Initiating CAPD with a regimen low in glucose and glucose degradation products, with icodextrin and amino acids (NEPP) is safe and efficacious.

BACKGROUND: The high Levels of glucose, glucose degradation products (GDPs), and lactate buffer present in standard peritoneal dialysis (PD) solutions contribute to peritoneal damage, malnutrition, and dyslipidemia. Therefore, we studied the feasibility of a PD regimen as low as possible in glucose and GDPs. METHODS: In a prospective 30-week study, patients new to continuous ambulatory PD (CAPD) were randomized to either a standard PD regimen (SPD; 4 dwells glucose-/lactate-based) or a low glucose-GDP regimen (NEPP; 1 dwell amino acids, 1 dwell icodextrin, and two dwells bicarbonate/lactate-buffered glucose-based solution). RESULTS: Results obtained during a 30-week study period for 63 new CAPD patients (30 NEPP, 33 SPD) were analyzed. Intraperitoneal glucose load was lower in the NEPP group (111 +/- 76 vs 159 +/- 40 g/day at 30 weeks, p < 0.001). Dialysis efficacy, ultrafiltration, weight, blood pressure, and laboratory results were similar in the groups, whereas, in the NEPP group, cancer antigen 125 in dialysate effluents decreased less but dialysate-to-plasma ratios were slightly higher. CONCLUSION: Short-term treatment of new CAPD patients with a PD regimen low in glucose and GDPs is feasible. Dialysis efficacy, ultrafiltration, and metabolic consequences are similar to those during a standard glucose-lactate-based regimen, whereas peritoneal transport seems slightly higher and preservation of mesothelial cell mass better during NEPP.

Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized placebo-controlled clinical trial with a 2-year open extension.

The efficacy and safety of oral pamidronate was examined in a double-blind, placebo-controlled trial in women and men with established osteoporosis. Seventy-eight postmenopausal women and 23 men with at least one prevalent vertebral fracture were randomized separately to 150 mg/day of pamidronate or placebo for 3 years followed by 150 mg/day of pamidronate for an additional 2 years. In addition, all patients received 400 U/day of cholecalciferol and 500 mg/day of elemental calcium. Pamidronate increased significantly bone mineral density of the lumbar spine (LS-BMD) and of the femoral neck (FN-BMD). The total increase in BMD of the spine after 5 years of treatment was 14.3%. Lateral spine radiographs were obtained at baseline and after 3 years of treatment. Fractures of previously normal vertebrae occurred in 15 of 45 patients treated with placebo (33.3%) and in 5 of 46 patients treated with pamidronate (11%). The relative risk was 0.33 (95% CI, 0.14-0.77). Treatment was well tolerated and there was no difference in gastrointestinal toxicity between pamidronate and placebo-treated patients. One hundred fifty milligrams daily of pamidronate is an effective and safe treatment of women and men with established osteoporosis.

Clinical effects of a peritoneal dialysis regimen low in glucose in new peritoneal dialysis patients: a randomized crossover study.

Standard glucose-based peritoneal dialysis (PD) solutions have unfavorable effects on the peritoneum and contribute to metabolic abnormalities. A PD regimen in which solutions with an alternative osmotic agent (icodextrin, amino acids) and solutions with a bicarbonate/lactate buffer are combined may reduce those effects. In a prospective crossover study, we randomized new continuous ambulatory peritoneal dialysis (CAPD) patients to one of two groups. One group used 4 exchanges of standard PD (SPD) solution (Dianeal: Baxter Healthcare BV, Utrecht, Netherlands) daily. The second group used 1 exchange of Nutrineal (Baxter Healthcare BV), 1 exchange of Extraneal (Baxter Healthcare BV), and 2 exchanges of Physioneal (Baxter Healthcare BV) daily (NEPP). After 30 weeks of treatment, each group switched over to the other regimen for 24 weeks. Statistical analysis used analysis of variance (ANOVA) for repeated measurements. Of the 74 patients enrolled into the study, 50 completed the full study period (24 NEPP-SPD, 26 SPD-NEPP). With regard to daily ultrafiltration and dialysis efficacy (Kt/V), the NEPP regimen was as efficacious as the standard regimen. The NEPP regimen was found to be safe: body weight, blood pressure, decline in urine volume, residual creatinine clearance, and laboratory measurements did not differ statistically significantly from those measured in the standard regimen. The NEPP regimen was well tolerated and was not accompanied by serious side effects. During the NEPP regimen, bicarbonate was found to be significantly higher in both groups. The NEPP regimen is a feasible treatment schedule for patients starting CAPD.

"NEPP" peritoneal dialysis regimen has beneficial effects on plasma CEL and 3-DG, but not pentosidine, CML, and MGO.

BACKGROUND: Standard peritoneal dialysis (PD) solutions contain high levels of glucose and glucose degradation products (GDPs), both contributing to the formation of advanced glycation end products (AGEs). We studied the contribution to plasma GDP and AGE levels of 2 PD regimens that differ in glucose and GDP loads: high load [standard PD (sPD) using 4 glucose-lactate exchanges] and low load [1 amino acid exchange, 1 icodextrin exchange, and 2 glucose-bicarbonate/lactate exchanges ("NEPP")]. METHODS: In a prospective crossover study (2 periods of 24 weeks), new continuous ambulatory PD patients were randomized to NEPP-sPD (n = 23) or to sPD-NEPP (n = 27). RESULTS: After the start of PD, absolute increases were observed in plasma levels of 3-deoxyglucosone (3-DG, 220.4 nmol/L, p < 0.0001) and in N(ε)-(carboxymethyl) lysine (CML) in plasma proteins (0.02 µmol/L CML per 1 mol/L lysine, p < 0.0001). During the first 6 weeks, 3-DG tended to increase more with sPD treatment (p = 0.08), and CML, with NEPP treatment (p = 0.002). In both groups, N(ε)-(carboxyethyl)lysine (CEL) in plasma proteins declined significantly with the start of PD. Treatment with NEPP resulted in higher levels of methylglyoxal (MGO) and lower levels of 3-DG and CEL. Pentosidine in the albumin fraction tended to increase less during NEPP treatment. CONCLUSIONS: A low glucose and GDP PD regimen (NEPP) resulted in plasma levels of 3-DG and CEL that were lower than those with a glucose-based sPD regimen. Starting PD with NEPP was associated with a steeper increase in CML, and continuing treatment with NEPP resulted in higher MGO levels.

A peritoneal dialysis regimen low in glucose and glucose degradation products results in increased cancer antigen 125 and peritoneal activation.

BACKGROUND: Glucose and glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are both thought to mediate progressive peritoneal worsening. METHODS: In a multicenter, prospective, randomized crossover study, incident continuous ambulatory peritoneal dialysis patients were treated either with conventional lactate-buffered PDF (sPD regimen) or with a regimen low in glucose and GDPs: Nutrineal×1, Extraneal×1, and Physioneal×2 (NEPP regimen; all solutions: Baxter Healthcare, Utrecht, The Netherlands). After 6 months, patients were switched to the alternative regimen for another 6 months. After 6 weeks of run-in, before the switch, and at the end of the study, 4-hour peritoneal equilibration tests were performed, and overnight effluents were analyzed for cells and biomarkers. Differences between the regimens were assessed by multivariate analysis corrected for time and regimen sequence. RESULTS: The 45 patients who completed the study were equally distributed over both groups. During NEPP treatment, D(4)/D(0) glucose was lower (p < 0.01) and D/P creatinine was higher (p = 0.04). In NEPP overnight effluent, mesothelial cells (p < 0.0001), cancer antigen 125 (p < 0.0001), hyaluronan (p < 0.0001), leukocytes (p < 0.001), interleukins 6 (p = 0.001) and 8 (p = 0.0001), and vascular endothelial growth factor (VEGF, p < 0.0001) were increased by a factor of 2-3 compared with levels in sPD effluent. The NEPP regimen was associated with higher transport parameters, but that association disappeared after the addition of VEGF to the model. The association between NEPP and higher effluent levels of VEGF could not be attributed to glucose and GDP loads. CONCLUSIONS: Study results indicate preservation of the mesothelium and increased peritoneal activation during NEPP treatment. Whether the increase in VEGF reflects an increase in mesothelial cell mass or whether it points to another, undesirable mechanism cannot be determined from the present study. Longitudinal studies are needed to finally evaluate the usefulness of the NEPP regimen for further clinical use.