icodextrin and Renal-Insufficiency

The next decade will face an increase in the number of patients affected by end-stage renal disease. In line with the growing incidence of type 2 diabetes, hypertension and old age in the general population, we can expect a dramatic increase of uremic patients needing a substitutive treatment of renal function. On the basis of the current trends, we expect an exponential growth of cardiovascular complications in both dialysis and transplant populations. Progress in the treatment of end-stage renal disease will aim at the prevention of cardiovascular complications, that remain the leading cause of morbidity and mortality in uremic patients. Preventive interventions for cardiovascular complications should focus on traditional risk factors, such as hypertension, dyslipidemia and obesity, diabetes mellitus, smoking, as well as on the non traditional risk factors inherent in the uremic state, such as anemia, hyperphosphoremia, hyperhomocysteinemia, inflammation and malnutrition. Recent and future innovations in peritoneal dialysis solutions include a larger use of icodextrin, a glucose polymer able to enhance ultrafiltration while inducing less glycation and caloric absorption, and perhaps improving blood pressure control. The gene therapy directed to the mesothelial cells should bring about improvements in nutrition, cardiovascular comorbidity, and dialysis adequacy. Patients submitted to increased hemodialysis time or to the implementation of a night or daily hemodialysis program have shown better blood pressure control, cardiovascular stability, tolerability and perhaps reduced mortality. Modifications of dialysis schedules clearly indicate another road to future improvements in renal replacement therapy. In the field of kidney transplantation, much improvement has already been achieved regarding the prevention of acute rejection, and the new therapeutic strategies are aimed at reducing the incidence of the adverse reactions of immunosuppressive drugs, as well as of the chronic allograft nephropathy. Induction of transplantation tolerance remains the most attractive target, which now seems closer than before because many of the mechanisms involved in the tolerance induction have been better elucidated.

Topics: Cardiovascular Diseases; Dialysis Solutions; Forecasting; Genetic Therapy; Glucans; Glucose; Hemodialysis, Home; Humans; Icodextrin; Kidney Transplantation; Peritoneal Dialysis; Renal Insufficiency; Risk Factors; Treatment Outcome

Until now, it remains unclear whether the addition of manual daytime exchanges or increasing the nightly dialysate flow is the best strategy to optimize automated peritoneal dialysis (APD) treatment. In this open-label randomized controlled crossover trial, 18 patients with high-average (HA) or low-average (LA) peritoneal transport rates sequentially underwent two different APD regimens for 7 days each, with an intermittent washout period of 7 days. 'Manual exchange' treatment was a conventional APD with low nightly dialysate flow and one manual daytime exchange. 'High-flow' treatment was defined by cycler therapy with high dialysate flow but without manual daytime exchange. Creatinine clearances (8.56+/-1.22 vs 7.87+/-1.04 l/treatment, P = 0.011) and urea nitrogen clearances (12.83+/-1.98 vs 11.68+/-1.06 l/treatment, P = 0.014) were significantly increased during 'high-flow' treatment compared to 'manual exchange' treatment. Sodium removal was significantly lower and glucose absorption was higher with the 'high-flow' regimen. Phosphate clearances, beta2-microglobulin clearances, ultrafiltration, and peritoneal protein loss were not different between the two treatment modalities. Subgroup analysis dependent on peritoneal transport types showed that the effect on clearances was most marked and significant in HA transporters, whereas sodium removal was lowest in LA transporters. We conclude that small solute clearances can be significantly improved and middle molecule clearances maintained in APD patients by increasing the nightly dialysate flow instead of adding a manual daytime exchange. However, the possible benefit of better clearances with higher nightly treatment volumes has to be weighed against increased costs and the possible negative impact of impaired sodium removal, especially in LA transporters.

Topics: Adult; Aged; Automation; Costs and Cost Analysis; Cross-Over Studies; Dialysis Solutions; Endpoint Determination; Female; Glucans; Glucose; Humans; Icodextrin; Male; Middle Aged; Peritoneal Dialysis; Renal Insufficiency; Sodium; Time Factors; Treatment Outcome

A postprandial increase in blood glucose in peritoneal dialysis (PD) patients with diabetes was observed in our previous study using continuous blood glucose monitoring. The response was observed in diabetic but not in nondiabetic PD patients. In addition, the response was reduced when patients used icodextrin; glucose absorbed from the peritoneum was responsible for the postprandial increase in blood glucose. Because our PD patients often change their PD fluid before meals, the present study aimed to determine the blood glucose and insulin responses to PD fluid. The 26 patients who agreed to participate in the study protocol [16 with diabetes (12 men, 4 women; 11 receiving insulin; 5 being controlled with oral antidiabetic drugs; average duration from diagnosis with diabetes: 16.4 ± 11 years); 10 without diabetes (4 men, 6 women)] had an average age of 60.5 ± 13.0 years. Average PD vintage was 578.7 ± 352.9 days. Blood samples were taken during a peritoneal equilibration test (PET) with 2.5% glucose solution at baseline and at 0.5, 2, and 4 hours. Levels of blood glucose and insulin were analyzed. A rapid increase in blood glucose (peak at 0.5 hours, 23.5 ± 22.2 mg/dL increase from baseline) was observed in nondiabetic patients. A delayed but higher peak response was observed in diabetic patients (peak at 1 hour, 54.9 ± 38.3 mg/dL increase from baseline). Peak response of insulin occurred at 0.5 hours in nondiabetic patients; in diabetic patients it occurred at 2 hours. No differences in the average insulin level during the PET were observed in the two groups (nondiabetic: 35.3 ± 15.6 μU/mL; diabetic: 38.9 ± 7.6 μU/mL). The study results suggest that a delayed insulin response after a PD fluid exchange could participate in the exaggerated postprandial increase in blood glucose in diabetic PD patients, particularly when the PD fluid exchange is performed before food intake.

Topics: Adult; Aged; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Complications; Dialysis Solutions; Female; Glucans; Glucose; Humans; Hypoglycemic Agents; Icodextrin; Insulin; Insulin Resistance; Male; Middle Aged; Peritoneal Dialysis; Peritoneum; Renal Insufficiency

Topics: Blood Glucose; Blood Pressure Monitors; Diabetes Mellitus; Dialysis Solutions; Glucans; Glucose; Humans; Icodextrin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Insufficiency

Topics: Drug Eruptions; Glucans; Glucose; Humans; Icodextrin; Renal Insufficiency; Skin Tests