) qui peut parfois se manifester initialement uniquement par des symptomes dermatologiques. Nous rapportons l’observation d’une MECC associee a une erythrodermie a l’origine d’un diagnostic errone de syndrome d’hypersensibilite medicamenteuse (HM). Observation Une femme de 66 ans presentait une erythrodermie a la suite de l’introduction d’allopurinol quelques mois plus tot. On notait une degradation recente de la fonction renale avec une creatininemie a 523 μmol/L et une hypereosinophilie (HE) a 5666/mm3. Les criteres n’etaient finalement pas suffisants pour retenir le diagnostic d’HM. En examinant les anciennes numerations il etait constate une HE fluctuante remontant a plus de 10 mois avant l’introduction d’allopurinol. La biopsie renale permettait de diagnostiquer une MECC. Conclusion Nous rapportons une presentation evocatrice d’une HM dans une MECC, dont les symptomes cliniques sont lies a l’HE et non pas aux emboles.

Simple Summary Assessing the tumor response to chemotherapy is a paramount predictive step to improve patient care. Infrared spectroscopy probes the chemical composition of samples, and in combination with statistical multivariate processing, presents the capacity to highlight subtle molecular alterations associated with malignancy characteristics. Microscopic infrared imaging of tissue samples reveals spectral heterogeneity within histological structures, providing a new approach to characterize tumoral heterogeneity. We have taken advantage of the analytical capabilities of mid-infrared spectral imaging to implement a classification model to predict the response of a tumor to chemotherapy. Our development was demonstrated in muscle-invasive bladder cancer (MIBC) by comparing samples from responders and non-responders to neoadjuvant chemotherapy. Abstract Background: Neoadjuvant chemotherapy (NAC) improves survival in responder patients. However, for non-responders, the treatment represents an ineffective exposure to chemotherapy and its potential adverse events. Predicting the response to treatment is a major issue in the therapeutic management of patients, particularly for patients with muscle-invasive bladder cancer. Methods: Tissue samples of trans-urethral resection of bladder tumor collected at the diagnosis time, were analyzed by mid-infrared imaging. A sequence of spectral data processing was implemented for automatic recognition of informative pixels and scoring each pixel according to a continuous scale (from 0 to 10) associated with the response to NAC. The ground truth status of the responder or non-responder was based on histopathological examination of the samples. Results: Although the TMA spots of tumors appeared histologically homogeneous, the infrared approach highlighted spectral heterogeneity. Both the quantification of this heterogeneity and the scoring of the NAC response at the pixel level were used to construct sensitivity and specificity maps from which decision criteria can be extracted to classify cancerous samples. Conclusions: This proof-of-concept appears as the first to evaluate the potential of the mid-infrared approach for the prediction of response to neoadjuvant chemotherapy in MIBC tissues.

International audience

The recent years have seen a surge in interest in determining the dielectric constant of biological tissues in the microwave domain. The tissues can be classified and differentiated without radiation by using a microwave sensor. The atherosclerotic plaque of the carotid artery, which is now predominantly classified by ultrasonography and the CT scanner was not studied yet. Ultrasonography describes the level of echogenicity of the plaques, and proposes that as a representation of the plaque's composition. In this study, a microwave subwavelength resonator was employed to measure 20 carotid artery plaques and compare the results with ultrasound b-mode images. The results of the study show a correlation between the echogenicity levels and the dielectric constant of the tissues investigated. The way in which it will be evaluated in the future is how it compares to other radiological techniques.

Chronic nephrotoxicity with potentially irreversible lesions is a major concern regarding calcineurin inhibitor (CNI) treatment in children with severe forms of idiopathic nephrotic syndrome (INS). We retrospectively included all children on CNI for steroid-dependent INS with a duration of CNI treatment of more than 1 year. Only patients in whom CNI could not be replaced by mycophenolate mofetil were included. All included patients underwent a kidney biopsy. All results were expressed as median and range. Twenty-one children (6 girls) were included. Age at disease onset was 49 (29–66) months and treatment duration on CNI was 30 (20–45) months. Age at kidney biopsy was 108 (78–170) months. Number of relapses was 7 (3–9) since disease onset. Serum creatinine level was transiently and moderately increased in two patients. Kidney biopsy revealed minimal change disease in 20/21 patients and focal segmental glomerulosclerosis in 1/21. Evidence for chronic CNI nephrotoxicity was found in one patient revealed by arteriolar hyalinosis and fibrosis in 50% of glomeruli. CNI-induced chronic nephrotoxicity was infrequent. In patients who require long-term and/or high-dose CNI treatment, kidney biopsies might be useful to exclude chronic CNI-induced lesions.

Action myoclonus – renal failure is a rare syndrome associated with a progressive myoclonic epilepsy and renal impairment that may lead to end-stage renal failure. It is an autosomal recessive genetic disease related to a loss-of-function mutation in SCARB2, which encodes for lysosomal integral membrane protein type 2. Renal involvement is poorly described, and we report here the first electron microscopy renal analysis after having performed a kidney biopsy in a 31-year-old Gambian patient.

Graft microvasculature is a major target of donor-specific antibodies (DSA) and endothelial damage is direct evidence of antibody-mediated rejection (ABMR). Using immunohistochemistry, we analyzed the expression of three microvascular endothelial activation markers (fascin, vimentin, and hsp47), suggestive of endothelial-to-mesenchymal transition (EndMT) in 351 graft biopsies from 248 kidney recipients, with concomitant screening of circulating antihuman leukocyte antigen (HLA) DSA at the time of the biopsy. The factors associated with EndMT marker expression were DSA and the presence of microvascular inflammation (MI). EndMT expressing grafts had significantly more allograft loss compared to EndMT negative grafts (P < .0001). The expression of EndMT markers positively correlated with anti-HLA DSA class II mean fluorescence intensity (MFI) levels and especially identified DQ and DR antibodies as being more closely associated with microvascular injury. Moreover, only DSA linked to positive EndMT score affected allograft survival, regardless of DSA MFI levels or presence of C4d deposition. Thus, EndMT markers could represent a clinically relevant tool for early identification of ongoing endothelial injury, harmful DSA, and patients at high risk for allograft failure.

BackgroundRenal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients.MethodsAll SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications.ResultsTwo hundred and fifty-six TJRBs—119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics—were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups.ConclusionsTJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.

The objective of this systematic review was to summarize our current knowledge of the role of immunohistochemistry (IHC) markers for identifying mismatch repair-deficient (MMRd) tumors in endometrial cancer (EC). Identification of MMRd tumors, which occur in 13% to 30% of all ECs, has become critical for patients with colorectal and endometrial cancer for therapeutic management, clinical decision making, and prognosis. This review was conducted by two authors applying the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the following terms: “immunohistochemistry and microsatellite instability endometrial cancer” or “immunohistochemistry and mismatch repair endometrial cancer” or “immunohistochemistry and mismatch repair deficient endometrial cancer”. Among 596 retrieved studies, 161 fulfilled the inclusion criteria. Articles were classified and presented according to their interest for the diagnosis, prognosis, and theragnostics for patients with MMRd EC. We identified 10, 18, and 96 articles using IHC expression of two, three, or four proteins of the MMR system (MLH1, MSH2, MHS6, and PMS2), respectively. MLH1 promoter methylation was analyzed in 57 articles. Thirty-four articles classified MMRd tumors with IHC markers according to their prognosis in terms of recurrence-free survival (RFS), overall survival (OS), stage, grade, and lymph node invasion. Theragnostics were studied in eight articles underlying the important concentration of PD-L1 in MMRd EC. Even though the role of IHC has been challenged, it represents the most common, robust, and cheapest method for diagnosing MMRd tumors in EC and is a valuable tool for exploring novel biotherapies and treatment modalities.

Purpose: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. Experimental Design: We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of IHC stainings. Genetic alterations were investigated using targeted next-generation sequencing. Results: Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an “immune-high” (IH) subtype (57% of the cases) and an “immune-low” (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (P < 0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Quantification of immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival. Conclusions: We have identified a subgroup of cHCC-CCA that displays features of an ongoing intratumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.

Background The coronavirus disease 2019 (COVID-19) may be associated with kidney injury, which may impact patient's prognosis. Methods We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury (AKI) and/or proteinuria and underwent a kidney biopsy in Paris and its metropolitan area. Results Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between 8 March and 19 May 2020 were included. The median age was 63 years (interquartile range 52–69). Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney disease (25.5%), cardiac diseases (38.6%) and respiratory diseases (27.3%). Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%) and diarrhoea (23.4%). Almost all patients developed AKI (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy (CG) and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while 8 (17%) had an alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and CG was only observed in patients harbouring a combination of APOL1 risk variants. At the last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 had died. Conclusions This study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

Epidemiological studies support a strong link between organ fibrosis and epithelial cancers. Moreover, clinical and experimental investigations consistently indicate that these diseases intertwine and share strikingly overlapping features. As a deregulated response to injury occurring in all body tissues, fibrosis is characterized by activation of fibroblasts and immune cells, contributing to progressive deposition of extracellular matrix (ECM) and inflammation. Cancers are driven by genetic alterations resulting in dysregulated cell survival, proliferation and dissemination. However, non-cancerous components of tumour tissues including fibroblasts, inflammatory cells and ECM play key roles in oncogenesis and cancer progression by providing a pro-mutagenic environment where cancer cells can develop, favouring their survival, expansion and invasiveness. Additional commonalities of fibrosis and cancer are also represented by overproduction of growth factors, like transforming growth factor β, epithelial-to-mesenchymal transition, high oxidative stress, Hippo pathway dysfunctions and enhanced cellular senescence. Here, we review advances in the analysis of cellular and molecular mechanisms involved in the pathogenesis of both organ fibrosis and cancer, with particular reference to chronic kidney diseases and renal cell cancers. Most importantly, improved understanding of common features is contributing to the development of innovative treatment strategies targeting shared mechanisms.

Nephrotic range proteinuria has been reported during the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19). However, the pathological mechanisms underlying this manifestation are unknown. In this article, we present two cases of collapsing glomerulopathy (CG) associated with acute tubular necrosis during the course of COVID-19, and review the literature for similar reports. In our two cases, as in the 14 cases reported so far, the patients were of African ancestry. The 14 patients assessed had an APOL1 high-risk genotype. At the end of the reported period, two patients had died and five patients were still requiring dialysis. The 16 cases detailed in the present report strongly argue in favour of a causal link between SARS-CoV-2 infection and the occurrence of CG in patients homozygous for APOL1 high-risk genotype for which the term COVID-associated nephropathy (COVIDAN) can be put forward.

The discovery of circulating antibodies specific for native podocyte antigens has transformed the diagnostic workup and greatly improved management of idiopathic membranous nephropathy (iMN). In addition, their identification has clearly characterized iMN as a largely autoimmune disorder. Anti-PLA2R1 antibodies are detected in approximately 70% to 80% and anti-THSD7A antibodies in only 2% of adult patients with iMN. The presence of anti-THSD7A antibodies is associated with increased risk of malignancy. The assessment of PLA2R1 and THSD7A antigen expression in glomerular immune deposits has a better sensitivity than measurement of the corresponding autoantibodies. Therefore, in the presence of circulating anti-podocytes autoantibodies and/or enhanced expression of PLA2R1 and THSD7A antigens MN should be considered as primary MN (pMN). Anti-PLA2R1 or anti-THSD7A autoantibodies have been proposed as biomarkers of autoimmune disease activity and their blood levels should be regularly monitored in pMN to evaluate disease activity and predict outcomes. We propose a revised clinical workup flow for patients with MN that recommends assessment of kidney biopsy for PLA2R1 and THSD7A antigen expression, screening for circulating anti-podocytes antibodies, and assessment for secondary causes, especially cancer, in patients with THSD7A antibodies. Persistence of anti-podocyte antibodies for 6 months or their increase in association with nephrotic proteinuria should lead to the introduction of immunosuppressive therapies. Recent data have reported the efficacy and safety of new specific therapies targeting B cells (anti-CD20 antibodies, inhibitors of proteasome) in pMN which should lead to an update of currently outdated treatment guidelines., SCOPUS: re.j, info:eu-repo/semantics/published

International audience

Henoch-Schönlein purpura is the most common vasculitis in children. Its long-term prognosis depends on renal involvement. The management of Henoch-Schönlein purpura nephritis (HSPN) remains controversial. This study reports the prognosis of children with HSPN presenting with class 2 International Study of Kidney Disease in Children (ISKDC) nephritis.All children with HSPN class 2 diagnosed between 1995 and 2015 in four pediatric nephrology centers were included, and clinical and biological data were collected from the medical files. The primary endpoint was proteinuria remission defined as a proteinuria200 mg/L.Ninety-two children were included in the study with a median follow-up of 36 (6-120) months; 28% had nephrotic syndrome, 31% proteinuria3 g/L, 52% proteinuria between 1 and 3 g/L, and 18% proteinuria1 g/L. Forty-seven percent of patients received orally treatment with steroids alone, 37% received methylprednisolone pulses followed by steroids orally, 18% received no steroids. Although 85% reached remission during follow-up, 12% did not maintain complete remission over time so that only 75% remained in complete remission by the end of the follow-up. Univariate analysis found a higher likelihood of remission in patients with higher proteinuria at disease onset (p = 0.009). This trend was not found in the multivariate analysis after adjusting for treatments, as patients with higher proteinuria were most often treated with steroids.Our study shows that one fourth of patients with HSPN class 2 remain proteinuric and thus carry the risk of developing chronic kidney disease over the long term. This finding, together with the better outcome of patients treated with steroids, is in favor of using high-dose steroids orally or IV in these patients.

International audience; Background: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid disorders (AITDs). These conditions have been associated to abnormalities in circulating regulatory T cells (Tregs). We postulated that immune perturbations could be more pronounced at the thyroid tissue level.Methods: The phenotype of PBMCs and immune cells infiltrating thyroid tissue from 19 patients with HT, 21 patients with GD, and 30 controls has been analyzed by flow cytometry.Results: We report that blood and thyroid Treg cell subsets are similarly represented in all AITDs patients and controls. Increased Lymphoid tissue inducer (LTi)-like ILC3 and CXCR5+ PD-1hi CD4+ T follicular helper cells (Tfh) tissue-infiltrating cells, together with the prevalence of tertiary lymphoid structures (TLS) and germinal centers (GCs) represented a typical immune signature in all HT and 60% of GD patients. In the remaining group of GD patients, the absence of the aforementioned abnormalities was associated with a higher prevalence of ophthalmopathy.Conclusion: Tissue infiltrating Lymphoid Tissue inducer—like group 3 Innate Lymphoid cells and T follicular helper cells are increased in most thyroid autoimmune disease.

Objective.To report the incidence, predictors, and outcome of rituximab (RTX)-associated autoimmune disease flare.Methods.We conducted a retrospective study in a tertiary referral center from 2005 to 2015. Disease flare was defined as the onset of a new organ involvement or worsening of autoimmune disease within 4 weeks following RTX.Results.Among the 185 patients, we identified 7 disease flares (3.4%). All were due to type II mixed cryoglobulinemia vasculitis. Vasculitis flare occurred after a median time of 8 days (range 2–16) following RTX infusion and included acute kidney insufficiency (n = 7), purpura with cutaneous (n = 7), gastrointestinal (GI) tract involvement (n = 4), and myocarditis (n = 1). Patients with RTX-associated cryoglobulinemia vasculitis flare had these conditions more frequently: renal involvement (p = 0.0008), B cell lymphoproliferation (p = 0.015), higher level of cryoglobulin (2.1 vs 0.4 g/l, p = 0.0004), and lower level of C4 (0.02 vs 0.05, p = 0.023) compared to patients without flare after RTX (n = 43). Four patients (57%) died after a median time of 3.3 months. The 1-year survival rate was poorer in patients with vasculitis flare after RTX compared to their negative counterpart [43% (95% CI 18–100) vs 97% (95% CI 92–100), p < 0.001]. Immunofluorescence analysis of kidney biopsy in patients with worsening RTX-associated vasculitis highlighted the presence of RTX-, IgM-, and IgG1-positive staining of endomembranous deposits and thrombi within kidney lesions.Conclusion.RTX-associated cryoglobulinemia vasculitis flare is associated with high mortality rate. We provided evidence that kidney lesions are due to immune complex deposition and to glomerular obstruction by cryoglobulinemia and RTX.

PURPOSE OF REVIEW: Continuous expansion of our knowledge in the pathogenesis of membranous nephropathy possible by the identification of antibodies recognized specific podocytes antigens results in unprecedent patient management strategy. RECENT FINDINGS: Circulating anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin domain 7A (THSD7A) antibodies strongly relate with the modifications of podocytes biology leading to the new molecular diagnosis of membranous nephropathy. Immunization against THSD7A involves extra-renal mechanism. However, the pathway of anti-PLA2R immunization still remains unresolved. Experimental data highlight the crucial role of THSD7A in the attachment of podocytes to the glomerular basement membrane, rewarding the THSD7A pathogenicity, whereas the third of Koch's postulates is still not fulfilled for anti-PLA2R antibodies. The anti-PLA2R antibodies epitope spreading will possibly be even more specific marker improving the molecular classification of membranous nephropathy. Two immune epitopes have been identified in the N-terminal tail of THSD7A but without evidence of epitope spreading as for anti-PLA2R. SUMMARY: In 2019, the Kidney Diseases: Improving Global Outcomes guidelines recognized anti-PLA2R antibodies (but not anti-THSD7A antibodies) as a valuable molecular risk factor for the pejorative evolution of kidney function and recommended their monitoring for the diagnosis and the assessment of membranous nephropathy immune activity. Screening for malignancy is particularly advised in THSD7A-mediated membranous nephropathy., SCOPUS: ar.j, info:eu-repo/semantics/published

It is estimated that out of the 100,000 or more species of mushrooms worldwide, more than 100 are toxic. In the United States, the National Poison Data System reported 133,700 cases of mushroom exposure from 1999 to 2016, and 6136 cases in 2017.1, 2 Identifying the specific mushroom species involved is mandatory because specific treatment exists for some mushroom poisoning. A recent algorithm to group the multiple species and syndromes of mushroom poisoning into 6 presenting syndromes has been proposed by White et al., depending on the clinical presentation.3 Among severe mushroom intoxications, amatoxin syndrome accounts for 68% to 89% of fatalities.1 Mushroom poisoning usually causes gastroenteritis prodrome. Hepatotoxicity is rare but is associated with a limited group of mushrooms. Renal failure can be due to severe dehydration or to specific toxin damage. Early syndromes (onset of nausea and vomiting in

OBJECTIVES Transvenous renal biopsy is an alternative way to obtain kidney samples from patients with bleeding risk factors (e.g., antiplatelet therapy and anticoagulation or coagulation disorders). This study was undertaken to determine the safety and diagnostic yield of transvenous renal biopsy of critically ill patients. DESIGN Monocenter, retrospective, observational cohort study. SETTING A 26-bed French tertiary ICU. PATIENTS All patients undergoing in-ICU transvenous renal biopsy between January 2002 and February 2018. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Eighty patients (male/female sex ratio, 0.95; mean ± SD age, 47.3 ± 18.3 yr) were included. A histologic diagnosis was obtained for 77 patients (96.3%), with acute tubular necrosis being the most frequent: 23 (29.9%). A potentially treatable cause was found for 47 patients (58.7%). The numbers of patients with 0, 1, 2, or 3 factors (i.e., antiplatelet therapy, thrombopenia [< 150 G/L], and preventive or curative anticoagulation) at the time of the biopsy were, respectively: seven (8.8%), 37 (46.2%), 31 (38.7%), and five (6.3%). Four (5%) and two (2.5%) patients, respectively, had renal hematoma and macroscopic hematuria; none required any specific treatment. Six patients (7.5%) died in-ICU, and 90-day mortality was 8 of 80 (10%). No death was related to transvenous renal biopsy, and median biopsy-to-death interval was 38 days (interquartile range, 19.7-86 d). CONCLUSIONS Based on this cohort of ICU patients with acute kidney injury, transvenous renal biopsy was safe and obtained a high diagnostic yield for these selected critically ill patients, even in the presence of multiple bleeding risk factors.

A symposium on kidney stones and mineral metabolism held on December 2017 in Brussels, Belgium was the first international multidisciplinary conference of the International Collaborative Network on Kidney Stones and Mineral Metabolism. This meeting addressed epidemiology, underlying pathophysiological mechanisms, genetics, pathological, as well as clinical and research topics. The participants included clinicians and recognized experts in the field from Europe and the United States interacted closely during the symposium which promoted a chance to explore new frontiers in the field of kidney stone disease. This manuscript summarizes some of the major highlights of the meeting., info:eu-repo/semantics/published

Glomeruloid haemangioma (GH) is considered a specific marker of POEMS syndrome, despite some published GH cases unrelated to POEMS syndrome. To present two cases with GH and atypical presentations of Erdheim-Chester disease (ECD) or POEMS syndrome, as well as a retrospective monocentric study of histologically-confirmed GH. Clinical, biological and histological data of the patients is presented. In addition to the two presented cases, 11 GH histologically-confirmed cases were retrospectively identified. Six patients were female (46.2%; 95 CI: 12-64.9) and median age was 54 years (31-85). For 11 patients (84.6%; 95 CI: 65-104.2), a diagnosis of POEMS syndrome was retained, one patient had autoimmune hepatitis, and another had ECD. GH was localised to the trunk in 10 cases (76.9%; 95 CI: 54-99) and the legs in the other three. The median number of haemangiomas in the cohort was three (SD: 3.08). Median level of VEGF was 1,490 (610-12,000) ng/mL. All immunohistochemical staining for human herpesvirus 8 (HHV-8) was negative. Of the 13 cases of GH, of which two were not clear-cut POEMS syndrome, we report the first case of GH associated with ECD. In this cohort, all patients had high serum levels of VEGF but no in situ HHV-8 latent infection. We hypothesise that GH might be linked to a high level of VEGF in these two rare diseases.

Introduction Apolipoprotein CII amyloidosis (AApoCII) is a rare form of amyloidosis. Here, we report a novel mutation associated with AApoCII amyloidosis in 5 patients and describe their clinical, renal biopsy, and mass spectrometry findings. Methods Five patients with renal AApoCII p.Lys41Thr amyloidosis were identified from our amyloid mass spectrometry cohort. Clinical features, kidney biopsy, and mass spectrometry findings were analyzed in this rare type of amyloidosis. Results The patients were older adults (mean age of 71.6 years at diagnosis), presented with nephrotic-range proteinuria, and often had declining renal function. All renal biopsy specimens showed massive mesangial nodules composed of weakly eosinophilic, periodic acid−Schiff negative, Congo red–positive amyloid deposits. There were no interstitial, vascular, or medullary deposits. In all cases, immunofluorescence studies were negative for Igs and electron microscopy showed amyloid fibrils. Proteomic analysis of Congo red−positive amyloid deposits detected large amounts of apolipoprotein CII (APOC2) protein. We also detected APOC2 p.Lys41Thr mutant protein in amyloid deposits of all patients. DNA sequencing in 1 patient confirmed the presence of the mutation. Both mutant and wild-type forms of APOC2 were detected in amyloid deposits of all patients. Molecular dynamic simulations showed the variant mediating a collapse of the native structure of APOC2, thereby destabilizing the protein. Conclusion We propose that AApoCII p.Lys41Thr amyloidosis is a new form of amyloidosis seen in elderly individuals, histologically exhibiting massive glomerular involvement, leading to nephrotic-range proteinuria and progressive chronic kidney disease.

Background Renal biopsy is the cornerstone of Lupus nephritis (LN) management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Antibody Syndrome (APS). Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. Objectives The primary objective of the study was to describe the safety and the diagnostic performance of TJRB in SLE and APS. Methods A retrospective review of SLE and/or APS patients who consecutively underwent a renal biopsy in our department between January 2004 and October 2016 was performed. Biopsies were divided into four groups: TCRB, TJRB with aspirin treatment (aspirin TJRB), TJRB with anticoagulant treatment (anticoagulant TJRB), and TJRB without anti-thrombotic drug (no-antithrombotic TJRB). Major complications were defined as decease, haemostasis nephrectomy, renal artery embolization, blood transfusion, sepsis and vascular thrombosis. Minor complications were defined as gross haematuria, renal hematoma and arterio-venous fistula. Results Fifty-four TCRB and 256 TJRB were analysed – 69 aspirin TJRB, 68 anticoagulant TJRB and 119 no-antithrombotic TJRB. Major complications rate was 1.9% for TCRB and 2.0% for TJRB (p=1). One patient in the TJRB group suffering from catastrophic antiphospholipid syndrome (CAPS) died suddenly 6 weeks after the biopsy. No patient died of bleeding complication. One patient in the anticoagulant TJRB group required a renal artery embolization and blood transfusion. Four other patients required blood transfusion (1 in the TCRB group, 1 in the aspirin TJRB group and 2 in the anticoagulant TJRB group). Minor complications rate was 1.9% for TCRB and 7.8% for TJRB (p=0.2). Among the 256 TJRB, the rate of complication (major or minor) was higher for patients with glomerular filtration rate CKD-EPI 30 mL/min (16/232 [7%], p 140/90 mmHg, APS or positive antiphospholipid biology without APS, Prothrombin Time 1.2, platelets The number of glomeruli sampled and the performance of the biopsy to establish a histologic diagnostic were similar in the 4 groups. Conclusions TJRB provides diagnostic yield and safety similar to those of TCRB. It should be considered as a first intention procedure for SLE and APS patients at risk of bleeding. Disclosure of Interest None declared

Aim: Subclinical pathological features in renal allograft biopsies predict poor outcomes, and noninvasive biomarkers are wanted. RNA quantification in urine predicts overt rejection. We hypothesized that a whole transcriptome analysis would be informative, even for discrete injury. Patients & methods: We performed an mRNA microarray with an optimized normalization method on 26 urinary cell pellets to study renal partial epithelial to mesenchymal transition (pEMT) in stable kidney allografts. Results & conclusion: Unbiased pathway analysis revealed immune response as the main underlying biological process. In a subgroup of pristine biopsies, isolated pEMT was associated with reduced metabolic functions. Thus, pEMT translates into specific urinary mRNA patterns, in other words, increased inflammation and decreased metabolic functions. Deposited in Gene Expression Omnibus (GSE89652).

International audience; Kidneys may fail post-partum in a number of circumstances due, for example, to post-partum haemorrhage, preeclampsia, amniotic fluid embolism or septic abortion. All these conditions in pregnancy and post partum represent a threat not only to the endothelium but also to the renal tubular epithelium, and as such may lead to rapid and also irreversible impairment of the renal function. This paper is a non-systematic review of the literature and of our experience, in which we discuss the main open issues on kidney disease in pregnancy and following delivery, in particular as regards tubular damage, with the aim to help reasoning on acute kidney injury (AKI) following delivery. The review will emphasize the often underestimated importance of the tubular epithelium in the peri-partum period and will: (1) describe the main characteristics of the renal tissues around delivery; (2) define pregnancy-related AKI according to recent Kidney Disease/Improving Global Outcome (KDIGO) guidelines; (3) discuss the most common circumstances of post-partum AKI; and (4) describe the input expected from urinalysis, renal imaging and kidney biopsy.

Hepatitis B virus (HVB) infection is a worldwide epidemic that, in addition to the liver, causes damage in other organs. HBV-membranous nephropathy (HBV-MN) is the most common renal manifestation in patients with HBV infection,1, 2, 3 possibly linked to subepithelial deposits of viral immune complexes.4, 5 HBV RNA and DNA were detected in glomerular and tubular cells, although a pathogenetic role for these viral nucleic acids remains to be confirmed.6 The effects of vaccination programs on the decline of HBV-associated MN, particularly in Asian and African children,7, 8 further support a possible relationship between HBV infection and MN.9 Identification in 2009 of PLA2R as the major antigen associated with idiopathic membranous nephropathy provided the first diagnostic biomarker.10 The 2 available assays (immunofluorescence test assay [IFTA] and enzyme-linked immunosorbent assay) for the detection of circulating anti-PLA2R antibodies (PLA2R-Abs) have shown that PLA2R-Abs are a specific and sensitive biomarker of MN, being detected in 70% to 80% of patients with primary MN worldwide in early serum samples, and consistently absent in healthy individuals and in patients with other nephropathies or autoimmune diseases.11 Because anti-PLAR antibody levels fluctuate and can rapidly decrease under immunosuppressive treatment, detection of PLA2R antigen in subepithelial immune deposits of patients with MN is even more sensitive than serology.12, 13 Although Hoxha et al. suggested that the diagnosis between primary MN and secondary MN could rely on the presence or absence of PLA2R antigen in the immune deposits,14 other investigators showed that the antigen could be detected in cases of active sarcoidosis,15, 16 hepatitis C virus,17 and HBV infection–associated MN.13, 18 In the Chinese population, 25 of 39 patients (64%) with HBV-MN had deposited subepithelial PLA2R antigen, and all tested sera contained anti-PLA2R antibody.18 These findings suggest that HBV infection could be the trigger of autoimmunity anti-PLA2R. Whatever the mechanism of autoimmunity, we are facing the conundrum of antiviral versus immunosuppressive therapy with the risk of aggravating the viral infection. Most data have been obtained in small-scale case series published before the availability of anti-PLA2R antibody assays, and a standard of care has not yet been established.19, 20 Here, we report the first 2 cases in which rituximab was used after controlling viral replication.

HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, non-collapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals.