Development Of Renal Lesions Research Articles

Renal ischemia/reperfusion injury contributes to renal damage in experimental anti-myeloperoxidase-associated proliferative glomerulonephritis

The occurrence of focal fibrinoid necrosis of capillary loops in the very early stages of ANCA-associated necrotizing crescentic glomerulonephritis (NCGN) and the increased prevalence of this disease at older age suggest that renal ischemia may play an additional role in its pathophysiology. In the present study we investigated the contribution of renal ischemia to the induction of anti-myeloperoxidase (MPO) associated NCGN in a previously described rat model of this disease. The development of renal lesions is dependent on the presence of an anti-MPO immune response and the localization of a lysosomal extract containing lytic enzymes and MPO in combination with hydrogen peroxide (H2O2) along the glomerular basement membrane (GBM). The hypothesis tested whether perfusion of hydrogen peroxide (H2O2) could be replaced by ischemia/reperfusion (I/R) injury, as I/R injury activates endothelial cells to produce oxygen metabolites. I/R was induced by clamping the renal artery for 20 minutes in kidneys in which the circulation had been restored several minutes after perfusion with the lysosomal extract in MPO immunized rats. Rats developed lesions characterized by intra- and extracapillary cell proliferation, periglomerular infiltration, ruptures in Bowman's capsule, ischemic tubuli, and interstitial mononuclear infiltrate. Immune deposits, however, persisted for a longer time along the GBM after perfusion of lytic enzymes followed by I/R injury compared to previous studies in which H2O2 in conjunction with lytic enzymes were perfused in MPO-immunized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflux Nephropathy: A Clinico-Pathological Study of 16 Cases

The pathologic features of 16 nephrectomy specimens obtained from patients with a radiological diagnosis of reflux nephropathy were analyzed. Chronic pyelonephritis was diagnosed in 7 cases, renal dysplasia in 5 and segmental atrophy in 4. Clear correlations between pathologic pictures and pathogenic mechanisms involved in the development of renal lesions in kidneys with reflux are difficult to establish. These results show, however, that 'reflux nephropathy' is a broad term, which encompasses both congenital and acquired renal lesions.

Undernutrition without Malnutrition Restricts the Numbers and Proportions of Ly-1 B Lymphocytes in Autoimmune (MRL/l and BXSB) Mice

MRL/Mp-lpr/lpr (MRL/l) and BXSB mice represent inbred mouse strains in which lymphoproliferative disease and autoimmune disease that includes lethal renal disease routinely occurs by 6 months of age. Chronic energy intake restriction increases longevity and health span of MRL/l and BXSB mice as it does in mice of other short-lived as well as long-lived strains. Chronic energy intake restriction forestalls development of the lymphoproliferative process, prevents development of renal lesions, decreases levels of circulating immune complexes, and permits maintenance of vigorous immunologic function with age. We have reported that in autoimmune-prone mice, a population of Ly-1 B lymphocytes that is associated with autoimmune disease and is greatly expanded among cells of the spleen, peritoneal exudate, and peripheral blood can be reduced in proportion as a consequence of undernutrition without malnutrition. Herein, we demonstrate that in MRL/l and BXSB mice, chronic energy intake restriction imposed at weaning inhibited accumulation of Ly-1 B lymphocytes throughout the lymphoid system, i.e., among cells of the spleen, thymus, mesenteric lymph nodes, bone marrow, peritoneal exudate, and peripheral blood when these tissues or fluids were studied at age 3 or 5 months. These results extend our previous finding that autoimmune-prone mice possess unusually large numbers of Ly-1 B cells in their lymphoid tissues which can be reduced in frequency as a function of diet toward the levels present in long-lived autoimmune-resistant mice.

Renal excretion of arginine-vasopressin in microalbuminuric diabetic patients.

Enhanced activity of haemodynamic hormones have been reported to be involved in the development of renal lesions of diabetic kidney1,2. Apart from other pressor factors even plasma arginine-vasopressin (AVP) have been found to be increased in uncontrolled diabetic patients very probably reflecting both a hypovolemic status and an increase in “effective” extracellular fluid osmolality; however, high circulating AVP levels have also been observed in certain well controlled diabetic patients thus suggesting that an alteration of mechanisms regulating AVP secretion exists in diabetes mellitus3,4.

Morphogenesis of decalin-induced renal alterations in the male rat

Adult male Fischer 344 rats were killed after 5, 12, 19 or 31 days' ‘occupational’ (6 hr/day, 5 days/wk), ‘semi-continuous’ (22 hr/day, 5 days/wk) or ‘continuous’ (22 hr/day, 7 days/wk) exposure to 125 ppm decalin vapour. Control rats were exposed to filtered air. Kidney sections were evaluated to determine the nature and time-course of development of decalin-induced lesions. The development of renal lesions was characterized by a specific sequence of light microscopically evident alterations. The extent of the alterations was dependent on time and exposure regimen. Severe exacerbation of the spontaneous protein accumulation (hyaline droplets) routinely observed in the kidneys of control male rats was present in kidneys of all decalin-exposed animals at day 5, and was considered to be the primary morphological alteration associated with decalin exposure. The following sequelae of the hyaline droplet response were observed: (1) the variable occurrence of light microscopically evident proximal convoluted tubule (PCT) epithelial cell degeneration/necrosis, presumably a reflection of cellular injury associated with excessive protein accumulation; (2) the occurrence of granular casts at the junction of the inner and outer bands of the outer zone of the medulla secondary to PCT epithelial cell injury; (3) chronic nephrosis, occurring secondary to tubular obstruction by granular casts. This triad of lesions (hyaline droplet accumulation, granular cast formation and chronic nephrosis) lends specificity to the decalin response and establishes a potential mechanistic relationship with other chemicals that induce these effects.

Experimental renal disease due to schistosomiasis

Although there is a marked variability in the development of renal lesions among individual animal models of schistosomal infections, much has been learned about the mechanisms leading to renal injury. The lesions in S. mansoni and S. japonicum infections correspond quite closely to the immune complex type of lesions, with complement involvement. The main antigens involved seem to be polysacharides of worm-gut origin, but participation of other antigens (including soluble egg antigens) cannot be excluded. Many observations testify to the localization of immune complexes, preformed in circulation, but the possibility that antigens, filtered through glomeruli, deposit incapillary walls first and bind with corresponding antibodies later on should be considered also. Deoxyribonucleic acids also may play a role in the pathogenesis. The perpetuation of the lesions is probably due to constant supply of antigens. In some models, renal pathology was related to the dose of infection, but in others there was no relation to worm burden. Renal pathology in S. haematobium infections is different, being related to the lower urinary tract, with obstructive lesions causing pyelonephritis and hydronephrosis.

Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus.

The relationship between expression of xenotropic virus and the development of autoimmunization was studied in the progeny of crosses between New Zealand Black (NZB) and SWR mice. The (F1 X SWR) and F2 progeny segregated into three phenotypes: high-virus, low-virus, and virus-negative; F1 and (F1 X NZB) progeny were always high-virus. Autoantibodies, immune deposit nephritis and lymphomas developed in the progeny of these crosses. The virological phenotype of the animal could be dissociated from the presence of either autoantibodies or nephritis. For example, mice that expressed titers of virus as high as the NZB parent failed to develop signs of autoimmunization, even up to 24 mo of age. By contrast, some (F1 X SWR) and F2 mice that expressed low titers of virus developed autoimmune disease. Furthermore, a proportion of virus-negative mice produced autoantibodies and were found to have typical immune deposit nephritis. No viral antigens could be detected in the renal lesions of such virus-negative animals. By contrast with the dissociation between expression of virus and occurrence of nephritis, the presence of antibodies to DNA correlated with the development of renal lesions. We conclude that the genes that determine the expression of infectious xenotropic virus in NZB mice segregate independently from those that are involved in the autoimmune disease of these animals.

Experimental Membranous Glomerulonephritis Induced in Rats by the Injection of Pronase-Digested Homologous Renal Tubular Epithelial Antigen : III.Relationship between Serum Content of Anti-Tubular Antibody and Development of Renal Lesions in the Chronic Stage of Experimentel Glomerulonephritis

Experimental Membranous Glomerulonephritis Induced in Rats by the Injection of Pronase-Digested Homologous Renal Tubular Epithelial Antigen : III.Relationship between Serum Content of Anti-Tubular Antibody and Development of Renal Lesions in the Chronic Stage of Experimentel Glomerulonephritis

Effect of trypsin inhibitors on Shwartzman phenomenon.

Summary1 Trypsin inhibitors injected intravenously at about the time of the provocative endotoxin injection, partially or completely inhibited the local Shwartzman phenomenon and prevented development of renal lesions (as seen in the generalized Shwartzman phenomenon). 2 Inhibitors administered intradermally mixed with the endotoxin skin preparatory dose, or intravenously at time of skin preparation, did not influence the reaction. 3 The data presented suggest that activated proteolytic enzymes are involved in the Shwartzman phenomenon. 4 The role of these enzymes in the pathogenesis of the phenomenon is discussed. Alterations of the clotting mechanism and vascular changes brought about by release of serotonin, histamine and activation of plasma kinins have been considered.

Renal and hepatic lipid alterations in choline deficiency: relationship to renal necrosis.

SummaryBefore and during the period of development of the characteristic renal lesions of choline deficiency in young rats consisting of a “hemorrhagic” cortical necrosis, observations were made on renal size, morphologic characteristics of the tubules, lipid content and choline content. These observations emphasize the rapid sequence of events in the development of the renal lesions. While the renal lesions are clearly preceded by a considerable increase in hepatic lipid, we were not able to demonstrate the presence of an appreciable degree of renal enlargement or increased renal lipid, in the absence of renal necrosis. After the onset of the renal lesions, with congestion and necrosis, there was an increase in renal size and in total lipid per kidney, but not in renal lipid concentration. Whether compression of capillaries by enlarged, fatty tubular cells is the cause of the renal necrosis, cannot be determined conclusively, in our opinion, by the methods presently or heretofore employed. It is not clea...

Experimental nephrotoxic nephritis in the rat treated with ACTH or cortisone.

ConclusionBoth ACTH and cortisone failed to inhibit the development of renal lesions in the rat produced by the injection of rabbit anti-rat kidney serum.

THE VALUE OF HEAT-KILLED CULTURES FOR THE PREVENTION OF THE BACILLUS ABORTUS INOCULATION DISEASE OF GUINEA PIGS

From the data presented it seems permissible to draw the following conclusions. 1. Guinea pigs cannot be rendered immune to the Bacillus abortus inoculation disease by treatment with heat-killed cultures of this organism. This agrees with the work of Ascoli, and with the general conclusions of many that dead cultures confer very little or no immunity to infectious abortion in cattle. 2. The progress of the disease can be delayed appreciably by such treatment. This is supported by the following observations: (a) the loss in body weight due to the disease is delayed; (b) the development of splenic enlargement is partially inhibited or delayed; (c) the development of renal lesions is delayed or prevented; and (d) the rapidity of multiplication of Bacillus abortus in the splenic pulp is reduced.