Potential effect of metabolic acidosis on beta 2-microglobulin generation
| Autor: | J Gogusev, Friedrich C. Luft, G Bessou, Winfried Siffert, H. P. Reusch, S Loric, Beate Quednau, J. Zingraff, Tilman B. Drüeke, M. Sonikian |
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| Rok vydání: | 1996 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Bicarbonate Molecular Sequence Data Cell Line chemistry.chemical_compound Reference Values Renal Dialysis In vivo Internal medicine medicine Humans Beta (finance) Dialysis Aged Base Sequence Beta-2 microglobulin business.industry Metabolic acidosis General Medicine Middle Aged medicine.disease In vitro Endocrinology chemistry Nephrology Molecular Probes Kidney Failure Chronic Female Hemodialysis Acidosis beta 2-Microglobulin business |
| Zdroj: | Journal of the American Society of Nephrology. 7:350-356 |
| ISSN: | 1046-6673 |
| DOI: | 10.1681/asn.v72350 |
| Popis: | Beta 2-microglobulin (beta 2M) is responsible for dialysis-associated amyloidosis. Level of beta 2M in plasma increase during chronic renal failure; however, retention does not appear to be the sole mechanism responsible. The effect of metabolic acidosis on beta 2M production was examined. Thirty-six patients with stable chronic renal insufficiency, 12 uremic patients before their first dialysis, 8 hemodialysis patients who were assigned to acetate or bicarbonate dialysate and then crossed over to the alternative regimen, and 6 normal subjects given NH4Cl to initiate metabolic acidosis were studied. In vitro studies in the human myeloid cell line U 937 were also performed. beta 2M protein was measured with ELISA, beta 2M mRNA was measured with reverse transcription polymerase chain reaction, and the U 937 cells were studied at two pH levels with FACScan flow cytometry. The cells were exposed in vitro up to 60 min in a buffered incubation medium to either pH 5.10 or pH 7.34. An inverse correlation was found between beta 2M and bicarbonate concentrations in plasma in the stable chronic renal failure patients (r = -0.54; P0.05) and in the uremic patients before their first dialysis (r = -0.72; P0.05). In hemodialysis patients, blood pH and plasma bicarbonate values were lower (P0.05) and beta 2M concentrations in plasma were higher (P0.05) with acetate than with bicarbonate dialysate. In normal men, NH4Cl resulted in an increase (P0.05) in beta 2M mRNA expression in lymphocytes by an average factor of 1.5 (range, 1.1 to 1.8). In U 937 cells, the cell surface expression of beta 2M and HLA Class I heavy chain assembled with beta 2M decreased at low pH compared with normal pH. Concomitantly, an increase in beta 2M release into the supernatant was observed, possibly as the result of beta 2M dissociation from cell surface HLA Class I complex. The results suggest that metabolic acidosis may enhance cellular beta 2M generation and release. |
| Databáze: | OpenAIRE |
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