Renal Glomerular Changes Research Articles

Differential renal glomerular changes induced by 5/6 nephrectomization between common marmoset monkeys (Callithrix jacchus) and rats

We have been investigating the relevance and availability of 5/6 nephrectomized (Nx) common marmoset monkeys (Callithrix jacchus) as a chronic renal failure model. As a part of this investigation, renal glomerular changes in the Nx marmosets were histopathologically and immunohistochemically evaluated, and then compared with those in 5/6 Nx SD rats. In the Nx marmosets, the blood and urine parameters were elevated, excluding urine protein; histopathologically, enlargement of Bowman's capsule and atrophy of the glomeruli were observed in all animals, and other slight changes were also observed in 1 or 2 marmosets. There were no significant changes in the mesangial matrix injury score, vimentin and desmin positivity or the number of WT1 positive cells between the control and Nx marmoset groups. On the other hand, in the Nx rats, the blood and urine parameters were elevated; histopathologically, various changes were observed in the glomeruli, and the mesangial matrix injury score, vimentin and desmin positivity were increased, while the number of WT1 positive cells was decreased; these histopathological impacts on the renal glomerulus at 13 weeks after Nx in rats were more severe than that in the Nx marmosets. Because the glomerular basement membrane (GBM) was much thicker in the marmosets than in the rats in electron microscopy, the weaker pathological changes in the Nx marmosets might be due to the GBM thickness. This study showed for the first time glomerular lesions developed in the Nx marmosets, and the possible pathogenesis of the glomerular lesions was discussed.

Experimental poststreptococcal glomerulonephritis elicited by IgG Fc‐binding M family proteins and blocked by IgG Fc fragment

The pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), a major nonsuppurative complication of group A streptococcal (GAS) throat or skin disease, remains unclear. During the years, various theories based on certain streptococcal extracellular factors, as well as immunological mimicry between streptococci and renal tissue, have been forwarded. We earlier reported that many clinical GAS isolates with documented nephritogenic capacity show non-immune binding of monomeric or aggregated IgG. Moreover, in a rabbit model of APSGN we obtained evidence for an important role of streptococcal IgG Fc binding proteins (IgGFcBPs) belonging to the M family surface proteins; thus, hyperimmunization by whole IgGFcBP-positive streptococci was shown to induce renal glomerular changes with deposition of IgG and complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by the appearance of circulating anti-IgG antibodies. In the present work, using the same rabbit model, each of two purified IgGFcBPs, isolated from type M22 GAS, were found to elicit glomerular degenerative damage comparable to that caused by whole bacteria, as well as formation of anti-IgG. In addition, the induction by whole streptococci (type M1) of experimental APSGN was inhibited by the i.v. administration of purified human or rabbit IgG Fc, but not Fab, fragment, supporting the importance of Fc-mediated mechanisms in causation of glomerulonephritis. We propose that anti-IgG antibody, induced by streptococcal IgGFcBP, facilitated renal accumulation of IgG-containing complexes, which in turn triggered complement deposition and proinflammatory cascades. Further studies on the possible beneficial effect of IgG Fc fragment in APSGN should be of interest.

Neonatal sympathectomy reduces adult blood pressure and cardiovascular pathology in Y chromosome consomic rats

The hypothesis was tested that the sympathetic nervous system (SNS) developmentally influences circulating testosterone (T), systolic blood pressure (SBP) and cardio-renal pathology in SHR/y animals. A sympathoplegic drug, guanethidine, and an antibody to nerve growth factor were administered to WKY and borderline hypertensive SHR/y male rats (n = 20/group) for the first 3 weeks of life; control groups (n = 20/group) received saline. SBP, serum T and luteinizing hormone (LH) were measured. SBP in the WKY and SHR/y sympathectomy (sympx) groups decreased 10 mmHg (p < 0.001) and 50 mmHg (p < 0.001), respectively, when compared to their control groups. Serum T levels in the sympx WKY group were lower (p < 0.01) than those in controls, and the rise of T typically observed in SHR/y from weeks 6-8 was delayed in the sympx SHR/y group, similar to the pattern in WKY. Serum LH levels were increased in the sympx WKY group, but not in the SHR/y group. Sympx caused a greater reduction in renal glomerular changes (p < 0.01), coronary artery collagen deposition (p < 0.01) and myocardial fibrosis (p < 0.01) in SHR/y than WKY rats. In conclusion, the SHR Y chromosome has a locus that enhances SNS activity, which can raise SBP and result in renal and cardiovascular tissue damage.

Age-related histochemical and ultrastructural changes in renal glomerular mesangium of APA hamsters.

Syrian hamsters of the APA strain (APA hamsters) develop spontaneous mesangial thickening in the renal glomeruli from an early age. They also develop focal and segmental glomerulosclerosis (FSG) at and after 6 months of age. In this study, histopathological, histochemical and electron microscopical examinations were conducted to clarify the age-related renal glomerular changes in spontaneous FSG of APA hamsters. Histopathological analysis revealed that expansion of the mesangial region and thickening of the glomerular basement membrane (GBM) in the glomeruli of APA hamsters progressed with age. These age-related changes appeared earlier in male animals. Immunohistochemical analysis suggested that type IV collagen was responsible for the expansion of the mesangial region and thickening of the GBM. In lectin histochemical analysis, positive sites for WGA with and without neuraminidase pretreatment and PNA with neuraminidase pretreatment were detected mainly in podocytes and were expanded with age. Ultrastructurally, the increase in basement membrane-like materials in the mesangial matrix, development of intracellular organella of mesangial cells and migration of a part of the mesangial cell cytoplasm into the GBM were observed at and after 6 months of age. These features suggested that mesangial cells played an important role in the age-related expansion of the mesangial region and thickening of the GBM.

IgA nephropathy in non-cirrhotic portal hypertension.

Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease.

RENAL GLOMERULAR CHANGES ASSOCIATED WITH LIVER CIRRHOSIS

Renal glomerular changes associated with 79 liver cirrhosis cases were studied by light and electron microscopy, and immunofluorescent methods. The glomerular changes were classified as follows: 1) Mixed membranous and proliferative glomerulonephritis type having subepithelial, subendothelial, mesangial and paramesangial deposits (37 cases), 2) membranous glomerulonephropathy type (6 cases), 3) IgA nephropathy type (3 cases), and 4) glomerulosclerosis types (5 cases). Clinically, the patients with marked renal glomerular changes and proteinuria, hematuria, and retention by the PSP test. It was suggested that the essential renal glomerular changes in liver cirrhosis was immune-complex mediated glomerulonephritis and that glomerular sclerosis was merely a secondary change to glomerulonephritis.

Strain-specific renal toxicity of heterologous antilymphocyte gamma-globulin in mice.

SUMMARY Severe glomerulonephritis followed one to five weekly i.p. injections in TLFM mice of rabbit antimouse lymphocyte γ-globulin (ALG). Glomerulonephritis did not occur in C57BL mice subjected to the same regimen. Administration of normal rabbit γ-globulin (NRG) to RFM mice also caused renal glomerular changes, but no obvious clinical illness or death. Electron microscopy revealed severe alterations in renal glomerular basement membranes after ALG treatment, including subepithelial deposition of electron-dense material and fusion of epithelial foot processes. Subepithelial and subendothelial deposits were seen after NRG treatment. Immunofluorescence microscopy revealed the presence of both rabbit and mouse y-globulins in damaged glomeruli after administration of ALG and NRG. These changes, together with the clinical signs, indicated that an immune complex scrum sickness nephritis followed ALG treatment in RFM mice. A mild form of the disease occurred after treatment with NRG. These results show that, dangerous hypersensitivity reactions may follow administration of highly purified ALG. The selective toxicity of ALG in RFM, but not in C57BL, mice may be related to preexisting renal or autoimmune disease in the RFM strain. The results imply a need for caution in using ALG in patients with coexisting renal disease or autoimmune disease.

General survey of diabetic features of yellow KK mice.

Yellow KK mice, carrying the yellow obese gene (Ay), developed marked adiposity and diabetic symptoms in comparison with their control littermates, black KK mice. The blood glucose and circulating insulin levels were increased progressively from 5 weeks of age in yellow KK mice. Age dependent alterlations were also observed in pancreas and kidney. Namely, degranulation and glycogen infiltration of B cells, first observed at 5 weeks of age, were followed by hypertrophy and central cavitation of islets. Renal glomerular changes, which were very similar to diffuse or exudative type of sclerosis in human diabetes, were also recognized in the mice at 16 weeks of age. These changes, though less remarkable, were also noted in their control littermates older than 16 weeks of age. Some metabolic defects were developed, as demonstrated by in vitro experiments. At younger age, lipogenesis by liver and adipose tissue was increased in yellow KK mice, but there was no noticeable difference in glucose oxidation by adipose tissue between both mice. Insulin sensitivity of adipose tissue was decreased with age in both mice, especially in yellow KK mice being reduced more remarkably to its complete loss at 16 weeks of age. These findings indicate that the yellow obese gene not only induces adiposity but also accelerates development of diabetic traits of KK mice. A possible mechanism for the observed diabetogenic action of the gene will be discussed.