Treatment with alpha-glucosidase inhibitor for severe reactive hypoglycemia: a case report.

Gastrectomy or vagotomy may result in reactive hypoglycemia, which, in some cases, can reduce the plasma glucose levels to 30-40 mg/dl due to rapid digestion and absorption of food, especially carbohydrates. It also occurs sometimes in patients on hemodialysis, where it is a potentially lethal complication. Because insulin has a longer half-life due to lack of renal degradation, hypoglycemia can be induced by insulin in patients with renal failure. We treated a patient with frequent episodes of severe hypoglycemia, that were sometimes accompanied by convulsions. He had undergone total gastrectomy 8 years before and had been maintained on hemodialysis for 3 years. Hyperinsulinemia caused by oxyhyperglycemia associated with post-gastrectomy led to severe hypoglycemia in this patient because of the lack of renal insulin degradation. Since nutritional treatment did not successfully manage his reactive hypoglycemia, an alpha-glucosidase inhibitor, acarbose, was administered to treat his oxyhyperglycemia. This therapy was very effective and he has not had any recurrence of reactive hypoglycemia since the initiation of the therapy.

Clinical assessment of the significance of platelet-derived growth factor in patients with immunoglobulin A nephropathy.

To examine the role of platelet-derived growth factor (PDGF) in the pathogenesis of IgA nephropathy (IgAN), we investigated the expression of PDGF and the PDGF receptor in glomeruli with immunohistochemistry, the plasma levels of PDGF with ELISA, and the expression of PDGF in peripheral blood monocytes (PBMCs) with reverse transcription polymerase chain reaction (RT-PCR). We also assessed the effect of corticosteroid therapy on the plasma levels of the PDGF B-chain. At the time of kidney biopsy, the expression of the PDGF B-chain and the PDGF beta receptor in the glomeruli was upregulated in patients with IgAN. In addition, the plasma concentration of the PDGF B-chain was significantly higher in patients with IgAN than in normal subjects. Moreover, mRNA expression of PDGF beta-chain in PBMCs was up-regulated in patients with IgAN when compared with other patients with glomerulonephritis. We divided the patients into two groups according to the grade of urinary protein excretion (U[p]) after corticosteroid therapy. In patients in group 1 in whom U(p) was decreased by more than 50% or 1 gm/day after corticosteroid therapy, the expression of the PDGF B-chain and the PDGF beta receptor in the glomeruli was up-regulated. Finally, corticosteroid therapy decreased the plasma levels of PDGF B-chain in patients in group 1. Up-regulation of the PDGF B-chain and beta receptor in the glomeruli, elevated plasma levels of PDGF B-chain, and increased expression of PDGF mRNA in PBMCs could be associated with the pathogenesis of IgAN. The plasma concentration of PDGF B-chain may be a useful marker for patients with IgAN who would be responsive to corticosteroid therapy.

[Glomerular lesion in patients with type II mixed cryoglobulinemia having antibodies to hepatitis C virus].

We report here two cases of mixed cryoglobulinemia showing renal involvement associated with hepatitis C virus (HCV) infection. The subjects were 62- and 63-year-old males. Both patients presented with purpura on the legs, which was diagnosed as allergic vasculitis by skin biopsy. Case 1 followed a clinical course of progressive nephrotic syndrome with mild hematuria. He also had diabetes mellitus and hypertension. In contrast, case 2 showed only mild hematuria without proteinuria at the time of the renal biopsy. Both cases had immunological disarrangements, such as severe hypocomplimentemia and seropositive rheumatic factor. Recently, it was reported that patients with type II mixed cryoglobulinemia had HCV seropositivity, and revealed membranoproliferative glomerulonephritis. These facts strongly suggested that renal lesions are the result of direct damage mediated by cryoglobulinemia and an activated complement pathway through an immune complex mechanism related to HCV.

Nephrotic syndrome associated with fibrillary deposits in the glomeruli.

A 48-year-old woman with nephrotic syndrome underwent renal biopsy. Light microscopy showed nodular sclerosis and thickening of the glomerular capillary wall. Immunoglobulins (Ig) G, especially IgG2, IgM, IgA, C3, C1q were detected along the glomerular capillary walls by immunofluorescent microscopy. Electron microscopy revealed that fibrillar materials of about 25 nm were accumulated in the subepithelial area of the glomerular basement membrane. These materials were negative for Congo-red staining. Neither cryoglobulinemia nor paraproteinemia including light chains was found. This case was diagnosed as membranous nephropathy by clinical findings and pathological examinations, and seemed to be a case of fibrillary glomerulonephritis.

A case of primary glomerular fibrosis associated with the accumulation of type I and type III collagen.

A 49-year-old woman suffering from nephrotic syndrome (NS) was admitted for renal biopsy and treatment of NS. Light microscopy demonstrated that the glomerular capillary wall was markedly thickened with diffuse accumulation of periodic acid Schiff- and periodic acid methenamine-positive materials, leading to lobular accentuation of glomerular tufts. By electron microscopy, numerous collagenous fibers were observed in the mesangium and subenodothelial area. The fibers were peculiarly curved and frayed, as reported in nail-patella syndrome. These materials were thought to be type I and type III collagen as a result of immunohistochemical studies. No laboratory data or pathological findings were found to be compatible with previously described glomerulonephritis. The primary glomerular fibrosis in the present patient seemed to be a case of collagenofibrotic glomerulonephropathy.

[The early lesions of renal amyloidosis].

Two patients with minimal amyloid deposition in association with nephrotic syndrome are reported. Since the amyloid deposits in each renal biopsy specimen were inconspicuous, both were first thought to be minimal glomerular changes. A few widely scattered, silver-positive, epimembranous spicules were found on careful reexamination by light microscopy. Congo red stain and electron microscopy confirmed the presence of small glomerular amyloid deposits and amyloid fibrils. Furthermore, immuno-fluorescence microscopy showed partial IgA deposits in the mesangial area and capillary wall. We therefore urge careful examination to detect amyloid deposits of all kidney biopsy specimens of minor glomerular abnormalities, or glomerulonephritis with IgA deposits from elderly patients with nephrotic syndrome. Light microscopy of Congo-red-stained sections and electron microscopy of the fibrillar structure very useful for the detection of small amyloid deposits.

Identification of GTP-binding proteins in human glomeruli.

The localization of GTP-binding proteins (G-proteins) in human glomeruli was examined using immunohistochemistry and immunoblotting. Immunohistochemical staining for G-protein subunits demonstrated the existence of Gs alpha, Gi alpha and Go alpha proteins in the glomeruli. Moreover, immunoblots further revealed Gs alpha (52 kD), Gi alpha 1/2 (40-41 kD), Gi alpha 3 (40 kD) and Go alpha (39 kD) in the glomerular membranes. The predominant subspecies of Gs was a 52-kD protein, and Go alpha was detectable in the smallest amounts of the G-protein subunits. However, immunoblots failed to demonstrate detectable amounts of G-proteins in cytosolic extracts. This is the first report that characterizes G-protein subunits in human glomeruli. Further study is required to determine the roles of G-proteins in signal transductions in human glomeruli.

The role of novel 30-kD protein in human podocytes: special relevance to proteinuria in glomerulonephritis.

A new monoclonal antibody (MAb) was raised against human glomerular components to investigate the possible existence of glomerular antigens reflecting cellular adaptation in glomerulonephritis. The MAb recognized a podocyte antigen as well as those expressed on renal arterial endothelial cells and smooth muscle cells by indirect immunofluorescence. An additional, but weaker immunoreaction was found in epithelial cells of the Bowman's capsule. This MAb recognized a 30-kD protein on western blotting of glomerular extracts under non-reducing and reducing conditions. Immunoperoxidase electron microscopy revealed that this antigen is present within the cytoplasm, but not on the cell membrane of the podocytes. Moreover, the antigen was found to be reduced in the glomeruli of patients with minimal change glomerulonephritis. These results suggest that the 30-kD protein is a novel protein, which we hypothesize is involved in maintenance of the structural and functional integrity of the podocytes. In addition, reduced expression of the 30-kD protein in the podocytes may be related to the increasing proteinuria in minimal change glomerulonephritis.

Cyclosporin A induces glomerular endothelial cell injury in vitro.

The chronic administration of cyclosporin A (CyA) could be associated with renal arteriolar damage. Endothelial cell injury is considered to be the first event in this pathological change. Bovine glomerular endothelial cells (GEN) were used to investigate whether CyA induces microvascular injury in vitro. The damage induced by CyA was demonstrated by cell detachment from the culture plate and cell lysis as characterized by the increase in lactate dehydrogenase (LDH) at the same time after CyA treatment. One mumol/L of CyA induced detachment of GEN within 3 h and lysis after 6 h. Cyclosporin A-induced GEN lysis appeared in a dose and time-dependent manner. These results indicate that GEN are vulnerable to CyA exposure, suggesting that GEN damage might be related to CyA-mediated glomerular injury.

[Role of glomerular mesangial cells in the regulation of glomerular endothelial cell growth].

Because of difficulties of propagating and cultivating glomerular endothelial cells (GEN), the role of glomerular mesangial cells (GMC) in the regulation of GEN growth is still unknown. We cloned individually GEN and GMC from the same adult bovine kidneys, and a direct coculture system was established to examine the interactions between GEN and GMC. When cocultured with GMC which was growth arrested by mitomycin C, the GEN growth was inhibited by 63% after 8 days of the beginning of coculture. No inhibitory activity was detected when media conditioned by individual culture of GMC. In contrast, media conditioned by GEN cocultured with GMC inhibited bromodeoxyuridine (BrdU) uptake of GEN detected by flow cytometry. Addition of anti-transforming growth factor (TGF)-beta antibody to media conditioned by coculture blocked the inhibitory actions of conditioned media on GEN growth. Western blotting analysis of conditioned media by coculture revealed an existence of TGF-beta in the media. These results indicate that latent TGF-beta is produced by these cells and activated in coculture of GEN and GMC.

[Clinicopathological study on the relationship between appearance of type I or III collagen in IgA nephropathy].

This study was designed to determine whether or not the appearance of type I or type III collagen in glomeruli and serum procollagen III peptide (PIIIP) concentration are affecting the prognosis of patients with IgA nephropathy. In cases with reduced creatinine clearance (Ccr < 80 ml/min) at the time of renal biopsy, the appearance of type III collagen increased, and subsequently type I collagen appeared as Ccr decreased. In addition, we measured serum PIIIP concentration in these cases. The increase of serum PIIIP correlated with the decrease of Ccr. These results suggest that the appearance of type I and III collagen in glomeruli and the increase in serum PIIIP concentration might be a useful marker to predict the outcome of IgA nephropathy.