Satoru Tsunoda

Glomerular deposition of hepatitis C virus in membranoproliferative glomerulonephritis.

Hideaki Yamabe, MD, Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki 036 (Japan) References Johnson RJ, Gretch DR, Yamabe H, et al: Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl JMed 1993;28:465-470. Yamabe H, Johnson RJ, Gretch DR, et al: Hepatitis C virus infection and membranoproliferative glomerulonephritis in Japan. J Am SocNephrol 1995;6:220-223. Doutrelepont JM, Adler M, Willems M, et al: Hepatitis C infection and membranoproliferative glomerulonephritis. Lancet 1993;341:317. Misiani R, Vicari O, Bellavita P, et al: Hepatitis C virus in renal tissue of patients with glomerulonephritis. Nephron 1994;68:400. Dear Sir, Membranoproliferative glomerulonephritis (MPGN) associated with hepatits C virus (HCV) infection has been recently reported [1] and its prevalence may be very high in primary MPGN [2]. This disease is clinically characterized by nephrotic syndrome, active HCV infection, frequent existence of cryoglobulinemia and hypocomple-mentemia and its pathogenesis is assumed to be caused by immune complex including HCV [1,2]. However, the glomerular deposition of HCV has not yet been demonstrated because the amount of HCV may be very small. We tried to detect the glomerular HCV deposition in this disease. Freezed kidney specimens obtained by renal biopsy in 6 patients were examined for glomerular HCV detection. Polyclonal rabbit antibody to HCV core antigen, which was provided by Dr. K. Shimotohno (National Cancer Center, Tokyo, Japan), was used as first antibody in the indirect immunofluorescence techniques. FITC-conjugated goat anti-rabbit IgG (Organon Teknika Co., Durham, N.C., USA) was used as second antibody. Negative control consisted of staining with normal rabbit serum or antibody to HCV absorbed with HCV core antigen, followed by FITCconjugated goat anti-rabbit IgG. Glomerular HCV deposition was observed in 2 of 6 patients with granular manner along the capillary wall and in the mesangium (fig. 1). Doutrelepont et al.

C-Type Natriuretic Peptide Inhibits Proliferation and Monocyte Chemoattractant Protein-1 Secretion in Cultured Human Mesangial Cells

Background: Mesangial cell proliferation and matrix accumulation are hallmarks of various progressive glomerular diseases. We examined whether C-type natriuretic peptide (CNP) that is known to regulate the proliferation of vascular smooth muscle cells could modulate these pathological processes using human glomerular mesangial cells (GMCs) in culture. Methods: Proliferation of GMCs cultured with different concentrations of CNP-22 for 48 h was determined by a colorimetric assay using a tetrazorium salt. Monocyte chemoattractant protein-1 (MCP-1) and type IV collagen secretion into the culture media by GMCs in the presence or absence of CNP-22 were evaluated by ELISA. Expression of mRNA for natriuretic peptide receptor B (NPR-B), a specific receptor for CNP, was examined by reverse transcription polymerase chain reaction (RT-PCR). Results: CNP-22 (1–10 µM) inhibited serum-induced GMC growth in a dose-dependent manner. The amount of MCP-1 in the culture supernatant was increased approximately 2.4-fold by 5 µg/ml of lipopolysaccharide. This increase was inhibited by CNP-22 at 0.1–1 µM in a dose-dependent fashion. CNP-22 (10 µM) inhibited GMC type IV collagen secretion stimulated by 20 ng/ml of platelet-derived growth factor. Expression of NPR-B mRNA was confirmed in GMCs by RT-PCR. Conclusions: CNP suppresses GMC proliferation and MCP-1 and type IV collagen secretion by GMCs. It may have a therapeutic potential against human proliferative glomerular diseases, especially those with the involvement of monocytes.

A case of sjögren's syndrome associated with sweet's syndrome

SummaryWe report a case of Sjögrens syndrome whose clinical course had been indolent until the patient presented with Sweets syndrome (acute febrile neutrophilic dermatosis). This patient showed renal failure and renal tubular acidosis. Sweets syndrome resolved within 3 weeks without corticosteroid therapy. Renal biopsy findings were consistent with interstitial nephritis. His renal manifestations responded to corticosteroid therapy and the renal function remained stable during 6 years follow-up without recurrence of Sweets syndrome. Although close association of both syndromes is already known, in our case Sjögrens syndrome may have been exacerbated by occurrence of Sweets syndrome.

Angiotensin II further enhances type IV collagen production stimulated by platelet-derived growth factor and fibroblast growth factor-2 in cultured human mesangial cells

SUMMARY: Angiotensin II (Ang II) is considered to play a role in the development of glomerulosclerosis, which is characterized by excessive accumulation of mesangial matrix after mesangial cell proliferation. We have reported that platelet‐derived growth factor (PDGF) and fibroblast growth factor‐2 (FGF‐2) stimulate type IV collagen production by cultured human mesangial cells (HMC). Although Ang II is well known to have a mitogenic effect in various kinds of cells, its role in the production of extracellular matrix is still undetermined. This study was designed to examine the effect of Ang II and its interaction with PDGF and FGF‐2 in type IV collagen production by HMC. Cultured HMC were incubated with Ang II with or without PDGF or FGF‐2 for 72 h and type IV collagen, fibronectin and laminin in the cell supernatants were measured. Ang II (10−6–10−8) itself did not change the production of type IV collagen, fibronectin, laminin and transforming growth factor‐β. PDGF and FGF‐2 enhanced type IV production, although they did not stimulate the production of fibronectin and laminin. Ang II further increased the stimulating effect of PDGF and FGF‐2 in type IV collagen production in a dose‐dependent manner. This effect of Ang II was completely blocked by Ang II type I receptor antagonist (Losartan). These data imply that Ang II is a potent stimulator of type IV collagen production by HMC in the presence of growth factors.

Minimal Change Nephrotic Syndrome Relapse after 52 Years of Remission: A Case Report

Minimal change nephrotic syndrome (MCNS) is the most common cause of nephrotic syndrome in children and can also present in adults. Corticosteroids generally induce remission of MCNS, and relapses are common after reduction or discontinuation of corticosteroids. We experienced a rare case of steroid-sensitive MCNS where the patient relapsed after 52 years of remission. The patient was a 61-year-old Japanese male who visited our clinic for an edema of the lower extremities which had already persisted for a few days. Laboratory testing showed massive urinary protein and low serum total protein and albumin levels. Therefore, he was diagnosed with nephrotic syndrome. He had a history of nephrotic syndrome that initially developed when he was 5 years old. Although corticosteroids reduced the urinary protein level, frequent relapses occurred when their doses were reduced, or when they were discontinued. He had previously experienced a relapse when he was 9 years old. For his current condition, treatment with corticosteroids and diuretics for 1 week reduced his edema and proteinuria. We suspected that this is a case of MCNS and that the present event is a relapse. Thus, we concluded that this is a very rare case of steroid-sensitive nephrotic syndrome that relapsed after 52 years of remission.

Interleukin 6 as a marker of mesangial cell proliferative activity

AbstractBackground. The role of Interleukin 6 (IL-6) in the pathogenesis of mesangial proliferative glomerulonephritis has been controversial. To test the hypothesis that glomerular mesangial cell (GMC)-derived IL-6 may not be a mitogen for GMCs, but, rather, a factor that reflects GMC proliferative activity, we investigated how the culture condition; namely, cell confluency, affected IL-6 production in human cultured GMCs. Methods. IL-6 in the culture supernatant was measured by enzyme-linked immunoassay (ELISA). The expression of IL-6, IL-6 receptor (IL-6R), and proliferating cell nuclear antigen (PCNA) mRNA in GMCs was examined by reverse transcriptase polymerase chain reaction (RT-PCR). The effects of human recombinant IL-6 (rIL-6) on the proliferation of GMCs and an IL-6 dependent cell line, B9 cells, were evaluated by a colorimetric assay. Results. The IL-6 ELISA study revealed that subconfluent GMCs secreted more IL-6 than confluent GMCs (12.9 ± 2.9 pg/104 cells versus 4.05 ± 0.2 pg/104 cells; P < 0.01). In the RT-PCR, the mRNA expression of both IL-6 and PCNA was upregulated in subconfluent GMCs as compared with confluent GMCs. An approximately four-fold increase in IL-6 mRNA expression and a two-fold increase in PCNA mRNA expression were shown. IL-6R mRNA expression was demonstrated in GMCs by RT-PCR. However, recombinant human IL-6, which stimulated the growth of B9 cells in a dose-dependent fashion, did not induce GMC proliferation. Conclusions. GMC-derived IL-6 may have significance as a marker of GMC proliferative activity, although GMC-derived IL-6 per se does not act as an autocrine growth factor for GMCs.