Jutta Passlick-Deetjen

Low dialysate calcium in continuous ambulatory peritoneal dialysis: A randomized controlled multicenter trial

Hypercalcemia is a common complication in continuous ambulatory peritoneal dialysis (CAPD) patients treated with calcium-containing phosphate binders and using the standard dialysate calcium concentration of 3.5 mEq/L (SCa). Lowering the dialysate calcium was proposed to overcome this problem. The current randomized controlled multicenter study was designed to investigate efficiency and safety of a low calcium dialysate (2.00 mEq/L; LCa) compared with SCa (3.5 mEq/L) in CAPD patients. After an 8-week run-in period, 103 stable CAPD patients, 68 men, 35 women, aged 54.5 years (range, 20 to 77)) were randomly allotted to treatment with either LCa or SCa. All patients received calcium carbonate as oral phosphate binder to achieve serum phosphate levels < 6.2 mg/dL. If persistent hypercalcemia arose, CaCO3 was replaced by Al(OH)3 until normocalcemia was achieved. All patients received 0.25 microgram calcitriol/d. Parameters monitored included total and ionized serum calcium, serum phosphate, phosphate binder intake, incidence of hypercalcemia, serum aluminium, intact parathyroid hormone (1,84PTH), osteocalcin, alkaline phosphatase, bone mineral density and hand skeletal x-ray. Primary end points were (a) number of hypercalcemic episodes, (b) tolerated doses of calcium-containing phosphate binders, and (c) 1,84PTH. After 6 months of therapy, total and ionized calcium were lower in LCa patients (total Ca:9.6 v 10.08 mEq/L, P = 0.005; iCa: 4.76 v 5.15 mg/dL; P = 0.013). In the LCa group, significantly fewer episodes of hypercalcemia were recorded (total S-calcium > 10.8 mg/dL: LCa 24 v SCa 86 episodes; P < 0.005). Use of LCa permitted the administration of more CaCO3 (mean daily tablet number: LCa, 5.9 v SCa, 4.2; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro effects of glucose polymer-containing peritoneal dialysis fluids on phagocytic activity☆

Commercially available peritoneal dialysis fluids (PDFs) are known to impair peritoneal cellular defense mechanisms. We have investigated the influence of glucose polymer-containing PDFs on phagocytic function in vitro. Polymorphonuclear neutrophils (PMNLs) and monocytes (MNs) from 10 continuous ambulatory peritoneal dialysis patients and 10 healthy donors were incubated in PDFs containing either 7.5% icodextrin (glucose polymer) or 1.5% glucose at original pH and pH 7.4. Chemiluminescence response and H202 production were measured following stimulation with preopsonized Staphylococcus epidermidis or phorbol myristate acetate. Phagocytosis of radiolabeled bacteria and killing capacity of the cells were determined. A comparison of the impact of glucose polymer versus glucose-containing solutions at their original pH on the oxidative metabolism of the cells showed a highly significant difference (P < 0.0001) in favor of glucose polymers for H202 production of PMNLs (7.78 +/- 4.5 nmol cytochrome C reduction/10(6) cells/min v 1.11 +/- 0.67 nmol cytochrome C reduction/10(6) cells/min) and MNs (7.66 +/- 3.6 nmol cytochrome C reduction/10(6) cells/min v 1.29 +/- 0.86 nmol cytochrome C reduction/10(6)cells/min). Correspondingly, PMNLs and MNs incubated in glucose polymers showed a significantly higher chemiluminescence response irrespective of the stimulant used (P < 0.0001). Applying the killing assay on PMNLs also revealed a significantly higher percentage of inactivated bacteria (45.5% +/- 11.0% v 29.2% +/- 15.5%; P < 0.05). After adjustment of pH to 7.4, a significant difference could only be found for H202 production of PMNLs in favor of glucose polymers (16.73 +/- 6.98 nmol cytochrome C reduction/10(6) cells/min v 11.65 +/- 5.37 nmol cytochrome C reduction/10(6) cells/min; P < 0.05). In addition, we compared the glucose-polymer solution to an otherwise equally composed equiosmolar solution that contained 0.274% glucose instead of glucose polymers. No significant differences were detected with any of the tests applied. Our data suggest that glucose polymer solutions are comparatively less suppressive to phagocytic function than currently used glucose-containing PDFs. This effect may be attributed to the low osmolarity of these solutions.

In vitro effects of amino-acid-based versus glucose-based continuous ambulatory peritoneal dialysis fluids on peritoneal macrophage function.

We studied the in vitro effects of peritoneal dialysis fluids (PDF) containing 1 and 1.5% amino acids (AA) as compared to approximately equiosmolar glucose (GLU)-based PDF (1.5 and 4.25%) and control buffer, respectively, on peritoneal macrophage (PMO) function. The media were tested at original pH (5.3-5.5) and after pH adjustment to 7.4. PMO were isolated from the effluents of 10 on continuous ambulatory peritoneal dialysis (CAPD) patients and tested for luminol- and lucigenin-enhanced chemiluminescence (CL), superoxide generation measured by cytochrome c reduction, killing capacity and phagocytosis after incubation (30 min, 37 degrees C) in the PDF used. All AA-based PDF exhibited a statistically significant depressive effect on integral CL response, O2- production and bacterial killing of PMO at pH 7.4 in comparison with pH-adjusted GLU-based PDF of similar osmolality and buffer. Exposure of PMO to acidic AA-based media did not result in a significantly different suppression of the oxidative metabolism and the killing capacity as compared to fresh GLU-based fluids. Phagocytosis of PMO did not show significant differences after incubation in the solutions studied. Thus, the AA-based PDF employed compromise the oxidative metabolism and the killing capacity of PMO at pH 7.4 in vitro significantly more than GLU-based fluids. Since pH-identical and almost equiosmolar PDF were compared, the specific composition of the AA-based fluids, especially the high content of lactate and several essential AA, could be responsible for this detrimental impact.

In vitro effects of low-calcium peritoneal dialysis solutions on peritoneal macrophage functions

The use of low-calcium peritoneal dialysis solutions (PDS) for continuous ambulatory peritoneal dialysis is becoming widely accepted to reduce the risk of serum hypercalcemia in patients taking calcium salts as phosphate binders. We compared the in vitro effects of low-calcium PDS (1,000 mumol calcium/L), calcium-free buffer, and buffers with increasing calcium concentrations (500 to 5,000 mumol calcium/L) on peritoneal macrophage (PMO) functions. Peritoneal macrophages isolated from 10 continuous ambulatory peritoneal dialysis patients were incubated in the different solutions and tested for phagocytic and killing capacity, superoxide generation (cytochrome-C reduction and lucigenin-enhanced chemiluminescence), and the rate of myeloperoxidase-dependent oxidative metabolism (luminol-enhanced chemiluminescence). All functions of the PMO incubated in calcium-free buffer were significantly suppressed compared with the PMO incubated in calcium buffers. No dose-dependent increase of a single PMO function could be found after incubating the PMO in calcium buffer with increasing concentrations. Incubation of PMO in otherwise identical PDS containing 1,000, 1,450, or 1,750 mumol calcium/L did not result in significantly different PMO functions. Acidic PDS (pH 5.3 to 5.5) suppressed all measured PMO functions as compared with their neutralized counterparts (pH 7.4), irrespective of the calcium concentration. Results of our in vitro study show that low-calcium PDS does not suppress PMO functions any more than standard-calcium PDS (1,750 mumol calcium/L) does.