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Correspondence
Resolution of Recurrent Focal Segmental Glomerulosclerosis after Retransplantation
To the Editor: Recurrent primary focal segmental glomerulosclerosis (FSGS) develops in over 40% of renal-transplant recipients and presents a major therapeutic challenge. The first marker of disease recurrence is often proteinuria in the nephrotic range that can appear 2 to 3 days after…
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Correspondence
Eculizumab for the Treatment of Dense-Deposit Disease
To the Editor: Dense-deposit disease (also known as membranoproliferative glomerulonephritis type II) is a rare glomerulopathy characterized by electron-dense deposits in the glomerular basement membrane as well as the glomerular deposition of complement. Within 10 years, the disease progresses to…
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Review Article
Medical Progress: Membranoproliferative Glomerulonephritis — A New Look at an Old Entity
Membranoproliferative glomerulonephritis (MPGN), also termed mesangiocapillary glomerulonephritis, is diagnosed on the basis of a glomerular-injury pattern that is common to a heterogeneous group of diseases. MPGN accounts for approximately 7 to 10% of all cases of biopsy-confirmed…
- CME
Correspondence
Eculizumab and Refractory Membranoproliferative Glomerulonephritis
To the Editor: Membranoproliferative glomerulonephritis (MPGN) mainly affects children, often progresses to end-stage kidney disease, and can recur after transplantation. Primary MPGN is one of several glomerulopathies that have recently been linked to dysregulation of the complement alternative…
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Correspondence
Eculizumab in a Patient with Dense-Deposit Disease
To the Editor: In 1999, an 11-year-old girl with the nephrotic syndrome received a biopsy-confirmed diagnosis of membranoproliferative glomerulonephritis. The level of plasma complement C3 was 7 mg per deciliter (normal range, 90 to 180). Glucocorticoids, administered for 5 years, were ineffective.…
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Original Article
Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1 Diabetes
An impaired glomerular filtration rate (GFR) is the final common pathway of diabetic kidney disease. Once the GFR is impaired, cardiovascular disease events and progression to end-stage renal disease occur at unacceptably high rates, even with proven medical management.– This underscores the need…
- CME
Review Article
Medical Progress: Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis accounts for approximately 20% of cases of the nephrotic syndrome in children and 40% of such cases in adults, with an estimated incidence of 7 per 1 million. It is the most common primary glomerular disorder causing end-stage renal disease in the United States,…
- CME
Original Article
INF2 Mutations in Charcot–Marie–Tooth Disease with Glomerulopathy
Charcot–Marie–Tooth disease refers to a heterogeneous group of inherited chronic peripheral motor and sensory neuropathies. Affected persons typically present with progressive distal-muscle weakness and atrophy, reduced tendon reflexes, and foot and hand deformities. Three…
Correspondence
Combined C3b and Factor B Autoantibodies and MPGN Type II
To the Editor: Membranoproliferative glomerulonephritis (MPGN) type II (MPGN II), also called dense-deposit disease, is a rare glomerular disease that often progresses to end-stage renal disease. MPGN II is associated with complement because of systemic C3 activation and deposition of C3 cleavage…
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Editorial
MYO1E, Focal Segmental Glomerulosclerosis, and the Cytoskeleton
Focal segmental glomerulosclerosis, one of the most common glomerulopathies, is typically heralded by massive proteinuria, often associated with unremitting nephrotic syndrome and inexorable progression to end-stage kidney disease.– Unfortunately, therapy is frequently unsuccessful — many…
Original Article
MYO1E Mutations and Childhood Familial Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis is a kidney lesion characterized by glomerulosclerosis that is focal (involving a subgroup of glomeruli) and segmental (involving a portion of the glomerular tuft). As the disease progresses, the pattern of glomerulosclerosis becomes predominantly global.…
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Original Article
Risk HLA-DQA1 and PLA2R1 Alleles in Idiopathic Membranous Nephropathy
Membranous nephropathy has an incidence of approximately 1 case per 100,000 persons per year, and its phenotype has been clearly defined on the basis of histologic features, making it a good subject for genomewide association studies. Recognized as a clinicopathological entity in the 1950s,…
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Editorial
Genes That Link Nephritis to Autoantibodies and Innate Immunity
The rapid evolution of array techniques and the completion of the map of the human genome have led to a host of genomewide association studies over the past few years. Yet many of these studies have been disappointing; they identify genes that confer only a moderate increase in risk and explain…
Correspondence
PLA2R Autoantibodies and PLA2R Glomerular Deposits in Membranous Nephropathy
To the Editor: Membranous nephropathy is a common cause of the nephrotic syndrome in adults. Treatment is controversial and challenging because of the heterogeneity of the disease and a lack of reliable biomarkers. M-type phospholipase A2 receptor (PLA2R) was recently identified as a major target…
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Clinical Implications of Basic Research
Basophils and Nephritis in Lupus
Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease that predominantly affects the kidneys in the form of lupus nephritis, although multiple organs can be involved. Lupus nephritis is characterized by the deposition in glomeruli of immune complexes formed by IgG, IgM, and…
Editorial
Goodpasture's Disease — New Secrets Revealed
In this issue of the Journal, Pedchenko et al. increase our understanding of the pathogenesis of two forms of antibody-mediated glomerulonephritis. One, Goodpasture's disease, is an organ-specific autoimmune disease that is mediated by anti–glomerular basement membrane (anti-GBM) antibodies and…
Original Article
Molecular Architecture of the Goodpasture Autoantigen in Anti-GBM Nephritis
Goodpasture's disease is an organ-specific autoimmune disorder characterized by rapidly progressive glomerulonephritis, pulmonary hemorrhage, and glomerular pathological findings that include linear deposits of antibodies along the glomerular basement membrane (GBM) (Figure 1A). (For this article…
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This study compared the conformation of the antibody epitopes in Goodpasture's disease and Alport's post-transplantation nephritis in search of the pathogenesis of anti–basement membrane glomerulonephritis. The authors report evidence that the initiation of such disease depends on the conformation involving perturbation of the quaternary structure of basement-membrane collagen, eliciting an autoimmune response.
Clinical Problem-Solving
More Than Meets the Ear
Foreword. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows. Stage. A 62-year-old, generally healthy…
Case Records of the Massachusetts General Hospital
Case 5-2010 — A 51-Year-Old Man with HIV Infection, Proteinuria, and Edema
Presentation of Case. A 51-year-old man with a history of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection was seen in the nephrology clinic of this hospital because of proteinuria, edema, and hypertension. The patient had been in his usual state of health until…
A 51-year-old man with human immunodeficiency virus and hepatitis C virus infections presented with proteinuria, edema, and worsening hypertension. He had obesity, hyperlipidemia, obstructive sleep apnea, and a history of hypertension and coronary artery disease. He had recently taken nonsteroidal antiinflammatory drugs for joint pain. A diagnostic procedure was performed.
Original Article
M-Type Phospholipase A2 Receptor as Target Antigen in Idiopathic Membranous Nephropathy
Idiopathic membranous nephropathy, a common cause of the nephrotic syndrome in adults, is an organ-specific autoimmune disease. Despite extensive investigation, a target antigen has been elusive. Studies of membranous nephropathy in a rat model (Heymann's nephritis) established that the…
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In this study of patients with membranous nephropathy, serum samples from 70% of patients with idiopathic, but not secondary, membranous nephropathy were found to have antibodies against a 185-kD glycoprotein in nonreduced glomerular extracts, identified as the M-type phospholipase A2 receptor (PLA2R). PLA2R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA2R is a major antigen in this disease.
