Mesangial Proliferative Nephritis Research Articles

Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation.

Mesangial cell proliferation is common in glomerulonephritis but it is unclear if proliferation is associated with any in vivo alteration in phenotype. We investigated whether mesangial of mesangial proliferative nephritis induced with antibody to the Thy-1 antigen present on mesangial cells. At day 3 glomeruli displayed de novo immunostaining for alpha-smooth muscle actin in a mesangial pattern, correlating with the onset of proliferation, and persisting until day 14. An increase in desmin and vimentin in mesangial regions was also noted. Immunoelectron microscopy confirmed that the actin-positive cells were mesangial cells, and double immunolabeling demonstrated that the smooth muscle actin-positive cells were actively proliferating. Northern analysis of isolated glomerular RNA confirmed an increase in alpha and beta/gamma actin mRNA at days 3 and 5. Complement depletion or platelet depletion prevented or reduced proliferation, respectively; these maneuvers also prevented smooth muscle actin and actin gene expression. Studies of five other experimental models of nephritis confirmed that smooth muscle actin expression is a marker for mesangial cell injury. Thus, mesangial cell proliferation in glomerulonephritis in the rat is associated with a distinct phenotypic change in which mesangial cell assume smooth muscle cell characteristics.

Mechanism of Localization of Immune Complexes in NZB/W Mice with Early Nephritis

We investigated the pathogenesis of mesangial proliferative lupus nephritis in NZB/W mice under conditions that allowed us to examine removal of immune complexes from the circulation, uptake by the mononuclear phagocyte system, and localization in kidney tissue. These studies were performed at a time when variables such as the quantity of endogenous immune complexes, complement concentration, and carrier state of blood cells (platelets) were controlled. NZB/W mice and C57BL/6 (control) mice showed comparable kinetics for removal of a subsaturating dose of immune complexes (2.5 mg bovine serum albumin-antibovine serum albumin) from the circulation; additionally, the liver uptake and kidney localization of these immune complexes were comparable between NZB/W and control mice. The localization of immune complexes in the glomerular mesangium of NZB/W mice could not be attributed to enhanced production of endogenous immune complexes, to decreased removal of immune complexes from the circulation, to impaired uptake by the liver, or to complement concentration and carrier state of blood cells. It appears, by exclusion, that mesangial deposits of immunoreactants in early lupus nephritis may result from interaction of antibodies with antigens in mesangia.

Screening for renal disease in school children: experience in Japan.

A program of urine screening for asymptomatic hematuria and proteinuria in school children has been conducted since 1973 by the Ministry of Education in Japan with great success in the early detection of asymptomatic renal disease. Prevalence of isolated persistent hematuria in school children was approximately 05%. Prevalence of isolated proteinuria and proteinuria with associated hematuria was 0.08% of primary school children and 0.4% of junior high school children. In order to know whether this nationwide program for 13 years causes some changes in the epidemiology of chronic glomerular disease in Japan, a multicenter survey was conducted on the number of patients with renal diseases. 70–80% of IgA and non-IgA mesangial proliferative glomerulonephritis and 65 to 80% of MPGN were detected by mass urine screening at school. Severe glomerular lesions were more frequently observed in children with chance proteinuria and hematuria, as well as IgA and non-IgA mesangial proliferative glomerulo nephritis who have severe proteinuria. Mild glomerular change was more frequent in patients with MPGN, IgA and non-IgA mesangial proliferative nephritis who were detected by our screening program rather than those seen with some of the nephritic signs and symptoms at diagnosis The above evidence appears that screening program may open the way for the early management of these diseases, especially for which treatment is already established.

Lessons learned from the Japanese nephritis screening study.

A program of urine screening for asymptomatic hematuria and proteinuria in school children has been conducted since 1973 by the Ministry of Education in Japan with great success in the early detection of asymptomatic renal disease. In order to know whether this nationwide program during 13 years has contributed to understanding of the epidemiology of chronic glomerular disease in Japan, a multicenter survey of the patients was conducted. Between 70% and 80% of IgA and non-IgA mesangial proliferative glomerulonephritis and 65%-80% of membrano-proliferative glomerulonephritis (MPGN) were detected by mass urine screening at school. Severe glomerular lesions were more frequently observed in children with chance proteinuria and hematuria, as well as IgA and non-IgA mesangial proliferative glomerulonephritis with significant proteinuria. Mild glomerular change was more frequent in patients with MPGN, IgA and non-IgA mesangial proliferative nephritis with minimal proteinuria who were detected by our screening program, rather than those seen with some of the nephritic signs and symptoms at diagnosis. The above evidence suggests that a screening program may open the way for the early management of these diseases, especially where treatment is already established.

Clinical Significance of Renal Biopsies Showing Mixed Mesangial and Global Proliferative Lupus Nephritis

Renal biopsies of 70 children with systemic lupus erythematosus were categorized, according to the World Health Organization classification, as normal (five, 7%), mesangial (23, 33%), focal segmental proliferative (11, 16%), diffuse global proliferative (20, 29%) (ie, greater than or equal to 80% of glomeruli showing mesangioendothelial cell proliferation and/or deposition of immune complexes along the subendothelial margin of glomerular capillaries), and membranous (six, 8%) lupus nephritis (LN). In addition, five (7%) biopsies showed global proliferative LN in less than 80% of glomeruli and mesangial LN in the others. We assessed the renal status of these five patients at the time of renal biopsy and at outcome following prednisone treatment, with or without azathioprine. Four patients improved and later had either a normal urinalysis or only trace proteinuria. A low chronicity index was calculated on the biopsies of these patients. The fifth patient, whose condition did not improve, demonstrated a high chronicity index on renal biopsy. Overall, the renal status at outcome in the patients showing mixed mesangial and global proliferative LN more closely resembled that of patients with mesangial than diffuse global proliferative LN.

Study of Lupus Nephritis: its Classification and the Significance of Subendothelial Depostis

This study describes the clinical and pathological characteristics of 74 patients with lupus nephritis classified according to renal biopsy findings using light, electron and immunofluorescent microscopy, and further, assesses the significance of subendothelial deposits in evaluating disease activity. In membranous lupus nephritis (14 cases), many cases showed normal renal function even with the nephrotic syndrome, although five cases had little or no urinary abnormalities. Glomerular cellular proliferation was very mild and subepithelial deposits with a few mesangial deposits were the main pathological alterations. Mesangial proliferative lupus nephritis (17 cases) clinically had very mild renal disease. Renal biopsies in this group revealed mesangial deposits with slight cellular proliferation. Although clinical features of mild diffuse proliferative lupus nephritis (16 cases) were similar to those of mesangial lupus nephritis, glomerular loop deposits were seen in addition to mesangial deposits. In moderate diffuse proliferative lupus nephritis (17 cases), renal function was slightly decreased, moderate proteinuria with haematuria were found, and C3 level was low. Renal biopsies showed active proliferative changes, and subendothelial deposits were frequently seen. In severe diffuse proliferative lupus nephritis (10 cases), the duration from onset of SLE to renal biopsy was short. Impairment of renal function, and nephrotic syndrome with haematuria and hypocomplementemia were frequent. Only three patients survived in this group. Renal biopsies demonstrated highly active proliferative and necrotizing changes, and electron microscopy showed massive subendothelial and mesangial deposits accompanied by subepithelial and intramembranous deposits. 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 revealed negative correlations with those deposits.

Immunohistochemical study of the human glomerular C3b receptor in normal kidney and in seventy-five cases of renal diseases: loss of C3b receptor antigen in focal hyalinosis and in proliferative nephritis of systemic lupus erythematosus.

The presence and distribution of C3b receptors in normal human kidneys and in biopsies from 75 patients with renal disease were investigated by immunohistochemical techniques using monospecific rabbit antibody to the 205,000-mol wt glycoprotein that is the C3b receptor of human peripheral blood cells. Anti-C3b receptor bound exclusively to podocytes in normal renal cortex, and was homogeneously distributed on the plasma membrane of these cells. Biosynthesis of the receptor by the podocyte was suggested by the presence of antigenic activity in the Golgi apparatus. Although occupancy of receptor sites following the interaction of kidney sections with aggregated IgG preincubated with normal serum inhibited binding to glomeruli of C3b coated cells, the C3b receptor remained accessible to anti-C3b receptor antibody. No staining of podocytes was found in extra-capillary proliferating cells in rapidly progressive glomerulonephritis (GN). Segmental loss of staining was found in focal hyalinosis, nodular diabetic glomerulosclerosis, and amyloidosis while no detectable C3b receptor antigen was found in severe proliferative nephritis of systemic lupus erythematosus (SLE). Normal staining of podocytes was found in other nephropathies with endocapillary proliferation such as acute GN and mesangial GN and in renal diseases associated with immune deposits containing C3 such as mesangial proliferative and membranous SLE nephritis, idiopathic membranous GN, membranoproliferative GN types I and II, mesangial GN with IgA or C3 deposition and Henoch Schönlein's purpura. Loss of C3b receptor antigen in the diffuse proliferative nephritis of SLE distinguishes it both from nonproliferative lupus nephritis and other immunologically mediated proliferative GN.

Tissue culture of isolated glomeruli from patients with glomerulonephritis

To study aspects of glomerular cell response in varying types of glomerulonephritis, we evaluated isolated glomeruli from 101 normal and diseased adult human renal biopsy specimens in tissue culture. Glomerular cell outgrowths from normal glomeruli consisted of large stellate cells (type I) and smaller fusiform cells (type II). A very occasional cell (type III), which had the features of a macrophage, was seen. The cellular outgrowth from isolated glomeruli reflected the numbers and types of cells present in the diseased glomeruli. Reduced numbers of cells were found in the outgrowth of sclerotic, hypocellular glomeruli. Glomeruli from biopsy specimens with altered morphologic appearances but no increase in cellularity (minimal change nephropathy, membranous nephropathy) produced the same growth pattern as from glomeruli isolated from normal kidneys. In mesangial proliferative nephritis, increased numbers of type II cells were detected in the outgrowth. Large numbers of macrophages were found in the glomerular outgrowth of patients with crescentic glomerulonephritis. Macrophages were absent when crescentic glomeruli were sclerosed, indicating the importance of macrophages in the acute hypercellular phase of crescent formation.