Accumulation of Low Molecular Weight Proteins in Patients Treated with Repeated Hemodialysis

Jerzy W. Naskalski, PhD, Department of Clinical Biochemistry, Copernicus School of Medicine, ul. Kopernika 15 B, 31501 Kraków (Poland) Dear Sir, Treatment of patients with end stage renal disease (ESRD) with repeated hemodialysis does not prevent the accumulation of pep-tides and low molecular weight proteins (LMWP) in the plasma of patients [1]. Little is known so far how LMWPs are cleared from plasma in patients with renal failure. The recent findings of ß2-microglobulin in amyloid deposits in ESRD patients [2] focused the attention on the importance of LMWPs for the pathogenesis of amyloidosis related to prolonged maintenance hemodialysis therapy. We determined the concentrations of acid ribonuclease, alkaline ribonuclease, ß2-microglobulin and retinolbinding protein and assessed the correlations beetween concentrations of these proteins in 34 ESRD patients treated with repeated hemodialysis from 3 to 72 months. Acid and alkaline ribonuclease activity was determined by their enzyme activities [3], and retincl-binding protein concentrations were determined by a radial diffusion method, ß2Microglobulin was determined by the EIA Boehring Enzygnost test. The obtained results showed, as expected, that serum concentrations of all studied LMWP levels were manifold increased in ESRD patients when compared to healthy controls: the increase was 11-fold for alkaline ribonuclease (2.52 ± 0.66 in ESRD patients vs. 0.23 ± 0.105 in healthy controls); 8.7-fold for the activity of acid ribonuclease (0.297 ± 0.0298 U/l in ESRD patients vs. 0.034 ± 0.0067 in healthy controls); 40-fold for the concentration of retinol-binding protein (1,820.4 ± 516.7 mg/l in ESRD patients vs. 45.0 ± 15 mg/l in healthy controls) and 28fold for the concentration of ß2-micro-globulin (51.74 ± 7.90 mg/l in ESRD patients vs. 1.85 ± 0.65 mg/l in healthy controls). The accumulation of the individual LMWPs studied, expressed as the multiple of the mean for the control group, was different. Neither were correlations found between concentrations of the studied proteins, except for activities of acid and alkaline ribonucleases (r = 0.469 at p > 0.05), nor between concentration levels of studied LMWPs and the time of treatment of patients with maintenance hemodialysis. The obtained results seem to suggest that in patients with renal failure individual LMWPs are removed from plasma and cata-bolized by mutually unrelated mechanisms. There is evidence that some amounts of these proteins are removed by the liver [4]. But the rate of liver ingestion of ribonuclease from plasma was only 5% of its renal filtration and catabolism. There is no information on protein composition of ESRD amyloid. Its formation in ESRD