Saliva urea dipstick test: application in chronic kidney disease.

BACKGROUND: A noninvasive test for determining elevated levels of blood urea nitrogen (BUN) may be useful under circumstances in which there is limited access to laboratories. Because saliva urea nitrogen (SUN) parallels BUN, we investigated the diagnostic performance of a semiquantitative SUN dipstick to test for elevated BUN levels in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: Patients with CKD Stages 1 to 5D were studied. 50 µl of saliva were transferred onto the SUN test strip (Integrated Biomedical Technology, Elkhart, Indiana, IN, USA). SUN was determined after 1 minute by visual comparison of the color of the moistened test pad with 6 calibrated color blocks. Interobserver reproducibility was evaluated by independent observers, masked to urea concentrations of 6 calibrated urea solutions. Correlation between SUN and BUN was quantified by Spearman's rank correlation coefficient (RS), Kappa Statistic was employed to evaluate within-sample reproducibility of duplicates. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance of SUN. RESULTS: 68 patients (31 females, 60 ± 14 years; 34 hemodialysis patients, 34 patients CKD Stages 1 - 4) were studied. Interobserver coefficient of variation was 4.9% at SUN levels > 50 mg/dl; within-sample reproducibility was 90%. SUN and BUN were correlated significantly (RS = 0.63; p < 0.01). Elevated BUN was diagnosed with high accuracy by SUN determination (area under the ROC curve: 0.90 (95% CI 0.85 - 0.95)). CONCLUSION: Semiquantitative dipstick measurements of SUN can reliably identify CKD patients with elevated BUN levels.

Leukopenia and hypoxemia. Unrelated effects of hemodialysis.

Hemodialysis-induced hypoxemia has been attributed to membrane-related complement activation leading to pulmonary leukostasis and to hypoventilation secondary to carbon dioxide losses via the dialyzer. We have separately assessed the role of membrane- and dialysis-related factors by using different dialyzers and sequential ultrafiltration and hemodialysis with first-use cellulose dialyzers produced both leukopenia and hypoxemia. With reused cellulose and polyacrylonitrile dialyzers, hypoxemia still occurred, but without leukopenia. Ultrafiltration produced leukopenia and no changes in Pao2; during the subsequent hemodialysis, hypoxemia developed as the leukocyte count increased by 50%. Our data indicate that leukopenia and hypoxemia are unrelated effects of hemodialysis, and favor hypoventilation as the major determinant of hypoxemia during hemodialysis.

Association of acidosis and nutritional parameters in hemodialysis patients.

There is extensive literature supporting an important role for acidosis in inducing net protein breakdown, both in experimental animals and humans. However, the clinical importance of the moderate intermittent metabolic acidosis frequently observed in hemodialysis patients has not been determined. We performed a cross-sectional analysis of the baseline laboratory data in the first 1,000 patients recruited to the Hemodialysis Study, looking for correlations between predialysis serum total carbon dioxide levels and parameters related to dietary intake and nutritional status. We found the mean predialysis serum total carbon dioxide level was moderately low (21.6 +/- 3.4 mmol/L; mean +/- SD) despite the use of bicarbonate dialysate and an average single-pool Kt/V of 1.54. Predialysis serum total carbon dioxide level correlated negatively with normalized protein catabolic rate (P < 0.001), suggesting patients with lower serum total carbon dioxide levels have a greater protein intake. The degree of acidosis observed in our patients does not seem to have a deleterious effect on the nutritional status of these patients because correlation of serum total carbon dioxide level with nutritional parameters, such as serum creatinine and serum albumin levels, was either negative or not statistically significant. Further investigation of the effect of modifying serum bicarbonate concentration on nutritional markers is needed to test these hypotheses.

Predictive value of access blood flow and stenosis in detection of graft failure.

AIMS: Low access flow and the diagnosis of high degrees of venous stenosis have been recommended as indications for prophylactic angioplasty. However, recent studies have shown that prophylactic angioplasty for > 50% stenosis did not prolong graft patency, and that a single flow measurement may not accurately predict graft failure. In this study we compared the value of monthly measurement of access flow and of the maximal degree of stenosis in the detection of graft failure over a three-month period. METHODS: Thirty-nine hemodialysis patients with polytetrafluoroethylene (PTFE) grafts were evaluated by Doppler ultrasound at monthly intervals for three months. Graft failures were defined as thrombosis, or surgical and angioplastic revisions required because of the presence of access recirculation, and patients with graft failure were followed within the subsequent one-month periods of observation. RESULTS: Twelve graft failures occurred during the three-month period of observation. The risk for subsequent graft failure significantly increased at flows < 300 ml/min. Nine (20%) graft failures occurred with stenoses of 30 to 50%, and three (13%) with stenoses of> 50%. The grafts that failed in the second and the third study months had a 25.8% (380 +/- 62 vs. 287 +/- 190 ml/min, p < 0.05) and a 36.5% (393 +/- 142 vs. 226 +/- 41 ml/min, p < 0.05) decrease in access flow, respectively. There was no significant change in access flow for the grafts patent throughout the study (911 +/- 333, 794 +/- 302, and 919 +/383 ml/min, p = ns). No significant increases in maximal stenosis were found for the grafts that failed in the second month (44 +/- 6.1 vs. 48 +/- 15%, p = ns) and the third month (48 +/- 9 vs. 51 +/- 16%, p = ns). There were no significant changes in the maximum stenosis for the grafts patent throughout the three-month study periods (37 +/- 15,43 +/- 11, and 44 +/- 15%, p = ns). CONCLUSIONS: Access flow is a more sensitive predictor of graft failure than stenosis. Examination of trend in decline of access flow is a more powerful indicator to detect graft dysfunction than an individual single flow value.

Clinical experience with heat sterilization for reprocessing dialyzers.

Use of heat sterilization for dialysis reprocessing offers significant advantages over chemical germicides. Polysulfone dialyzers (Fresenius 60M or 80M) can be sterilized by heating to 105 degrees C for 20 hr, thus permitting clinical trials of this method. One hundred eighty patients received 9,000 treatments. Pyrogenic reactions, sepsis, and subjective symptoms have not occurred. In vitro clearances (Qb 500 ml/min, Qd 800 ml/min) at baseline and after 2-8 uses did not differ (340 +/- 29 vs. 352 +/- 4 ml/min, respectively). KoA determined in vivo did not decrease (baseline 709 +/- 131 vs. 7th use 632 +/- 50 ml/min). Kt/V for urea was not different in 18 patients treated with heat sterilized dialyzers over 6 months when compared with a baseline period with formaldehyde sterilized dialyzers (1.37 +/- 0.12 vs. 1.32 +/- 0.11 at similar time and blood flows). Mean use number was 7.4 (dialyzers limited to 11 uses). Of discarded dialyzers, 44% failed a bedside integrity test (blood side pressurized at > 400 mmHg for 1 min), 36% failed automated fiber bundle or pressure holding tests, 8% had a blood leak, and 12% reached 11 uses. Clinical blood leaks occur in < 0.5% of treatments. Heat sterilization is a safe and effective method of dialysis reprocessing, but quality control of the process is essential. Based on initial clinical experience, heat sterilization of dialyzers for reuse is a promising alternative to chemical disinfection.

Predictive value of access blood flow in detecting access thrombosis.

The aim of this study was to evaluate whether repeated measurement of access blood flow (Qac) using the ultrasound dilution technique could predict access failure in patients on hemodialysis. One hundred thirty-one patients were evaluated at intervals of 8 weeks for a period of 6 months. The incidence of thrombosis was determined within each study period. During the 6 month follow-up, 36 thrombotic events occurred in 27 of 68 polytetrafluoroethylene (PTFE) grafts, and only six thrombotic events in 5 of 63 arteriovenous (AV) fistulas. The relative risk for access thrombosis for patients with PTFE grafts was 5.6 times greater than for patients with AV fistulas. Qac was significantly lower in thrombotic compared with patent PTFE grafts (958 +/- 506 ml/min vs 1141 +/- 482 ml/min, p < 0.05). A significant relationship was found between the incidence of subsequent PTFE graft thrombotic events and Qac (p < 0.001). Compared with accesses with high blood flow (1100-1400 ml/min), the risk for subsequent thrombosis tripled in grafts with a Qac of less than 500 ml/min. This relationship was not seen with AV fistulas. In patent PTFE grafts, Qac remained unchanged within each 2 month interval, whereas it decreased in thrombotic PTFE grafts. Thus, repeated measurements of Qac have the potential to predict future access failure in PTFE grafts; however, an increased measuring frequency might improve the predictive value of graft failure with high Qac.

Filtration of dialysate using an on-line dialysate filter.

UNLABELLED: Increased concerns about pyrogenic contamination of dialysate have led to the development of an on-line dialysate filtration system. Bacteriological testing of the system was performed (n = 6) by introducing bicarbonate concentrate contaminated with E. coli 026:B 6 (3 x 10(9) cfu/ml) into a dialysis machine equipped with a two-stage polysulfone filtration system. The bacterial concentration of the dialysate entering the filtration system was maintained above 10(6) cfu/ml and endotoxin levels ranged from 30-300 ng/ml during the 3-hour test period. Bacterial and endotoxin levels on the input side of the first-stage filter reached minimum concentrations of 5.4 x 10(9) cfu/ml and 30,000 ng/ml respectively. All output samples of filtered dialysate showed no bacterial growth and endotoxin levels were below the sensitivity (0.003 ng/ml) of the LAL assay. A dialysis machine (QD = 500), equipped with a single stage filtration system, was used for 18 months of clinical testing. In order to evaluate the system's reliability with regard to membrane failures and reduced dialysate flow, filter membrane integrity was verified weekly using a pressure holding test and dialysate flow was measured under routine clinical conditions. No membrane failures occurred, and dialysate flow was maintained at 511 +/- 17 ml/min (n = 70) during the test period. IN CONCLUSION: dialysate filtration is an effective and practical method for prevention of pyrogenic reactions due to high levels of bacteria and endotoxins.

Blood flow distribution in sorbent beds: analysis of a new sorbent device for hemoperfusion.

A new polymer-based sorbent cartridge has been recently developed for enhancing middle molecule removal during hemodialysis. The cartridge (Betasorb, Renaltech, New York, USA) has been designed to be placed in series with the dialyzer in the blood circuit. It is therefore important to evaluate the distribution of flow into the blood compartment of the device in order to assess if the surface of the sorbent is utilized to the best. For this purpose, a special imaging technique was utilized. Cartridges were analyzed during a simulated in vitro circulation at 250 and 350 ml/min of blood flow and 25% and 40% hematocrit. Cartridges were placed in vertical position and a cross longitudinal section 1 cm thick was analyzed in sequence by a helical scanner. Dye was injected into the arterial inlet and the progressive distribution was evaluated by sequential densitometrical measures carried out automatically by the machine. The sequential images analyzed by the scanner demonstrated excellent distribution of the flow in the blood compartment with minimal difference between the central and the peripheral regions of the compartment. In particular the following flow velocity pattern could be observed under the different experimental conditions tested. We may conclude that the cartridge design is adequate and no channelling effects could be detected in the blood compartment. The flow distribution is slightly affected by changes in flow rate and hematocrit showing an optimal utilization of the available surface for molecule adsorption.

Relationship between dialyser type and signs and symptoms.

A crossover study to compare the effects of seven different dialysers on intradialytic symptoms in 37 patients during dialysis with acetate-containing dialysate was performed at five centres in four countries. The same manufacturing lot of each dialyser and of blood line sets were used by all centres. The same clinical data (duration of dialysis, blood pressure, weights, temperature, drugs, symptoms, and treatments) and technical data (blood flow, dialyser clearance, and ultrafiltration rate) were collected. Kt/V for urea was used to determine dialysis prescribed. Intradialytic symptoms and signs were measured hourly or when observed by staff using the haemodialysis treatment form (see Introduction). After each week of treatment with a particular dialyser, patients completed a questionnaire relating to the presence and severity of symptoms. (Only presence or absence of symptoms are presented.) Wide differences in dialysis duration and blood flow between centres were noted. These may have contributed to the differences between centres in relationship to staff reported responses to different dialyser: Dialysers with the lowest incidence of both signs and symptoms and of chest pain, back pain, and itching (arbitrarily designated bioincompatibility symptoms) were the Duo-Flux and Filtral, with the G120 M, the CD 4000, and the T 150 having the highest incidence. By patient questionnaire the most biocompatible dialysers were the T 150, F 60, and the Filtral, with the most symptom producing being the G120 M and the G10-3N. Perceptions of symptoms between patients and staff differed substantially overall and between centres. Hypersensitivity reactions were noted in two patients, both occurring with cuprammonium cellulose hollow-fibre dialysis, despite adherence to manufacturers' instructions concerning saline priming and removal. Both patients showed antibody titres greater than 1:160 against ethylene oxide-HSA. Ethylene oxide was not detected (limit of detection 1 part per million) in dialysers, blood line sets, or fistula needles. The study suggests that dialysis symptom reporting is complicated by individual perceptions, staff reactions, and the efficiency of recording. In this study ethnic and cultural differences must be added to the haemodynamic differences and other prescription-related elements in influencing symptoms. Despite these problems a hierarchy of dialyser-related symptoms and signs could be discerned which largely paralleled laboratory findings of biocompatibility. Future comparative studies relating symptomatology to membrane and dialyser structure should consider the variables identified as influencing symptoms and their reporting.

Clinical experience with short-time hemodialysis.

After at least 6 months on conventional hemodialysis (cellulosic dialyzers, acetate dialysate, and a 3- to 4-hour treatment time), 56 patients were changed to short-time hemodialysis (less than 180 minutes) using polysulfone dialyzers and bicarbonate-containing dialysate. Treatment time decreased (191 +/- 5 v 147 +/- 5 min; P = 0.001), while Kt/V (1.22 +/- 0.04 v 1.29 +/- 0.06; P = NS) and normalized protein catabolic rate (pcr) (1.10 +/- 0.05 v 1.10 +/- 0.07 g/kg/d; P = NS) remained constant. When compared with the conventional period, 30 months of short-time hemodialysis resulted in no changes in predialysis blood pressure (BP) (151 +/- 2/84 +/- 1 v 151 +/- 2/86 +/- 1 mm Hg), postdialysis BP (144 +/- 2/81 +/- 1 v 143 +/- 3/84 +/- 1 mm Hg), interdialytic weight gain (2.4 +/- 0.1 v 2.7 +/- 0.2 kg), or blood urea nitrogen (BUN) (26.1 +/- 0.71 v 25.3 +/- 1.07 mmol/L [73 +/- 2 v 71 +/- 3 mg/dL]). Shorter treatment times were not associated with an increase in intradialytic complications. Actually, the frequency (%) of dialysis treatments associated with nausea (5.94 +/- 1.33 v 2.21 +/- 0.52), vomiting (3.12 +/- 0.87 v 0.54 +/- 0.14; P less than 0.05), headaches (5.60 +/- 1.13 v 2.03 +/- 0.52; P less than 0.05), and back pain (0.91 +/- 0.25 v 0.05 +/- 0.05; P less than 0.05) was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a reduced inner diameter of hollow fibers in hemodialyzers.

BACKGROUND: The clearance of middle molecules in high-flux hemodialyzers is due to the higher contribution of convection in the overall solute transport. Although net filtration can be maintained low by the machine control, internal filtration in the proximal part of the dialyzer remains high. The final fluid balance is achieved by significant amounts of backfiltration in the distal part of the dialyzer. To increase further middle molecule clearance (MMK), hemodiafiltration has been used. This technique, however, requires complex machines and large amounts of substitution fluid. We present a novel solution to increase the convective transport of middle molecules in high flux dialyzers without the need for substitution fluids. In particular, high-flux dialyzers with a reduced hollow fiber diameter are compared with standard dialyzers in terms of internal filtration and solute clearances. METHODS: Hemodialyzers with 175 micro inner diameter polysulfone fibers were compared with standard 200 micro polysulfone hollow fiber dialyzers. The study was carried out in vitro using a previously published method to measure internal filtration and backfiltration rates. The method is based on the detection by a gamma camera of segmental variations in concentration along the length of the dialyzer of a nondiffusable Tc99-labeled marker molecule injected in the blood in vitro circuit. At the same time, pressures were detected in the blood and dialysate compartment. The system was operated at zero net filtration maintaining volumetrically constant both dialysate and blood circuits. In vivo clearances were also measured for solutes with different molecular weight. RESULTS: The pressure drop in the blood compartment at 300 mL/min of blood flow passed from 112 to 159 mm Hg. At the same blood flow, the internal filtration-backfiltration rates increased from 23. 1 to 48.2 mL/min. This resulted in a significant increase of in vivo in clearances of vitamin B12 and inulin of more than 30%. Urea, creatinine, and phosphate clearance did not display any change. CONCLUSIONS: A reduction of the inner diameter of the hollow fibers in high-flux dialyzers may result in a significant increase of the blood compartment resistance. In turn, this results in increased rates of internal filtration and backfiltration. The practical effect in clinical dialysis is demonstrated on middle molecules. While, in fact, the clearances for small solutes such as urea and creatinine are not affected, the clearances of larger solutes such as vitamin B12 or inulin increase significantly (P < 0.01).

Development of a new approach to vascular access.

Three modes of access for hemodialysis (HD) have been available for over 20 years, the native arterial to venous (A-V) fistula, the polytetrafluorethylene (PTFE) graft fistula, and the central venous catheter. Overall, vascular access remains the single most costly source of morbidity and hospitalization in HD patients, indicating a severe need for improvement in this area. A significant contributor to access morbidity is the HD catheter, which protrudes through the skin and is subject to frequent infection. Subcutaneous ports have been developed to overcome this problem with catheters, but their application to HD has been elusive for 2 reasons, the use of a degradable septum that becomes vulnerable to infection with the use of large bore needles and the presence of a nonlinear flow path which produces damage to blood cells and stimulates thrombus formation at the required high flow rates. A new device, the Dialock, overcomes these objections by its use of a mechanical valve that maintains a linear flow path without directly contacting the blood. Results of a pilot study with 23 patients demonstrated a 78% cumulative survival rate after 1 year with a reduced rate of infection compared to catheters and sustained blood flow of 330 ml/min. The device represents a most promising advance in vascular access.

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.

High flux dialysis membranes improve plasma lipoprotein profiles in patients with end-stage renal disease.

A major cause of the morbidity and mortality of patients with end-stage renal disease (ESRD) is related to disorders of large blood vessels, especially coronary heart disease. Atherosclerosis, the most common form of this disease, is known to result from abnormalities in plasma lipoproteins, as well as from factors that damage the vessel wall. Two well-known risk factors for coronary heart disease are elevated plasma concentrations of LDL and reduced concentrations of HDL. This latter disorder is often accompanied by elevated triglycerides. Low HDL and elevated triglycerides are commonly associated with ESRD. Dialysis with high flux membranes differs from conventional dialysis in a number of ways. These include better biocompatibility and increased flux of larger molecules. Although several previous studies had suggested that dialysis with high flux membranes improves plasma lipoprotein profiles, a definitive cross-over designed study to assess the roles of high flux versus biocompatibility in altering lipoprotein profiles had not been done. Preliminary data from such a study are presented. These data confirm the beneficial effects of high flux membranes to reduce plasma triglycerides and suggest that this effect is primarily due to the high flux, and not the biocompatible, feature of the membranes.

Improvement of plasma lipoprotein profiles during high-flux dialysis.

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.

Behaviour of white blood cells and the complement system.

Seven different types of dialysers were investigated in five dialysis centres in four countries with respect to behaviour of white blood cells and the complement system. The results of this controlled crossover study demonstrated significant differences in the dialysers. Those containing cuprammonium cellulose (G10-3N and G120 M) showed the greatest changes in white blood cell count, including monocytes and neutrophils, as well as the greatest complement activation. With regard to lymphocytes the subpopulation of low-mobility cells, which were predominantly the B-cells, showed the greatest mobility with dialysers containing cuprammonium cellulose. The PAN copolymer- and PMMA-containing dialysers Filtral and T 150 clearly caused the least changes in white blood cells and complement factors. Dialysers containing cellulose acetate and polysulphone membranes (Duo-Flux Artificial Kidney, CD 4000, and F 60) produced only a moderate decrease of WBC, monocyte, neutrophil, and lymphocyte counts, and this result corresponded to a relatively small change in complement factors.

Effects of hemodialyzer reuse on clearances of urea and beta2-microglobulin. The Hemodialysis (HEMO) Study Group.

Although dialyzer reuse in chronic hemodialysis patients is commonly practiced in the United States, performance of reused dialyzers has not been extensively and critically evaluated. The present study analyzes data extracted from a multicenter clinical trial (the HEMO Study) and examines the effect of reuse on urea and beta2-microglobulin (beta2M) clearance by low-flux and high-flux dialyzers reprocessed with various germicides. The dialyzers evaluated contained either modified cellulosic or polysulfone membranes, whereas the germicides examined included peroxyacetic acid/acetic acid/hydrogen peroxide combination (Renalin), bleach in conjunction with formaldehyde, glutaraldehyde or Renalin, and heated citric acid. Clearance of beta2M decreased, remained unchanged, or increased substantially with reuse, depending on both the membrane material and the reprocessing technique. In contrast, urea clearance decreased only slightly (approximately 1 to 2% per 10 reuses), albeit statistically significantly with reuse, regardless of the porosity of the membrane and reprocessing method. Inasmuch as patient survival in the chronic hemodialysis population is influenced by clearances of small solutes and middle molecules, precise knowledge of the membrane material and reprocessing technique is important for the prescription of hemodialysis in centers practicing reuse.