Subendothelial Deposits Research Articles

Role of neutrophils in murine cryoglobulinemia.

Murine IgG3 anti-IgG2a rheumatoid factor (RF) monoclonal antibodies (mAb) with cryoglobulin activity, are able to induce, in normal mice, skin leukocytoclastic vasculitis and lupus-like glomerulonephritis resembling 'wire-loop' lesions (subendothelial immune deposits). The development of glomerular, but not skin, lesions in immunoglobulin-deficient mice (lacking the corresponding IgG2a autoantigen) receiving IgG3 RF cryoglobulins indicates that the RF activity of IgG3 monoclonal cryoglobulins and subsequent formation of IgG3-IgG2a immune complexes play a critical role in the development of skin vasculitis. In contrast, nephritogenic activity is solely contributed by IgG3-associated cryoglobulin activity. Polymorphonuclear leukocyte (PMN) infiltration is one of the major pathologic changes observed in both types of lesions. Treatment with mAbs against the adhesion molecules leukocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) (both known for their involvement in PMN-endothelial cell interaction) inhibits the development of skin vascular lesions. However, it has no effect on the generation of glomerulonephritis. Apparently, adhesion molecule requirements for PMN interaction with glomerular capillary endothelial cells are different from those for PMN infiltration of the skin. However, the PMN depletion experiment has clearly shown that PMNs play an active role in the development of 'wire-loop' glomerular lesions. In the absence of the glomerular PMN infiltration, IgG3 RF cryoglobulins induce a different type of glomerular lesion, characterized by voluminous intracapillary thrombi and mesangial deposits, yet lacking subendothelial deposits. This is consistent with the fact that the latter lesions can be induced by certain IgG3 mAbs, which are unable to provoke glomerular PMN infiltration. Finally, the activation of the complement system does not appear to play a major role in either skin or glomerular lesions induced by IgG3 RF cryoglobulins.

Infrainguinal aneurysm formation in arterialized autologous saphenous vein grafts

True aneurysm formation in arterialized autologous veins is an unusual complication. We studied a patient with 2 aneurysms occurring in the mid and distal portion of an in situ femoropopliteal bypass. The first aneurysm led to graft occlusion 4 years after the primary intervention, requiring replacement of the ectatic graft segment. The graft was still patent when the patient was examined 7 years after the primary intervention and 3 years after the first aneurysm. In the mid portion of the graft, a true aneurysm measuring 5 by 8 cm had developed. The aneurysm was replaced by a reversed segment of the contralateral greater saphenous vein. Recovery was uneventful. Advanced atherosclerotic changes with extensive intimal fibroplasia, subendothelial cholesterol deposits, and ulcerations were revealed by means of histopathology of the aneurysm wall. Atherosclerosis is considered to be the main cause of aneurysm formation in vein grafts, but a review of the literature suggests the additional etiopathogenic factors should be further investigated. (J Vasc Surg 1998;28:944-8.)

Immunohistological and ultrastructural differences between recurrent type I membranoproliferative glomerulonephritis and chronic transplant glomerulopathy.

In renal transplant recipients with type I membranoproliferative glomerulonephritis (MPGN), the posttransplantation course can be complicated by a recurrence of the original disease. However, it is well known that a recurrence of type I MPGN and chronic transplant glomerulopathy (CTG) cannot easily be distinguished. It has been suggested that the two entities can be differentiated by using electron microscopy (EM) and immunofluorescence (IF) techniques. However, studies are lacking that compare biopsy specimens from patients with either a recurrence of type I MPGN or CTG. We have studied renal biopsy specimens from 10 patients with CTG and compared the ultrastructural and IF findings with biopsy specimens from 12 patients with a possible recurrence of type I MPGN. All the patients with CTG showed an electron-lucent zone of finely flocculent material in the subendothelial space, whereas all patients with a recurrence of type I MPGN showed subendothelial electron-dense deposits on EM. On IF, all patients with CTG showed Immunoglobulin M (IgM) with greater intensity than C3. For the patients with recurrent type I MPGN, the opposite was true. Eleven specimens showed C3 deposits with greater intensity than IgM, and in one patient, C3 and IgM were found in equal intensity. In conclusion, when IF and EM studies are available, CTG and recurrence of type I MPGN can reliably be distinguished.

Renal involvement in hepatitis C infection: Cryoglobulinemic glomerulonephritis

Patient 1. A 49-year-old man reported recurrent episodes of arthralgia, purpura, and abdominal colic over 2 years. He was transferred to the San Carlo Hospital in Milan from another hospital, where he had been admitted because of fever, abdominal pain, purpura and edema of the legs, slightly increased serum creatinine (1.5 mg/dl), nephrotic-range proteinuria (4–5 g/day), and positive serum cryoglobulins (cryocrit 1%). On admission to San Carlo Hospital, the proteinuria was still in the nephrotic range, with reduced total serum proteins (4.9 g/dl), and the cryocrit was 11%, with mixed cryoglobulins characterized as IgG-IgM. Serum C4 was almost undetectable, with C3 moderately reduced; ALT was 57 U/liter. Hepatomegaly was present, and a liver biopsy disclosed mild active chronic hepatitis. Markers for HBV were negative, while anti-HCV antibodies were detected a posteriori in the stored serum. His blood pressure was markedly elevated, and severe retinal lesions (grade 3 hypertensive retinopathy) were present.

Membranoproliferative glomerulonephritis type III: Association of glomerular deposits with circulating nephritic factor-stabilized convertase

Deposits in the glomerular ultrastructure of 44 renal biopsy specimens from 21 patients with membranoproliferative glomerulonephritis (MPGN) type III have been compared with those in the ultrastructure of 34 biopsy specimens from 19 patients with MPGN type I. Previous studies have concluded that subepithelial deposits on the paramesangial portion of the glomerular basement membrane in MPGN types II and III are closely associated with circulating nephritic factor-stabilized convertase. In the present study, subendothelial deposits in MPGN type III were also found to be closely associated with nephritic factor; they were present in 14 of 26 (54%) biopsy specimens obtained during hypocomplementemia but in none of the 18 biopsy specimens obtained during normocomplementemia (P < 0.001). Subepithelial loop deposits in type III were also more frequent in biopsy specimens obtained during hypocomplementemia and are probably in some way also associated with circulating stabilized convertase. Taken together, the results of this and previous studies are compatible with the hypothesis that an excess of the C3b-dependent convertase in the circulation is basic to the pathogenesis of MPGN types II and III as well as of several other nephritides associated with factor H dysfunction. The half-life, structural complexity, and size of the convertases circulating in these nephritides increase in the following order: native convertase, convertase stabilized by the nephritic factor of the amplification loop (NFa), and convertase stabilized by nephritic factor of the terminal pathway (NFt). In the same order, the nephritides associated with these convertases more frequently manifest and have increasing amounts of glomerular deposit. This relationship of glomerular deposits with circulating convertase, however, is only circumstantial. There is no evidence that the convertase or a part thereof is a constituent of the deposits. The lesion that is the hallmark of MPGN type III is one in which interruptions of lamina densa are associated with subendothelial and subepithelial deposits, often confluent, and interspersed with multiple layers of new lamina densa-like material. This “type III lesion,” which by implication is also associated with circulating nephritic factor, is the most persistent of the glomerular deposits. For reasons that are not yet clear, the type III lesion was absent in three patients who were severely hypocomplementemic, and the diagnosis of type III was made only after this lesion appeared in biopsy specimens obtained later. In MPGN type I, differing from type III, subendothelial deposits were present in 100% of biopsy specimens obtained during hypocomplementemia and in 47% of those obtained during normocomplementemia. Their persistence in type I may reflect rearrangement and condensation of the deposited material, shown by other investigators to be dependent on the presence of immunoglobulin G, which is largely absent from the deposits in type III. The comparison of deposits in types I and III indicates that relating the presence of subendothelial and paramesangial deposits to the C3 level at the time of biopsy can be helpful in distinguishing types I and III when the type III lesion is not present. (Am J Kidney Dis 1998 Jul;32(1):56-63)

Lupus Nephritis: Mesangial and Membranous Forms (WHO II and V)

The AJKD Atlas of Renal Pathology presents a compilation of figures on a specific pathologic entity. You may download the figures to create your own personal, non-commercial library of images or to create slides for teaching purposes. The AJKD Atlas of Renal Pathology presents a compilation of figures on a specific pathologic entity. You may download the figures to create your own personal, non-commercial library of images or to create slides for teaching purposes. Fig 2Immunofluorescence shows mesangial staining in WHO Class IIb lupus nephritis, without peripheral capillary loop deposits (immunofluorescence with anti-IgM; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 3Electron-dense mesangial deposits are present in mesangial lupus nephritis WHO Class IIb. There is paramesangial extension of a deposit in the upper left, indicating incipient progression to a proliferative form of lupus nephritis. Reticular aggregates are also present in endothelial cell cytoplasm (transmission electron microscopy; original magnification ×8,000).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 4Membranous lupus nephritis, with diffuse holes and small spikes visualized on the silver stain, along with mild mesangial expansion with small areas of pink staining in mesangial areas, indicative of mesangial deposits. Very mild endocapillary increase of cells is also present, and occasional subendothelial deposits were present by electron microscopy, indicating a combination of lupus WHO Class V and very early proliferative changes. This may be classified as lupus WHO Class Vc, or if light microscopic changes warrant, combined WHO Class IV and V (Jones silver stain; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 5Combined proliferative and membranous lupus nephritis (WHO Class IV + V), evidenced by basement membrane splitting, small spikes and holes in tangential sections, and a small area of parietal epithelial cell proliferation and basement membrane disruption, indicative of an early crescent formation (Jones silver stain; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 6Immunofluorescence in membranous lupus nephritis, WHO Class Vb, with diffuse granular capillary wall and mesangial positivity (immunofluorescence with anti-IgG; original magnification ×400).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 7Diffuse subepithelial dense deposits and lesser mesangial deposits in this field in membranous lupus nephritis. Reticular aggregates are also present in endothelial cell cytoplasm in most cases of lupus nephritis (see Fig 9)(transmission electron micrograph; original magnification ×8000).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 8Combined proliferative and membranous form of lupus nephritis, WHO Class IV and V, with massive subepithelial and intramembranous deposits, frequent mesangial and occasional subendothelial deposits and endocapillary proliferation, distorting capillary loops (transmission electron microscopy; original magnification ×3,000).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Fig 9Close-up of subepithelial deposits in lupus membranous glomerulonephritis, with well developed spike formation and early basement membrane formation overlying some deposits. This case was classified as WHO Class Vb (mesangial deposits not shown in this micrograph). Two endothelial cells with well developed reticular aggregates are shown in the middle of the field (transmission electron micrograph; original magnification ×10,000).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

From atherosclerotic silent plaque to disrupted and activated plaque: histology versus angiographic, angioscopic and intravascular ultrasound imaging

Activated or silent plaque means a plaque associated or not with symptoms and signs of an acute coronary syndrome. In turn, the plaque activation should correspond to its rupture/fissuration leading to intimal hemorrhage, thrombosis and embolization causing unstable angina and/or myocardial infarction and/or sudden death. The rational, therefore, is the demonstration in vivo of this activation for diagnostic, prognostic and therapeutical purposes. The aim of this review is to briefly discuss the significance of different types of imaging in vivo in relation to plaque structure; keeping in mind that in the majority of atherosclerotic people with or without ischemic disease the natural history and structure of the atherosclerotic plaque diverge from that obtained by hypercholesterol diet or found in familial or acquired hypercholesterolemia: smooth muscle cell hyperplastic coronary plaque versus hypercholesterol coronary plaque. The former begins with a nodular smooth muscle cell/elastic hyperplasia followed by substitutive fibrosis, proteoglycan deposition in the deep layer below the fibrotic capsule, permeation of lipo-protein/cholesterol and/or calcium salts in the proteoglycan pool. There is no evidence of early subendothelial deposition of lipo-proteic material, platelet adhesion, mural fibrin-platelet thrombi or macrophages. On the contrary, hypercholesterol plaque starts with subendothelial lipo-proteic infiltration and macrophagic reaction [1].

Electron microscopy study of genesis and dynamics of immunodeposition in IgMk-IgG cryoglobulin-induced glomerulonephritis in mice

Cryoglobulinemic glomerulonephritis is particularly frequent in type II mixed IgMk-IgG cryoglobulinemia. The typical form is a membranoproliferative glomerulonephritis with a particular monocyte infiltration. In the most severe cases, there is occlusion of the capillary lumina by the same immunoglobulin constituents of the cryoprecipitate. While it is generally accepted that the “hyaline thrombi” are endoluminal aggregates of IgG-IgM immune complexes, probably favored by high endocapillary concentration of cryoglobulins, the modality of generation has not been studied. To study the dynamic formation of such “thrombi,” we reproduced an experimental model of cryoglobulinemic glomerulonephritis in mice by injecting them twice a day for 3 days with 4 mg human IgMk-IgG cryoglobulins previously solubilized at 37 degrees C. The dynamic formation of immunodeposits was studied by immunofluorescence and electron microscopy. After 1 day, only mesangial deposits were found; after 3 days, in addition to mesangial deposition, all the capillary lumina were occluded by huge electron-dense bodies. To look for and quantify the contacts between such “thrombi” and mesangial or subendothelial deposits, we obtained serial, ultrathin, 0.5-microm sections that allowed us to reconstruct the whole glomerular tuft. Within each serial section, there was continuity between hyaline thrombi and mesangial or subendothelial deposits ranging from 80% to 85% of the capillary loops. The percentage was 100% for two adjacent serial sections. In conclusion, our data demonstrate directly for the first time that hyaline thrombi follow mesangial deposits. The high percentage of contacts between thrombi and mesangial or subendothelial deposits suggests that they result from in situ build-up of true huge endoluminal immunodeposits after saturation of the clearance capacity of the mesangium. (Am J Kidney Dis 1998 Mar;31(3):435-42)

In situ complement activation in porcine membranoproliferative glomerulonephritis type II

Pigs genetically deficient in complement factor H all develop lethal membranoproliferative glomerulonephritis (MPGN) type II characterized by massive glomerular deposits of complement, intramembranous dense deposits, and mesangial hypercellularity. To elucidate the chronological relationship between these glomerular changes, and to precisely determine the localization of glomerular complement deposits, we studied kidney specimens from factor H-deficient piglets at different ages from fetal life until terminal kidney failure had developed. Deposits of C3 and the terminal complement complex localized within the glomerular basement membrane (GBM) were present already in factor H-deficient fetuses, without concurrent intramembranous dense deposits or mesangial hypercellularity. Incipient subendothelial dense deposits containing complement appeared no earlier than four days after birth, and intramembranous dense deposits in older piglets with established MPGN type II also contained large amounts of complement as detected by immune electron microscopy. Onset of kidney failure coincided with pronounced mesangial hypercellularity and expansion, compromising glomerular capillary patency. Formation of glomerular capillary wall double contours coincided with electron microscopic evidence of laminar disintegration of intramembranous dense deposits. Complement was also deposited in the mesangial matrix, but not on glomerular cells. We conclude that all components of the alternative and terminal pathways of complement have access into the GBM and the mesangial matrix. In the absence of factor H, complement is spontaneously activated and deposited in situ in these locations resulting in dense deposit formation. It is proposed that factor H dysfunction may play an essential role even in human MPGN type II.

Carcinoma of Urinary Bladder Associated with Nephrotic Syndrome

Carcinoma of Urinary Bladder Associated with Nephrotic Syndrome

Clinicopathologic features of glomerular lesions associated with hepatitis C virus infection in Japan

We determined the incidence of hepatitis C virus (HCV)-related glomerulonephritis in Japan and the glomerular localization of HCV-related antigens in this disorder. We analyzed urinalysis findings in 100 consecutive Japanese patients with HCV chronic liver disease from 1993 to 1994. Immunohistochemical analysis using monoclonal or polyclonal antibodies to HCV-core antigen and polyclonal antibodies to HCV-envelope antigen was done on kidney specimens from 11 of 29 patients with antibody to HCV (anti-HCV-Ab). Eight of 100 patients had proteinuria, but only 2 cases (2%) were related to HCV nephropathy. Pathohistologic analysis showed 10 patients to have hepatic glomerulosclerosis, and 9 patients had mesangial proliferative glomerulonephritis involving primary immunoglobulin A nephropathy. Membranoproliferative glomerulonephritis was seen in 4 biopsy specimens that showed subendothelial electron-dense deposits and annular structures with characteristic cryogloblin. HCV core antigen was detected along the capillary walls with the same pattern as that of immunoglobulin G deposition and electron-dense deposits in 5 of 6 specimens from patients with both anti-HCV-Ab and HCV ribonucleic acid positive in the sera, but could not be detected in any of 3 specimens, from patients with anti-HCV-Ab but no HCV ribonucleic acid. Envelope antigen was not detected in the glomeruli of any specimens. Glomerular lesions associated with HCV infection were characterized by deposition of immune complexes containing HCV core antigen and immunoglobulin G, and by the subendothelial deposition of cryoglobulin. These HCV-related glomerular diseases are rare in Japan (2% incidence), and these lesions should be distinguished from hepatic glomerulosclerosis related to advanced liver disease and other primary glomerular diseases.

Processes in atherogenesis: complement activation

The complement system consists of a complex group of plasma proteins, which, on activation, lead to a cascade of interactions culminating in the production of a variety of pro-inflammatory molecules. The system also contains cellular receptors for complement fragments produced during activation and regulatory molecules. It is part of the innate immune system representing humoral defence, but in certain circumstances may itself contribute to disease. In the formation of atherosclerotic lesions, there are two outstanding cellular phenomena, monocyte recruitment, with subsequent development of lipid-filled foam cells and smooth muscle cell activation. Subendothelial deposition of low density lipoprotein appears to be an important stimulus in these events and substantial evidence suggests that complement activation may be a link between lipoprotein deposition and subsequent lesion development.

Glomerular handling of immune complex in the acute phase of active in situ immune complex glomerulonephritis employing cationized ferritin in rats. Ultrastructural localization of immune complex, complements and inflammatory cells.

The ultrastructural localization of immune complex (IC) and inflammatory mediator systems in the glomerulus was investigated in active in situ IC glomerulonephritis employing cationized ferritin in rats. Glomerulonephritis was induced by unilateral renal perfusion of cationized ferritin as antigen (Ag) in preimmunized rats, and anti-ferritin antibody (Ab), C3 and the rat C5b-9 complex were localized by means of immunogold electron microscopy. Ag-Ab complexes were initially formed subendothelially, associated with C3, and attracted platelets, polymorphonuclear leucocytes (PMN) and monocytes. Then Ag-Ab complexes, without C3, passed across the glomerular basement membrane to re-aggregate subepithelially accompanied by C3 deposition after 1 day. Ag-Ab complexes without C3 accumulated in the inter-podocyte space within 1 day and were seen in the epithelial cells at 6 h. C5b-9 complexes were found in subepithelial immune deposits and in membrane vesicles of the epithelial cells, but only in very small amounts in subendothelial immune deposits. Accumulated platelets, PMN, and monocyte were in direct contact with endothelial cells or subendothelial IC. PMN and monocytes contained Ag, Ab and C3 in intracytoplasmic vacuoles. Ag-Ab complexes were also found in the mesangial matrix adjacent to the subendothelial region after 2 h and increased slightly in number, with expansion of the mesangial area thereafter. Most ICs formed in the subendothelial space rapidly formed lattices of a size that activated C3 and were then translocated to the subepithelial space. The potential ability of C3 to solubilize ICs in the subendothelial region may be important in this process. Endocytosis of subendothelial ICs by PMN and/or monocytes and the movement of ICs to the mesangial matrix may also contribute to the removal of IC from the subendothelial space.

Ultrastructure of Evolving Deep Venous Collaterals

Objective: To explore the structure of obstructive venous collaterals. Design: A total of 25 rats underwent unilateral ligation of the distal common femoral vein. Bilateral (control and test) vein segments with collaterals were harvested and studied with conventional light microscopy and electron microscopy at 2-week intervals for 10 weeks post-ligation. Results: Obstructive collaterals were quite unlike normal controls throughout the study. Initially, post-obstructive collateral walls showed disorganization of collagen, elastin, smooth muscle cells, and adventitia, while endothelial cells became more rounded and compact. The dense protein subendothelial deposits noted early became organized and moved more deeply into the wall at subsequent study intervals. Minimal motivation of smooth muscle cells, coalescence of elastic lamina, condensation of collagen and some organization of the wall were noted. Conclusion: Inability of deep collaterals to function with normal wall properties is likely to be secondary to the disruption of connective tissue and sustained disorganization of the vein wall noted throughout the evolution of collateral formation.

Cold-induced stress stimulates the sympathetic nervous system, causing hypertension and proteinuria in rats.

To determine whether cold-stress stimulation of the soles of the paws would produce a preeclampsia-like syndrome in rats. Pregnant or nonpregnant rats were kept in 0 degree C floor and 23 degrees C room temperature cages (the cold-stressed group) or in 23 degrees C floor and 23 degrees C room temperature cages (the control group) for 2 weeks. Their blood pressure, proteinuria, and plasma catecholamines were measured, and histologic studies were performed on all groups. There were no significant differences in systolic blood pressure between the two groups during the first week of the experimental period; however, during the last week of gestation the blood pressure of the cold-stressed group did not fall and was significantly higher than that of the control group. A significant increase in urinary protein excretion was observed in the cold-stimulated pregnant rats, in contrast to the control rats. The concentrations of norepinephrine and epinephrine in the cold-stressed pregnant rats were markedly higher than those in the control rats. A decrease in trophoblast invasion, congestion, and fibrinoid deposits of the labyrinth were observed in the cold-stressed rats. A marked increase in subendothelial fibrinoid deposits in the glomerular capillary was found only in the cold-stressed pregnant rats. The blood pressure, biochemical parameters, and histologic findings in the nonpregnant rats were almost the same as those in the pregnant rats. Chronic local cold stimulation of the soles of the paws induces preeclampsia-like phenomena in pregnant and nonpregnant rats, and this model suggests that the cause of preeclampsia is involved in chronic stimulation of the sympathetic nerve.

Morphologic, immunohistochemical, and ultrastructural characterization of a distinctive renal lesion in dogs putatively associated with Borrelia burgdorferi infection: 49 cases (1987-1992).

A distinctive renal lesion consisting of glomerulonephritis, diffuse tubular necrosis with regeneration, and interstitial inflammation was found in 49 biopsy/necropsy cases obtained from 1987 to 1992. This lesion is manifested clinically as a rapidly progressive glomerular disease that was uniformly fatal. Immune-mediated membranoproliferative glomerulonephritis predominated (43/49, 88%). Membranous glomerulonephritis (5/49, 10%) and amyloidosis (1/49, 2%) were also noted. Subendothelial deposits, IgG, IgM, and C3 were present along glomerular basement membranes. IgA was absent. The exact cause of the tubular necrosis is unknown. Affected dogs were significantly younger (5.6 +/- 2.6 years) than dogs with other forms of glomerulonephritis (7.1 +/- 3.6 years) and amyloidosis (7.8 +/- 3.5 years) both in the studied population for the same period and in the reported canine population. Labrador and Golden retrievers were 6.4 and 4.9 times more likely, respectively, to develop this lesion. This is the first report of a breed predilection for spontaneous canine glomerulonephritis. Previous reports have associated this lesion with Borrelia burgdorferi exposure. All dogs in this study were from Lyme disease-endemic areas. Of 18 dogs serologically tested, all were positive for exposure. Silver stain examination of kidneys revealed rare spirochetes, suggesting that the presence of spirochetes in the kidney is apparently unrelated to lesion development. The role of vaccination in development of the renal lesion is undetermined. The association of this histologically and clinically unique lesion, Lyme nephritis, with Borrelia burgdorferi infection is significant because it is the only fatal form of canine Lyme borreliosis.

Membranous lupus nephritis with antineutrophil cytoplasmic antibody-associated segmental necrotizing and crescentic glomerulonephritis

Focal segmental necrotizing and crescentic lupus nephritis accompanied by perinuclear antineutrophil cytoplasmic antibody (P-ANCA) seropositivity is an unusual occurrence. We report the first biopsy-documented cases of membranous lupus nephritis class V with associated “pauci-immune” segmental necrotizing glomerulonephritis and P-ANCA seropositivity. The absence of subendothelial electron-dense deposits favored a manifestation of superimposed ANCA-associated glomerulonephritis rather than class III lupus nephritis. The pathogenetic implications of this association are explored.

Evidence for Preeclampsia in a Baboon Pregnancy with Twins

A primigravid baboon pregnant with twins developed a spontaneous clinical syndrome with characteristics similar to human preeclampsia. Evidence of preeclampsia included increased mean blood pressure, the occurrence of proteinuria, a decrease in platelet count, and renal endotheliosis (i.e., glomerular capillary subendothelial deposits, mesangial fibrin deposition and expansion, and double-contouring of the glomerular basement membrane with endothelial cell swelling and lysis). These lesions occurred spontaneously and resolved postpartum.

Hepatitis C virus-associated membranoproliferative glomerulonephritis in renal allografts.

In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.

Structural and ultrastructural study of glomerular changes in African swine fever

The pathological effect of haemorrhagic fever viruses on the kidney have not been clearly documented. This study reports glomerular lesions in African swine fever. In the acute form of the disease there was an acute diffuse proliferative glomerulonephritis, which was believed to be related to virus replication in circulating monocytes and glomerular mesangial cells, and to the presence of abundant circulating cell debris resulting from viral replication at other sites. In the subacute form, the proliferative mesangial glomerulonephritis observed may have been associated with systemic immune-mediated phenomena, and with subendothelial and mesangial deposits of immunoglobulins and complement components.