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Venous catheters differ from peripheral arteriovenous (AV) access devices in many important ways. This discussion focuses on their performance as a conduit for blood flow between the patient and the dialyzer and on how catheter function is both limited and enhanced relative to the more common peripheral accesses. Catheter flow is limited by the high resistance inherent in the extended length of venous catheters relative to dialysis needles, but the high rate of flow in central veins also diminishes the opportunity for access recirculation. Cardiopulmonary recirculation is absent in patients with catheter access unless the patient also has a peripheral access. In the latter case, the same detrimental effect on urea clearance is seen regardless of which access device is used. Flow-dependent recirculation through circuits other than the peripheral AV access reduces the efficiency of dialysis (regardless of the type of access, catheter, or peripheral AV device used) across both catheters and peripheral AV devices. The inside diameter of the catheter plays a sensitive role in determining catheter resistance to flow. Slight increases in diameter under the same pressure head are associated with large increases in flow. Negative pressure at the catheter inflow port generated by the blood pump is magnified relative to peripheral devices, predisposing to partial collapse of the pump tubing segment and erroneous blood flow readings by the pump motor speed indicator. Setting a limit on prepump negative pressure can minimize this error. Future applications of dialysis may require lower pump speeds, which would allow more liberal use of catheter access if their potential for infection and clotting can be reduced. [ABSTRACT FROM AUTHOR]

Successful replacement of renal function with dialysis supports the concept that uremia is a toxic state resulting from accumulated solutes and that toxicity results from high concentrations of these solutes in body fluids. Dialyzer clearance of urea, a surrogate toxin, is the currently accepted best measure of dialysis and dialysis adequacy, but it is admittedly a compromise due to current lack of knowledge about and inability to measure more toxic solutes. This failure could be explained if uremic toxicity is actually a summation effect of multiple toxins, each at individual subtoxic levels in the patient. Other solutes could be used as surrogates to measure clearance, but urea happens to be available in high concentrations, is easily measured by all clinical laboratories, and is easily dialyzed, so changes in concentration are sensitive indicators of clearance. Measurements of creatinine clearance are confounded by the disequilibrium that occurs across red cells within the dialyzer and in the patient. Other solutes probably behave more like creatinine than urea, so urea stands out as uniquely diffusible, a property that actually spoils its effectiveness as a surrogate toxin, especially when applied to more frequent and continuous dialysis. Accumulation of other solutes may correlate better with toxic uremic symptoms and the residual syndrome. More studies are needed to examine the kinetics of other solutes, their generation rates, and their distribution volumes to provide clinicians with more knowledge and tools to optimize dialysis treatments. Examination of the effectiveness of solute removal in patients dialyzed more frequently may provide significant insight into the pathogenesis of uremia. [ABSTRACT FROM AUTHOR]

Deals with a study which examined the prevalence of anti-hepatitis C virus (HCV) antibodies and the factors that predispose patients to have antibody to HCV. Methods; Results; Discussion.

Explains urea kinetics on patients who receive dialysis through central vein catheters but have an unusual arteriovenous (AV) access. Difference in urea kinetics during dialysis between venovenous and arteriovenous accesses; Common occurrence of venovenous dialysis with the presence of an unused AV access.

Introduction: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity., Methods: Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis., Results: In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (-28.0 [95% CI -40.5 to -15.4] g) than in the higher predialysis SNa group (-2.0 [95% CI -15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance., Discussion/conclusion: In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

In previous reports of the Frequent Hemodialysis Network trials, frequent hemodialysis (HD) reduced extracellular fluid (ECF) and left ventricular mass (LVM), with more pronounced effects observed among patients with low urine volume (UVol). We analyzed the effect of frequent HD on interdialytic weight gain (IDWG) and a time-integrated estimate of ECF load (TIFL). We also explored whether volume and sodium loading contributed to the change in LVM over the study period. Treatment effects on volume parameters were analyzed for modification by UVol and the dialysate-to-serum sodium gradient. Predictors of change in LVM were determined using linear regression. Frequent HD reduced IDWG and TIFL in the Daily Trial. Among patients with UVol <100 ml/day, reduction in TIFL was associated with LVM reduction. This suggests that achievement of better volume control could attenuate changes in LVM associated with mortality and cardiovascular morbidity. TIFL may prove more useful than IDWG alone in guiding HD practice. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=441966., (© 2016 S. Karger AG, Basel.)

Hypertension is a common complication of chronic kidney disease and persists among most patients with end-stage renal disease despite the provision of conventional thrice weekly hemodialysis (HD). We analyzed the effects of frequent HD on blood pressure in the randomized controlled Frequent Hemodialysis Network trials. The daily trial randomized 245 patients to 12 months of 6× ("frequent") vs. 3× ("conventional") weekly in-center hemodialysis; the nocturnal trial randomized 87 patients to 12 months of 6× weekly nocturnal HD vs. 3× weekly predominantly home-based hemodialysis. In the daily trial, compared with 3× weekly HD, 2 months of frequent HD lowered predialysis systolic blood pressure by -7.7 mmHg [95% confidence interval (CI): -11.9 to -3.5] and diastolic blood pressure by -3.9 mmHg [95% CI: -6.5 to -1.3]. In the nocturnal trial, compared with 3× weekly HD, 2 months of frequent HD lowered systolic blood pressure by -7.3 mmHg [95% CI: -14.2 to -0.3] and diastolic blood pressure by -4.2 mmHg [95% CI: -8.3 to -0.1]. In both trials, blood pressure treatment effects were sustained until month 12. Frequent HD resulted in significantly fewer antihypertensive medications (daily: -0.36 medications [95% CI: -0.65 to -0.08]; nocturnal: -0.44 mediations [95% CI: -0.89 to -0.03]). In the daily trial, the relative risk per dialysis session for intradialytic hypotension was lower with 6×/week HD but given the higher number of sessions per week, there was a higher relative risk for intradialytic hypotensive requiring saline administration. In summary, frequent HD reduces blood pressure and the number of prescribed antihypertensive medications., (© 2015 International Society for Hemodialysis.)

In the intention-to-treat analysis of the Hemodialysis Study, all-cause mortality did not differ significantly between the high versus standard hemodialysis dose groups. The association of mortality with delivered dose within each of the two randomized treatment groups was examined, and implications for observational studies were considered. Time-dependent Cox regression was used to relate the relative risk (RR) for mortality to the running mean of the achieved equilibrated Kt/V (eKt/V) over the preceding 4 mo. eKt/V was categorized by quintiles within each dose group. Analyses were controlled for case-mix factors and baseline anthropometric volume. Within each randomized dose group, mortality was elevated markedly when achieved eKt/V was in the lowest quintile (RR, 1.93; 95% confidence interval [CI], 1.40 to 2.66; P < 0.0001 in the standard-dose group; RR, 2.04; 95% CI, 1.50 to 2.76; P < 0.0001 in the high-dose group; RR relative to the middle quintiles). The mortality rate in the lowest eKt/V quintile of the high-dose group was higher than in the full standard-dose group (RR, 1.59; 95% CI, 1.29 to 1.96; P < 0.0001). Each 0.1 eKt/V unit below the group median was associated with a 58% higher mortality in the standard-dose group (P < 0.001) and a 37% higher mortality in the high-dose group (P < 0.001). The magnitude of these dose-mortality effects was seven- to 12-fold higher than the upper limit of the 95% CI from the intention-to-treat analysis. The effects were attenuated in lagged analyses but did not disappear. When dialysis dose is targeted closely, as under the controlled conditions of the Hemodialysis Study, patients with the lowest achieved dose relative to their target dose experience markedly increased mortality, to a degree that is not compatible with a biologic effect of dose. The possibility of similar (albeit smaller) biases should be considered when analyzing observational data sets relating mortality to achieved dose of dialysis.

Practicing nephrologists are spending more time caring for end-stage renal disease (ESRD) and chronic kidney disease (CKD) patients. Despite this focus, and considerable advances in the understanding of those aspects of care that impact on clinical outcomes, morbidity, mortality, and quality of life for these patients has not improved substantially over the past decade. One of the possible explanations for this lack of progress is the structure of current nephrology training programs, where ESRD and CKD patient care is not emphasized. To address this issue, we developed a short preceptorship for second-year nephrology fellows, including didactic lectures and workshops. Of 67 participating fellows, 50% were from programs offering 3 or fewer months of exposure to outpatient hemodialysis, and 25% reported no exposure to peritoneal dialysis. Of more concern, 25% reported no "official rounds" with an attending nephrologist on dialysis patients. If nephrologists are to take their appropriate place as leaders of the care delivery team, nephrology fellowships must be restructured with appropriate emphasis placed on the comprehensive care of ESRD and CKD patients.

Background: Gender and body size have been associated with survival in hemodialysis populations. In recent observational studies, overall mortality was similar in men and women and higher in small patients. The effect of dialysis dose in each of these subgroups has not been tested in a clinical trial., Methods: The HEMO Study was a controlled trial of dialysis dose and membrane flux in 1846 hemodialysis patients followed up for 6.6 years in 15 centers throughout the United States. We examined the effect of dialysis dose on mortality and on selected secondary outcomes in subgroups of patients., Results: Adjusting for age only, overall mortality was lower in patients with higher body weight (P < 0.001), higher body mass index (P < 0.001), and higher body water content determined by the Watson formula (Vw) (P < 0.001), but was not associated with gender (P= 0.27). The RR of mortality comparing the high dose with the standard dose group was related to gender (P= 0.014). Women randomized to the high dose had a lower mortality rate than women randomized to the standard dose (RR = 0.81, P= 0.02), while men randomized to the high dose had a nonsignificant trend for a higher mortality rate than men randomized to the standard dose (RR = 1.16, P= 0.16). Analysis of both genders combined showed no overall dose effect (R = 0.96, P= 0.52), as reported previously. Vw was greater than 35 L in 84% of men compared with 17% of women. However, the RR of mortality for the high versus standard dose remained lower in women than in men after adjustment for the interaction of dose with Vw or with other size parameters, including weight and body mass index. Conversely, the dose effect was not significantly related to size parameters after controlling for the relationship of the dose comparison with gender., Conclusion: The data suggest that mortality and morbidity might be reduced by increasing the dialysis dose above the current standard in women but not in men. This effect was not explained by differences between men and women in age, race, or in several indices of body size. Because multiple comparisons were considered in this analysis, the role of gender on the effect of dialysis dose is suggestive and invites further study.

One of the most important advances in chronic dialysis therapy was the establishment of a method for determining delivered dose. There has been a meaningful relationship between higher delivered dialysis dose and improved outcome in the end-stage renal disease (ESRD) patient. The question of establishing a similar dialysis dose method in the patients with acute renal failure (ARF) is hampered with several specific issues to the ARF patient. The state of catabolism in ARF is not eubolic, but rather catabolic. Patient volume or urea space is highly variable among ARF patients and even within the same patient over very short periods of time. Finally, there are comorbidities that play a major role in both the ultimate patient outcome and the generation of many of the indicators used in dialysis dose generation. Thus, the mere transition from the ESRD dose methodology, where these issues are quite stable, to the ARF population is not an easy process. It is, however, of utmost importance that a dose methodology be established. Only after will we be able to address the dose/outcome relationship. The current article reviews what is known, what is theorized and what needs to be established in an effort to determine a dialysis dose methodology in ARF patients., (Copyright 2002 by the National Kidney Foundation, Inc.)

Increasing the frequency of hemodialysis increases its efficiency, which causes the popular dialysis yardstick, single-pool Kt/V, to underestimate the dose just as it overestimates the dose of less frequent dialysis. The frequency dependence of hemodialysis can be explained by examining solute kinetics. Several factors, including the logarithmic fall in solute concentration and solute disequilibrium within the patient, account for the improved efficiency of both daily hemodialysis and continuous peritoneal dialysis, but to fully explain the marked difference in clinical targets for dosing peritoneal versus hemodialysis, one must go outside the realm of urea kinetics. Solutes that dialyze easily, such as urea, but diffuse less readily within the patient, require a 2-compartment model to accurately predict their concentration profiles and to measure efficiency. When applied to appropriately selected solutes, the model can account for the difference in clinical targets and can explain the failure of other indices, such as middle molecule clearance, eKt/V, and EKR, to account for the differences. A cumulative toxic effect of these relatively secluded compounds might offer a better explanation of uremic toxicity and an objective rationale for increasing dialysis frequency and time. Simplified methods for measuring the dose of dialysis fail when the patient is treated more often than 3 times per week, but 2 new and independently derived methods that include parameters to account for the improved efficiency have been developed for measuring frequent dialysis. The new expressions of dose as a weekly analog of urea clearance are similar in magnitude and independent of frequency, giving present-day clinicians a choice of methods to compare 2 to 7 treatments per week. The kinetic behavior of solutes removed by dialysis and the new expressions of dose support the subjective improvement reported by patients, many of whom have embraced a transition to more frequent and prolonged hemodialysis., (Copyright 2001 by the National Kidney Foundation, Inc.)

Continuous venovenous hemofiltration (CVVH) is an effective form of renal replacement therapy for acute renal failure (ARF) that offers greater hemodynamic stability and better volume control than conventional hemodialysis in the critically ill, hypotensive patient. However, the application of CVVH in the intensive care unit (ICU) has several disadvantages, including intensive nursing requirements, continuous anticoagulation, patient immobility, and expense. We describe a new approach to the treatment of ARF in the ICU, which we have termed extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42 patients: 25 patients were treated with EDD for a total of 367 treatment days, and 17 patients were treated with CVVH for a total of 113 days. Median treatment time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile) versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial blood pressures (MAPs) did not differ significantly for patients treated with EDD when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P = 0.078), midway through daily treatment (70 versus 68 mm Hg for CVVH; P = 0.083), or at the end of treatment (71 versus 69 mm Hg for CVVH; P = 0.07). Net daily ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000 mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P = 0.514). Anticoagulation requirements were significantly less for patients treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus 21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P < 0.001). We found that EDD eliminated the need for constant supervision of the dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage more than one treatment. Overall, EDD was well tolerated by the majority of patients, offered many of the same benefits provided by CVVH, and was technically easier to perform.

Background: The volume of urea distribution (V) is usually derived from single-pool variable volume urea kinetics. A theoretical analysis has shown that modeled single-pool V (Vsp) is overestimated when the urea reduction ratio (URR) is greater than 65 to 70% and is underestimated when the URR is less than 65%. The "true" volume derived from double-pool kinetics (Vdp) does not exhibit this effect. An equation has been derived to adjust Vsp to the expected Vdp., Methods: To validate these theoretical predictions, we examined data from the Hemodialysis (HEMO) Study to assess the performance of Vdp as estimated from Vsp using the previously published prediction equation. For increased precision, both Vsp and Vdp were factored by anthropometric volume (Va). Patients were first dialyzed with a target equilibrated dialysis dose (eKt/V) of 1.45 during a baseline period and were then randomly assigned to eKt/V targets of either 1. 05 (a URR of approximately 67%) or 1.45 (a URR of approximately 75%). A blood sample was obtained one hour after starting dialysis during one dialysis in each patient., Results: Vsp/Va was (mean +/- SD) 1.014 +/- 0.127 in 795 patients during the baseline period when the URR was approximately 1.45. During the first modeled dialysis after randomization, the Vsp/Va fell to 0.961 +/- 0.138 in the group with an eKt/V target of 1.05, but did not change significantly under the high eKt/V goal. The correction of Vsp to Vdp using the prediction equation resulted in a Vdp/Va ratio of 0.96 to 0.98 in all three circumstances without significant differences. When a blood sample was drawn one hour after starting dialysis, the apparent Vsp/Va ratio at one hour was much lower at 0.708 +/- 0.139. However, the mean Vdp/Va ratio, computed using the correction equation, was 0.968 +/- 0.322, which was similar to the Vdp/Va ratio calculated from the postdialysis blood urea nitrogen., Conclusions: These data suggest that the previously derived formula for adjusted Vsp is valid experimentally. The Vsp/Vdp correction should be useful for prescribing hemodialysis with either a very low Kt/V (for example, daily and early incremental dialysis) or a very high Kt/V.

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.

Cardiovascular disease is the leading cause of mortality in patients whose lives depend on hemodialysis. We developed a method for measuring cardiac output (CO) and central blood volume (CBV) in hemodialyzed patients that may help to elucidate the mechanisms and consequences of cardiac disease in this population. This report describes the technique, focusing on the main sources of error and how they can be prevented. Three principal sources of error were identified: (1) access recirculation (existing or induced during injection); (2) the second pass of the indicator through the cardiopulmonary system, exacerbated by prolonging the duration of intravenous injection; and (3) the transit time of the indicator through the dialysis blood lines. After the algorithms were adjusted to prevent the above errors, the reproducibility of CO and CBV, expressed as the absolute percent deviation from the average of duplicates (3,488 values duplicated within 5 minutes), was 4.3 +/- 3.8% for CO and 4.1 +/- 3.8% for CBV. To determine the clinical value of routine CO and CBV measurements, morbid events (nausea, vomiting, and/or muscle cramps) were prospectively recorded in 73 randomly selected hemodialysis patients. CO and CBV were measured near the beginning and near the end of 98 dialysis sessions during which 28 morbid events were identified. In 10 of these sessions, where morbid events took place within 30 minutes of the measurements, CBV appeared to be a more sensitive indicator of morbid events than CO. We conclude that CO and CBV can be routinely and reliably measured during hemodialysis if precautions are taken to avoid specifically identified sources of error. Preliminary studies suggest that these measurements may have significant prognostic value.

Background: The postdialysis blood urea nitrogen (BUN; Ct) is a pivotal parameter for assessing hemodialysis adequacy by conventional blood-side methods, but Ct is relatively unstable because of hemodialysis-induced disequilibrium. The uncertainty associated with this method is potentially reduced or eliminated by measuring urea removed on the dialysate side, a more direct approach that can determine adequacy from the fraction of urea removed and by substituting an estimate of the equilibrated postdialysis BUN (Ceq) for Ct. For a patient with a known urea volume (V), Ceq, the equilibrated Kt/V (eKt/V), and the solute removal index (SRI) can be calculated from the predialysis BUN (C0), total urea nitrogen removed (A), and V from simple mass balance calculations (dialysate/volume method). However, a theoretical error analysis showed that relatively small errors in A, C0, or V are magnified when SRI or eKt/V is calculated using this method, especially at higher eKt/V values (for example, if eKt/V = 1.4 per dialysis, a 7% dialysate collection error causes a 20% error in eKt/V)., Methods: During three to four baseline dialyses in each of 39 patients enrolled in the pilot phase of the HEMO Study, "A" was measured using an instrument that sampled dialysate frequently (Biostat), and V was calculated from A, C0, and Ceq (median CV for V = 5.6%). The mean V was then applied to the dialysate/volume method to estimate eKt/V and SRI during two to five subsequent dialyses per patient (comparison dialyses). The accuracy and precision of these estimates were assessed by comparing them with eKt/V and SRI derived from a direct measurement of Ceq drawn 30 minutes after dialysis (reference method), from mathematical curve-fitting of sequential dialysate urea concentrations (dialysate curve-fit method), and from another blood-side method that estimates eKt/V from single pool Kt/V and the fractional rate of solute removal (rate method): eKt/V = spKt/V - 0.6.K/V + 0.03., Results: During 128 comparison dialyses, median absolute errors for calculated eKt/V compared with the reference method were 0.169, 0.061, and 0.071 for the dialysate/volume method, the rate method, and the dialysate curve-fitting method, respectively. The corresponding correlation coefficients were 0.47, 0.88, and 0.81. For SRI, median absolute errors were 0.044, 0.018, and 0.027, and the correlation coefficients were 0.54, 0.85, and 0.74 for the three methods., Conclusions: The precision of eKt/V and SRI measurements was significantly lower for the dialysate/volume method compared with the blood-side methods. Inclusion of the dialysate curve analysis provided by the Biostat restored precision to the dialysate method to a level comparable to that of the blood-side methods. New techniques employing dialysate urea analysis should include a concentration profile to avoid these inherent methodological errors and assure the accuracy of eKt/V and SRI.

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.

The Hemodialysis (HEMO) Study is a multicenter, prospective, randomized, 2 x 2 factorial clinical trial designed to evaluate the efficacy of the dose of dialysis delivered ("standard" v "high") and dialysis membrane flux ("low" v "high") in reducing the morbidity and mortality of patients. The study is nearly half complete. Although both patients and investigators are blinded to the overall findings, which will not be available for another 3 years, important data have been generated from which a more accurate expression has been derived for the dose of dialysis received by each patient in the trial. This new expression of the effectiveness of dialysis, eKt/V, is a two-pool approximation derived from the traditional single-pool Kt/V (spKt/V) and time on dialysis. The dialysis prescription for the HEMO Study subjects is individualized to achieve the target dose for each patient and is closely monitored by measuring the more accurate and validated expression of eKt/N. Comparisons of the HEMO Study dose of dialysis with other studies have been confused by this unique expression (eKt/V) of the dialysis dose and adequacy adopted for the HEMO Study. The target eKt/V dose in the "standard" arm of the Study is 1.05 and in the "high" arm is 1.45 per dialysis thrice weekly. Based on data available from 426 subjects randomized to each arm, the target of 1.05 in the "standard" dose of the HEMO Study is equivalent to an spKt/V of 1.32, and that of the "high" dose, 1.67. Thus, volunteers in the "standard" arm of the Study are receiving a tightly controlled and closely monitored dose, which is above the current national mean spKt/V, and above that of the accepted minimum standard spKt/N of 1.2. When completed, the HEMO Study will show whether there are merits of a tightly controlled hemodialysis dose that is consistently delivered over a prolonged period and whether a high dose is beneficial and safe to prescribe.

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.

Background: Fiber bundle volume (FBV), the space within the blood compartment of hollow fiber dialyzers, may decrease during treatment due to clotting. The clots may be flushed out of the dialyzer prior to measurements of FBV by dialyzer reprocessing equipment and a significant drop in FBV during the session may go unrecognized., Methods: FBV was measured (1) from the transit time of a saline bolus passing through the dialyzer as recorded by ultrasound dilution sensors placed on the arterial and venous blood lines; (2) from the change in blood concentration induced by a step change in the rate of ultrafiltration as recorded by the venous sensor., Results: In vitro FBV ranged from 47 to 121 ml. Paired absolute differences between the ultrasound and volumetric measurements (flushing saline out of the dialyzer into a graduated cylinder) were 0.16 +/- 4.23% (N = 42) and 2.10 +/- 7.26% (N = 13) for the bolus and ultrafiltration methods, respectively. In vivo reproducibility of the bolus and ultrafiltration methods were 2.65 +/- 2.11% (N = 122) and 3.79 +/- 3.93% (N = 32), respectively. During 31 treatments the FBV by dilution showed an average decrease of 4.17 +/- 8.60%, and in 6 cases FBV fell more than 10%, while measurements of the same FBV by reuse equipment showed an increase of 0.99 +/- 5.82%, P < 0.01., Conclusions: FBV measured by the dilution methods was accurate and reproducible. Preliminary results suggest that in vivo FBV may differ significantly from results reported by reprocessing machines.

The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean +/- SD eKt/V for patients randomized to these targets was 1.14 +/- 0.11 and 1.52 +/- 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 +/- 0.11 and 1.50 +/- 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling.