Peritoneal homocysteine clearance is inefficient in peritoneal dialysis patients

Objectives: To investigate the degree and the determinants of peritoneal ho mocysteine (Hcy) clearance and to compare measured Hey clearance with the H ey clearance predicted based on molecular weight (MW). Design: Cross-sectional observational analysis. Setting: Tertiary care inst itutional dialysis center. Patients: Sixty-five stable peritoneal dialysis (PD) patients. Outcome Measures: Fasting blood and 24-hour pooled dialysate effluents were collected for determination of peritoneal clearances of Hey (CpHcy), urea (CpUr), and creatinine (CpCr). The dialysate-to-plasma creatinine ratio at 4 hours (D/P Cr 4 h) and levels of red cell folate, B-12 ferritin, and C-re active protein (CRP) were measured concurrently. Observed CpHcy was compare d with predicted clearance, based an Hey plasma protein binding and the rel ative molecular weights of Hey, urea, and creatinine. Results: Plasma concentrations of Hey averaged 24.6 +/- 1.1 mu mol/L and we re elevated above the upper limit of normal in 59 (91%) patients. The mean dialysate concentration of Hey was 2.9 +/- 0.3 mu mol/L, equating to a dail y peritoneal elimination of 34.6 +/- 3.6 mu mol. Observed CpHcy was closely approximated by predicted CpHcy (8.7 +/- 0.6 L/week/1.73 m(2) vs 9.0 +/- 0 .3 L/week/1.73 m(2) respectively, p = 0.55), Patients maintained on automat ed PD (n = 5) had a CpHcy similar to that of patients treated with continuo us ambulatory peritoneal dialysis (8.9 +/- 1.0 L/week/1.73 m(2) vs 8.7 +/- 0.6 L/week/1.73 m(2), p = 0.92). The CpHcy was significantly correlated wit h C-reactive protein (CRP), D/P creatinine, CpUr, CpCr, and peritoneal prot ein loss, but not with plasma Hey, albumin, B-12, ferritin, age, dialysis d uration, peritonitis episodes, or daily dialysate effluent volume. By multi variate analysis, the only variables that remained significant independent predictors of CpHcy were CRP and D/P Cr 4 h. High and high-average transpor ters had a higher CpHcy than low and low-average transporters (9.7 +/- 0.8 L/week/1.73 m(2) vs 7.0 +/- 0.7 L/week/1.73 m(2), p < 0.05), despite compar ably elevated plasma Hey concentrations [25.2 +/- 1.5 <mu>mol/L vs 23.4 +/- 1.6 mu mol/L, p = nonsignificant (NS)]. Conclusions: Elevated plasma concentrations of Hey are not efficiently redu ced by PD. The relatively low peritoneal clearance of Hey is largely accoun ted for by a high degree of plasma protein binding and is significantly inf luenced by peritoneal membrane permeability.