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Background. Steroids have been used for patients with some histologic groups of lupus nephritis with/without nephrotic-range proteinuria. However, many patients exhibit steroid-resistance, steroid-dependence, and/or frequent relapse, and there are many adverse effects. Recently, cyclosporin (CsA) has been reported to be effective for steroid-resistant nephrotic syndrome; however, with high-dose use, it produces specific adverse effects, especially nephrotoxicity. Here, we report results with the administration of low-dose CsA to patients with systemic lupus erythematosus (SLE). Methods. We treated three patients with steroid-resistant lupus nephritis with CsA (80–100 ng/ml blood trough level) for 6 months, and investigated the effect of CsA on lupus nephritis and SLE activity. Results. Mean pretreatment and posttreatment values for both 24-h urine protein excretion and total protein improved after treatment. Furthermore, SLE disease activity index scores, and levels of complements, anti-unclear antibody (ANA), anti-DNA antibody, and immune complexes in the three patients also improved. Conclusions. Our results support the idea that low-dose CsA is effective for nephrotic-range proteinuria caused by lupus nephritis, and show that this treatment may decrease SLE activity, without producing severe adverse effects. [ABSTRACT FROM AUTHOR]

Key words: ascites; Crow-Fukase syndrome; immunoadsorption plasmapheresis; interleukin-6 [ABSTRACT FROM PUBLISHER]

The ultrastructure of anionic sites in the lamina rara externa (LRE) of rat glomerular basement membrane (GBM) was studied in three dimensions by a quick-freezing and deep-etching method using polyethyleneimine (PEI) as a cationic tracer. Results were compared with those obtained with conventional ultrathin sections examined by transmission electron microscopy. Examination with the quick-freezing and deep-etching method was done without (group 1) or with (group 2) contrasting/fixation with a phosphotungstic acid and glutaraldehyde mixture and post-fixation with osmium tetroxide, which were necessary for visualization of PEI particles by conventional ultrathin sections. Using the quick-freezing and deep-etching method without following contrasting/fixation and post-fixation (group 1), many PEI particles were observed to decorate around fibrils, which radiated perpendicularly from the lamina densa to connect with the podocyte cell membrane. The arrangement of PEI particles was not as regular as that previously reported using conventional ultrathin sections. In contrast, the tissue that was studied with quick-freezing and deep-etching followed by contrasting/fixation and post-fixation (group 2) showed a shrunken appearance. The arrangement of PEI particles was regular (about 20 particles/1000 nm of LRE) as that previously observed using conventional ultrathin sections. However, the number of PEI particles on the LRE was markedly decreased and interruption of decorated fibrils was prominent, as compared with group 1. Ultrastructural examination using conventional ultrathin sections with contrasting/fixation and post-fixation (group 3) demonstrated PEI particles on the LRE in reasonable amounts (18-21 particles/1000 nm of LRE) with fairly regular interspacing (45-65 nm) as reported previously. This is the first report to identify the three-dimensional ultrastructure of anionic sites of GBM, and provides new information on the location and distribution of anionic sites in the glomerular capillary wall. In addition, these studies suggest that several chemical procedures used in conventional transmission electron microscopy to visualize PEI tracers, may produce structural changes and disarrangement of PEI particles that can be avoided with the quick-freezing and deep-etching method. [ABSTRACT FROM AUTHOR]

Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage. [ABSTRACT FROM AUTHOR]

Bcl-2 may account in part for the maintenance of hypercellularity in human glomerular diseases through preventing cell death and by counteracting bax which may be expressed to regulate excessive proliferation. This process is associated with the effect of PDGF B-chain expression. Bax expression may be important in the cell loss leading to glomerulosclerosis and TGF-β1 participates in this process by increasing bax expression. Thus, the balance of bcl-2/bax expression may be critical in the course of human glomerular diseases. [ABSTRACT FROM PUBLISHER]

Presents an abstract of a study that examined the effect of the enzyme inhibitor simvastatin on glomerular pathology in a rat mesangial proliferative glomerulonephritis (GN).