Biomedical subjects

Isao Shirato

Publications and source records attributed to Isao Shirato.

At least 19 recordsLinked to original sources

PubMed2004

Podocyte migration during nephrotic syndrome requires a coordinated interplay between cathepsin L and alpha3 integrin.

Podocyte foot process effacement and disruption of the slit diaphragm are typically associated with glomerular proteinuria and can be induced in rats by the injection of puromycin aminonucleoside. Here, we show that the induction of puromycin aminonucleoside nephrosis involves podocyte migration conducted by a coordinated interplay between the cysteine protease cathepsin L and alpha(3) integrin. Puromycin aminonucleoside treatment up-regulates cathepsin L expression in podocytes in vivo as well as expression and enzymatic activity of cathepsin L in podocytes in vitro. Isolated podocytes from mice lacking cathepsin L are protected from cell puromycin aminonucleoside-induced cell detachment. The functional significance of cathepsin L expression was underscored by the observation that puromycin aminonucleoside-induced cell migration was slowed down in cathepsin L-deficient podocytes and by the preservation of cell-cell contacts and expression of vital slit diaphragm protein CD2AP. Cathepsin L expression and activity were induced in podocytes lacking alpha(3) integrin. Similarly, acute functional inhibition of alpha(3) integrin in wild type podocytes with a blocking antibody increased the expression of cathepsin L activity. Down-regulation of alpha(3) integrin protected against puromycin aminonucleoside-induced podocyte detachment. In summary, these data establish that podocyte foot process effacement is a migratory event involving a novel interplay between cathepsin L and alpha(3) integrin.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Tensin is potentially involved in extracellular matrix production in mesangial cells.

Tensin, a focal adhesion protein, is expressed in renal tubular epithelial cells (TECs). Tensin-null mice develop multiple large cysts in the renal proximal tubules. However, the role of tensin in human glomeruli remains unclear. In this study, we assessed tensin localization in human kidney and interaction between tensin and other adhesion components. In human mesangial cells (MCs) and TECs, we confirmed mRNA and protein expressions of tensin by RT-PCR and immunoprecipitation. In normal kidney, immunohistochemistry revealed that tensin was localized in MCs and parietal epithelial cells as well as TECs. In biopsy specimens, the expression of tensin was significantly increased in areas of mesangial expansion in patients with IgA nephropathy and diabetic nephropathy. These results suggest that the expression of tensin is associated with extracellular matrix (ECM) production. In vitro, immunocytochemistry revealed that MCs express tensin mainly at the ends of actin stress fibers and apparently in the focal adhesion areas. Integrin alpha5, but not alpha1 and alpha3, colocalized with tensin. Vinculin and focal adhesion kinase (FAK) were coprecipitated by tensin, suggesting that tensin can mediate signal transduction between cell and ECM through these molecules. Tensin may play important roles in mesangial ECM production through an adhesion complex with integrin alpha5, FAK, and vinculin.

Diabetic Nephropathies↗

PubMed2004

A case of primary immunoglobulin light chain amyloidosis with a delayed appearance of Bence Jones protein in urine.

We report here a case of a 58-year-old man who had nephrotic syndrome and immunoglobulin light chain (AL) amyloidosis. This patient underwent a renal biopsy to confirm the diagnosis. Treatment with permanganate before Congo red staining showed systemic secondary amyloidosis (AA) fibrils, which were sensitive to permanganate oxidation. Although this patient was initially diagnosed as having AA amyloidosis, he did not have any chronic inflammatory disease and/or malignancy. The level of amyloid A protein (7.9 microg/mL) in sera was within the normal range (0-8.0 microg/mL). Therefore, we performed an immunostaining of the precursor protein (amino terminus of constant region: kappa and lambda light chains, and AA protein) using duodenal biopsy specimens for a precise diagnosis. Immunostaining was positive for the amino terminus of constant region of the lambda light chain, and negative for the amino terminus of constant region of the kappa light chain and AA protein. No plasma cell proliferation in the bone marrow was observed. We finally diagnosed this patient as having primary AL amyloidosis. It appears that a pathological diagnosis must be performed by immunostaining the precursor proteins with the permanganate digestion technique in tissue of patients with amyloidosis. There were no abnormalities in serum and urine immunoelectrophoresis at the time of renal biopsy in this patient. During the follow-up period, after discharge, Bence Jones protein appeared in the urine, but not in the serum. It is necessary to observe patients with primary AL amyloidosis carefully to determine if they their condition will progress to multiple myeloma.

Amyloidosis↗

PubMed2004

Tensin is expressed in glomerular mesangial cells and is related to their attachment to surrounding extracellular matrix.

Glomerular expression of tensin was immunohistochemically studied in normal and diseased rat kidneys to determine whether tensin might be related to specific binding in individual glomerular cells. Normal rat kidneys displayed an intense immunofluorescence reaction for tensin along the basal aspects of proximal and distal tubule cells and parietal epithelial cells of Bowman's capsules. In glomeruli, a positive reaction for tensin was detected only in the mesangial areas. Immunoelectron microscopy revealed a positive reaction in the mesangial cell (MC) processes. RT-PCR and immunoprecipitation demonstrated mRNA and protein levels of tensin in cultured rat MCs. Mesangial tensin expression was decreased when the mesangium was injured by Habu snake venom. During the regenerative process after mesangiolysis, tensin expression was not detected in early-phase proliferating MCs that did not have extracellular matrix (ECM). The expression of tensin recovered in late-phase proliferating MCs, which became attached to regenerated ECM. It appears that tensin is related to MC attachment to surrounding ECM, which suggests that signal transduction regulated by tensin may be related to a specific mechanism of MC matrix regeneration. Furthermore, tensin can act as a marker for rat MCs because the expression of tensin was detected only in MCs in glomeruli.

Animals↗

PubMed2003

MAP-LC3, a promising autophagosomal marker, is processed during the differentiation and recovery of podocytes from PAN nephrosis.

Microtubule-associated protein 1 light chain 3 (LC3) is a unique modifier protein. LC3-I, the cytosolic form, is modified to LC3-II, the membrane-bound form, by a mechanism similar to ubiquitylation by E1- and E2-like enzymes, Apg7p and Apg3p, respectively. In the present study, we found that LC3-I is processed to LC3-II during the differentiation and recovery from puromycin aminonucleoside-induced nephrosis of podocytes. LC3 is especially expressed in the podocytes of rat kidney as the membrane-bound form LC3-II. Biochemical analysis using a conditionally immortalized mouse podocyte clone (MPC) revealed that LC3-I is processed to LC3-II during the differentiation of cells into mature podocytes and accumulates in the membrane-rich fraction of the cell lysate. LC3-II-localized vesicles, which differ from lysosomes and endosomes, in differentiated MPC cells are morphologically similar to autophagic vacuoles during starvation-induced autophagy. During starvation-induced autophagy, autophagosomes fuses with lysosome and LC3-II on autophagosomes is finally degraded by lysosomal proteases. However, in differentiated MPC cells, little LC3-II on the vesicles is degraded by lysosomal proteases, suggesting that little LC3-II-localized vesicles in differentiated MPC cells fuse with lysosome. Furthermore, the LC3-II level in differentiated MPC cells increases with recovery from damage caused by experimental puromycin aminonucleoside-induced nephrosis. These results suggest that LC3-II-localized vesicles play an important role in the physiological function of podocytes.

Animals↗

PubMed2003

Pre-existing glomerular immune complexes induce polymorphonuclear cell recruitment through an Fc receptor-dependent respiratory burst: potential role in the perpetuation of immune nephritis.

In immune complex (IC) diseases, FcR are essential molecules facilitating polymorphonuclear cell (PMN) recruitment and effector functions at the IC site. Although FcR-dependent initial tethering and FcR/integrin-dependent PMN accumulation were postulated, their underlying mechanisms remain unclear. We here addressed potential mechanisms involved in PMN recruitment in acute IC glomerulonephritis (nephrotoxic nephritis). Since some renal cells may be recruited from bone marrow (BM) lineages, reconstitution studies with BM chimeras and PMN transfer between wild-type (WT) and FcR-deficient mice (gamma(-/-)) were performed. Severe glomerular damage was induced in WT and W gamma chimeras (BM from WT to irradiated gamma(-/-)), while it was absent in gamma(-/-) and gamma W chimeras (gamma(-/-) BM to WT). Moreover, WT PMN transfer, but not gamma(-/-) PMN, reconstituted the disease in gamma(-/-), indicating that FcR on resident cells is not a prerequisite for PMN recruitment in this disease. Surprisingly, transferred WT PMN were recruited coincidentally with NF-kappa B activation and TNF-alpha overexpression even in glomeruli with preformed IC (nephrotoxic Ab administered 3 days previously), suggesting that PMN can initially be recruited via its own FcR without previous chemoattractant release. Furthermore, H(2)O(2) inhibition by catalase attenuated the acute WT PMN recruitment and the induction of NF-kappa B and TNF-alpha much more than integrin (CD18) blockade, indicating a role for the respiratory burst before integrin-dependent accumulation. In coculture experiments with IC-stimulated PMN and glomeruli, PMN caused acute glomerular TNF-alpha expression predominantly via FcR-mediated H(2)O(2) production. In conclusion, glomerular IC, even preformed, can cause PMN recruitment and injury through PMN FcR-mediated respiratory burst during initial PMN tethering to IC.

Animals↗

PubMed2003

Significance of serum IgA levels and serum IgA/C3 ratio in diagnostic analysis of patients with IgA nephropathy.

Diagnostic analysis of clinical markers including serum IgA levels and serum IgA/C3 ratio in patients with IgA nephropathy is described. One hundred patients with IgA nephropathy (IgA nephropathy group) and 100 patients with other primary glomerular diseases (non-IgA nephropathy group) were examined. The analysis was performed to distinguish between these two groups using four clinical markers: 1) more than five red blood cells in urinary sediments, 2) persistent proteinuria (urinary protein of more than 0.3 g/day), 3) serum IgA levels of more than 315 mg/dl, and 4) a serum IgA/C3 ratio of more than 3.01. Patients with three or four clinical markers were easily diagnosed as having IgA nephropathy in this study. Furthermore, there was a significant difference in these clinical markers between the good prognosis and relatively good prognosis groups (Groups I and II) and the relatively poor prognosis and poor prognosis groups (Groups III and IV) of IgA nephropathy patients. It appears that the presence of microscopic hematuria and/or persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratio are useful for distinguishing IgA nephropathy from other primary renal diseases. It is postulated that these clinical markers are also useful for diagnosis of IgA nephropathy without renal biopsy.

Analysis of Variance↗

PubMed2003

Involvement of p300 in TGF-beta/Smad-pathway-mediated alpha2(I) collagen expression in mouse mesangial cells.

BACKGROUND: Transforming growth factor beta 1 (TGF-beta1) induces alpha2(I) collagen gene (COL1A2) expression in mesangial cells through physical and functional cooperation of Smad proteins and Sp1. A transcriptional coactivator, p300, is also suggested to play an important role in TGF-beta1/Smad signal transduction. However, the role of p300 in TGF-beta1/Smad-pathway-mediated transcriptional activation of the COL1A2 gene in mesangial cells is still obscure. METHODS: Endogenous p300 expression and its modulation by TGF-beta1 were evaluated by Western blotting and immunofluorescence. The physical interaction of p300 with Smad2/3 was examined by immunoprecipitation followed by Western blotting. The functional role of p300 in TGF-beta1/Smad-pathway-mediated COL1A2 transcription was investigated in cotransfection experiments using a COL1A2 promoter-luciferase reporter gene construct and p300 expression plasmids. RESULTS: TGF-beta1 induced COL1A2 gene expression in cultured mouse mesangial cells which was blocked by overexpression of inhibitory Smad7. In addition, TGF-beta1-induced nuclear export of endogenous Smad7 was observed in mouse mesangial cells. Endogenous p300 was expressed in the nucleus of the cells. TGF-beta1 induced interaction of endogenous p300 with Smad2/3, and a dominant negative construct of p300 inhibited the TGF-beta1-induced COL1A2 expression in cultured mouse mesangial cells. CONCLUSIONS: p300 may be involved in TGF-beta1/Smad-pathway-mediated type I collagen gene transcription in mouse mesangial cells. Our findings would reveal a molecular basis of TGF-beta1-induced type I collagen gene transcription in mouse mesangial cells.

Animals↗

PubMed2002

Susceptibility to T cell-mediated injury in immune complex disease is linked to local activation of renin-angiotensin system: the role of NF-AT pathway.

FcR provides a critical link between ligands and effector cells in immune complex diseases. Emerging evidence reveals that angiotensin (Ang)II exerts a wide variety of cellular effects and contributes to the pathogenesis of inflammatory diseases. In anti-glomerular basement membrane Ab-induced glomerulonephritis (GN), we have previously noted that FcR-deficient mice (gamma(-/-)) surviving from lethal initial damage still developed mesangial proliferative GN, which was drastically prevented by an AngII type 1 receptor (AT1) blocker. We further examined the mechanisms by which renin-Ang system (RAS) participates in this immune disease. Using bone marrow chimeras between gamma(-/-) and AT1(-/-) mice, we found that glomerular injury in gamma(-/-) mice was associated with CD4(+) T cell infiltration depending on renal AT1-stimulation. Based on findings in cutaneous delayed-type hypersensitivity, we showed that AngII-activated renal resident cells are responsible for the recruitment of effector T cells. We next examined the chemotactic activity of AngII-stimulated mesangial cells, as potential mechanisms coupling RAS and cellular immunity. Chemotactic activity for T cells and Th1-associated chemokine (IFN-gamma-inducible protein-10 and macrophage-inflammatory protein 1alpha) expression was markedly reduced in mesangial cells from AT1(-/-) mice. Moreover, this activity was mainly through calcineurin-dependent NF-AT. Although IFN-gamma-inducible protein-10 was NF-kappaB-dependent, macrophage-inflammatory protein 1alpha was dominantly regulated by NF-AT. Furthermore, AT1-dependent NF-AT activation was observed in injured glomeruli by Southwestern histochemistry. In conclusion, our data indicate that local RAS activation, partly via the local NF-AT pathway, enhances the susceptibility to T cell-mediated injury in anti-glomerular basement membrane Ab-induced GN. This novel mechanism affords a rationale for the use of drugs interfering with RAS in immune renal diseases.

Angiotensin II↗

PubMed2002

Podocyte process effacement in vivo.

Foot process effacement is the most characteristic change in podocyte structure under a wide variety of human and experimental glomerulopathies with heavy proteinuria. It consists of simplification and even total disappearance of the interdigitating foot process pattern, resulting in the formation of a diffuse cytoplasmic sheet along the glomerular basement membrane. Although abundant evidence related to structural changes in podocyte foot processes has been reported, cellular or molecular mechanisms that occur within podocytes during the development of foot process effacement remain unclear. This review summarizes recent advances concerning structural and functional aspects of foot process effacement in vivo. Following a description of the general morphology of foot process effacement, the role of the cytoskeleton and its related proteins in the effacement are discussed. Finally, the relevance of foot process effacement in glomerular function is considered.

Animals↗

PubMed2002

Selective accumulation of CCR4+ T lymphocytes into renal tissue of patients with lupus nephritis.

OBJECTIVE: Some chemokine receptors, such as CCR5 and CCR4, are differentially expressed on Th1 and Th2 cells. To determine whether differential expression of the chemokine receptors occurs in patients with lupus nephritis, we examined the expression of CCR4 and CCR5 on peripheral blood lymphocytes and mononuclear cells infiltrated into the renal tissue of patients with lupus nephritis. METHODS: The expression of CCR4 and CCR5 on CD4+,CD45RO+ cells was analyzed by flow cytometry and compared between patients with systemic lupus erythematosus (SLE) and healthy controls. Correlation between the absolute number of CCR4+ or CCR5+ cells and clinical parameters was also analyzed. Mononuclear infiltrates in the renal tissue of SLE patients were analyzed for the expression of CCR4, CCR5, and CD4 by immunohistochemical staining. RESULTS: The absolute number of CCR4+, but not CCR5+, T lymphocytes in the peripheral blood was significantly decreased in the patients with SLE compared with that in the healthy controls, and this positively correlated with the serum levels of C3 and CH50. Most of the CD4+ T lymphocytes that infiltrated into the renal tissue of the patients with lupus nephritis expressed CCR4, but not CCR5. CONCLUSION: These results suggest that CCR4+ T lymphocytes in peripheral blood, which represent Th2 cells, preferentially migrate into the renal tissue of patients with lupus nephritis. The maldistribution of CCR4+ T lymphocytes might be involved in the pathogenesis of lupus nephritis.

Adolescent↗

PubMed2002

Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), and renal injuries in patients with type 2 diabetic nephropathy.

We examined the correlation among the levels of urinary monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), hyperglycemia, and renal injuries in patients with type 2 diabetic nephropathy. The levels of urinary MCP-1, IL-8, protein excretion, blood urea nitrogen (BUN), serum creatinine (s-Cr), glycohemoglobin A1c (HbA1c), and fasting plasma glucose (FPG) were measured in 24 patients with type 2 diabetic nephropathy and 14 healthy adults as controls. Diabetic nephropathy was classified into three stages: stage 1 = normoalbuminuric, stage 2 = microalbuminuric, and stage 3 = macroalbuminuric. All of the patients showed normal ranges in renal function tests. Levels of urinary MCP-1 in all patients with diabetic nephropathy were significantly higher than those in healthy adults (P < 0.05). The levels of urinary MCP-1 in patients with diabetic nephropathy increased gradually according to the clinical stage of this disease. In contrast, the levels of urinary IL-8 in patients with diabetic nephropathy increased in stages 2 and 3. There was a significant correlation between the levels of urinary IL-8 and those of HbA1c. High glucose may stimulate MCP-1 and/or IL-8 production and their excretion into the urine independently of the phases or pathological lesions of this disease. It appears that IL-8 increased in the early stage of diabetic nephropathy, and MCP-1 increased in the advanced stage of this disease. It was concluded that measurement of urinary MCP-1 and IL-8 may be useful for evaluating the degree of renal injuries in patients with type 2 diabetic nephropathy.

Analysis of Variance↗

PubMed2002

Selective modulation of the secretion of proteinases and their inhibitors by growth factors in cultured differentiated podocytes.

UNLABELLED: Selective modulation of the secretion of proteinases and their inhibitors by growth factors in cultured differentiated podocytes. BACKGROUND: Podocyte damage is considered to be an important factor in the development of glomerulosclerosis. Morphological studies on experimental models of progressive glomerular disease have identified the detachment of podocytes from the glomerular basement membrane (GBM) as a critical step in the development and progression of glomerulosclerosis. Degradation of the GBM by proteinases also might be a potential mechanism of the detachment because the process impairs the connection between podocytes and the GBM. The present study examined the effects of basic fibroblast growth factor (bFGF), transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor (PDGF) on the secretion of proteinases [cathepsin L and matrix metalloproteinases (MMPs)] and their inhibitors [cystatin C and tissue inhibitor of metalloproteinase-2 (TIMP-2)] from differentiated podocytes in culture. METHODS: Expression of mRNAs for receptors of growth factors (bFGF, PDGF, TGF-beta1), the proteinases and their inhibitors in differentiated podocytes were shown by RT-PCR. The secretion of cathepsin L, cystatin C and TIMP-2 from differentiated podocytes were shown by immunoblot analysis. The activities of MMPs-2 and -9 from differentiated podocytes were shown by gelatin zymography. RESULTS: Expression of mRNAs for receptors of the growth factors, the proteinases and their inhibitors were confirmed. bFGF increased the secretion of cathepsin L (5.04-fold at 20 ng/mL), but did not alter the secretion of its extracellular inhibitor, cystatin C. In contrast, TGF-beta1 increased the activities of MMPs-2 and -9 (3.23-fold at 10 ng/mL and 25.3-fold at 10 ng/mL, respectively) from differentiated podocytes, but did not enhance the secretion of its inhibitor, TIMP-2. In addition, bFGF enhanced the secretion of TIMP-2 (2.75-fold at 20 ng/mL) and TGF-beta1 enhanced the secretion of cystatin C (2.32-fold at 20 ng/mL). These results demonstrate the imbalance of the secretion of proteinases and their inhibitors after incubation of such growth factors. Of particular interest was the observation of differences in regulation of proteinases and their extracellular inhibitors in response to bFGF and TGF-beta1. PDGF only slightly increased the secretion of cathepsin L (2.54-fold at 20 ng/mL) but exerted no effect on the secretion of cystatin C, MMPs, and TIMP-2 from differentiated podocytes. CONCLUSION: These results indicate, to our knowledge for the first time, that in differentiated podocytes, both cathepsin L and its inhibitor are independently regulated by different growth factors. It appears that increases in proteolytic activities may induce degradation of the glomerular basement membrane (GBM), which plays an important role in the progression of glomerulosclerosis.

Animals↗

PubMed2002

Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients.

It is well known that genetic factors are involved in the progression of secondary hyperparathyroidism (HPT) in hemodialysis (HD) patients. The purpose of the present study is to determine the relationship between restriction fragment length polymorphisms (RFLPs) of the parathyroid hormone (PTH) gene and serum intact PTH levels in HD patients. Eighty-six HD patients not treated with vitamin D and 80 healthy controls were analyzed. PTH genotypes were determined by polymerase chain reaction and RFLPs of BstBI and DraII. The presence or absence of BstBI and DraII restriction sites of the PTH gene were indicated by B or b and D or d, respectively. There were no significant differences in frequencies of each genotype between HD patients and healthy controls. In HD patients, serum intact PTH levels in the Dd/dd genotype were significantly greater than those in the DD genotype (P < 0.02). However, there was no significant difference in serum intact PTH levels between Bb/bb and BB genotypes. Serum intact PTH levels in the non-BBDD haplotype were significantly greater than those in the BBDD haplotype (P < 0.01). Serum intact PTH levels correlated negatively with serum calcium (Ca) and magnesium (Mg) levels and positively with alkaline phosphatase levels in simple regression analysis. However, in forward stepwise multiple regression analysis, only serum Ca and Mg levels predicted serum intact PTH levels. We conclude that PTH genotypes may influence secondary HPT in HD patients.

Adult↗

PubMed2002

Chronic graft-versus-host autoimmune disease in Fc receptor gamma chain-deficient mice results in lipoprotein glomerulopathy.

Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by intraglomerular lipoprotein thrombi associated with severe proteinuria and frequent progression to renal failure. The histologic hallmark of LPG is the presence of laminated thrombi, consisting of lipid droplet, within the lumina of dilated glomerular capillaries. The findings of thrombi consisting of lipoproteins raised the possibilities that LPG might be related to a primary abnormality in lipid metabolism. However, the precise pathogenic basis of LPG remains unresolved. It was herein found that chronic graft-versus-host disease (GVHD) induced by the transfer of Ia-incompatible spleen cells from B6.C-H2(bm12) into coisogenic C57BL/6 mice with deficiency of Fc receptor gamma chain (FcRgamma) resulted in glomerulopathy that resembled LPG. The uptake of acetylated LDL was partially decreased in peritoneal macrophages isolated from FcRgamma-deficient mice compared with wild-type mice, suggesting that partial impairment of modified LDL uptake might contribute to the development of LPG associated with chronic GVHD in FcRgamma-deficient mice. LPG has been suggested to be a disorder of primary abnormality in lipid metabolism; these findings would therefore provide novel insight into the disease process.

Animals↗

PubMed2002

Effects of oral adsorbent AST-120 (Kremezin) on renal function and glomerular injury in early-stage renal failure of subtotal nephrectomized rats.

The aim of the present study was to determine if treatment with an oral adsorbent (AST-120, Kremezin) might decrease the urinary albumin excretion and serum indoxyl sulfate (s-IS), and prevent glomerular sclerosis in early-stage renal failure, i.e. 0.9-1.2 mg/dl of serum creatinine (s-Cr) and 60-95 mg/dl of blood urea nitrogen (BUN), in subtotal (3/4) nephrectomized rats. Levels of s-Cr and s-IS in the AST-120-treated rats were significantly lower than those in the untreated control rats. The AST-120-treated rats showed an increase of creatinine clearance. Urinary protein and indoxyl sulfate excretion in the AST-120-treated rats were also significantly lower than those in the untreated control rats. The ratio of glomerular tuft area to the area of Bowman's capsules (GT/BC) in the AST-120-treated rats was significantly lower than that in the untreated control rats. The degree of glomerular sclerosis and tubulointerstitial fibrosis in the AST-120-treated rats was significantly lower than that in the untreated control rats. Furthermore, there was a significant relationship among the degree of GT/BC, glomerular sclerosis, tubulointerstitial fibrosis and the levels of urinary protein excretion. It appears that AST-120 might decrease the accumulation of s-Cr and s-IS, and prevent glomerular sclerosis in early stage renal failure in the subtotal nephrectomized rats.

Adsorption↗

PubMed2002

Serum cystatin C is a more sensitive marker of glomerular function than serum creatinine.

We determined the relationship between the levels of serum cystatin C or creatinine (s-Cr) and the grade of creatinine clearance (CCr) in patients with various glomerular diseases. Serum samples from 96 patients with glomerular diseases were obtained from our hospital. The levels of serum cystatin C were measured using the Dade Behring Cystatin C assay with the automated Dade Behring Nephelometer II (BNII). CCr levels were classified into six groups according to the Guidelines of the Japanese Society of Nephrology as follows: grade 1 (normal renal function); grade 2 (slight decrease of renal function); grade 3 (moderate decrease of renal function); grade 4 (severe decrease of renal function); grade 5 (renal failure), and grade 6 (uremia). The mean levels of serum cystatin C in grade 3 patients were significantly higher than those in grade 1. The mean levels of serum cystatin C in grades 4, 5 and 6 patients were also significantly higher than those in grade 1. However, the mean levels of serum Cr in grade 3 patients were not significantly higher than those in grade 1. The levels of s-Cr in grades 4, 5 or 6 patients were significantly higher than those in grade 1. In this study, an increase of serum cystatin C levels occurred earlier than that of s-Cr in various glomerular diseases. It appears that the levels of serum cystatin C may provide early prognostic marker of patients with various glomerular diseases rather than the levels of s-Cr.

Biomarkers↗

PubMed2002

Serum IgA/C3 ratio may predict diagnosis and prognostic grading in patients with IgA nephropathy.

Recently, the authors reported that the ratio of serum IgA to C3 (serum IgA/C3 ratio) is a good marker to distinguish patients with IgA nephropathy from non-IgA nephropathy patients together with serum IgA levels using an international reference preparation (IFCC/CRM470). In this study, the authors investigated whether the serum IgA/C3 ratio might be an indicator of prognostic grading in patients with IgA nephropathy. Two hundred and thirteen patients with IgA nephropathy and 96 other glomerular diseases including diffuse or focal mesangial proliferative glomerulonephritis without mesangial IgA deposition (non-IgA PGN), membranous nephropathy and thin basement membrane syndrome were examined. The levels of serum IgA and C3 in these patients were adjusted by the specified formula to those using international standard serum (IFCC/CRM470) in this study. The results of this study showed the highest levels of IgA/C3 ratio in patients with IgA nephropathy. The serum IgA/C3 ratio appears to gradually increase according to the prognostic grading of this disease. Therefore, measurement of the serum IgA/C3 ratio may be useful for prediction of diagnosis and prognostic grading in patients with IgA nephropathy.

Biomarkers↗