Increased Fas antigen in uremia accelerates adhesion of mononuclear cells to endothelial and sinovial cells via stimulated hyaluronan production.

We examined influences of increased soluble Fas (sFas) and hyaluronan in uremia on apoptosis and peripheral blood mononuclear cell (MNC) adhesiveness. Synovocytes, human umbilical cord endothelial cells (HUVEC), human coronary artery smooth muscle cells (CASMC), and MNC were prepared in this study. In cultures of synovocytes, HUVEC, and CASMC, sFas or high molecular hyaluronan was added to media at medium change. After 1 day, Fas-positive cells were calculated by fluorescence-activated cell sorting. Uremic level of sFas enhanced Fas-positive cells in all cell lines (P < 0.01) not in CASMC. On the contrary, hyaluronan inhibited Fas expression in all cell lines (P < 0.05). In culture with uremic serum, Fas were induced in all cell lines. At this time, the hyaluronan levels of the supernatant were measured and hyaluronan production was estimated. In contrast to the results using sFas supplement, hyaluronan production was increased in culture with sFas and uremic sera. MNC adhesiveness was increased in synovocytes and HUVEC lines by adding hyaluronan or sFas. Higher adherent cell numbers were recognized when both sFas and hyaluronan were added to the media. A most remarkable increase in cell numbers was observed in uremic MNC suspension as compared with that of MNC from healthy subjects. In conclusion, these results indicate that increased sFas in uremia stimulates apoptosis and hyaluronan production. Both sFas and hyaluronan are responsible for accelerated MNC adhesiveness in uremia.

Fas-Fas ligand system in the peripheral blood of patients with renal diseases.

To clarify the role of the Fas-Fas ligand (FasL) system in the peripheral blood from patients with various renal diseases, the Fas and FasL expression on mononuclear cells (MNCs) and serum levels of soluble Fas (sFas) and soluble FasL were investigated. Patients were selected from those with various types of glomerular diseases showing various degrees of renal function. Fas expression on MNCs was analyzed by a FACScan, sFas and soluble FasL were measured with an ELISA kit, and FasL expression on MNCs was counted using a FACScan after a bioassay. Fas-positive MNCs and sFas increased with statistical significance concomitantly with deterioration in renal function. Moreover, there was a significant correlation between them. sFas- and FasL-positive MNCs were significantly correlated with proteinuria. However, the Fas expression percentage on MNCs and/or serum levels of sFas did not correlate with the number of TUNEL-positive cells in the glomeruli. Also, there was no disease specificity in the activation of Fas. These results indicate that Fas expression on MNCs is activated in accordance with the deterioration in renal function without disease specificity, corresponding to the elevation of serum sFas levels to protect against Fas-mediated apoptosis.

[Quantitation of proteinuria by the use of protein-to-creatinine ratios in random urine samples].

Measurements of protein-to-creatinine ratios (Up/Cr) in simple voided urine samples were compared with 24-hour urinary protein excretions in order to quantify [correction of guantify] proteinuria in inpatients and outpatients. A highly significant linear correlation (r = 0.73), was observed between the two variables. A closer correlation was found in the urine samples obtained from outpatients with non-nephrotic syndrome and normal renal function. Furthermore, in the investigation of urine samples from inpatients, there was a significant correlation between the two variables in urine obtained during the morning, but neither in the early morning nor at night. However, there was no significant correlation between males and females. The results of our study indicate that Up/Cr in urine samples obtained during the morning provides an accurate quantitative estimate of protein excretion. Furthermore, in clinical practice, this is a suitable method of quantifying proteinuria in patients with renal diseases, particularly, non-nephrotic syndrome and normal renal function.

Relationship between serum IgA levels and CD4 subsets in IgA nephropathy.

In this study, the relationship between serum levels of IgA (s-IgA) and CD4 subsets in peripheral blood was investigated in patients with IgA nephropathy (IgA N). We have also recently reported that the percentage of CD4+ CD45RA+ cells was significantly decreased in this disease. Serum levels of immunoglobulins (IgG, IgA, IgM) and the percentage of CD4+CD45RA+ cells or CD4+CD45RO+ cells were measured by two-color analysis in blood samples obtained from 45 patients with IgA N, 30 patients with various glomerulonephritides and 30 healthy volunteers. A significant decrease of CD4+ CD45RA+ cells and a significant increase of CD4+CD45RO+ cells were observed in the IgA N group. Moreover, in the IgA N group, s-IgA correlated negatively with the percentage of CD4+CD45RA+ cells and correlated positively with that of CD4+CD45RO+ cells. After 1 and 2 years, the same analyses were serially performed in 15 nonmedicated patients with IgA N. Similar results concerning the relationship between s-IgA and CD4 subsets were obtained both after 1 and 2 years. The percent changes of s-IgA (delta s-IgA) correlated with delta CD4+CD45RO+ cells: r = -0.66483 (p < 0.01) after 1 year, r = -0.69688 (p < 0.01) after 2 years. On the other hand, delta s-IgA correlated with delta CD4+CD45RA+ cells (p < 0.05) after 1 year, but no after 2 years. It was concluded that s-IgA levels strongly correlate with the percentage of CD4+ CD45RO+ cells in peripheral blood, in patients with IgA N.