Effect of epoetin on HO-1 mRNA level and plasma antioxidants in hemodialysis patients.

OBJECTIVE: Patients with renal failure and undergoing hemo- (HD) or peritoneal dialysis are under oxidative stress which is thought to contribute to the long-term complications noted in this patient population. One effect of HD-induced oxidative stress is via red blood cell (RBC) membrane lipid peroxidation leading to RBC destruction and anemia. Interaction of this oxidative stress with epoetin (EPO) treatment to increase RBC number and Hb concentration remains unexplored. PATIENTS AND METHODS: This preliminary study used RT-PCR as well as colorimetric based assay approaches to evaluate the effect of EPO-alpha treatment on markers of oxidative stress in hemodialysis patients. Eighteen patients (12 males, 6 females, age range 45 - 68), were treated with EPO-alpha (Eprex) 50 UI/kg thrice weekly over an 8-month study period. Monocytes were isolated at baseline, then monthly thereafter, monocyte heme-oxygenase-1 (HO-1) and plasma Hb and antioxidant power (AOP) were determined. RESULTS AND CONCLUSIONS: Treatment with EPO increased Hb (9.4 +/- 0.7 g/dl to 10.9 +/- 0.5, mean +/- SD p < 0.001). In addition, both monocyte HO-1 mRNA (0.34 +/- 0.08 vs. 0.59 +/- 0.02 d.u. p < 0.001) and plasma AOP (1,379.8 +/- 175 micromol/l to 1,624 +/- 170, p < 0.04) increased. While AOP changes showed no correlation with other indices, increases in HO-1 and Hb were positively correlated using 2 different measures: delta Hb (peak Hb - baseline Hb) vs. delta HO-1 (peak HO-1 mRNA - baseline HO-1 mRNA) as well as delta Hb(5 months-baseline) vs. delta HO-1 (5 months - baseline) mRNA (r = 0.81, p < 0.001 and r = 0.76, p < 0.001; respectively). In conclusion, the increases upon EPO treatment of both HO-1 gene expression and plasma AOP as well as the significant correlation between delta Hb and delta HO-1 mRNA suggest that EPO treatment reduces oxidative stress via a combination of effects. These could potentially include effects on oxidative stress directly as well as effects on the levels and types of antioxidants present in plasma.

Day-to-day variability of adequacy indexes in peritoneal dialysis.

BACKGROUND: The achievement of dialysis adequacy targets in peritoneal dialysis (PD) is assessed by the calculation of the Kt/V and creatinine clearance (C(Cr)) obtained by collecting dialysate and urine, usually two or three times a year. Prescription decisions are based on such adequacy assessments, regardless of any variability in the single measurements. The aim of our study was to assess the day-to-day variability of common dialysis adequacy parameters and to evaluate its impact on the adequacy indexes in PD. METHODS: Twenty-four patients (14 CAPD, 10 APD) at two centres were studied by means of a triple dialysate and urine collection for a period of 1 week. Variability in the findings for a given patient was expressed by the coefficient of variation (CV%) calculated for peritoneal (p), renal, and total (tot) adequacy parameters. The target Kt/V and C(Cr) values were recalculated on the basis of variability. RESULTS: Kt/V was less variable (CV 4.0 and 4.4% for peritoneal Kt/V (pKt/V) and total Kt/V (totKt/V) respectively) than C(Cr) (4.7 and 6.0% for peritoneal creatinine clearance (pC(Cr)) and total creatinine clearance (totC(Cr)) respectively) and proved to be a more reliable indicator of adequacy in terms of the CV. Both variability parameters became worse if renal clearance was added to peritoneal clearance. CV in APD proved to be no different from CAPD for all the parameters considered. In our centres dialysis adequacy target correction for variability provided safe values for weekly Kt/V (pKt/V=1.78-2.10 and totKt/V=1.82-2.15 target 1.7-2.0) and C(Cr)/1.73 (pC(Cr)=53.7-64.4 l and totC(Cr)=55.1-66.1 l; target 50-60 l). CONCLUSIONS: Evaluating the adequacy of PD by means of a single measurement should take into account the weekly variability as demonstrated by a triple dialysate and urine collection. Standard adequacy targets can be corrected to allow for variability. Thus one can obtain safe values for prescription decisions based on a single collection result.