Technical advances in hemodialysis therapy.

Other than pharmaceutical advancements, the improvements in hemodialysis have largely been due to technical changes. This article summarizes the various technical areas that are noteworthy: hemodialysis membranes; dialysate buffer, electrolyte concentration, and temperature; prescription monitoring; reprocessing; volume-ultrafiltration control; information system interface; arteriovenous access monitoring; water treatment; and continuous and nocturnal dialysis. Within each category, subjective and objective conclusions are drawn as to whether the technical advancements have translated to improved clinical outcomes. In addition, an hypothesis is proposed that due to a confluence of ownership of research and development, manufacturing of equipment, and dialysis facilities conflicts may arise which could slow future technical developments.

The effect of membrane biocompatibility on plasma beta 2-microglobulin levels in chronic hemodialysis patients.

Several studies have shown that patients who have been dialyzed with high-flux biocompatible membranes have a lower plasma level of beta 2-microglobulin and a lower incidence of amyloid disease compared with patients who have been dialyzed with low-flux bioincompatible membranes. However, because high-flux membranes are associated with significant dialytic removal of beta 2-microglobulin, the specific role of membrane biocompatibility in influencing the rate of increase of beta 2-microglobulin has not been previously determined. This study investigated the effect of biocompatibility on the rate of increase of plasma levels of beta 2-microglobulin in 159 new hemodialysis patients from 13 dialysis centers (ten centers affiliated with Dallas Nephrology Associates and three with Vanderbilt University Medical Center) by using two low-flux membranes with widely different biocompatibilities. These patients were prospectively randomized to be dialyzed with either a low-flux biocompatible membrane or a low-flux bioincompatible membrane. Plasma beta 2-microglobulin levels were measured at 0, 3, 6, 9, 12, and 18 months. Sixty-six patients completed the 18-month study. Plasma beta 2-microglobulin increased in all patients; however, the increase was not significantly different from baseline at any time point in the group that used the biocompatible membrane. In this group, beta 2-microglobulin increased from (mean +/- SD) 27.8 +/- 14.8 mg/L to 34.0 +/- 10.0 mg/L at 18 months (P = not significant), and the mean increase at 18 months was 2.6 +/- 14.7 mg/L. In contrast, the increase in plasma beta 2-microglobulin level in the bioincompatible membrane group became significant in Month 6 when the levels had increased from a baseline of 24.8 +/- 9.6 mg/L to 29.5 +/- 12.2 mg/L (P < 0.001); these increases continued to be significant until Month 18, when serum beta 2-microglobulin reached 36.8 +/- 13.9 mg/L with an average increase of 11.8 +/- 11.2 mg/L (P < 0.0001). The higher rate of plasma B2-microglobulin increase in the group that had been dialyzed with the bioincompatible membrane was also evident when only patients who had completed the study were analyzed. There were no significant differences in the actual level of beta 2-microglobulin or in residual renal function between the two groups during the 18 months of the study. It was concluded that over a period of 18 months, the use of biocompatible membranes, even in the low-flux configuration, is associated with a significantly slower increase in plasma beta 2-microglobulin, independent of the influence of residual renal function.

Effect of the membrane biocompatibility on nutritional parameters in chronic hemodialysis patients.

Malnutrition is highly prevalent in chronic hemodialysis patients and is an important determinant of their morbidity and mortality. Several recent studies have suggested that the inflammatory response associated with the biocompatibility of the dialysis membranes is a potential contributing factor. In a prospective study of 159 new hemodialysis patients from two centers randomized to either a low-flux biocompatible (BCM) membrane or a low-flux bioincompatible (BICM) membrane, we measured the long-term effects of biocompatibility on several nutritional parameters, including estimated dry weight, serum albumin, insulin-like growth factor-1 (IGF-1), and prealbumin over 18 months. Our results show that the BCM group had a mean (+/- SD) increase in their dry weight of 2.96 +/- 6.88 kg at month 12 and 4.36 +/- 8.57 kg at month 18 (P < 0.05 vs. baseline for both), whereas no change in mean weight was observed in BICM group. Following initiation of hemodialysis, a significant increase was observed in serum albumin levels in both groups of patients. However, the biocompatible group had an earlier and more marked increase in serum albumin levels compared to the BICM group. The average increase in serum albumin compared to baseline was consistently greater than 0.25 g/dl after seven months in the BCM group, but did not reach this level until 12 months after initiation of dialysis in the BICM group. The difference between the groups was statistically significant at months 7, 8, and 10 (P < 0.05, higher in the BCM group). Furthermore, the overall difference in serum albumin concentration between the two groups was larger in the center where the dose of dialysis was equivalent (P < 0.001). A consistently higher value was also observed in IGF-1 levels for BCM patients compared to BICM group (P = NS). In a further analysis, changes in IGF-1 levels, but not prealbumin, predicted the subsequent changes in serum albumin. We conclude that biocompatible hemodialysis membranes favorably impact on the nutritional status of chronic hemodialysis patients, independently of the flux characteristics of the membranes, and that IGF-1 may be an early marker of nutritional status.

Role of dialysis dose on morbidity and mortality in maintenance hemodialysis patients.

The United States dialysis population has an excessive mortality rate that cannot be fully explained by comorbid conditions or demographic factors. The quantity of dialysis has been suggested to be insufficient. This report reviews the several dialysis-related factors that impact on mortality. Since the National Cooperative Dialysis Study in 1983, there have been no controlled trials. However, numerous retrospective and two recent larger prospective studies indicate that increasing the quantity of dialysis by 40% to 50% of that traditionally provided in the United States will significantly improve survival. This is equivalent to a Kt/V of less than 1.2 and possibly less than 1.4 using single pool urea kinetics. It is estimated that this would save an additional 8,000 to 16,000 lives per year.

Survival of hemodialysis patients in the United States is improved with a greater quantity of dialysis.

The mortality rate for hemodialysis patients in the United States is higher than in other industrialized countries. Some attribute this to insufficient quantities of prescribed and delivered dialysis. A multicenter study in Dallas dialysis centers (Dallas Nephrology Associates) was begun in 1989 to assess the impact of increasing the delivered quantity of dialysis on mortality in subsequent years. Dialysis dose was measured by urea kinetic modeling. Kt/V, reflecting the fractional volume of body water clearance of urea during a dialysis treatment, was purposefully increased from 1.18 starting in 1989 to 1.46 in 1992. Additionally, the dialysis dose measured by the urea reduction ratio, the fractional reduction of blood urea nitrogen concentration caused by a dialysis treatment, increased from 63.0% to 69.6% between 1990 and 1992. Outcome analytical methods included both crude and standardized mortality rates and mortality ratios standardized to large end-stage renal disease databases at the United States Renal Data System and at National Medical Care, Inc. Crude mortality rates at Dallas Nephrology Associates decreased from 22.5% in 1989 to 18.1% in 1992. In comparison, between 1990 and 1992 the urea reduction ration in National Medical Care facilities increased from 57.1% to 62.5%. During that time crude mortality rates decreased from 21.8% to 19.5%. Crude mortality in the United States remained essentially unchanged in the same time period. By 1992, Dallas Nephrology Associates and National Medical Care had standardized mortality ratios of 0.77 and 0.74, respectively, compared with the US dialysis population, indicating almost 30% fewer observed deaths than expected. Monitoring dialysis dose by urea kinetic modeling or urea reduction ratio are equally effective in predicting improvement in patient survival. Improved survival is possible in the US end-stage renal disease program with greater amounts of dialysis. This strategy can save an estimated 8,000 to 16,000 lives per year.

Glomerular filtration rates in persons evaluated as living-related donors--are our standards too high?

We have retrospectively analyzed the glomerular filtration rate by 125-I iothalamate clearance and creatinine clearance in a group of 661 persons evaluated as potential kidney donors. The average GFR in this population is lower than that reported in previous studies and ranges from 102 +/- 15 and 114 +/- 17 ml/min for males and females age 21-30 to 84 +/- 13 and 79 +/- 15 ml/min for males and females age 51-60. Furthermore, there has been a gradual decrease in GFR in this population from 1970 to 1990 in both the entire population and in those under the age of 40. The cause of this drop is not apparent. These data can be utilized to determine the appropriateness of a potential donor for donation, and may indicate that our current standards are too high.

Adequacy of hemodialysis.

Despite technical advances in the delivery of hemodialysis over the past decade, the mortality rate of hemodialysis-dependent, end-stage renal disease (ESRD) patients in the United States remains high. The increase in the number and severity of comorbid conditions of patients entering ESRD is a factor contributing to this high mortality. Nevertheless, there is increasing evidence that the dose of dialysis received by US patients is inadequate and that this plays a major role in the observed high mortality. In this review, we examine some of the parameters used to judge the adequacy of dialysis, as well as factors that can result in differences between prescribed and delivered dose of hemodialysis. Based on available evidence, we propose that for most patients the optimum dose of dialysis, above which further improvement of morbidity and mortality is doubtful, is represented by a delivered dose of dialysis equivalent to a Kt/V of 1.4 or greater, using biocompatible membranes. The prescription of this optimal dose of dialysis must be coupled with an ongoing effort to monitor delivery of the appropriate dose.

Evaluation of a new disinfectant for dialyzer reuse.

Glutaraldehyde has been proposed to be as effective as formaldehyde as a disinfectant for reprocessing capillary hemodialyzers. Formaldehyde has become the standard to which all disinfectants are compared. The two products are compared for microbiological efficacy, reuse, membrane integrity, biocompatibility, performance, residual binding and ease of removal, environmental hazards, and immunogenicity. Glutaraldehyde (0.8%) is as effective as 4% formaldehyde in its microbiocidal effect. The disinfectants are comparable except in the following areas: the use of glutaraldehyde leads to lower reuse rates than formaldehyde, significantly less glutaraldehyde than formaldehyde remains in the dialyzer following standard predialysis rinse procedures, and less glutaraldehyde than formaldehyde is found in environmental air.

Effect of aspartame on plasma amino acid profiles of diabetic patients with chronic renal failure.

A randomized, double-blind study was conducted to determine the possible effects of aspartame on the plasma amino acid profiles of 23 diabetic patients with renal failure who were undergoing maintenance hemodialysis. Subjects were given a single dose of 10 mg aspartame/kg (approximately equivalent to 25 packets of Equal [NutraSweet Consumer Products, Inc, Chicago, IL] or the amount of phenylalanine in a 300-mL glass of milk) or a placebo in a crossover study design. Three postdialysis blood samples were drawn just before and 1 and 2 h after aspartame or placebo consumption. After aspartame consumption statistically significant increases in only two amino acids, phenylalanine and tyrosine, were noted at 1 and 2 h when compared with placebo values. The increases in phenylalanine were within the normal postprandial range for healthy subjects; no other increases in essential or nonessential amino acids, except for tyrosine, were detected. This study supports the view that aspartame is safe for diabetic subjects with chronic renal failure.

Uremic pruritus: skin divalent ion content and response to ultraviolet phototherapy.

Pruritus is a frequent and troublesome consequence of end-stage renal disease. We have surveyed 155 chronic dialysis patients and found pruritus to be a significant problem in approximately 70%. Seventeen patients reporting severe pruritus were treated thrice weekly with total body exposure to either UVA or UVB light. UVB light resulted in resolution of pruritus in all cases. UVA light was without significant effect. Skin biopsies obtained before and after UV phototherapy revealed elevated contents of calcium, magnesium, and phosphorus in all pruritic patients. The resolution of pruritus following UVB treatment was associated with a reduction of skin phosphorus to values comparable with nonpruritic uremics or healthy volunteers. Uremic pruritus may be due to increased skin divalent ion content resulting in microprecipitation of calcium or magnesium phosphate.

Absorption of phosphate in the jejunum of patients with chronic renal failure before and after correction of vitamin D deficiency.

To examine the role of vitamin D in human phosphate absorption, we studied patients with chronic renal disease on hemodialysis, before and after correction of vitamin D deficiency. Thirty-centimeter segments of jejunum were perfused with test solutions containing varying concentrations of phosphate; phosphate absorption rate and electrical potential difference were measured. The data reveal that dialysis patients have depressed phosphate absorption, but the degree of this depression is modest, compared to the extent of their depressed calcium absorption. Therapy with 1,25-(OH)2D3 for 1 wk restored phosphate absorption rate to near normal. With or without 1,25-(OH)2D3 therapy, phosphate absorption was not influenced by calcium in the perfused test solutions. Examination of kinetic data suggests that the vitamin D deficiency of chronic renal failure causes a reduction by half in the rate of active phosphate absorption. By contrast, our data suggest that vitamin D deficiency does not alter passive phosphate absorption. By aspirating jejunal contents after ingestion of different foods, with and without aluminum hydroxide, the physiologic luminal phosphate concentration was found to vary between 0.7 and 12.2 mM. At the lower end of this range, phosphate absorption would be mediated entirely by active transport; at the higher phosphate concentrations, phosphate absorption would be mainly mediated by passive transport.