Lipoprotein glomerulopathy associated with a mutation in apolipoprotein e

Lipoprotein glomerulopathy is a pathological condition characterized by lipid accumulation in the glomerular capillaries that has been associated with the presence of rare mutants of apolipoprotein E (ApoE). We describe a 51-year-old Italian patient presenting Type III hyperlipidemia and proteinuria in whom renal biopsy showed capillary ectasia and intraluminal lipid deposits, suggesting the diagnosis of lipoprotein glomerulopathy. The patient, who had elevated plasma ApoE level, was found to be heterozygous for a mutation in ApoE (Arg150Cys), designated apoEMODENA. This mutation induces the formation of ApoE dimers that are detectable under non-reducing conditions. Treatment with hypolipidemic drugs did not result in a complete remission of the proteinuria and was accompanied by a slow but progressive worsening of renal function with the persistence of intracapillary lipid thrombi. The introduction of low-density lipoprotein aphaeresis combined with a more aggressive lipid lowering and antihypertensive therapy resulted in the remission of proteinuria and a substantial improvement of renal function. Switching from low-density lipoprotein aphaeresis to plasma filtration did not result in an equivalent control of renal damage. The patient died of intracranial hemorrhage during an acute episode of malignant hypertension

Evaluation of the Classification Accuracy of the Kidney Biopsy Direct Immunofluorescence through Convolutional Neural Networks

Background and objectives: Immunohistopathology is an essential technique in the diagnostic workflow of a kidney biopsy. Deep learning is an effective tool in the elaboration of medical imaging. We wanted to evaluate the role of a convolutional neural network as a support tool for kidney immunofluorescence reporting. Design, setting, participants, & measurements: High-magnification ( 7400) immunofluorescence images of kidney biopsies performed from the year 2001 to 2018 were collected. The report, adopted at the Division of Nephrology of the AOU Policlinico di Modena, describes the specimen in terms of \u201cappearance,\u201d \u201cdistribution,\u201d \u201clocation,\u201d and \u201cintensity\u201d of the glomerular deposits identified with fluorescent antibodies against IgG, IgA, IgM, C1q and C3 complement fractions, fibrinogen, and \u3ba- and \u3bb-light chains. The report was used as ground truth for the training of the convolutional neural networks. Results: In total, 12,259 immunofluorescence images of 2542 subjects undergoing kidney biopsy were collected. The test set analysis showed accuracy values between 0.79 (\u201cirregular capillary wall\u201d feature) and 0.94 (\u201cfine granular\u201d feature). The agreement test of the results obtained by the convolutional neural networks with respect to the ground truth showed similar values to three pathologists of our center. Convolutional neural networks were 117 times faster than human evaluators in analyzing 180 test images. A web platform, where it is possible to upload digitized images of immunofluorescence specimens, is available to evaluate the potential of our approach. Conclusions: The data showed that the accuracy of convolutional neural networks is comparable with that of pathologists experienced in the field

The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta-analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition

ADPKD is erroneously perceived as a not rare condition, which is mainly due to the repeated citation of a mistaken interpretation of old epidemiological data, as reported in the Dalgaard's work (1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD in the general population is uncertain, with a wide range of estimations reported by different authors. In this work, we have performed a meta-analysis of available epidemiological data in the European literature. Furthermore we collected the diagnosis and clinical data of ADPKD in a province in the north of Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well as the main clinical characteristics of ADPKD in this region

Identification and characterization of a new autoimmune protein in membranous nephropathy by immunoscreening of a renal cDNA library.

Membranous Nephropathy (MN) represents a large amount of Nephrotic Syndromes in the adult population and its definitive diagnosis is currently carried out through biopsy. An autoimmune condition has been demonstrated in idiopathic MN (iMN) in which some kidney structures are targeted by patient autoantibodies. Some candidate antigens have been described and other likely involved target proteins responsible for the disease are not known yet. In this work our aim is to identify these proteins by screening a lambda-phage library with patients' sera. We enrolled four groups of patients: two MN groups of 12 full iMN patients; one control group of 15 patients suffering from other renal diseases; one control group of 15 healthy individuals. A commercial cDNA phagemide library was screened using the above described sera, in order to detect positive signals due to antigen-antibody bond. We detected one phagemide clone expressing a protein which was shown to be targeted by the antibodies of the iMN sera only. Control sera were negative. The sequence analysis of cDNA matched the Synaptonemal Complex protein 65 (SC65) coding sequence. Further proteomic analyses were carried out to validate our results. We provide evidence of an involvement of SC65 protein as an autoimmune target in iMN. Considering the invasiveness and the resulting risk coming from renal biopsy, our ongoing aim is to set a procedure able to diagnose affected patients through a little- or non-invasive method such as blood sampling rather than biopsy

Coexistence of Different Circulating Anti-PodocyteAntibodies in Membranous Nephropathy

19openopenCorrado Murtas; Maurizio Bruschi; Giovanni Candiano; Gabriella Moroni; Riccardo Magistroni; Andrea Magnano; Francesca Bruno; Antonella Radice; Luciana Furci; Lucia Argentiero;| Maria Luisa Carnevali;| Piergiorgio Messa; Francesco Scolari; Renato Alberto Sinico; Loreto Gesualdo; Fernando C. Fervenza; Landino Allegri; Pietro Ravani; Gian Marco GhiggeriCorrado, Murtas; Maurizio, Bruschi; Giovanni, Candiano; Gabriella, Moroni; Riccardo, Magistroni; Andrea, Magnano; Francesca, Bruno; Antonella, Radice; Luciana, Furci; Lucia, Argentiero; | Maria Luisa, Carnevali; | Piergiorgio, Messa; Scolari, Francesco; Renato Alberto, Sinico; Loreto, Gesualdo; Fernando C., Fervenza; Landino, Allegri; Pietro, Ravani; Gian Marco, Ghigger

Identification and Characterization of a New Autoimmune Protein in Membranous Nephropathy by Immunoscreening of a Renal cDNA Library

<div><p>Membranous Nephropathy (MN) represents a large amount of Nephrotic Syndromes in the adult population and its definitive diagnosis is currently carried out through biopsy. An autoimmune condition has been demonstrated in idiopathic MN (iMN) in which some kidney structures are targeted by patient autoantibodies. Some candidate antigens have been described and other likely involved target proteins responsible for the disease are not known yet. In this work our aim is to identify these proteins by screening a lambda-phage library with patients’ sera. We enrolled four groups of patients: two MN groups of 12 full iMN patients; one control group of 15 patients suffering from other renal diseases; one control group of 15 healthy individuals. A commercial cDNA phagemide library was screened using the above described sera, in order to detect positive signals due to antigen-antibody bond. We detected one phagemide clone expressing a protein which was shown to be targeted by the antibodies of the iMN sera only. Control sera were negative. The sequence analysis of cDNA matched the Synaptonemal Complex protein 65 (SC65) coding sequence. Further proteomic analyses were carried out to validate our results. We provide evidence of an involvement of SC65 protein as an autoimmune target in iMN. Considering the invasiveness and the resulting risk coming from renal biopsy, our ongoing aim is to set a procedure able to diagnose affected patients through a little- or non-invasive method such as blood sampling rather than biopsy.</p> </div

Attivazione precoce dei geni del sistema renina-angiotensina e della cascata fibrogenetica nella glomerulonefrite da IgA

Giornale Italiano di Nefrologi