silicon and Uremia

Most of the 400,000+ patients in the United States with kidney failure depend on dialysis treatments in dedicated dialysis centers for 3 h to 5 h, usually 3 times a week, but they still suffer from accelerated cardiovascular disease and infections. Extended daily dialysis, for 6 to 8 hours every day, seems to be associated with better outcomes but would overwhelm the dialysis networks and severely limit patient activity. Technology to miniaturize and automate home dialysis will be necessary to offer extended daily dialysis to most dialysis patients. Miniaturization of existing hollow-fiber polymer membranes is constrained by requirements for high driving pressures for circulation and convective clearance. Recent advances in membrane technology based on microelectromechanical systems (MEMS) promise to enable the development of continuous implantable renal replacement therapy. Silicon nanoporous membranes with a highly monodisperse pore size distribution have been produced using protocols amenable to low-cost batch fabrication similar to those used to produce microelectronics. Hydraulic permeability of the flat-sheet membranes with critical pore sizes in the range of 8-100 nm has been measured to confirm that conventional fluid transport models are sufficiently accurate for predictive design for bulk liquid flow in an implantable hemofilter. Membrane biocompatibility was tested in vitro with human proximal tubule cells and revealed that silicon does not exhibit cytotoxicity, as evidenced by the formation of confluent cell layers with tight junctions and central cilia. Filtration characterization demonstrated that the nanoporous membranes exhibit size-dependent solute rejection in agreement with steric hindrance models. These advances in membrane technology are fundamentally enabling for a paradigm shift from an in-center to implantable dialysis system.

Topics: Biocompatible Materials; Cell Culture Techniques; Dialysis Solutions; Equipment Design; Forecasting; Hemofiltration; Humans; Kidney Failure, Chronic; Kidney Tubules; Kidneys, Artificial; Materials Testing; Membranes, Artificial; Nanotechnology; Prostheses and Implants; Renal Dialysis; Renal Replacement Therapy; Silicon; United States; Uremia

Topics: Aluminum; Humans; Renal Dialysis; Renal Insufficiency; Selenium; Silicon; Trace Elements; Uremia; Vanadium; Zinc

The relationship between calcium (Ca) content and aluminum (Al) and silicon (Si) content in uraemic rats was examined. Significant correlations with serum [Ca] x [Pi] products and serum Al levels and serum Si values were found (r = 0.73, p less than 0.01). There were significant (r = -0.26, p less than 0.05; r = -0.46, p less than 0.05) relationships between corpuscular [Ca] x [Pi] products and corpuscular Al levels and corpuscular Si values. We found that renal tissue [Ca] x [Pi] products tend to increase with the increase of renal tissue Al content and renal tissue Si content. Serum and corpuscular Al content and Si content can be used as one of the indicators of renal osteodystrophy.

Topics: Aluminum; Animals; Calcium; Kidney; Male; Phosphates; Rats; Rats, Inbred Strains; Silicon; Uremia

It has been recognized that storage inflammation in organs of uraemic patients is due to silicone particle migration from tubing segments of the haemodialysis circuit to blood. Nevertheless, iatrogenic storage of foreign material containing Si has been also observed in long-term dialysis patients which, in our Unit, used only PVC or PU-PVC tubings. The origin and the nature of the particulate has been investigated in vivo and in vitro on bioptical samples as well as on cuprophan dialyser and PVC tubing eluates. This study carried out by means of TEM, SEM and microprobe EDS revealed the presence of variously shaped material and particles containing Si in bioptical samples and in eluates. Si containing contaminants were not demonstrated in eluates filtered in absence of the dialyser. This result suggests that leachable products can result from the dialyser and that such release can be an additional risk for uraemic patients.

Topics: Electron Probe Microanalysis; Humans; Inflammation; Kidneys, Artificial; Microscopy, Electron; Silicon; Uremia

The urinary excretion of silicon (Si) in humans was studied in normal subjects on a low Si diet, a normal diet, and after ingestion of silicate antacid. Measurements of 24-hour urinary excretion of Si showed that urinary Si was derived mainly from dietary intake. The serum concentration of Si was determined in normal individuals and in patients with chronic renal failure. In health, serum Si is maintained within a narrow range, but a significant hypersilicaemia occurs in uraemia. The concentration of Si was measured in the water supply, dialysate and pre-dialysis and post-dialysis serum in patients on regular haemo-dialysis in three areas with low, intermediate and high concentrations of Si in the water supply. Si was removed during dialysis in the region where it was naturally low in the water or where reverse osmosis was used, but it was dialysed into patients in regions with intermediate and high concentrations in the water. Serum Si levels returned to normal after renal transplantation. Preliminary analysis of the geographical variation in the Si content of tap water suggests that uraemic hypersilicaemia may protect haemodialysed patients from the development of aluminium dementia. The kidney would appear from these studies to be the major organ for elimination of absorbed Si.

Topics: Adult; Diet; Humans; Intestinal Absorption; Kidney Failure, Chronic; Reference Values; Renal Dialysis; Selenium; Silicon; Uremia

Nephrocalcinosis with a deposition of aluminum and silicon has been previously reported in uremic rats. To clarify the origin of these elements thin sections of renal cortex were examined by means of electron microscopy and energy dispersive x-ray microanalysis. Studies were performed on subtotally nephrectomized rats (SNX) and sham-operated control animals. Electron microscopy of proximal tubular epithelial cells in SNX rats unlike control rats revealed severe mitochondrial disorganization; irregularity of the tubular basement membrane which exhibited various inclusions; and lamellar bodies within the brush border membrane. On x-ray microanalysis disorganized mitochondria contained calcium and silicon, while secondary lysosomes displayed aluminum and silicon. The tubular basement membrane of SNX rats, as well as lamellar body-like inclusions within the brush border contained calcium, aluminum and silicon together. It is suggested that lysosomal and mitochondrial interaction in proximal tubular cells of uremic rats may contribute to the deposition of calcium together with aluminum and silicon in the renal parenchyma, resulting in nephrocalcinosis.

Topics: Aluminum; Animals; Calcinosis; Calcium; Eating; Electron Probe Microanalysis; Kidney; Male; Microscopy, Electron; Rats; Silicon; Tissue Distribution; Uremia

The nature of uremic nephrocalcinosis was studied by means of X-ray microanalysis in 5/6 nephrectomized rats. The data show that calcified deposits in the renal parenchyma of uremic rats contained substantial amounts of calcium, magnesium, aluminum and silicon. Since calcificates did not reveal a uniform composition they were arbitrarily divided into 3 categories: 'high-calcium' with Mg:Al:Si: Ca molar ratios 7:3:8:37; 'low-calcium' particles were characterized by Fe:Mg:Al:Ca:Si molar ratios 7:3:5:6:13; while 'intermediate-calcium' particles showed Al:Mg:Si:Ca molar ratios equivalent to 2:4:6:7. The variability of calcified deposits in the renal parenchyma of 5/6 nephrectomized rats might be due to different sources, different environmental conditions along the nephron and different stages of calcification process. It is suggested that aluminum and silicon content of deposits may be of value in further characterization of uremic nephrocalcinosis.

Topics: Aluminum; Animals; Calcium; Electron Probe Microanalysis; Magnesium; Male; Metals; Nephrocalcinosis; Rats; Silicon; Spectrometry, X-Ray Emission; Uremia; X-Ray Diffraction