Electron-dense subepithelial deposits in membranous GN (arrows). Notice also the projections of basement membrane-like material surrounding deposits. EM, original magnification, X6.000. Figur3 24. Subendothelial deposits in membranoproliferative GN (red arrows). Notice also a capillary segment with double contour. EM original magnification, X6.000 At later time-points, only subepithelial immune deposits were present. The fast component of disappearance, attributed to subendothelial deposits, had a half-life of 3.89±0.32 h. The slow component of disappearance from glomeruli, attributed to subepithelial deposits, had a half-life of 85.5±3.1 h
The incidence of light chain lambda predominance was lower in patients with IgAN-SD (47% vs. 63%; p = 0.03). Hump-shaped subepithelial deposits and intramembranous deposits were observed in nine and 17 patients with IgAN-SD, respectively. Patients with IgAN-SD tended to have the characteristics of IgA-IRGN rather than IgAN-NSD For instance, subepithelial immune complex deposits are not exposed to the circulation. Therefore, complement activation results in podocyte damage in the absence of inflammatory cells. In contrast, subendothelial deposits are exposed to the circulation - Student says: I can never remember which conditions are subepithelial deposits vs subendothelial. à Cool. Well you ready for something epic? à If the renal condition has proliferative in the name, it has subendothelial deposits. If it doesn't have proliferative in the name, it must not be subendothelial By electron microscopy, the immune deposits of post-infectious glomerulonephritis are predominantly subepithelial, as seen above with electron dense subepithelial humps above the basement membrane and below the epithelial cell. The capillary lumen is filled with a leukocyte demonstrating cytoplasmic granules Subepithelial 'humps' (finely granular, dome-shaped, electron dense, representing immune complex deposits), no spikes (compare to membranous glomerulonephritis) Obliteration of epithelial cell foot processes Subepithelial, intramembranous, subendothelial and mesangial deposits in the acute phas
Given the numerous anterior and posterior segment complications of HZO, all patients with this diagnosis should be seen by an ophthalmologist. BLINK SUBMISSIONS: Send us your ophthalmic image and its explanation in 150-250 words. E-mail to email@example.com, fax to 415-561-8575, or mail to EyeNet Magazine, 655 Beach Street, San Francisco, CA 94109 Lastly, type III is characterized by complex subendothelial and subepithelial deposits and a fragmented, disrupted, GBM. Although a substantial body of literature has emerged to support the classification of type III MPGN as a distinct pathologic disorder, this is not universally accepted. Some still regard type III solely as a variant of type. The incidence of light chain lambda-predominance was lower in patients with IgAN-SD. Subendothelial deposits and mesangial interposition tended to be seen in patients with IgAN-SD . Hump-shaped subepithelial deposits were observed in nine patients (18%) and intramembranous deposits in 17 (33%)
Subendothelial deposits will have a much better prognosis than subepithelial deposits. Child vs. Adult PostStrep Glomerulonephritis Children are more prone to get this conditons, but adults will most likely have a more sever form if it develops in the . Scattered subepithelial deposits, involving less than half the glomeruli and less than half the loops, may be present. If most glomeruli and loops show subepithelial deposits, additional membranous LN (class V. Pathological analysis revealed significant differences in M1 (83.3% vs. 56.0%, p = 0.002), ratio of subendothelial electron dense deposits (EDDs, 58.6% vs. 16.5%, p < 0.0001) and subepithelial EDDs (48.3% vs. 16.5%, p = 0.0001), and glomerular basement membrane (GBM) lysis (58.6% vs. 27.1%, p = 0.0006) between both groups
The amount of subendothelial deposits correlated with those of mesangial deposits and subepithelial deposits in the cases with diffuse proliferative lupus nephritis. Urinary protein loss and histologic activity showed statistically significant correlations with the amount of subendothelial deposits, but C3 levels and creatinine clearance. The most consistent and classic diagnostic finding is the presence of glomerular subepithelial electron-dense immune-type deposits, often referred to as humps (see the image below) Post-infectious glomerulonephritis: Subepithelial 3. Lupus glomerulonephritis: Subendothelial deposits 4. IgA Nephropathy: Mesangial deposits 5. Goodpasture's Syndrome: Antibody binding to GBM 6. Glomerular injury with proteinuria: Podocyte effacement Nephrotic vs Nephritic Disorders Nephrotic: profound proteinuria Immune complex deposits.
The formation of new basement membrane is demonstrated under the endothelial cell (Figure 15). There is effacement of foot processes (podocytes) and occasional subepithelial small electron-dense deposits. Figure 14. Subendothelial electron-dense deposits. In this case they proved to be positive for IgG and C3 (by immunofluorescence) Podocytes are known to express various complement factors including complement factor H (CFH) and to promote the removal of both subendothelial and subepithelial immune complex (IC) deposits -Student says: I can never remember which conditions are subepithelial deposits vs subendothelial. à Cool. Well you ready for something epic? à If the renal condition has proliferative in the name, it has subendothelial deposits. If it doesn't have proliferative in the name, it must not be subendothelial Subendothelial-deposits Symptom Checker: Possible causes include Membranoproliferative Glomerulonephritis. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane thickening, activating complement and damaging the glomeruli.. MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.. It should not be confused with membranous glomerulonephritis, a.
The ultrastructural finding of subepithelial humps, from deposits located between glomerular capillary basement membrane and the epithelial, was first described by Kimmelstiel et al. ; however, it is now recognized that the deposits may be found in subendothelial and intramembranous locations MPGN III is similar to MPGN I, except that subepithelial deposits are noted as well as subendothelial deposits. Based on the EM findings, MPGN III is further classified into two principal variants: the Strife and Anders variant and the Burkholder variant, which have different patterns of electron dense deposits and disorganization of the. No subepithelial or subendothelial deposits by light microscopy Class III Focal lupus nephritis Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving <50% of all glomeruli, typically with focal subendothelial immune deposits Mesangial deposits are present in the great majority of cases of acute poststreptococcal GN and may be abundant, and show subendothelial deposits in most cases, although these tend to be small and segmental (Nasr, et al., 2008; Silva, 2005). Extraglomerular deposits are not a feature of this disease Electron dense deposit are exclusively subepithelial and intramembranous Predominantly IgG4 (isotype-specific stain not routinely done) Secondary: Presence of Tubuloreticular structure (tubular structures in ER of endothelial cells) - lupus nephritis Mesangial or subendothelial deposits - suggest circulating immune complexe
EM deposits WG, NCGN subendothelial Castleman [b] 1969 1 Nd Gammaglobulin/ WG, NCGN granular, GBM Aldo [c] 1970 1 Nd EM deposits WG, NCGN subendothelial Horn 1974 2 Nd EM deposits WG, NCGN subepithelial Wolff [d] 1974 3 Nd EM deposits WG subepithelial Balow [e] 1978 7 Nd IgG, C3/ WG focal‐segmenta A few isolated subepithelial or subendothelial deposits may be seen on immunofluorescence or electron microscopy. Visible subendothelial deposits on light microscopy or any global or segmental glomerular scars (which are thought to be the result of previous endocapillary hypercellularity, necrosis, or crescents) are inconsistent with the. Subendothelial electron dense deposits sometimes evolve to more hyaline transmembrane deposits, with a lower electron density found in C3GN [18, 20, 34]. Many patients show subepithelial electron dense deposits, in some cases reminiscent of hump-like deposits seen in post-infectious glomerulonephritis
Immunofluorescence microscopy usually shows immune complex deposition with IgG and complement in a granular pattern. On electron microscopy, these deposits are semilunar or hump-shaped and are located in the subepithelial area. The presence of these deposits and of small subendothelial and mesangial deposits initiates a complement-mediated inflammatory reaction that leads to glomerular damage •Subendothelial and mesangial depositis on EM. IF: full house pattern in SLE, IgM and C3 in HepC. Complement mediated: •Dysregulated persistent alternative complement pathway activation: C3 nephropathy, dense deposit disease. •C3 staining of capillary walls and mesangium. EM deposits: subendothelial, mesangial +/- subepithelial, GB
(subendothelial deposits) •Bad prognosis •Nephrotic - membranous form (mostly subepithelial deposits) •Chronic, low grade •Minor urinary abnormalities- mesangial proliferation due to mesangial deposits Subendothelial deposits were present in a total of 16 cases, all of which were secondary. None of these cases with subendothelial deposits were positive for PLA2R1 Membranous lupus nephritis (MLN) (Class V lupus nephritis [LN]) is a distinct form of LN defined by the presence of subepithelial immune complex deposits seen on kidney biopsy. MLN is often associated with the nephrotic syndrome. The histology of MLN closely resembles that of idiopathic (primary) membranous nephropathy (pMN). However, MLN typically has abundant mesangial deposits that are. (ribbon-shaped deposits around basement membrane of glomerulus, C3 nephritic factor = C3 convertase --> low C3) Alport syndrome Sx: can't pee, can't see, can't hear a bee = cataracts/dislocation of lens, nephritic syndrome, sensorineural hearing los
Subepithelial and intramembranous immune deposits; subendothelial deposits present only when associated proliferative component is present. Clinical manifestations. Clinical and laboratory features of nephrotic syndrome, usually without manifestations of active SLE. Class VI. Advanced sclerosis lupus nephritis. Light microscopy finding Subendothelial deposits, low C3 and not light chain lambda predominance are also observed in IgA dominant-infection related nephropathy (IgA-IRGN). Therefore, some cases of IgAN-SD might in reality be IgA-IRGN, but not get diagnosed as IgA-IRGN owing to lack of clinical history of infection
-47 vs. 14 per 1000 patients HR 9.3 (CI 1.8-47) •Faurschou M et al. J Rheumatology 2006;33:1563-69. -Subendothelial deposits •Class IV: Diffuse proliferative lupus nephritis -Subepithelial immune deposits -Pure class V treatment •Cyclophosphamide vs. Cyclosporine vs. Cellcept(newer). Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected. . The immune system, which is responsible for fighting disease, begins to attack healthy cells in the kidney, destroying the function of the filtering units of the kidney Glomerular Capillary Pathology (see previous slide) 1. Membranous nephropathy: Subepithelial deposits 2. Post-infectious glomerulonephritis: Subepithelial 3. Lupus glomerulonephritis: Subendothelial deposits 4. IgA Nephropathy: Mesangial deposits 5. Goodpasture's Syndrome: Antibody binding to GBM 6 Frequency of Renal Biopsy Diagnoses vs Age at UNC from 1985-2007 Subepithelial, mesangial and rare subendothelial immune complex containing antigen (e.g. HBV ag) and antibody Secondary Membranous Glomerulopathy. small subepithelial electron dense deposits (arrows)
1. Subepithelial Deposits: Post infectious GN and 2. Membranous Nephropathy. 3. Subendothelial and 4. Mesangial deposits: can be formed locally, but more commonly from passive entrapment of circulating ICs. 5. Anti-GBM Ab Disease: Abs bind in a linear fashio proteinuria. Those proliferative variants with subendothelial immune deposits correspond to class III/IV LN, based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classiﬁcation , while subepithelial immune deposits correspond to class V LN. Beyond this ﬁrst wave of immune effectors which mainly target the. A renal biopsy showed the granular deposition of immunoglobulin G in the glomerular basement membrane and subepithelial electron-dense deposits, crescent formation, C4d-positive staining of the peritubular capillary, and subendothelial swelling, suggesting that the main pathological diagnosis was membranous nephropathy and that chronic graft. The electron microscopy is different for the two types. In type I are there subendothelial deposits. In type II is the lamina densa and subendothelial space of the glomerular basement membrane transformed into an irregular, ribbon-like dense structure. MPGN manifests mostly as nephrotic syndrome but may have components of nephritic syndrome as. Mesangial proliferative GN. 1. Mesangial proliferative GN. 2. • Mesangioproliferative pattern of glomerular injury is characterized by the expansion of mesangial matrix and the mesangial hypercellularity. These changes can occur in immune complex-mediated diseases, such as IgA nephropathy or class II lupus nephritis or non-immune diseases.
Nephrotic syndrome is a collection of signs and symptoms indicating damage to the glomerular filtration barrier. It is characterized by massive proteinuria ( > 3.5 g/24 hours ), hypoalbuminemia, and edema. In adults, the most common causes of nephrotic syndrome include focal segmental glomerulosclerosis ( FSGS) and membranous nephropathy Significantly subendothelial and subepithelial deposits were frequently observed in this group. Matching-IgAN group showed relatively advanced sclerotic lesions with more global sclerosis and fibrous crescent. Conclusion. Local inflammation involved glomerular capillary wall in IgA-IRGN, in contrast to relatively chronic and sclerotic renal. The overlying epithelial foot processes are effaced with intact lamina densa (original magnification ×7000). B, Diagram of extensive, large, subendothelial deposits with small, scattered, subepithelial deposits. Varying mesangial hypercellularity and deposits are observe Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of chronic nephritis that occurs primarily in children and young adults. This entity refers to a pattern of glomerular injury based on characteristic histopathologic findings, including: (1) proliferation of mesangial and endothelial cells and expansion of the mesangial matr..
A few isolated subepithelial or subendothelial deposits may be visible by immunofluorescence or electron microscopy, but not by light microscopy. Class V: Membranous lupus nephritis: global or segmental subepithelial immune deposits or their morphologic sequelae by light microscopy and by immunofluorescence or electron microscopy, with or. . Occurrence: ♂ = ♀; Peak incidence: 60-85 years  Renal function declines rapidly over days to week
deposits May be a few isolated subepithelial or subendothelial deposits visible by immunofluorescence or electron microscopy, but not by light microscopy Class III Focal lupus nephritisa Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving <50% of all glomeruli, typicall Occasional intramembranous and subepithelial deposits, even large subepithelial humps, may occur. In type III MPGN, extensive glomerular subendothelial, subepithelial, and transmembranous deposits are seen along the glomerular capillaries (39, 40). These deposits are frequently less electron dense than in type I MPGN, and they may blend. Table 2 .2Urinary C5b-9 excretion in experimental glomerular disease Glomerular C5b-9 Urinary excretion Protein C5b-9 N Day deposits mg/24 h u/24 hr Passive Heymann 8 5 + subepithelial 53 l6 3.6 1.2k nephritis Cationized IgG 5 2 + subepithelial 165 40 <0.71 0.19 anti-IgG Nephrotoxic 6 1 linear GBM 423 60 <0.43 0.14 nephritis Con-A anti-con-A.
MPGN I (Subendothelial Deposits) MPGN II (Dense deposits in GBM) MPGN III (Subendothelial + Subepithelial Deposits) Secondary; HCV (is the most common cause) New way to look at MPGN; Immune-Complex Mediated (Classic pathway activation) Autoimmune Ds; Paraproteinemia due to MGRS; HCV (main cause of MPGN) and other infections; Lab evaluation: Low. Large subendothelial lipohyaline deposits may be present at the periphery of the glomerular tuft (hyaline caps) Similar deposits along the Bowman capsule capsular drops, which are specific In later stages, segmental glomerulosclerosis, especially at the tubular outlet tip lesion, is common Electron dense subepithelial deposits Expansion of. No subepithelial or subendothelial deposits were described, but 44% of patients (8 of 18 cases) had mesangial deposits concurrent with a class I or class II LN (mesangial LN). Kraft and colleagues. 1. Kraft S.W. Schwartz M.M. Korbet S.M. Lewis E.J. Glomerular podocytopathy in patients with systemic lupus erythematosus
adds specificity to the IF findings and can precisely localize the deposits. Immune complexes are seen as densities in the mesangium and/or peripheral capillary loop. In the peripheral loop they are said to be subepithelial (between the GBM and the podocyte) or as subendothelial (between the GBM and the endothelial cells) Subendothelial deposits West et al, J Pediatr 1965 • MPGN Type II / DDD: Deposits in lamina densa of glomerular basement membrane Galle, Thesis 1962; Habib et al, Kidney Int 1975 • MPGN Type III: Subendothelial and subepithelial deposits Burkholder et al, Am J Pathol 1969 Anders et al, Virchows Arch A Pathol Anat Histol 199 Compared to A, the subendothelial and intramembranous deposits appear isodense with the glomerular basement membrane, and are difficult to detect (white arrowhead) (×12 000), (C) Scattered subendothelial and intramembranous staining of IgG (black arrow) in Case 1 (×15 000), (D) Subepithelial IgG deposits in a case of idiopathic membranous. Segmental subendothelial deposits are usually demonstrable in the glomeruli with segmental endocapillary proliferative lesions, but they may be absent if the more severely affected glomeruli are not sampled in the tissue processed for electron microscopy. Scattered subepithelial deposits are also frequently seen, often in an irregular distribution
Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving <50% of glomeruli, typically with focal subendothelial immune deposits, with or without mesangial. 2. Subepithelial deposits 3. Subendothelial deposits 4. Hematuria with URTI 5. Progress to CRF 6. Associated with ARF 7. Wire-looping capillaries 8. Granular IF appearance 9. Linear IF appearance 10. Rim patterned serum test 11. HLA-BR2 association 12. SLE association 13. Self resolving 14. Wegner's granulomatosis 15. Mesangial deposits 16.
mesangial, subendothelial, or subepithelial ED deposits KDIGO. ASSESSMENT OF HISTOLOGICAL ACTIVITY KDIGO. ASSESSMENT OF HISTOLOGICAL CHRONICITY KDIGO. PROGNOSIS • 1/3 remission, often spontaneous • 1/3 gradual progession to end stage • 1/5 intermittent exacerbatio Subendothelial and mesangial deposits that frequently contain C3 and immunoglobulins Large subepithelial deposits in acute postinfectious glomerulonephritis. The capillary loop deposits become less frequent after a few weeks, but the mesangial deposits persist for a longer period Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in non-diabetic Caucasian adults over 40 years of age. It has an estimated incidence of 8-10 cases per 1 million. Fifty per cent of patients diagnosed with primary MN continue to have nephrotic syndrome and 30% of patients may progress to end-stage renal disease over 10 years. Although it was recognised as a distinct.
microscopy subepithelial deposits were seen in 94% of cases, followed by mesangial deposits in 90.4% and subendothelial deposits in 74.7% of cases . The location of these deposits can be attributed to the stage of renal disease where deposits are mainly subepithelial in the early and acute phase, in th In cases of resolving APIGN, the subepithelial deposits were preferentially located at the glomerular basement membrane reflection over the mesangium (that is, the mesangial waist). Subendothelial deposits were typically small and infrequent, but were nonetheless detectable in three-quarters of cases Subepithelial deposits Membranoproliferative GN Type I: Immune complex disease Idiopathic or secondary to Neoplasm, Autoimmune disease, Infections, Drugs Subendothelial immune complexes. Type II: Complement activation BM deposits (dense deposit disease) 50% progress to chronic renal failure (CRF
Scattered subendothelial deposits (subendothelial meaning behind the GBM, on the urine side of things) Stage 2: Large uniform deposits; Spikes of epithelium between them Foot processes are being destroyed by the membrane attack complex (invoked by complement cascade, the alternative pathway) Stage 3: DEPOSITS ENCIRCLED and incorporated into th subendothelial space. Some cases also have subepithelial or intramembranous deposits.1-3 The deposits of ITG are immunoglobulin derived, and can be either polyclonal (30 to 40%) or monoclonal (60 to 70%).1 Interestingly, in a few patients with ITG and chronic lymphocytic leukaemia or related B-cell lymphoma, monoclonal deposits with •Subepithelial immune deposits •Thickening of BM between deposits -eventually envelopes and covers the deposits. 30. 31. Membranous GN •Light microscopy (LM) • - Subendothelial immune complexes Type II: - Complement activation • -BM deposits (dense deposit disease nephritic syndrome endothelial and mesangial cells injury: inflammation, red blood cells and protein in urine proliferative glomerulonephritis) grou -between endothelium & BM (subendothelial)-between podocytes & BM (subepithelial)-endothelial cells-mesangial cells-parietal epithelial cells. Deposits may be located. at more than one site in a given cas (1) Subepithelial humps, as in acute glomerulonephritis (2) Epimembranous deposits, as in membranous nephropathy and Heymann nephritis (3) Subendothelial deposits, as in lupus nephritis membranoproliferative glomerulonephritis (4) Mesangial deposits, as in IgA nephropath