Membrane Plasmapheresis Raises the Serum Concentrations of Pseudouridine

Therapeutic plasmapheresis lowers protein concentations in plasma. However, the concentrations tend to raise again rapidly as a result of several factors (13). It was our aim to determine whether accelerated protein synthesis plays a role in the increase in the plasma concentrations of proteins following plasmapheresis. Pseudouridine (PSI) was employed for this purpose. PSI is a modified nucleoside found predominantly in tRNA. Once released from tRNA, it is no longer metabolised and reemployed for RNA synthesis. As the end product, it enters the blood then urine. PSI provides information about tRNA turnover and, hence, indirectly about protein synthesis. Because of this particular property, PSI has been proposed as a yardstick for nutritional status assessment (4) and as a marker of malignancy (5). It was also proposed as an indicator of impaired renal function (6). PSI behaviour was evaluated in ten membrane plasmapheresis procedures using an A 2008 PF monitor with Plasmaflux P2 filters (manufactured by Fresenius, FRG). We removed one calculated volume of plasma (3.4 ± 0.2 I) replacing it with isooncotic albumin (7). The rate of replacement was 29.2 ± 0.6 ml/min. The procedures were carried out at one-week intervals in three patients with systemic lupus erythematosus, one of whom was receiving immunosuppressants (cyclophosphamide) at the time of study. One day before plasmapheresis, on the day of the procedure, and on days 1 and 2 thereafter, the patients were provided with sufficient and balanced energy intake. Their resting energy expenditure, assessed by indirect calorimetry, and nitrogen balance, were, likewise balanced. PSI was determined by highperformance liquid chromatography, creatinine by Jaffe's reaction with alkalic picrate, immunoglobulins by turbidimetry. For statistical analysis Wilcoxon's paired test was employed. Data are presented as arithmetical means ± SEM. The plasma concentrations of proteins behaved as expected: at the end of plasmapheresis, the concentrations of IgG, IgA, IgM declined to 44.0 ± 3.4, 45.6 ± 2.6, and 46.3 ± 3.2 % of baseline values, rising back as high as 89.8 ± 8.1, 93.6 ± 5.8, 99.6 ± 9.3 % respectively by day 3 after the procedure. PSI was easily filtered through the membrane, its clearance (24.7 ± 2.5 ml/min) being virtually the same as the filtration rate. Serum concentrations of PSI were significantly higher at the end of the procedure and on day 2 after it (Tab. I). Our patients showed a decrease in glomerular filtration rate with a consequent rise in serum creatinine (Tab. I) Loss of renal function results in a major change in PSI behaviour, leading to a decrease in its excretion and a rise in its serum concentrations. To exclude the effect of decreased renal function on serum PSI concentrations, the concentrations must be expressed as serum PSI/serum creatinine (5, 7, 8). This approach offered a different picture from that obtained by assessing PSI concentrations alone. While significantly higher halfway through the procedure and at its end, serum PSI/serum creatinine when measured further no longer differed from baseline (Tab. I). PSI was not detectable in a replacement solution. Serum PSI concentrations may rise following high protein intake. However, in our study plasmapheresis was not preceded by a high protein intake. Another possible explanation is PSI release from destroyed cells. During plasmapheresis, cells may be damaged as a result of bioincompatibility. However, it is unlikely that the amount of PSI released from blood cells was