Liem P. Oe

Biocompatibility of a Glucose-Polymer-Containing Peritoneal Dialysis Fluid

The currently available glucose-containing peritoneal dialysis fluids (PDF), which are all hyperosmolar, are toxic to the cells present in the peritoneal cavity. However, glucose-polymer solutions, being isosmolar, may have improved biocompatibility in this respect. We therefore compared in vitro the effects of PDF containing glucose-polymers with that of glucose solutions on the function of donor granulocytes and monocytes (MN), and on the viability of mesothelial cells. In addition, the function of peritoneal macrophages (PMO) of eight patients was studied in a randomized cross-over setting following intraperitoneal exposure to glucose-polymer-versus glucose-monomer-containing fluid of comparable ultrafiltration capacity. Donor granulocytes, as well as MN, showed significantly better phagocytosis of both Staphylococcus epidermidis and Escherichia coli after incubation in the glucose-polymer solution as compared with the 3.86% glucose-containing fluid. Their oxidative metabolism, as measured by chemiluminescence, also showed that the glucose-polymer solution was less inhibitory than fluids containing 2.27 or 3.86% glucose. Patient-derived PMO showed a significantly better phagocytic capacity for S epidermidis and E coli, a significantly higher killing of E coli, and a significantly higher chemiluminescence response after intraperitoneal exposure to the glucose-polymer solution as compared with the glucose-monomer-based fluid. Increasing the osmolality of the glucose-polymer solution to that of the respective glucose solutions blunted the favorable effect on phagocyte function, suggesting the beneficial effect to be osmolality-mediated. However, no major difference was observed between the glucose-polymer solution and the glucose-based fluid in their effects on mesothelial viability.(ABSTRACT TRUNCATED AT 250 WORDS)

The adjustment of post dialytic dry weight based on non-invasive measurement of extracellular fluid and blood volumes.

One of the major problems in the clinical practice of hemodialysis is an incorrect estimation of post dialytic (PD) dry weight. Underestimation of dry weight leads to hypovolemia induced hypotension, and overestimation to hypertension, pulmonary edema, and left ventricular hypertrophy. Because of the insensitivity of clinical variables to estimate dry weight, a more accurate technique is warranted. For this purpose and for the continuous surveillance of changes in blood volume (BV) during hemodialysis, two non-invasive techniques were applied. Based on post dialytically obtained extracellular fluid volume (EFV) values, measured by means of a conductivity method, 30 stable hemodialysis patients were divided into three groups for further analysis: de- (n = 9), normo- (n = 15), and overhydrated (n = 6). Using an on-line optical reflection method, changes in BV were measured continuously during therapy. Mean BV decrease, corrected for UF, differed slightly between the three groups (0 = 1.84 +/- 2.06, N = 3.20 +/- 1.80, D = 4.20 +/- 1.60 %/L). However, eight hypotensive episodes occurred in group D versus none in groups N and O. These hypotensive episodes were characterized by a greater reduction of BV--corrected for ultrafiltration--from the start of treatment until the moment of hypotension (6.96 +/- 2.21 %/L), compared with the 22 non hypotensive controls (2.16 +/- 2.01 %/L, p < 0.001). Based on the PD EFV dry weight of the overhydrated and dehydrated patients was decreased and increased, respectively, by 500 g after each session, until PD EFV was within normal bounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-calcium peritoneal dialysis fluid should not impact peritonitis rates in continuous ambulatory peritoneal dialysis.

It has been suggested that reducing the calcium content of peritoneal dialysis fluid (PDF) to 2.5 mEq/L decreases peritoneal macrophage (PMO) function and increases the incidence of peritonitis (especially Staphylococcus epidermidis peritonitis) in continuous ambulatory peritoneal dialysis patients. We studied the uptake and killing of S epidermidis and Escherichia coli by PMOs and peripheral blood leukocytes incubated in control buffer (Hanks balanced salt solution containing 0.1% gelatin [GHBSS]) and PDF containing varying concentrations of calcium (O to 3.5 mEq/L) and magnesium (O to 1.5 mEq/L) using ether diamine tetraacetic acid and ethylenediaminetetraacetic acid chelation, respectively. In addition, interleukin-1-beta-induced interleukin-6 production by human mesothelial cells was measured in the presence of concentrations of calcium increasing from 0 to 3.0 mmol/L. Fc receptor- mediated uptake of S epidermidis by PMO in the complete absence of Ca++ was comparable to that by PMO incubated in GHBSS with calcium. In contrast, the complement-dependent uptake of E coli was significantly lower in GHBSS devoid of Ca++ (46% +/- 5% v 24% +/- 3%; 0.05 < P < 0.02). No effect on intracellular killing of either microorganism by PMO was observed. The same held true for the phagocytic and killing capacity of polymorphonuclear granulocytes and monocytes obtained from healthy donors. Using Ca++ (2 to 3.5 mEq/L) and Mg++ (0.5 to 1.5 mEq/L) concentrations as applied in commercial PDFs, however, phagocytes performed as well as in control buffer. Interleukin-6 production by stimulated human mesothelial cells also required a small amount of Ca++ only, being normal above the 0.1 to 3 mmol/L Ca+ + range tested. Thus, complement- dependent uptake of bacteria by phagocytes is calcium dependent, whereas antibody-dependent uptake of S epidermidis is not. The concentrations of calcium in the current PDFs, however, will not compromise human mesothelial cells and leukocyte functions, and therefore should not impact the peritonitis rate.

Doxazosin in the treatment of patients with mild or moderate hypertension and mild or moderate renal insufficiency.

The antihypertensive efficacy and safety of doxazosin, a selective alpha 1-inhibitor, were assessed in 23 hypertensive patients with renal insufficiency. The study involved three phases: (1) a 2-week baseline period, (2) a 10-week period during which patients received doxazosin, 1 to 16 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks of active treatment, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by 8.9/9.2 and 4.6/9.1 mm Hg to final values of 153/90 and 149/91 mm Hg in the supine and standing positions, respectively. The mean dose of the efficacy evaluable patients was 9.8 mg/day. Eleven patients experienced one or more side effects, most of which were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. There were no significant differences in serum creatinine levels between baseline and final visits. The overall lipid profile indicated a decrease in total cholesterol with increases in high-density lipoprotein cholesterol and the high-density lipoprotein/total cholesterol ratio. From baseline to final visit there was a highly significant reduction of 19% (p less than 0.05) in calculated risk scores for coronary heart disease on the basis of the Framingham equation.