[A clinicopathological study of recurrent IgA nephropathy following renal transplantation].

The present study was conducted to examine the clinicopathological features of recurrent IgA nephropathy (IgAN) following renal transplantation. Serial renal biopsies were performed regularly at 0-hour, 1-hour and 2-hours, and 39 episode biopsies were carried out when patients had increased serum creatinine levels and proteinuria. In 49 renal allograft recipients with IgAN, 12 patients were proved to be recurrent IgAN (24.5%). There was a significantly increased five- and ten-year risk of graft loss in the renal allograft recipients with biopsy-proved recurrent IgAN. Graft survival in 49 renal allograft recipients with IgAN was worse (68.8% at 5 years and 40.4% at 10 years) than that in 997 whole transplants (80.7% at 5 years, and 67.7% at 10 years). We found significant differences in the prevalence of HLA-DR4 (66.7%) and BW35 (25%) in the renal allograft recipients with recurrent IgAN when compared with normal healthy subjects. The renal allograft recipients with recurrent IgAN had a high incidence of proteinuria (8/12), hypertension (9/12) and renal dysfunction of less than 50 ml/min (7/12). Mean hemodialysis duration before renal transplantation in recurrent IgAN transplants was 12.5 months, which was shorter than in those without recurrent IgAN. Histopathological studies revealed that renal lesions due to IgAN frequently appeared in the renal allograft recipients with recurrent IgAN. Taken together, these findings suggest that donor-recipient matching may be carefully reconsidered, and recurrent IgAN after renal transplantation must be treated with effective immunosuppressive 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.

[Effects of recombinant human erythropoietin (rHuEpo) on the interactions between glomerular endothelial cells and mesangial cells: regulation of cell proliferation via endothelin (ET)-1].

To elucidate the effects of recombinant human erythropoietin (rHuEpo) on the interactions between glomerular endothelial cells (GENs) and mesangial cells (GMCs), we investigated whether or not cultured bovine GENs alter endothelin (ET)-1 secretion from bovine MCs and MC proliferate under basal or rHuEpo-stimulated conditions. Incubation for 24 hours with synthetic ET-1 stimulated MC in a dose-dependent manner. In addition, 100 pg/ml of ET-1 significantly stimulated MC proliferation after more than 12 hours incubation. Moreover, rHuEpo stimulated ET-1 secretion from GENs in a dose-dependent manner and showed less stimulation of ET-1 secretion from GMCs than GENs. DNA synthesis in both GENs and GMCs was significantly stimulated with more than 5 U/ml of rHuEpo. ET-1 secretion from GENs co-cultured with GMCs was higher than that from cultured GENs only. Conditioned medium, obtained from co-culture of GENs and GMCs, stimulated the proliferation of GMCs that were significantly inhibited with 10(-6) M approximately 10(-5) M BQ-123, a ETA receptor antagonist. These results suggest that rHuEpo directly stimulates the proliferation of GENs and GMCs, and this stimulatory effect is in part due to ET-1 secreted from these cells, especially GENs.

The coexistence of psoriasis vulgaris, Sjögren's syndrome, and Hashimoto's thyroiditis.

A 52-year-old woman presented with psoriasis vulgaris, Sjögren's syndrome, and Hashimoto's thyroiditis with a 5-year history. She had a number of immunological abnormalities and typical psoriatic plaques over her entire body. The relationship between psoriasis, Sjögren's syndrome, and Hashimoto's thyroiditis is discussed from the viewpoint of immunology, and similar cases in the literature are reviewed. This is the first report of a coexistence of psoriasis vulgaris, Sjögren's syndrome, and Hashimoto's thyroiditis.