The acute effect of amino acid based dialysis solution on peritoneal kinetics of amino acids and plasma proteins in comparison to conventional glucose-based dialysate was studied in 9 patients with end-stage renal failure on continuous ambulatory peritoneal dialysis. Instillation of 2.6% amino acid solution resulted in raised plasma concentrations of all essential amino acids included in the dialysis fluid (p < 0.005). The amino acid solution induced an augmented leakage of plasma proteins into the dialysate at all dwell times investigated (1-8 h). After a dwell time at 8 h, the dialysate total protein increased from 2.62 ± 0.45 g with glucose dialysate to 3.85 ± 0.42 g with amino acid solution (p < 0.05). Corresponding results were obtained for pV microglobulin, albumin, transferrin, IgG, and for the non-essential amino acids alanine, citrulline, and glutamine (p < 0.025) not included in the initial amino acid composition of the dialysis fluid. During the use of amino acid based dialysis fluid, the effluent prostaglandin E2 concentration increased by more than 80% in comparison to glucose dialysate (p < 0.025). The augmented loss of proteins induced by the amino acid solution was positively correlated with increased dialysate prostaglandin E2 (r = 0.8894; p < 0.001). Peritoneal ultrafiltration was not affected by the use of amino acid based dialysate fluid. The present results indicate that amino acid based dialysis fluid enhances the peritoneal permeability for plasma proteins and amino acids, probably mediated by locally generated prostanoids.
The effect of long-term treatment with human recombinant erythropoietin (rHuEPO) has been studied in nine end-stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD). RHuEPO was administered subcutaneously twice weekly in rising doses starting with 50 Ukg-1 body weight. After 3 months of rHuEPO haemoglobin increased from 77.7 +/- 3.2 to 112.7 +/- 5.6 g l-1 (P less than 0.03), haematocrit rose from 22.8 +/- 1.2 to 30.3 +/- 1.7% (P less than 0.01). A consistent decrease in ferritin concentration was observed during this time (P less than 0.05). After 12 months of rHuEPO treatment and increased oral iron supplementation the rises of haemoglobin and haematocrit remained stable without other significant haematological changes. The rHuEPO-induced rise in haematocrit was associated with an increased peritoneal ultrafiltration (UF) without change in diuresis and body weight. UF improved from 128 +/- 28 ml 4 h-1 dwell time to 273 +/- 45 ml 4 h-1 (P less than 0.03) within 3 months of rHuEPO treatment, and remained stable during the following study period (month 12: 253 +/- 43 ml 4 h-1, P less than 0.05). The rise in UF resulted in improved peritoneal clearances of creatinine, urea, potassium, and phosphate (P less than 0.05, month 3). No change was observed in serum urea, creatinine, calcium, and potassium. Serum phosphate increased throughout the first 6 months of rHuEPO (P less than 0.05). No severe adverse effects of rHuEPO treatment could be observed. The present results demonstrate that long-term subcutaneous administration of rHuEPO is effective in correcting renal anaemia in CAPD patients and may improve dialysis efficiency by increased peritoneal ultrafiltration.
The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1st month 10 mg; 2nd month 20 mg and 3rd month 40 mg day-1). Simvastatin reduced total serum cholesterol (300.0 + 15.5 vs. 193.0 ± 8.0; -35%), LDL cholesterol (203.8 ± 13.0 vs. 104.7 ± 6.0; -48.0%) as well as apolipoprotein B (132.3 ± 6.6 vs. 77.8 ± 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 ± 0.016 vs. 0.64 ± 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 ± 5.6 vs. 30.4 ± 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 ± 0.3 vs. 4.28 ± 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 ± 4.4 to 57.9 ± 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 ± 73 vs. 145 ± 26 U/l), but were not influenced significantly by simvastatin treatment (539 ± 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors.
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