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Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore compared binding and uptake of native LDL and oxidized LDL (Ox-LDL) to cultured mesangial cells (MC) and the resulting effects on prostaglandin generation and cell proliferation. Ox-LDL, prepared from native LDL by incubation with copper, was bound to MC in a concentration dependent manner with a four- to fivefold increase in binding over LDL. In competition binding experiments Ox-LDL competed to 90% with LDL for binding sites, but LDL only displaced Ox-LDL to 15%. Furthermore polyinosinic acid, which blocks binding of Ox-LDL to macrophages, inhibited binding of Ox-LDL but not that of LDL to MC. Mesangial cells also preferentially took up Ox-LDL over LDL, and Ox-LDL resulted in higher [14C] oleate incorporation into cholesteryl esters than LDL, findings consistent with different handling of Ox-LDL and LDL by MC. LDL slightly stimulated mesangial cell proliferation at low concentration (10 to 50 micrograms/ml of LDL) returning to control levels at 100 and 250 micrograms/ml. In contrast Ox-LDL inhibited cell proliferation in a concentration-dependent manner, starting at concentrations as low as 10 to 25 micrograms/ml of Ox-LDL. Direct observations of mesangial cells by phase contrast microscopy confirmed the cytotoxic effects of Ox-LDL. Addition of Ox-LDL to mesangial cells resulted in a concentration-dependent increase in PGE2 synthesis within one hour, while at this time point LDL had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)

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DNA-containing immune complexes (IC) are believed to have a central causal role in the glomerulonephritis of systemic lupus erythematosus. Extracellular DNA which provides the antigenic source for these ICs circulates as oligonucleosomes (ON). The in vivo glomerular uptake of radiolabeled ON in rats, as well as its binding by cultured rat mesangial cells, was examined. The data show that the binding of ON to kidney, and specifically glomeruli, was almost fourfold greater than that of purified DNA. Uptake appeared dose-dependent and saturable, while there were no differences in hepatic or splenic uptake. Most of the nucleosomal DNA recovered from glomeruli was TCA-precipitable, and on gel electrophoresis was about 100 to 300 bp, a size sufficient to allow formation of large ICs. In vitro studies demonstrated that ON are bound by cultured mesangial cells in a dose-dependent and saturable manner, with a dissociation constant of 1.25 x 10(-10) M/liter and 750 binding sites per cell. Autoradiography of cell cultures incubated with radiolabeled ON showed deposition along the plasma membrane which was inhibited by excess unlabeled ON. The data show that binding of ON to glomeruli exceeds that of purified DNA and may be mediated by histones. ON bind to mesangial cells in a receptor-mediated fashion. The data support the hypothesis of in situ formation of DNA-containing ICs and suggest a role for the mesangial cell in lupus glomerulonephritis.

Objective In view of the limitations of albumin in peritoneal dialysis (PD), we set out to evaluate whether total lymphocyte counts (TLC) could serve as a better prognostic indicator. We were also interested in how these parameters might differ between PD and hemodialysis (HD) patients. Design In a retrospective study, we reviewed 113 charts from our dialysis unit. All laboratory analyses were performed by the Department of Clinical Pathology of the Nassau County Medical Center, using standard procedures. Intact parathyroid hormone (PTH) was sent out to Nichols Laboratories. Setting All patients originated from the renal clinic at Nassau County Medical Center, a 612 bed public hospital. Patients The 38 PD and 75 HD patients selected had been receiving dialysis for at least 12 months and up to 3 years. The PD patients received either continuous ambulatory and/or cycler PD. For the survivors, the averages of their routine chemical analyses were considered their representative values. For the nonsurvivors, the most recent laboratory values prior to their end point were considered. Main Outcome Measures Mortality or apparent malnutrition leading to transfer to HD represented the end points for PD patients. Mortality alone was used as the end point for HD patients. Results Within the PD population, serum albumin was not significantly lower in nonsurvivors compared to survivors, while the TLC was significantly lower in nonsurvivors (1277 ± 146/mm3 vs 2249 ± 236/mm3, p = 0.0036). The HD population demonstrated a significant difference in both TLC and serum albumin levels between its two prognostic groups; albumin was the better discriminator. Nonsurvivors had a 20% lower serum albumin than did the survivors (27.0 ± 1.6 g/L vs 34.0 ± 0.5 g/L, p = 0.0001). Patients on PD had a higher TLC than those on HD ( p = 0.0001). Conclusions In the HD population, but not in the PD population, both serum albumin and TLC were significantly higher in the group that survived. Serum albumin is a more powerful discriminator of mortality in the HD population, while TLC is a better discriminator of mortality in the PD population. For uncertain reasons, PD patients have a higher TLC than those on HD.

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The bedside formula appears superior to APACHE II in predicting ARF or death in MICU but not SICU. This suggests that these two ICU populations are different.