Use of ACE inhibitors is associated with prolonged survival of arteriovenous grafts.

Vascular access complications are common in hemodialysis patients. To investigate whether the use of angiotensin-converting enzyme (ACE) inhibitors influences the rate of polytetrafluoroethylene (PTFE) graft complications, we compared the rate of intervention-free graft survival among patients treated versus not treated with ACE inhibitors. We retrospectively analyzed the survival of grafts placed at our institution between January 1, 1995, and October 31, 1999. Among 121 grafts, 25 grafts were placed in 19 patients treated with ACE inhibitors and 96 grafts were placed in 68 patients not treated with ACE inhibitors. Follow-up ranged from 1 month to 5 years. Ten of 25 grafts failed in the ACE-inhibitor group and 62 of 95 grafts failed in the non-ACE-inhibitor group. Actuarial intervention-free access survival rates (Kaplan-Meier) were significantly greater in the ACE-inhibitor than non-ACE-inhibitor group (71% versus 53% at 6 months, 58% versus 35% at 12 months, and 44% versus 22% at 24 months; P = 0.04). Using a Cox model adjusting for age, race, sex, and diabetes, the relative risk (RR) for access failure in the ACE-inhibitor group was 53% less than in the non-ACE-inhibitor group (RR, 0.47; p < 0.03). In a more complex Cox model with additional adjustment for comorbid conditions, the RR was even lower (RR, 0.32; P = 0.003) for the ACE-inhibitor compared with non-ACE-inhibitor group (reference = 1.00). The lower RR was observed for patients with and without congestive heart failure. These results suggest that ACE inhibitors offer clinical promise in the prevention of PTFE graft failure. A prospective randomized trial is warranted to confirm the benefit of ACE inhibitors.

Relationship of dialysis membrane and cause-specific mortality.

A number of studies have suggested that type of dialysis membrane is associated with differences in long-term outcome of patients undergoing hemodialysis, both in terms of morbidity and mortality. The purpose of this study was to determine the relationship of membrane type and specific causes of death. Data from the United States Renal Data System Case Mix Adequacy Study, a national random sample of hemodialysis patients who were alive on December 31, 1990, were used. Our study was limited to patients in this data set who were undergoing dialysis for at least 1 year (n = 4,055). For the main analytic models, membrane type was classified into two categories: unmodified cellulose or MC/SYN (which combines modified cellulose [MC] and synthetic membranes [SYN]). The relationships of membrane type and major causes of mortality were analyzed using Cox proportional hazards models, which adjusted for multiple (21) covariates, including demographics, comorbidity, Kt/V, and other parameters. Patients were censored at transplantation or 60 days after a switch to peritoneal dialysis. Compared with patients dialyzed with unmodified cellulose membranes, the adjusted relative mortality risk (RR) from infection was 31% lower (RR = 0.69; P = 0.03) and from coronary artery disease was 26% lower (RR = 0.74; P = 0.07) for patients dialyzed with MC/SYN membranes. No statistically significant difference (all P > 0.1) was found in mortality risk from cerebrovascular disease (RR = 1.08), other cardiac causes (RR = 0.86), malignancy (RR = 0.90), or other known causes (RR = 0.82) between patients dialyzed with MC/SYN compared with unmodified cellulose membranes. These results offer support to reported experimental and observational clinical studies that have found that unmodified cellulose membranes may increase the risk for both infection and atherogenesis. Further studies are necessary to evaluate the possibility of confounding factors, compare more specific membrane types, and determine the pathophysiology linking membrane type to cause-specific mortality.

Characteristics and treatment of patients not reusing dialyzers in reuse units.

Dialyzer reuse is practiced in more than 75% of the patients and dialysis units in the United States. However, reuse is not practiced in a small fraction of patients treated in reuse units (RUUs). This study evaluates both patient and facility characteristics associated with nonreuse in RUUs. The data source is from the Dialysis Mortality and Morbidity Study, Waves 1, 3, and 4, of the US Renal Data System. Only facilities that practiced dialyzer reuse were included in the analysis. A total of 12,094 patients from 1,095 reuse facilities were studied. Patients undergoing hemodialysis as of December 31, 1993, were selected. Of all patients treated in RUUs, 8% did not reuse dialyzers. Nonreuse was significantly (P < 0.02) more common, based on adjusted odds ratios (ORs), among patients who were younger (OR = 1.16 per 10 years younger), had primary glomerulonephritis (OR = 1.26 versus diabetes), had lower serum albumin level (OR = 1.72 per 1 g/dL lower), had more years on dialysis, and had higher level of education. Nonreuse patients were more likely to be treated with low-flux dialyzers (OR = 7.35; P < 0. 0001) and have a lower dialysis dose. No reuse was more likely in larger units and in not-for-profit and hospital-based units. Patient refusal accounted for one fourth of nonreuse in RUUs and was associated with the same factors, as well as with fewer comorbid conditions and non-Hispanic ethnicity. Significant geographic variations (up to eightfold) were documented. Nonreuse patients are treated with smaller, low-flux dialyzers and, on average, receive a lower Kt/V than reuse patients in the same units.

Mortality risk by hemodialyzer reuse practice and dialyzer membrane characteristics: results from the usrds dialysis morbidity and mortality study.

Hemodialyzer reuse is commonly practiced in the United States. Recent studies have raised concerns about the mortality risk associated with certain reuse practices. We evaluated adjusted mortality risk during 1- to 2-year follow-up in a representative sample of 12,791 chronic hemodialysis patients treated in 1,394 dialysis facilities from 1994 through 1995. Medical record abstraction provided data on reuse practice, use of bleach, dialyzer membrane, dialysis dose, and patient characteristics and comorbidity. Mortality risk was analyzed by bootstrapped Cox models by (1) no reuse versus reuse, (2) reuse agent, and (3) dialyzer membrane with and without the use of bleach, while considering dialysis and patient factors. The relative risk (RR) for mortality did not differ for patients in reuse versus no-reuse units (RR = 0.96; 95% confidence interval [CI], 0.86 to 1.08; P > 0.50), and similar results were found with different levels of adjustment and subgroups (RR = 1.01 to 1.05; 95% CI, lower bound > 0.90, upper bound < 1.19 each; each P > 0.40). The RR for peracetic acid mixture versus formalin varied significantly by membrane type and use of bleach during reprocessing, achieving borderline significance for synthetic membranes. Among synthetic membranes, mortality was greater with low-flux than high-flux membranes (RR = 1.24; 95% CI, 1.02 to 1.52; P = 0.04) and without than with bleach during reprocessing (RR = 1.24; 95% CI, 1.01 to 1.48; P = 0.04). Among all membranes, mortality was lowest for patients treated with high-flux synthetic membranes (RR = 0.82; 95% CI, 0.72 to 0.93; P = 0.002). Although mortality was not greater in reuse than no-reuse units overall, differences may exist in mortality risk by reuse agent. Use of high-flux synthetic membrane dialyzers was associated with lower mortality risk, particularly when exposed to bleach. Clearance of larger molecules may have a role.

Effect of dialysis membranes and middle molecule removal on chronic hemodialysis patient survival.

The type of dialysis membrane used for routine therapy has been recently shown to correlate with the survival of chronic hemodialysis patients. We examined whether this effect of dialysis membrane could be explained by differences in dialyzer removal of middle molecules using data from the 1991 Case Mix Adequacy Study of the United States Renal Data System. The sample analyzed included patients who had been treated by hemodialysis for 1 year or more, who were dialyzed with the 19 most commonly used dialyzers in 1991, and for whom delivered urea Kt/V could be calculated from predialysis and postdialysis blood urea nitrogen concentrations. Vitamin B12 (1,355 daltons) was used as a marker for middle molecules, and the clearance of vitamin B12 was estimated based on in vitro data. After adjustments for case mix, comorbidities, and urea Kt/V, the relative risk of mortality for a 10% higher calculated total cleared volume of vitamin B12 was 0.953 (P < 0.0001 v 1.000). Similar results were obtained when middle molecule removal was adjusted for body size. We conclude that both small and middle molecule removal indices appear to be independently associated with the risk of mortality in chronic hemodialysis patients. Differences in mortality when using different types of dialysis membrane may be explained by differences in middle molecule removal.

Trends in treatment and survival for hemodialysis patients in the United States.

Details regarding dialysis therapy have been studied by the US Renal Data System (USRDS) in four random samples of US hemodialysis patients during the years 1986 to 1997. During this decade, the delivered dose of hemodialysis therapy has increased by at least 0.2 Kt/V. The frequency of twice weekly dialysis prescription decreased, whereas the duration of each treatment showed only minor changes. A large shift to more biocompatible membranes, particularly to synthetic membranes, was observed. The use of acetate dialysate almost disappeared. Outcomes research by the USRDS showed significantly lower mortality risk associated independently with higher delivered Kt/V, substituted cellulose or synthetic membranes, and bicarbonate dialysate. The projected reduction in mortality risk from these changes in hemodialysis therapy was of a similar magnitude to the observed 14% to 17% reduction in mortality rate during the years 1990 to 1996. National observational studies of dialysis patients may influence the practice of dialysis and lead to improved survival.

Complement activation and hypersensitivity reactions to dialysis membranes.

Certain patients receiving hemodialysis experience recurrent chest pain, dyspnea, and hypotension during exposure to new cuprophane-membrane dialyzers (the "first-use syndrome"). Because activation of complement may be involved in these events, we examined in vivo complement activation with new cuprophane membranes and in vitro activation by zymosan in 6 such patients, and compared them with 10 patients who did not have symptoms during dialysis. All patients with the first-use syndrome had maximal complement activation 10 minutes after initiation of dialysis, with C3a des-arginine (desArg), the stable metabolite of C3 activation, equal to 8533 +/- 157 ng per milliliter (mean +/- S.E.M.). In asymptomatic patients the maximal C3a desArg value occurred at 15 minutes and was only 2907 +/- 372 ng per milliliter (P less than or equal to 0.0001). At a concentration of 3.8 x 10(-5) g of zymosan per milliliter, patients with the first-use syndrome had a C3a desArg level of 29.6 +/- 1.4 micrograms per milliliter, whereas it was only 16.6 +/- 2.3 micrograms per milliliter in asymptomatic patients (P less than or equal to 0.0001). Two other patients, who experienced cardiopulmonary collapse during the first two minutes of dialysis, had a C3a desArg level of 18,900 and 7800 ng per milliliter, respectively. We conclude that the occurrence of adverse symptoms associated with new cuprophane-membrane dialyzers correlates with complement activation.

A protamine filter for extracorporeal blood heparin removal.

Heparin employed in extracorporeal circuits often leads to hemorrhagic complications. Protamine employed for heparin neutralization can cause adverse hemodynamic responses. To control both types of complications, the authors propose an approach that consists of placing a filter device containing immobilized protamine (defined as a protamine filter) at the termination of the extracorporeal blood circulation (ECBC) procedure. This protamine filter would remove heparin from the extracorporeal circuit before heparin is returned to the patient. Meanwhile, the filter would also permit external protamine treatment. Since protamine toxicity generally results from the interaction of protamine with certain cells present in the liver, lungs, and tissues, the use of external protamine would minimize its potential adverse effects. Protamine was immobilized on a hollow fiber bundle obtained from a conventional hemodialyzer. Preliminary studies show that the protamine bound bundle is capable of neutralizing the anticoagulant activity of heparin both in vitro and in vivo. In addition, the protamine filter has abolished the hypotensive response normally associated with protamine reversal of heparin, as indicated by the insignificant changes in blood pressure, pulse rate, pulmonary artery systolic/diastolic pressures, and cardiac output. Further in vivo studies involving the use of dogs, as well as investigation of the activation of the complement system by the protamine filter, are currently being conducted.

Analysis of the association of dialyzer reuse practices and patient outcomes.

This historic prospective study assessed the relationship between dialyzer reuse practices and hemodialysis patient mortality through 1 year of follow-up. Medicare patient demographic and survival data were combined with dialyzer reuse data from the Centers for Disease Control and Prevention's annual survey of dialysis-related diseases. Data were analyzed for the US Medicare hemodialysis population of never transplanted patients prevalent on January 1, 1989, and January 1, 1990, who were treated in freestanding dialysis units that used primarily conventional (not high-flux) dialyzers. Time to mortality, or transplant, and other censoring on December 31st of each year was regressed with proportional hazards models on patient, dialysis unit, and reuse measures. Age-, race-, and diagnosis-standardized mortality ratios for dialysis units were also regressed with weighted least squares techniques against dialysis unit and reuse measures. The results showed that patients treated in dialysis units that disinfected dialyzers with a peracetic acid, hydrogen peroxide, acetic acid mixture, or glutaraldehyde experienced higher mortality than patients treated in units that used formalin or in units that did not reuse dialyzers. The relative risk of mortality, compared with patients treated in nonreuse dialysis units, was 1.17 (P = 0.010) for glutaraldehyde and 1.13 (P < 0.001) for the peracetic acid mixture. The relative risk for formalin compared with the reference group of nonreuse was 1.06 (P = 0.088). With adjustment for several patient and dialysis unit characteristics, dialyzer reuse with certain germicides was associated with a significantly elevated mortality risk. This elevated risk, the etiology of which is currently not known, may represent a large number of potentially avoidable deaths per year. Only a large, nationally based analysis of this type has sufficient sample size to detect mortality risks such as these.

Predictors of type of vascular access in hemodialysis patients.

OBJECTIVE: Complications from vascular access account for 15% of hospital admissions among US hemodialysis patients. Complications are less frequent with arteriovenous fistulas than with synthetic grafts. We assessed clinical and nonclinical predictors of whether patients with end-stage renal disease (ESRD) starting hemodialysis receive a fistula or graft. We also investigated changes in practice between 1986-1987 and 1990. DESIGN: Cross-sectional study. SETTING: United States hemodialysis population. PATIENTS: Random, national samples of ESRD patients who started hemodialysis in 1986-1987 (n=2741) or 1990 (n=1409) from United States Renal Data System Special Studies. MAIN OUTCOME MEASURE: Type of permanent vascular access (arteriovenous fistula vs synthetic graft), analyzed using multivariate logistic regression. RESULTS: Clinical and demographic factors as well as socioeconomic status, region of residence, and year starting hemodialysis predicted the type of vascular access. Overall, 56% of patients had grafts 30 days after starting dialysis, but graft use increased from 51% in 1986-1987 to 65% in 1990 (adjusted odds ratio [AOR], 1.67 for 1990 vs 1986-1987; 95% confidence interval [CI], 1.43-1.95; P<.001). Graft use (relative to fistula) varied by region of residence (ranging from AOR, 0.20; 95% CI, 0.14-0.28; P<.001 [New England], to AOR, 2.69; 95% CI, 2.03-3.58; P<.001 [East South Central]; both relative to the national average). CONCLUSIONS: This national study documents large variations in the relative use of fistulas and grafts and a trend away from fistulas. The prevalence of comorbid conditions fails to explain these findings. Presentation and referral of patients early in the process of their ESRD, teaching surgeons to place fistulas, and training dialysis nurses to access fistulas may increase their use.

Effect of the dialysis membrane on mortality of chronic hemodialysis patients.

Mortality of prevalent chronic hemodialysis patients remains high. The potential effect of the dialysis membrane on this mortality has not been previously investigated in a large population of chronic hemodialysis patients. Using data from the United States Renal Data System (USRDS), we analyzed a random sample of 6,536 patients receiving hemodialysis on December 31, 1990. The study design was a historical prospective study. By limiting the study to patients dialyzed for at least one year with bicarbonate dialysate, in whom the dose of dialysis could be calculated, and in whom dialysis membrane and co-existing morbidities were defined, the sample size was reduced to 2,410 patients. A Cox proportional hazards model was used to estimate relative mortality risk. The types of dialysis membranes used were broadly classified into three categories: unsubstituted cellulose, modified cellulose (generally cellulose membranes that have been modified by substitutions of some or most of their hydroxyl moieties) and synthetic membranes that are not cellulose-based. The results of the study suggest that after adjusting for the dose of dialysis and the presence of co-morbid factors, the relative risk of mortality of patients dialyzed with modified cellulose or synthetic membranes was at least 25% less than that of patients treated with unsubstituted cellulose membranes (P < 0.001). To account for the possibility that these differences were due to regional practice patterns, we further stratified the data for nine different regions. There was still a 20% difference in relative risk of mortality between membrane groups with the mortality statistically significantly less in patients treated with synthetic membranes (P < 0.045) compared to patients dialyzed with unsubstituted cellulose membranes. The results of this study suggest that the dialysis membrane plays an important role in the outcome of chronic hemodialysis patients. However, more definitive studies are needed before a cause and effect relationship can be proven.