Humans ; Glomerulonephritis, Membranoproliferative/pathology* ; Fibronectins

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.
Complement Activation ; Complement Pathway, Alternative ; Dichlorodiphenyldichloroethane ; Glomerular Basement Membrane ; Glomerulonephritis ; Glomerulonephritis, Membranoproliferative ; Microscopy, Electron ; Microscopy, Fluorescence ; Pathology ; Prevalence

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.
Animals ; Cytokines ; Dendritic Cells ; Glomerulonephritis ; Glomerulonephritis, IGA ; Glomerulonephritis, Membranoproliferative ; Kidney ; Mice ; Mice, Transgenic ; Nephritis ; T-Lymphocytes ; Th2 Cells

A 38-year-old man, who underwent a second kidney transplantation (KT), was admitted because of antibody-mediated rejection (AMR) complicated by BK virus-associated nephropathy (BKVAN). He was placed on hemodialysis at the age of 24 years because of membranoproliferative glomerulonephritis. At the age of 28 years, he underwent a living donor KT from his father; however, 1 year after the transplantation, he developed a recurrence of the primary glomerular disease, resulting in graft failure 2 years after the first KT. Ten years later, he received a deceased-donor kidney with a B-cell-positive-cross-match. He received 600 mg of rituximab before the KT with three cycles of plasmapheresis and immunoglobulin (0.5 g/kg) therapy after KT. During the follow-up, the first and second allograft biopsies at 4 and 10 months after KT revealed AMR with a recurrence of primary glomerular disease that was reclassified as C3 glomerulonephritis (C3GN). He received a steroid pulse, rituximab, plasmapheresis, and immunoglobulin therapies. The third allograft biopsy demonstrated that the BKVAN was complicated with AMR and C3GN. As the azotemia did not improve after repeated conventional therapies for AMR, one cycle of bortezomib (1.3 mg/m²×4 doses) was administered. The allograft function stabilized, and BK viremia became undetectable after 6 months. The present case suggests that bortezomib therapy may be applicable to patients with refractory AMR, even in cases complicated with BKVAN.
Adult ; Allografts ; Azotemia ; Biopsy ; BK Virus ; Bortezomib* ; Fathers ; Follow-Up Studies ; Glomerulonephritis* ; Glomerulonephritis, Membranoproliferative ; Graft Rejection ; Humans ; Immunization, Passive ; Immunoglobulins ; Kidney ; Kidney Transplantation ; Living Donors ; Plasmapheresis ; Recurrence ; Renal Dialysis ; Rituximab ; Transplants ; Viremia

Brucellosis is the most common zoonotic disease in Greece, with an endemic distribution and can affect any organ. Infiltration of the renal parenchyma causes acute and chronic interstitial nephritis with granulomas, whereas renal glomeruli are rarely affected. The disease has been sporadically reported, and it causes various histopathologic patterns. Herein, we describe the case of a 39-year-old stock breeder with a history of recurrent episodes of bacteremia caused by Brucella melitensis over a period of 3 years. Two months after the last episode of bacteremia, he presented with mild renal insufficiency, nephrotic range proteinuria, and microscopic hematuria. A renal biopsy revealed membranoproliferative glomerulonephritis with a pattern of focal-segmental nodular sclerosis and moderate tubulointerstitial fibrosis. The patient received antimicrobial and corticosteroid therapy with partial remission of the nephrotic syndrome.
Adult ; Bacteremia ; Biopsy ; Brucella melitensis ; Brucellosis* ; Fibrosis ; Glomerulonephritis, Membranoproliferative* ; Granuloma ; Greece ; Hematuria ; Humans ; Nephritis, Interstitial ; Nephrotic Syndrome ; Proteinuria ; Renal Insufficiency ; Sclerosis ; Zoonoses

The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.
Adaptive Immunity ; Antigen-Antibody Complex ; Autoimmune Diseases ; Autoimmunity ; B-Lymphocytes ; Complement Activation ; Complement Factor H ; Complement System Proteins* ; Glomerulonephritis, Membranoproliferative ; Hemolytic-Uremic Syndrome ; Immunity, Innate ; Lupus Erythematosus, Systemic ; Macular Degeneration ; Physiology* ; Regeneration

Glomerulonephritis, Membranoproliferative ; Humans ; Kidney Glomerulus ; pathology

Acquired partial lipodystrophy, also known as Barraquer-Simons syndrome, is a rare disease characterized by progressive atrophy of adipose tissue primarily on the face, leading to a gaunt appearance. Usually manifesting in childhood and in women, the evolution of fat loss occurs in a cephalocaudad manner. The lower extremities are spared and may present with paradoxical hypertrophy. Common findings are C3 hypocomplementemia and positive C3 nephritic factor (C3Nef) but the pathogenesis remains unknown. The prognosis depends on presence of co-morbidities such as membranoproliferative glomerulonephritis. We report a 41-year-old woman who presented with a 23 year history of progressive fat atrophy on the face, trunk, and upper extremities with no skin changes or other symptoms. Subsequently, a three-year history of fat hypertrophy in both lower extremities was noted. Histopathologic findings and decreased C3 ultimately led to a diagnosis of acquired partial lipodystrophy. A thorough approach to this case is reported, along with a review of current literature on pathogenetic mechanisms suspected in the disease. Amongst the lipodystrophy syndromes, acquired partial lipodystrophy portends a relatively good prognosis. However, the cosmetic disfigurement and risk for membranoproliferative glomerulonephritis necessitate a multidisciplinary form of supportive management from a medical, surgical, and psychological point of view. With watchful supportive therapy, patients may lead normal, fulfilling lives.

Human ; Female ; Adult ; Adipose Tissue ; Atrophy ; Complement C3 Nephritic Factor ; Glomerulonephritis, Membranoproliferative ; Hypertrophy ; Lipodystrophy ; Lower Extremity ; Skin ; Torso

BACKGROUND: All types of membranoproliferative glomerulonephritis (MPGN) are progressive diseases with poor prognoses. Recently, a newly proposed classification of these diseases separated them into immune complex- and complement- mediated diseases. We investigated the frequency of C3 glomerulonephritis among previously diagnosed MPGN patients. METHODS: We conducted a retrospective study of patients diagnosed with MPGN at three tertiary care institutions between 2001 and 2010. We investigated the incidence of complement-mediated disease among patients diagnosed with MPGN. Progressive renal dysfunction was defined as a 50% reduction in the glomerular filtration rate or the need for renal replacement therapy. RESULTS: Among the 3,294 renal biopsy patients, 77 (2.3%) were diagnosed with MPGN; 31 cases were excluded, of which seven were diagnosed with systemic lupus nephritis, and the others were not followed for a minimum of 12 months after biopsy. Based on the new classification, complement-mediated MPGN was diagnosed in two patients (4.3%); only one patient developed progressive renal dysfunction. Among the immune complex-mediated MPGN patients, 17 patients developed progressive renal dysfunction. Serum albumin and creatinine levels at the time of MPGN diagnosis were risk factors of renal deterioration, after adjusting for low C3 levels and nephrotic syndrome. CONCLUSION: Complement-mediated glomerulonephritis was present in 4.3% of patients previously diagnosed with MPGN.
Biopsy ; Classification* ; Complement C3 ; Creatinine ; Diagnosis ; Glomerular Filtration Rate ; Glomerulonephritis ; Glomerulonephritis, Membranoproliferative* ; Glomerulonephritis, Membranous ; Humans ; Incidence ; Lupus Nephritis ; Nephrotic Syndrome ; Prognosis ; Renal Replacement Therapy ; Retrospective Studies ; Risk Factors ; Serum Albumin ; Tertiary Healthcare

No abstract available.
Classification* ; Glomerulonephritis, Membranoproliferative*