Determinants of the serum concentrations of low molecular weight proteins in patients on maintenance hemodialysis

Abstract

Factors influencing the serum concentrations of low molecular weight proteins (LMWP) during long-term hemodialysis were studied in 112 patients undergoing dialysis for an average of 61.1 months (range 1 to 243). These patients were treated with AN69, cellulose acetate, cuprophan or polysulfone membranes. The following proteins were measured in serum before and after a four hour dialysis session: cystatin C (CYST C), β2-microglobulin (β2m), Clara cell protein (CC16) and retinol-binding protein (RBP). Pre-dialysis levels of the four proteins were markedly elevated. In simple regression analysis, pre-dialysis serum concentrations of β2m and CC16 weakly correlated with the duration of dialysis treatment, but these relations completely disappeared when a stepwise regression analysis was performed using as predictors age, sex, residual diuresis, body weight loss (BWL), duration of hemodialysis and the type or ultrafiltration coefficient (UFC) of the membranes. The only significant determinants which emerged from this analysis were the residual diuresis and age which negatively correlated with CYST C, β2m and CC16 (residual diuresis only), and sex which influenced CYST C. During the dialysis session, the microproteins underwent changes that were related to their molecular radius, the membrane UFC and the BWL. After adjustment for the latter, high flux membranes (UFC ≥ 15 ml/h · m2 · mm Hg) allowed up to 50% of CYST C and 25% of β2m to be removed. No significant elimination of CC16 and RBP was evident. On the basis of these results, we estimated the effective pore radius of high flux membranes between 1.5 and 1.7 nm and that of low flux membranes as below 1.5 nm. In conclusion, we demonstrated a marked elevation of the pre-dialysis serum levels of four LMWP. These levels are determined, before dialysis, by residual diuresis, age and sex, and during the dialysis sessions, by the size of the protein, the BWL and the UFC of the membrane. The latter had no significant impact on the pre-dialysis serum levels of LMWP.