Blood eosinophilia in patients undergoing maintenance peritoneal dialysis.

To determine the prevalence of blood eosinophilia in patients receiving maintenance peritoneal dialysis, routine peripheral WBC counts of 49 such patients were reviewed. In 29 patients, blood eosinophilia was noted. Elevations in blood eosinophil counts tended to be mild and episodic. They were often associated with concomitant elevation of peritoneal fluid eosinophil counts. Possible predisposing factors included recent peritoneal catheter insertion and antibiotic therapy for peritonitis.

Failure of neutrophils to recover their ability to produce superoxide after stunning by a conventional, acidic, lactate-based peritoneal dialysis solution.

Exposure of human neutrophils to conventional, acidic, lactate-based peritoneal dialysis solutions for 5 minutes results in a depression of superoxide generation. In spite of restoration of extracellular pH to 7.4, these stunned cells failed to recover their ability to generate the anion after a period of an hour.

Increasing plasma phosphorus values by enriching with phosphorus the "acid concentrate" of a bicarbonate-buffered dialysate delivery system.

Each of seven hypophosphatemic hemodialysis patients was dialyzed with a phosphorus-enriched, bicarbonate-buffered dialysate. The latter was prepared by the introduction of sodium phosphate salts to the "acid concentrate" of a bicarbonate-buffered dialysate delivery system. The patients tolerated the procedure well and their hypophosphatemia improved.

Neutrophilic intracellular acidosis induced by conventional, lactate-containing peritoneal dialysis solutions.

Exposure of human neutrophils to a conventional, acidic, lactate-containing peritoneal dialysis solution (PDS) resulted in the development of a prompt and substantial intracellular acidosis. It is possible that this intracellular acidosis contributes to cellular dysfunction.

Suppression of neutrophil superoxide production by conventional peritoneal dialysis solution.

The pH of conventional peritoneal dialysis solution is normally in the range of 5.0 to 5.5, because acid has been added during the manufacturing process to prevent caramelization of dextrose during sterilization. We studied the effects of normalizing the pH of conventional peritoneal dialysis solution on superoxide production by normal human neutrophils. At a pH of 6.0, superoxide generation was 4.07 +/- 2.56 (SD) nanomoles per million cells. With normalization of pH to 7.4, superoxide production was 19.3 +/- 7.3 (p less than 0.001). The results suggest that the unphysiologic acidity of conventional peritoneal dialysis solution has deleterious consequences on neutrophil superoxide formation.

Superoxide generation by neutrophils after exposure to a conventional peritoneal dialysis solution for different time periods.

Neutrophils were isolated from canine blood and exposed to a conventional, acidic, lactate-containing peritoneal dialysis solution for 0, 2 and 4 minutes in one study and 0, 4, 7 and 10 minutes in another. Superoxide generation, expressed in nanomoles per million cells, was determined using a method based on the superoxide dismutase-inhibitable reduction of ferricytochrome c. Brief exposure of neutrophils to a conventional dialysis solution could significantly inhibit the generation of superoxide by neutrophils.

Heparin-associated thrombocytopenia in maintenance hemodialysis patients.

Thrombocytopenia associated with the presence of a heparin-dependent platelet aggregating factor developed in two patients after hemodialysis with heparin. It resolved in one patient after heparin was stopped; but persisted in the other during a two-week heparin-free period and intermittently thereafter. We suggest that when heparin causes thrombocytopenia in dialysis patients the heparin should be stopped whenever possible, but this may not be necessary in all patients.

Acetate relaxation of isolated vascular smooth muscle.

The vasorelaxant effects of acetate in arginine vasopressin (AVP)-contracted rat tail artery strips were examined in order to study mechanism of action. Dose-dependent relaxation by acetate was found in the clinically important range of 4 to 16 mM. Relaxation was not due to complexing of ionized calcium, persisted after mechanical removal of the endothelium, and was not altered by pretreatment with indomethacin. Although acetate also inhibited contraction by alpha-1 and alpha-2 agonists, the relaxant effect was not altered by destruction of sympathetic nerve terminals using 6-hydroxydopamine. The degree of relaxation in this model by various anions correlated with their lyotropic properties; however, the vasorelaxant effect of acetate exceeded that which would be expected on the basis of its position in the lyotropic series. The vasorelaxant effect of acetate was shared by other short-chain fatty acids that can be conjugated with coenzyme A (CoA), such as propionate and malonate. In contrast, a much lesser or absent relaxant effect was found with nonfatty-acid precursors of acetyl CoA, such as pyruvate, lactate, and alanine. The vasorelaxant effect of acetate was abolished by pretreatment with DIDS, an inhibitor of organic anion uptake, suggesting that cellular uptake of acetate is essential to its vasorelaxant action. The results suggest that the relaxant effect of acetate in vascular smooth muscle is non-specific, is not mediated by prostaglandins, does not depend upon the presence of either endothelium or the sympathetic nervous system, and may be due to metabolism of acetate to acetyl CoA with attendant conversion of ATP to AMP.

Hemodialysis hemodynamics in an animal model: effect of using an acetate-buffered dialysate.

Acetate-buffered dialysis (procedure A) was performed in conscious, nonuremic, splenectomized dogs. In some animals, dialysis was repeated after sympathectomy with 6-hydroxydopamine. During procedure A, hemodynamic changes were most pronounced 1 minute after starting dialysate flow (acute phase), and included a marked rise in cardiac output, pulse rate, and mean pulmonary artery pressure, but no change in mean arterial pressure (MAP) in intact animals. However, a precipitous fall in MAP was noted in sympathectomized dogs. Plasma acetate levels at this time averaged 2.0 +/- 0.5 mmol/L. Six to 30 minutes into procedure A, hypotension could be demonstrated in the intact, but not in the sympathectomized animals, at which time plasma acetate levels averaged 2.2 to 2.7 mmol/L. At 60 to 90 minutes into dialysis, when plasma acetate levels averaged 3.0 +/- 0.8 mmol/L, hypotension with procedure A was no longer significantly greater than with bicarbonate-buffered dialysis (procedure B). Plasma acetate levels at 30 to 90 minutes correlated with the change in cardiac output (r = 0.86, P less than 0.05) and total peripheral resistance (r = -0.76, P less than 0.05), but not with the decrease in MAP (r = -0.43, P not significant). Substantial hemodynamic changes were not seen when bicarbonate-buffered dialysis was used. Our results suggest that acute hypotension during procedure A in the dog model is prevented by an intact sympathetic nervous system. Hypotension occurring later during procedure A is difficult to demonstrate and does not appear to be accentuated after chemical sympathectomy. During procedure A the increase in cardiac output correlates with plasma acetate level.

Acute hypotension during acetate-buffered dialysis in chemically sympathectomized dogs.

Hemodialysis of chemically sympathectomized dogs using acetate-buffered dialysate was associated with a profound early drop in blood pressure due to a decrease in peripheral vascular resistance. Subsequently, blood pressure and peripheral resistance recovered to near normal levels. An increased pulse rate was also noted. None of these hemodynamic changes occurred when bicarbonate-buffered dialysate was used.

Demonstration of Fabry's disease deposits in placenta.

Involvement of the placenta by glycosphingolipid deposits in Fabry's disease has not been previously reported. We describe the presence of such deposits in the maternal half of a placenta obtained from a heterozygous carrier of the disease.

Hemodynamic effects of intradialytic food ingestion and the effects of caffeine.

Although the hypotensive effects of food ingestion during hemodialysis have been documented, the hemodynamic mechanism is unclear. It could be decreased cardiac output due to splanchnic sequestration or decreased vascular resistance due to splanchnic vasorelaxation. Also, the effects of caffeine, which block postprandial hypotension in the elderly, have not been studied in a dialysis setting. Central hemodynamics were monitored by thoracic electric bioimpedance in 10 dialysis patients who ingested a test meal 1 h into dialysis. All ultrafiltration was done during the initial 2 h. Bicarbonate dialysate was used. Each patient was studied three times in a double-blind (with respect to placebo/caffeine) cross-over trial: placebo/no meal, placebo/meal, and caffeine/meal. Blood pressure decreased sooner and to a great extent in the treatments in which food ingestion accompanied ultrafiltration (e.g., at 30 min after food ingestion, percent change in mean arterial pressure was -12.4 +/- 1.8 versus -2.4 +/- 3.5 mm Hg when food was not ingested; P < 0.05). The hemodynamic mechanism of food-associated hypotension was found to be a fall in systemic vascular resistance (SVRI). Caffeine pretreatment (200 mg), which resulted in intradialytic plasma caffeine levels of about 4 micrograms/mL at time of food ingestion, had no effect on food-associated reductions in blood pressure or SVRI. The results suggest that food ingestion during dialysis causes hypotension primarily because of decreased SVRI. The effects of food ingestion on mean arterial pressure and SVRI are not attenuated by the ingestion of 200 mg of caffeine 1 h before dialysis.

Use of a phosphorus-enriched dialysis solution to hemodialyze a patient with lithium intoxication.

A normophosphatemic patient suffering from lithium intoxication was hemodialyzed with a phosphorus-enriched, bicarbonate-based dialysis solution. A post-dialysis fall in plasma phosphorus level was prevented.

Splanchnic erythrocyte content decreases during hemodialysis: a new compensatory mechanism for hypovolemia.

Splanchnic and splenic erythrocyte volumes decrease during postural changes and exercise to help maintain central blood volume and cardiac output. The contribution of this compensatory mechanism to hemodynamic stability during dialysis has not been studied, however. In 8 ESRD patients, age 51.0 +/- 4.5 years old, we measured changes in the splanchnic/splenic erythrocyte volume during dialysis by tagging the patients' erythrocytes with technetium and following abdominal radioactivity over time. Splanchnic radioactivity decreased to 90.2 +/- 3.8% (mean +/- SEM) of the baseline value after 2 hr of accelerated fluid removal (3.7 +/- 0.4 liters) during dialysis (DUF), while it remained relatively unchanged after two hours of dialysis without fluid removal (DD) [106.5 +/- 2.3%, P (DUF vs. DD) = 0.03]. Splenic radioactivity decreased to 89.2 +/- 5.0% of the initial value during DUF versus 103 +/- 3.8% during DD, but the decrease was noted only during the last 30 minutes of DUF and did not attain statistical significance. Autonomic nervous system integrity was measured by the spontaneous variation of the R-R interval during deep respiration (E/I ratio) and by the Valsalva ratio. The mean E/I and Valsalva ratios in the eight patients were 1.13 +/- 0.03 (+/-SEM) and 1.42 +/- 0.1 respectively, suggesting reasonably adequate autonomic nervous system functioning. The results suggest that contraction of the splanchnic, and possibly the splenic, vascular beds occurs during fluid removal associated with hemodialysis. The resultant addition of erythrocytes to the circulation may help maintain central blood volume and cardiac output.

Preparation of ethanol-enriched, bicarbonate-based hemodialysates.

We describe a method to produce bicarbonate-based dialysates containing approximately 100 mg/dl ethanol by introducing the alcohol into one of the dialysate concentrate solutions geared for the production of bicarbonate-based dialysates.

Use of lactate as a base in hemodialysis.

The purpose of our study was to investigate the feasibility of using lactate as a complete or partial substitute for acetate in hemodialysis solutions. Six patients, each serving as his own control, were dialyzed once against a dialysis solution containing 40 mM acetate, once against a dialysis solution containing 40 mM DL-lactate and once against a dialysis solution containing 20 mM each of acetate and DL-lactate. Six additional patients underwent hemodialysis using acetate + lactate for a 3-week period, and the blood acid-base values during this period were compared to those obtained during periods when acetate was used. All dialysis treatments were well tolerated without hypotension or other clinical manifestations. When acetate + lactate was used, only a slight delay in the correction of acidosis during dialysis occurred and the net change in the plasma bicarbonate value appeared to be comparable to that measured with acetate. On the other hand, when lactate was used, the increase in the plasma bicarbonate level during and immediately after dialysis was reduced. With acetate + lactate, intradialytic blood D-lactate levels remained between 1 and 2 mM and returned promptly to near baseline within 1 h after dialysis. During 3 weeks of dialysis using acetate + lactate, predialysis plasma bicarbonate values were similar to those achieved when using acetate, but with acetate + lactate, the intradialytic plasma acetate levels were reduced by 50%. The results suggest that DL-lactate merits further evaluation as a potential base for hemodialysis solutions, and that both the D- and the L-lactate isomers are metabolized in maintenance hemodialysis patients.