Rate of synthetic oligosaccharide degradation as a novel measure of amylase activity in peritoneal dialysis patients.

BACKGROUND: Plasma alpha-amylase activity is elevated in uremic patients but lower in peritoneal dialysis (PD) patients using icodextrin in comparison to healthy controls. We studied the rate by which an exogenous oligosaccharide (maltoheptaose; G7) is degraded ex vivo by amylase in plasma from PD patients treated with glucose or icodextrin PD solutions. METHODS: Plasma amylase (pancreatic and total) activity and concentration were measured in 11 controls and in PD patients treated with glucose (n = 11) and icodextrin (n = 19). The plasma was spiked with G7 and/or synthetic amylase and the metabolites formed were measured by HPLC following incubation at 37 degrees C for 4 hours. RESULTS: The relationship between amylase activity and amylase concentration was similar in all patients and controls. The G7 degradation rate was slower in plasma from icodextrin patients but it was also reduced in patients using glucose compared with the controls, in spite of the higher amylase activity in the glucose group. Normalization (by spiking) of patient plasma with porcine amylase increased but did not normalize the speed of G7 degradation. At a given endogenous amylase activity level, the efficiency of G7 degradation was similar for both patient groups. CONCLUSIONS: An ex vivo model to study the relationship between amylase activity and the actual rate of carbohydrate (represented by G7) breakdown was developed and showed that PD patients using glucose and icodextrin degrade G7 at a slower speed than controls. This suggests that amylase-mediated carbohydrate metabolism is reduced in PD patients. Further clinical studies are needed to confirm if these findings hold true also in other groups of uremic patients with varying degrees of kidney failure, as well as in patients undergoing hemodialysis.

Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription.

BACKGROUND: Peritoneal dialysis is associated with changes in membrane function that can lead eventually to ultrafiltration (UF) failure. Factors driving these changes are thought to include hypertonic glucose exposure, but previously reported associations are confounded by the presence of residual renal function. METHODS: Longitudinal membrane function (solute transport and UF capacity) were measured annually in a prospective cohort of 177 functionally anuric patients as part of the European Automated Peritoneal Dialysis Outcomes Study (EAPOS). Subgroup analysis was performed according to glucose exposure and icodextrin use at baseline. RESULTS: The whole cohort experienced an increase in solute transport and reduction in UF capacity at 12 and 24 months that could not be explained by informative censoring. These changes were accelerated and more severe in patients using either 2.27% or 3.86% glucose, or those not using icodextrin at baseline. These differences could not be explained by age, comorbidity score, previous time spent on renal replacement, differential dropout from the study, peritonitis rates, or, by definition, residual renal function. Patients using icodextrin at baseline had worse membrane function and were more likely to be diabetic. There was an association between membrane function changes and achieved 24-hour ultrafiltration over the 2-year study period. CONCLUSION: Anuric automated peritoneal dialysis (APD) patients experience significant detrimental changes in membrane function over a relatively short time period. Glucose appears to enhance these changes independent of residual renal function. Icodextrin use in these circumstances is associated with less deterioration in membrane function.

Growth hormone treatment in hemodialysis patients--a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Renal failure and hemodialysis (HD) affect the anabolic growth hormone (GH)-insulin-like growth factor (IGF) axis. A positive correlation between serum IGF-I and normalized protein catabolic rate (PCRn) in HD patients has been reported, and the aim of this study was to assess the metabolic impact of recombinant human (rh)GH in these patients. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled study, rhGH was given to 35 HD patients for 8 weeks: 0.025 IU/kg/day for 1 week, increasing to 0.05 IU/kg/day. Patients with diabetes, malignancy or clinical signs of infection and those receiving steroid treatment were excluded. RESULTS: All patients completed the study. Side-effects were rare and equally distributed between the two groups. Post-treatment, serum IGF-I and IGF-I standard deviation score (IGF-I SD) increased in the rhGH group compared to the placebo group: 283+/-33 vs 151+/-16 mg/l (p = 0.001) and 1.8+/-0.6 vs -0.2+/-0.6 (p = 0.002), respectively. IGF binding protein-3 was higher in the rhGH group compared to the placebo group: 5859+/-285 vs 4369+/-321 mg/l (p = 0.002). PCRn was significantly higher in the rhGH group compared to the placebo group: 1.09+/-0.06 vs 0.90+/-0.06 g/kg/day (p = 0.029). No differences were found in body weight, serum albumin or leptin between the two groups. There was no change in C-reactive protein (CRP) in the rhGH group compared to the placebo group: 17.4+/-9.0 vs 12.3+/-4.6 mg/l (p = NS). When the patients were subgrouped according to the CRP level (< or > 10 mg/1), the effect on PCRn persisted only in rhGH-treated subjects with a normal CRP level: 1.10+/-0.08 vs 0.81+/-0.09 g/kg/day (p = 0.025). CONCLUSION: Treatment of HD patients with rhGH at a moderate dose causes augmentation of PCRn which is considered to indicate a higher dietary protein intake. The anabolic effect of rhGH seems to be abolished by subclinical inflammation.

Efficacy and safety of a 7.5% icodextrin peritoneal dialysis solution in patients treated with automated peritoneal dialysis.

In a randomized, prospective, multicenter study, we compared the safety, efficacy, and metabolic effects of a 7.5% icodextrin solution (Extraneal) with a 2.27% glucose solution for long dwell exchanges in patients undergoing automated peritoneal dialysis. Thirty-nine stable patients on automated peritoneal dialysis were randomized to receive either icodextrin (n = 20) or glucose 2.27% solution (n = 19). The study included a 2-week baseline period followed by a 12-week icodextrin treatment phase and a 2-week follow-up period when switching back to glucose. The average net ultrafiltration during the long dwell period was 278 +/- 43 mL/d for the icodextrin group and -138 +/- 81 mL/d for the control group (P < 0.001). The higher ultrafiltration volume with icodextrin was associated with higher creatinine (2.59 +/- 0.09 mL/min versus 2.16 +/- 0.11 mL/min) and urea (2.67 +/- 0.09 mL/min versus 2.28 +/- 0.12 mL/min) peritoneal clearances for the long dwell (both P < 0.001). Ultrafiltration rate per mass of carbohydrate absorbed was +5.2 +/- 1.2 microL/min/g in the icodextrin group and -5.5 +/- 2.8 microL/min/g in the glucose group (P < 0.001). In the icodextrin group, there was a decrease in serum sodium and chloride compared with baseline (P < 0.01). Total dialysate sodium removal increased in the icodextrin group from 226.7 mEq to 269.6 mEq (week 12, P < 0.001). Serum alpha-amylase activity decreased from 103 U/L to 16 U/L (P < 0.001). The total icodextrin plasma levels reached a steady-state concentration of 6,187 +/- 399 mg/L after 1 week of treatment. Urine volume and residual renal function were not specifically affected by icodextrin compared with glucose. None of the laboratory changes resulted in any reported clinically meaningful side effect. Icodextrin produced increased, sustained ultrafiltration during the long dwell period, increasing (convective) peritoneal clearance and sodium removal in automated peritoneal dialysis patients.