DOCSLIB.ORG

Human Lupus Nephritis and Tubulointerstitial Inflammation in In

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Human Lupus Nephritis and Tubulointerstitial Inflammation in In In Situ B Cell-Mediated Immune Responses and Tubulointerstitial Inflammation in Human Lupus Nephritis This information is current as Anthony Chang, Scott G. Henderson, Daniel Brandt, Ni Liu, of September 26, 2021. Riteesha Guttikonda, Christine Hsieh, Natasha Kaverina, Tammy O. Utset, Shane M. Meehan, Richard J. Quigg, Eric Meffre and Marcus R. Clark J Immunol 2011; 186:1849-1860; Prepublished online 27 December 2010; Downloaded from doi: 10.4049/jimmunol.1001983 http://www.jimmunol.org/content/186/3/1849 Supplementary http://www.jimmunol.org/content/suppl/2010/12/27/jimmunol.100198 http://www.jimmunol.org/ Material 3.DC1 References This article cites 85 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/186/3/1849.full#ref-list-1 Why The JI? Submit online. by guest on September 26, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology In Situ B Cell-Mediated Immune Responses and Tubulointerstitial Inflammation in Human Lupus Nephritis Anthony Chang,*,1 Scott G. Henderson,†,1 Daniel Brandt,† Ni Liu,† Riteesha Guttikonda,† Christine Hsieh,† Natasha Kaverina,† Tammy O. Utset,† Shane M. Meehan,* Richard J. Quigg,‡ Eric Meffre,x and Marcus R. Clark† The most prevalent severe manifestation of systemic lupus erythematosus is nephritis, which is characterized by immune complex deposition, inflammation, and scarring in glomeruli and the tubulointerstitium. Numerous studies indicated that glomerulonephritis results from a systemic break in B cell tolerance, resulting in the local deposition of immune complexes containing Abs reactive with ubiquitous self-Ags. However, the pathogenesis of systemic lupus erythematosus tubulointerstitial disease is not known. In this article, we demonstrate that in more than half of a cohort of 68 lupus nephritis biopsies, the tubulointerstitial infiltrate was or- ganized into well-circumscribed T:B cell aggregates or germinal centers (GCs) containing follicular dendritic cells. Sampling of the Downloaded from in situ-expressed Ig repertoire revealed that both histological patterns were associated with intrarenal B cell clonal expansion and ongoing somatic hypermutation. However, in the GC histology, the proliferating cells were CD1382CD20+ centroblasts, whereas they were CD138+CD20low/2 plasmablasts in T:B aggregates. The presence of GCs or T:B aggregates was strongly associated with tubular basement membrane immune complexes. These data implicate tertiary lymphoid neogenesis in the pathogenesis of lupus tubulointerstitial inflammation. The Journal of Immunology, 2011, 186: 1849–1860. http://www.jimmunol.org/ he clinical manifestations of systemic lupus erythematosus renal manifestation most clearly related to the central pathogenic (SLE) are myriad and range from mild arthralgias and skin feature of SLE: systemic loss of B cell tolerance (1, 7, 8). T rashes to life-threatening nephritis (1). Patients with focal The presence of serum anti-dsDNA Abs identifies lupus patients or diffuse proliferative lupus nephritis (LN) have a more rapidly at increased risk for GN, whereas increasing titers of anti-dsDNA progressive disease and require more aggressive treatment than do Abs often herald renal flares in individual SLE patients (1). Anti- those with mesangial proliferative or membranous LN (2). Sig- dsDNA Abs have been isolated from SLE renal biopsies (9, 10), nificant morbidity and mortality are consequences of the nephritis and infusion of some murine and human anti-dsDNA Abs can and the cytotoxic therapeutic regimens used to treat it (3). induce GN in mice (11, 12). Furthermore, recent immunoelectron by guest on September 26, 2021 Pathologically, LN is characterized by immune complex de- microscopic studies directly demonstrated the presence of anti- position and inflammation in glomeruli and the tubulointerstitium dsDNA Ab-containing immune complexes in diseased glomeruli that, if left untreated, can result in scarring and irreversible organ (13, 14). These observations led to the hypothesis that anti-dsDNA failure. Of the pathological manifestations of LN, glomerulone- IgG Abs play a central role in the pathogenesis of lupus GN. phritis (GN) is the best studied and the feature most often replicat- However, tubulointerstitial inflammation (TI) is also a com- ed in murine models of autoimmune disease (4–6). GN is also the mon feature of LN (15–17) (C. Hsieh, A. Chang, R. Guttikonda, D. Brandt, T. O. Utset, and M.R. Clark, submitted for publication). On renal biopsy, the presence and degree of TI identify those *Department of Pathology, University of Chicago, Chicago, IL 60637; patients with LN who are at risk for progression to renal failure † Section of Rheumatology, Department of Medicine and Knapp Center for Lupus (15, 16) (C. Hsieh et al., submitted for publication). In contrast, Research, University of Chicago, Chicago, IL 60637; ‡Section of Nephrology, De- partment of Medicine, University of Chicago, Chicago, IL 60637; and xDepartment the National Institutes of Health activity index, which primarily of Rheumatology, Hospital for Special Surgery, Cornell University, New York, NY assesses glomerular inflammation, does not correlate with prog- 10021 nosis (15, 18, 19). Furthermore, the presence of tubulointerstitial 1 A.C. and S.G.H. contributed equally to this work. scarring on renal biopsy is more predictive of subsequent renal Received for publication June 16, 2010. Accepted for publication November 23, failure than is glomerular scarring (15, 16) (C. Hsieh et al., sub- 2010. mitted for publication). TI can occur independently of GN (20, This work was supported by grants from the Lupus Research Institute and the 21), and TI severity does not correlate with titers of anti-dsDNA National Institutes of Health (AI082724, AR055646). Abs (C. Hsieh et al., submitted for publication). These data indicate Address correspondence and reprint requests to Dr. Marcus Clark, Section of Rheu- matology, Department of Medicine, University of Chicago, 5841 S. Maryland Ave- that TI is an important manifestation of LN that might arise from nue, Chicago, IL 60637. E-mail address: [email protected] different pathogenic mechanisms from those implicated in GN. The online version of this article contains supplemental material. Organ-specific inflammation is a defining feature of many au- Abbreviations used in this article: FDC, follicular dendritic cell; FWR, framework toimmune diseases, including Hashimoto’s thyroiditis (22), rheu- region; GC, germinal center; GN, glomerulonephritis; IMGT, international ImMuno- matoid arthritis (RA) (23), Sjo¨gren’s syndrome (24), and multiple GeneTics information system; LCM, laser capture microdissection; LN, lupus ne- phritis; R, replacement; RA, rheumatoid arthritis; S, silent; SLE, systemic lupus sclerosis (25). In these diseases, infiltrating lymphocytes are often erythematosus; TBM, tubular basement membrane; TBMIC, tubular basement mem- highly organized and resemble lymphoid structures found in sec- brane immune complex; TI, tubulointerstitial inflammation; TLN, tertiary lymphoid ondary lymphoid organs during a normal immune response. This neogenesis. feature is referred to as tertiary lymphoid neogenesis (TLN). Copyright Ó 2011 by The American Association of Immunologists, Inc. 0022-1767/11/$16.00 B cells within these lymphoid structures secrete autoantibodies www.jimmunol.org/cgi/doi/10.4049/jimmunol.1001983 1850 IN SITU IMMUNE RESPONSES IN LUPUS NEPHRITIS (26, 27) and are required to locally maintain activated T cells Laser capture microdissection of interstitial CD38+ or Ki-67+ (28). Several reports noted that infiltrating T cells are a prom- cells inent feature of LN (29–33), whereas the presence of B cells At the time of procurement, renal biopsies were immediately frozen in OCT was recently noted (34–36). However, the significance of these media (Tissue-Tek, Torrance, CA) and stored at 280˚C. These consisted of lymphocyte populations in the interstitial infiltrate was unclear. 10 kidney biopsies from 10 patients. Patients A, B, C, D, and F were In this article, we demonstrate that in moderate or severe TI the females (23–40 y of age; one white, three African American, and one inflammatory infiltrates are usually organized into structures re- Hispanic) with established diagnoses of SLE from 4 mo to 10 y who were treated with low doses of prednisone prior to kidney biopsy. Patients E, G, miniscent of those observed in secondary lymphoid organs. Most H, and J were females (13–37 y of age; three African American and one commonly, aggregates of T and B cells containing plasmablasts Hispanic) with new-onset SLE and no significant immunosuppressive were observed. However, in some renal biopsies there were ger- therapy prior to renal biopsy. Patient I was
Load more

Recommended publications
  • The Case for Lupus Nephritis
    Journal of Clinical Medicine Review Expanding the Role of Complement Therapies: The Case for Lupus Nephritis Nicholas L. Li * , Daniel J. Birmingham and Brad H. Rovin Department of Internal Medicine, Division of Nephrology, The Ohio State University, Columbus, OH 43210, USA; [email protected] (D.J.B.); [email protected] (B.H.R.) * Correspondence: [email protected]; Tel.: +1-614-293-4997; Fax: +1-614-293-3073 Abstract: The complement system is an innate immune surveillance network that provides defense against microorganisms and clearance of immune complexes and cellular debris and bridges innate and adaptive immunity. In the context of autoimmune disease, activation and dysregulation of complement can lead to uncontrolled inflammation and organ damage, especially to the kidney. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance, autoantibody production, and immune complex deposition in tissues including the kidney, with inflammatory consequences. Effective clearance of immune complexes and cellular waste by early complement components protects against the development of lupus nephritis, while uncontrolled activation of complement, especially the alternative pathway, promotes kidney damage in SLE. Therefore, complement plays a dual role in the pathogenesis of lupus nephritis. Improved understanding of the contribution of the various complement pathways to the development of kidney disease in SLE has created an opportunity to target the complement system with novel therapies to improve outcomes in lupus nephritis. In this review, we explore the interactions between complement and the kidney in SLE and their implications for the treatment of lupus nephritis. Keywords: lupus nephritis; complement; systemic lupus erythematosus; glomerulonephritis Citation: Li, N.L.; Birmingham, D.J.; Rovin, B.H.
    [Show full text]
  • What Is Lupus Nephritis
    What is lupus nephritis (LN)? Lupus nephritis (LN) is inflammation of the kidney that occurs as a common symptom of systemic lupus erythematosus (SLE), also known as lupus. Proteins in the immune system called antibodies damage important structures in the kidney. ⅱ Why are the kidneys important? To understand how lupus nephritis damages the kidney, it is important to understand how the kidneys work. The kidneys’ main function is to filter out excess waste and water from the blood through the urine. Kidneys also balance the salts and minerals circulating in the blood, help control blood pressure and make red blood cells. So, when the kidneys are damaged or fail, they can’t do their job as well. As a result, the kidneys are not able to filter out waste and water into the urine causing it to stay in the blood. What are the signs and symptoms of LN? Signs to ask the doctor about include blood in the urine or foamy urine which can mean that there is excess protein. Other signs to notice are swelling of legs, ankles, hands or tissue around the eyes as well as weight gain that can be caused by fluid the body isn’t getting rid of. ⅲ Symptoms of lupus nephritis also include high blood pressure, joint/muscle pain, high levels of waste (creatinine) in the blood, or impaired/failing kidney. ⅳ How common is LN? Lupus nephritis is the most common complication of lupus. Five out of 10 adults with lupus will have lupus nephritis, while eight out of 10 children with lupus will have kidney damage, which usually stems from lupus nephritis.
    [Show full text]
  • Management of Lupus Nephritis
    Journal of Clinical Medicine Review Management of Lupus Nephritis Farah Tamirou * and Frédéric A. Houssiau Department of Rheumatology, Cliniques Universitaires Saint-Luc and Institut de Recherche Expérimentale et Clinique, UCLouvain, 1200 Bruxelles, Belgium; [email protected] * Correspondence: [email protected] Abstract: Lupus nephritis (LN) is a frequent and severe manifestation of systemic lupus erythemato- sus. The main goal of the management of LN is to avoid chronic kidney disease (CKD). Current treatment strategies remain unsatisfactory in terms of complete renal response, prevention of relapses, CKD, and progression to end-stage kidney disease. To improve the prognosis of LN, recent data suggest that we should (i) modify our treat-to-target approach by including, in addition to a clinical target, a pathological target and (ii) switch from conventional sequential therapy to combination therapy. Here, we also review the results of recent controlled randomized trials. Keywords: lupus nephritis; treat-to-target approach; repeat kidney biopsy; combination therapy 1. Introduction Lupus nephritis (LN) occurs in 12 to 69% of patients suffering from systemic lupus erythematosus (SLE), depending on case series [1]. Based on clinical and laboratory findings, it affects around 50% of SLE patients, while the rates of biopsy-proven LN are somewhat lower [2]. LN is more prevalent in Asian than in African or Hispanic and European patients [3]. 2. Pathophysiology of Lupus Nephritis Citation: Tamirou, F.; Houssiau, F.A. Management of Lupus Immune complexes (IC), produced in lymph nodes, spleen, or other lymphoid tissues Nephritis. J. Clin. Med. 2021, 10, 670. are deposited in the glomeruli of LN patients [4].
    [Show full text]
  • Lupus Nephropathy
    Rev. Colomb. Nefrol. 2014; 1(2): 101- 114. http//www.revistanefrologia.org Rev. Colomb.Review Nefrol. article2014; 1(2): 101-114 http//doi.org/10.22265/acnef.1.2.182 Lupus nephropathy Luis Fernando Pinto Peñaranda1 1Internal Medicine - Rheumatology, Medical Specialties - Research Unit, Hospital Pablo Tobón Uribe, Medellín – Colombia Abstract Lupus nephritis (LN) occurs between 30% and 70% of patients with systemic lupus erythematosus (SLE), depending on race and sex. LN appears early in the disease with prevalence of severe forms such as classes III, IV and mixed (V + III IV or V +). 50% of adults and 70% of children with lupus born in Colombia, suffer LN sometime in their lifetime; in this population 25% of children and 38% of adults have nephrotic syndrome. The remission rate at six months is low, the proteinuria in nephrotic range, and the incraease of baseline creatinine predict failure to achieve remission at 6 months. Key words: Lupus, Nephritis, Nephrotic Syndrome, Proliferative glomerulonephritis. Nefropatía lúpica Resumen La nefritis lúpica (NL) se presenta entre el 30 y 70% de los pacientes con lupus eritematoso sistémico (LES), dependiendo de la raza y el sexo, ocurre temprano en la enfermedad y predominan las formas gra- ves, clases III, IV y mixtas (V + III o V + IV). El 50% de los adultos y 70% de los niños colombianos con lupus sufren NL en algún momento de la vida; en esta población el 25% de los niños y el 38% de los adultos presentan síndrome nefrótico, la tasa de remisión a 6 meses es baja, la proteinuria en rango nefrótico y la elevación de creatinina basal, predicen falla en el logro de remisión a 6 meses.
    [Show full text]
  • Pathogenesis of Human Systemic Lupus Erythematosus: a Cellular Perspective Vaishali R
    Feature Review Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective Vaishali R. Moulton,1,* Abel Suarez-Fueyo,1 Esra Meidan,1,2 Hao Li,1 Masayuki Mizui,3 and George C. Tsokos1,* Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting Trends multiple organs. A complex interaction of genetics, environment, and hormones Recent work has identified patterns of leads to immune dysregulation and breakdown of tolerance to self-antigens, altered gene expression denoting resulting in autoantibody production, inflammation, and destruction of end- molecular pathways operating in organs. Emerging evidence on the role of these factors has increased our groups of SLE patients. knowledge of this complex disease, guiding therapeutic strategies and identi- Studies have identified local, organ- fying putative biomarkers. Recent findings include the characterization of specific factors enabling or ameliorat- ing SLE tissue damage, thereby dis- genetic/epigenetic factors linked to SLE, as well as cellular effectors. Novel sociating autoimmunity and end-organ observations have provided an improved understanding of the contribution of damage. tissue-specific factors and associated damage, T and B lymphocytes, as well Novel subsets of adaptive immune as innate immune cell subsets and their corresponding abnormalities. The effectors, and the contributions of intricate web of involved factors and pathways dictates the adoption of tailored innate immune cells including platelets therapeutic approaches to conquer this disease. and neutrophils, are being increasingly recognized in lupus pathogenesis. Studies have revealed metabolic cellu- SLE, a Devastating Disease for Young Women lar aberrations, which underwrite cell SLE afflicts mostly women [1] in which the autoimmune response is directed against practically and organ injury, as important contri- all organs, leading to protean clinical manifestations including arthritis, skin disease, blood cell butors to lupus disease.
    [Show full text]
  • Glomerulonephritis Histopathological Pattern Change
    AlYousef et al. BMC Nephrology (2020) 21:186 https://doi.org/10.1186/s12882-020-01836-3 RESEARCH ARTICLE Open Access Glomerulonephritis Histopathological Pattern Change Anas AlYousef1* , Ali AlSahow2, Bassam AlHelal3, Ahmed Alqallaf4, Emad Abdallah3, Mohammed Abdellatif1, Hani Nawar2 and Riham Elmahalawy4 Abstract Background: Glomerulonephritides (GN) are relatively rare kidney diseases with substantial morbidity and mortality. They are often difficult to treat, sometimes with no cure, and can lead to chronic kidney disease (CKD) and end stage kidney disease (ESKD). Kidney biopsy is the diagnostic procedure of choice with variable indications from center to center. It helps in identifying the exact specific diagnosis, assessing the level of disease activity and severity, and hence aids in proper therapy and helps predicting prognosis. There is a global change of pattern of glomerular disease over the last five decades. Methods: Retrospective analysis of all kidney biopsies (545 cases) that were done in patients over 12 year-old over last six years in four major hospitals in Kuwait. The indications for kidney biopsy were categorized into six clinical syndromes: nephrotic syndrome, sub-nephrotic proteinuria, nephrotic syndrome plus acute kidney injury (AKI), sub- nephrotic proteinuria plus AKI, isolated hematuria, and Unexplained renal impairment. We calculated the incidence of each type of kidney disease and indication of biopsy. Results: most common indication of kidney biopsy was sub-nephrotic proteinuria associated with AKI in 179 cases (32.8%). Primary Glomerulonephritis was the main diagnosis that was reported in 356 cases (65.3%). Immunoglobulin A Nephropathy (IgAN) was the commonest lesion in primary glomerulonephritis in 85 (23.9%) cases.
    [Show full text]
  • Iga Nephropathy in Systemic Lupus Erythematosus Patients
    r e v b r a s r e u m a t o l . 2 0 1 6;5 6(3):270–273 REVISTA BRASILEIRA DE REUMATOLOGIA w ww.reumatologia.com.br Case report IgA nephropathy in systemic lupus erythematosus patients: case report and literature review Leonardo Sales da Silva, Bruna Laiza Fontes Almeida, Ana Karla Guedes de Melo, Danielle Christine Soares Egypto de Brito, Alessandra Sousa Braz, ∗ Eutília Andrade Medeiros Freire School of Medicine, Universidade Federal da Paraíba, João Pessoa, PB, Brazil a r t i c l e i n f o a b s t r a c t Article history: Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has Received 1 August 2014 nephritis as one of the most striking manifestations. Although it can coexist with other Accepted 19 October 2014 autoimmune diseases, and determine the predisposition to various infectious complica- Available online 16 February 2015 tions, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent Keywords: primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear Systemic lupus erythematosus IgA nephropathy fine speckled pattern, and anticardiolipin IgM and 280 U/mL. Renal biopsy revealed mesan- Glomerulonephritis gial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, show- ing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed con- dition.
    [Show full text]
  • Acute Poststreptococcal Glomerulonephritis: Immune Deposit Disease
    Acute poststreptococcal glomerulonephritis: immune deposit disease. A F Michael Jr, … , R A Good, R L Vernier J Clin Invest. 1966;45(2):237-248. https://doi.org/10.1172/JCI105336. Research Article Find the latest version: https://jci.me/105336/pdf Journal of Clinical Investigation Vol. 45, No. 2, 1966 Acute Poststreptococcal Glomerulonephritis: Immune Deposit Disease * ALFRED F. MICHAEL, JR.,t KEITH N. DRUMMOND,t ROBERT A. GOOD,§ AND ROBERT L. VERNIER || WITH THE TECHNICAL ASSISTANCE OF AGNES M. OPSTAD AND JOYCE E. LOUNBERG (From the Pediatric Research Laboratories of the Variety Club Heart Hospital and the Department of Pediatrics, University of Minnesota, Minneapolis, Minn.) The possible role of immunologic mechanisms in the kidney in acute glomerulonephritis have also acute poststreptococcal glomerulonephritis was revealed the presence of discrete electron dense suggested in 1908 by Schick (2), who compared masses adjacent to the epithelial surface of the the delay in appearance of serum sickness after glomerular basement membrane (11-18). injection of heterologous serum to the latent pe- The purpose of this paper is to describe immuno- riod between scarlet fever and onset of acute glo- fluorescent and electron microscopic observations merulonephritis. Evidence in support of this con- of the kidney in 16 children with acute poststrepto- cept is the depression of serum complement during coccal glomerulonephritis. This study demon- the early stages of the disease (3) and glomerular strates 1) the presence of discrete deposits of yG- localization of immunoglobulin. Immunofluores- and fl3c-globulins along the glomerular basement cent studies have revealed either no glomerular membrane and its epithelial surface that are similar deposition of a-globulin (4) or a diffuse involve- in size and location to the dense masses seen by ment of the capillary wall (5-9).
    [Show full text]
  • Characterization of Iga Deposition in the Kidney of Patients with Iga Nephropathy and Minimal Change Disease
    Journal of Clinical Medicine Article Characterization of IgA Deposition in the Kidney of Patients with IgA Nephropathy and Minimal Change Disease Won-Hee Cho 1, Seon-Hwa Park 2, Seul-Ki Choi 2, Su Woong Jung 2, Kyung Hwan Jeong 3, Yang-Gyun Kim 2 , Ju-Young Moon 2, Sung-Jig Lim 4 , Ji-Youn Sung 5, Jong Hyun Jhee 6, Ho Jun Chin 7,8, Bum Soon Choi 9 and Sang-Ho Lee 2,* 1 Department of Medicine, Graduate School, Kyung Hee University, Seoul 02447, Korea; [email protected] 2 Division of Nephrology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea; [email protected] (S.-H.P.); [email protected] (S.-K.C.); [email protected] (S.W.J.); [email protected] (Y.-G.K.); [email protected] (J.-Y.M.) 3 Division of Nephrology, Department of Internal Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; [email protected] 4 Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul 05278, Korea; [email protected] 5 Department of Pathology, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul 02447, Korea; [email protected] 6 Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea; [email protected] 7 Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea; [email protected] 8 Department of Internal Medicine, College of Medicine, Seoul National University, Seoul 03080, Korea 9 Division of Nephrology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; [email protected] * Correspondence: [email protected] Received: 5 July 2020; Accepted: 9 August 2020; Published: 12 August 2020 Abstract: Approximately 5% of patients with IgA nephropathy (IgAN) exhibit mild mesangial lesions with acute onset nephrotic syndrome and diffuse foot process effacement representative of minimal change disease (MCD).
    [Show full text]
  • Therapy of Membranous Nephropathy in Systemic Lupus Erythematosus
    Therapy of Membranous Nephropathy in Systemic Lupus Erythematosus By James E. Balow and Howard A. Austin, III Historic changes in the criteria for pathologic diagnosis and classification of lupus membranous nephropathy (LMN) have precluded definitive descriptions of the natural history, prognosis, and treatment of this disorder. The interim practice, based on the 1982 World Health Organization classification system, of admixing membranous and proliferative lupus nephropathies under the rubric of LMN has confounded the medical literature. Cases with mixed histology should be treated according to recommendations for proliferative lupus nephritis. Patients with LMN should be treated early with angiotensin antagonists to minimize proteinuria, as well as lifestyle changes and appropriate drugs to reduce attendant cardiovascular risk factors. In patients with protracted nephrotic syndrome, consideration should be given to immunosuppressive therapies including corticosteroids, cyclosporine, myco- phenolate, and cyclophosphamide. Prospective controlled trials clearly are needed to establish solid clinical practice guidelines for use of these drugs and other experimental therapies currently under study in LMN. This is a US government work. There are no restrictions on its use. ORE THAN ONE HALF of patients with specific intervention to reduce the risk for renal Msystemic lupus erythematosus (SLE) de- failure. Typical recommendations were to tailor velop clinically significant nephropathy during the immunosuppressive drugs according to the re- course of their disease. Approximately 20% of quirements for control of extrarenal SLE disease those with SLE renal involvement are found on activity. renal biopsy examination to have lupus membra- The original perspective on renal prognosis was nous nephropathy (LMN). Unfortunately, LMN altered dramatically by the 1982 World Health has not been defined in a uniform fashion over the Organization classification system to subsume cer- past several decades.
    [Show full text]
  • Membranous Nephropathy with Crescents
    PATHOPHYSIOLOGY of the RENAL BIOPSY www.jasn.org Membranous Nephropathy with Crescents Amanda Walton Basford,* Julia Lewis,* Jamie P. Dwyer,* and Agnes B. Fogo*† Division of Nephrology and Hypertension, Departments of *Medicine and †Pathology, Vanderbilt University Medical Center, Nashville, Tennessee ABSTRACT Membranous nephropathy is a common cause of nephrotic syndrome in adults concentration of 3.4 g/dl, urinalysis with and can be primary or secondary to systemic lupus erythematosus, chronic 2ϩ protein, one red blood cell, and five infection, or drugs. Rapid decline in renal function in patients with membranous white blood cells (WBCs) without casts. nephropathy may be due to renal vein thrombosis, malignant hypertension, or On admission, serum sodium was 136 an additional superimposed destructive process involving the renal paren- mEq/L, potassium was 4.3 mEq/L, chlo- chyma. Crescents are rare in primary membranous nephropathy and thus sug- ride was 107 mEq/L, bicarbonate was 20 gest another underlying disease process, such as combined membranous and focal mmol/L, blood urea nitrogen was 36 mg/ or diffuse lupus nephritis. However, in some patients with membranous nephrop- dl, serum creatinine was 2.84 mg/dl, athy and crescents, the crescentic lesion may be due to a distinct, separate disease magnesium was 2.2 mg/dl, phosphorus process, such as anti-glomerular basement membrane antibodies or anti- was 4.6 mg/dl, total bilirubin was 0.7 mg/ neutrophil cytoplasmic antibodies-related pauci-immune glomerulonephritis. Here dl, amylase was 17 U/L, and lipase was 14 we describe a case with such renal biopsy findings, review previous reported cases, U/L.
    [Show full text]
  • Glomerular Diseases
    PLEASE CHECK Editing file BEFORE! ​ ​ ​ ​ GLOMERULAR DISEASES ★ Objectives: ​ 1- To understand the pathophysiology of Glomerular Diseases. 2- To correlate the clinical findings with the underlying renal pathology. 3- To recognize the important features of Nephrotic syndrome. 4- Learn the most common causes of NS in adults. 5- To recognize the most important Glomerular diseases that cause Nephritic pattern ( Glomerulonephritis). ★ Resources Used in This lecture: Class note – Davidson - step up to medicine – master the board ​ ​ ​ ​ ​ ​ ​ Done by: Tarfa bin Maymoon & Hadeel B.Alsulami Contact us at: [email protected] ​ ​ ​ Edited and Revised by: Omar Al-Rahbeeni ​ Introduction. *Normal urine will have: • NO Protein. But in healthy individuals, less than 150 mg of protein is excreted in the ​ ​ ​ ​ urine each day. Include 4-7 mg/day of Albumin. ​ • NO Red Blood Cells ( Accept: up to 12 500 cells/mL is normal ). • NO Cellular Casts. • No fat • No sugar *Renal cortex is the most important functional part of the kidney, because it has the Glomeruli. *Healthy kidneys contain approximately 1 million individual nephrons. *Each nephron consists of a glomerulus, which is responsible for ultrafiltration of blood. *The glomerulus comprises a tightly packed loop of capillaries supplied by an afferent arteriole and drained by an efferent arteriole covered by an extension of the tubules called Bowman’s capsule. Normal Glomerular structure is needed to: • Keep the glomerular filtration normal, thus maintains normal kidney function. • keeps the urine volume maintained, so preventing fluid retention in the body which causes edema and high blood pressure. • Prevents the blood components (cells, proteins) from leaving the blood stream and appearing in the urine.
    [Show full text]