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One proposed threshold ultrafiltration rate (UFR) of concern in hemodialysis patients is 13 ml/h per kg. We evaluated associations among UFR, postdialysis weight, and mortality to determine whether exceeding such a threshold would result in similar levels of risk for patients of different body weights.Data were analyzed in this retrospective cohort study for 1 year following dialysis initiation (baseline) and over 2 years of follow-up in incident patients receiving thrice-weekly in-center hemodialysis. Patient-level UFR was averaged over the baseline period. To investigate the joint effect of UFR and postdialysis weight on survival, we fit Cox proportional hazards models using bivariate tensor product spline functions, adjusting for sex, race, age, diabetes, and predialysis serum albumin, phosphorus, and systolic blood pressure (BP). We constructed contour plots of mortality hazard ratios (MHRs) over the entire range of UFR values and postdialysis weights.In the studied 2542 patients, UFR not scaled to body weight was strongly associated with MHR, whereas postdialysis weight was inversely associated with MHR. MHR crossed 1.5 when unscaled UFR exceeded 1000 ml/h, and this relationship was largely independent of postdialysis weight in the range of 80 to 140 kg. A UFR warning level associated with a lower MHR of 1.3 would be 900 ml/h, whereas the UFR associated with an MHR of 1.0 was patient-size dependent. The MHR when exceeding a UFR threshold of 13 ml/h per kg was dependent on patient weight (MHR = 1.20, 1.45, and2.0 for a 60, 80, and 100 kg patient, respectively).UFR thresholds based on unscaled UFR give more uniform risk levels for patients of different sizes than thresholds based on UFR/kg.

Background To what extent hemodiafiltration (HDF) improves management of hyperphosphatemia over hemodialysis (HD) is a subject of ongoing investigation. Methods We modified a previously described phosphate kinetic model to include incorporation of EUDIAL recommended equations for hemodiafiltration (HDF) clearance. We used the model to predict the recovery of phosphate from spent dialysate/hemofiltrate and compared this with averaged data from five published studies. Mean study average predialysis serum phosphate was 1.81 ± 0.20 mmol/L. Session length was close to 240 min per treatment. All HDF was done postdilution, at an average rate of 65 ± 24 mL/min. Results Measured mean phosphate removal was 1039 ± 136 mg (33.5 ± 4.41 mmol, slightly lower than the model-predicted mean value of 1092 ± 127 mg (35.3 ± 4.09 mmol). The measured ratio of phosphate removal with HDF compared with HD averaged 1.15 ± 0.22, ranging from 1.01 to 1.44. Using mean study input parameters for patient size and treatment characteristics, the predicted ratio of phosphate removal with HDF compared with HD averaged 1.095 ± 0.029, ranging from 1.05 to 1.13. Conclusions Addition of EUDIAL-recommended convective clearance equations to a phosphate kinetic model predicts a 10% or greater benefit in terms of phosphate removal for HDF compared with HD at typical dialysis and hemodiafiltration treatment settings. These predictions are similar to the HDF advantage reported in the literature in studies where phosphate removal has been measured in spent dialysate.

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.

Objective Normalized creatinine generation rate (CGRn) can be computed for a variety of dialysis schedules using a recently described kinetic modeling program. However, the availability of estimating equations might facilitate broader study of this metric. We developed equations to estimate CGRn based on modeling and then tested them against modeled CGRn values in the Frequent Hemodialysis Network Nocturnal Trial baseline (3/week) dataset. Design and Methods We used a "what-if" derivation of a previously published variable volume 2-pool creatinine kinetic model to generate predicted predialysis values of serum creatinine that would result from creatinine generation rates of 250–2000 mg/day in patients with creatinine distribution volumes of 20 to 50 L, dialyzed from 60 to 480 min per treatment three times a week. Then, in patients with residual kidney function, we calculated an "anuric expected predialysis serum creatinine value" before applying the same equations. We then compared estimated CGRn values as predicted by this approach with modeled values in patient data from the Frequent Hemodialysis Network Nocturnal Trial. Results The estimating equations for CGRn yielded results similar to those obtained with formal modeling, in both anuric patients and those with residual kidney function, with mean percent error of 0.845 ± 6.15 (SD) in anuric patients, and ‒0.29 ± 4.90 in patients with a mean creatinine clearance of 5.44 ± 4.82 mL/min, with R-squared values of 0.96 in both anuric patients and those with residual renal clearance of creatinine. Conclusions In patients dialyzed 3/week, CGRn can be estimated using prediction equations. Use of these equations may facilitate broader investigation of CGRn as a measure of nutritional status and outcome.

Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described.We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of100 mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period. Urine was collected for 24 hours prior to the midweek treatment session and concentrations of urea, creatinine, and phosphate were measured.Thirty-eight patients (24 men, 14 women) with a mean age of 70.4 ± 12.4 (SD) years were included in this analysis. All patients were dialyzed 3 times per week with mean treatment duration of 243 ± 7.89 minutes. Twenty patients were undergoing hemodiafiltration and 18 patients high-flux hemodialysis. In total, 102 dialysis sessions, of which 52 were hemodiafiltration, and urine collections were analyzed. Mean urine volume was 457 ± 254 mL per 24 hours. Residual renal clearance rates of urea (Kr Urea), creatinine (Kr Cr), and phosphate (Kr Phos) were 1.60 ± 0.979, 4.69 ± 3.79, and 1.98 ± 1.36 mL/minute, respectively. Mean ratios of Kr Cr/Kr Urea, Kr Phos/Kr Urea, and Kr Phos/Kr Cr were 2.83 ± 1.21, 1.23 ± 0.387, and 0.477 ± 0.185, respectively. There was a modest correlation between Kr Phos and daily urine volume (r = 0.605, P = .001).In maintenance hemodialysis and hemodiafiltration patients, residual renal phosphate clearance is approximately 23% higher than residual renal urea clearance. Urine volume is a modestly accurate surrogate for estimating residual renal phosphate clearance, but only when urine volume is300 mL/day.

Rationale & Objectives Conventional monitoring of hemodialysis dose is implemented using urea kinetic modeling based on single-pool Kt/V, which requires both pre- and postdialysis serum urea nitrogen (SUN) measurements. We compared this conventional approach to one in which Kt/V is calculated using conductivity clearance, thereby reducing the need for regular postdialysis SUN measurements. Study Design Comparative study of 2 diagnostic tests. Setting & Participants Prevalent patients receiving maintenance hemodialysis for at least 2 years for whom both urea reduction ratio (URR) and average conductivity clearance (Kecn) were measured. Tests Compared During the initial 8 months (baseline interval), average Kecn and URR were used to calculate a median patient-specific, modeled, calibration solute distribution volume (Vcal). During months 9 to 16 (period 1) and 17 to 24 (period 2), Kt/V was conventionally computed using URR and also by a new method using Vcal and Kecn without postdialysis SUN values. We examined the percentage error between these 2 methods of calculating Kt/V. Outcomes Concordance between the 2 methods of calculating Kt/V. Results Among 1,093 patients, mean individual-level median single-pool Kt/V values derived using the conventional method during the baseline interval, period 1, and period 2 were 1.62±0.24 (SD), 1.66±0.24, and 1.67±0.24, respectively. During periods 1 and 2, patient-level median Kt/V values derived using Kecn were 1.64±0.24 and 1.65±0.24, respectively. Percent differences between patient-level median values of Kt/V (conductivity minus conventional URR methods) were−0.63%±7.7% and−0.75%±8.4% for periods 1 and 2. Normalized protein nitrogen appearance were comparable between the 2 methods. Limitations Data were collected over 2 years. Study was limited to in-center hemodialysis patients dialyzed 3 times per week. Dialysis session length was not adjusted for treatment interruptions. Conclusions A new method of calculating Kt/V based on Kecn that requires fewer postdialysis SUN measurements provided diagnostic data comparable to those from conventional use of URR and has the potential to avoid errors related to postdialysis blood sampling and measurement.

Dialyzer manufacturers characterize performance of their devices based on measurements of clearance using crystalloid solutions. Typically, in vitro dialyzer mass transfer area coefficients for urea (K0A) are substantially higher than values measured in vivo. The reason for this reduction has not been clearly determined. We hypothesized that the known effect of viscosity on reducing solute diffusivity might partially or fully account for this reduction. In vitro dialyzer clearances of urea, glucose, and lactate were measured using crystalloid solutions as well as bovine blood with varying hematocrit and plasma viscosity under a wide range of operating conditions. Viscosities of crystalloid solutions, of blood plasma, and of whole blood were measured at 37°C at a shear rate of 100/s. Diffusivity and relative K0A values (K0Arel) in eight dialyzers were computed for each solute under these different conditions. Plasma was 1.84 times more viscous compared with crystalloid solution (ηrel = 1.84), suggesting a correction multiplier of 1/ηrel = 0.54 for in vivo K0A relative to the in vitro value. Experimental K0Arel at that ηrel was on average reduced to 52% of crystalloid in vitro K0A values. The multiplier 0.52 measured in this study is close to the multiplier 0.55 predicted for average plasma viscosities and also close to the multiplier 0.54 assumed for urea kinetic modeling to provide reasonable urea distribution volumes. The known effect of viscosity on solute diffusivity is therefore sufficient to explain the reduction in dialyzer K0A for urea and glucose in vivo compared with in vitro measurements.

It is now well established that higher ultrafiltration (UF) rates during a hemodialysis session are associated with a higher propensity to intradialytic hypotension, cardiac stunning, and mortality ([1][1],[2][2]). These associations have been derived from observational dataset reports, with all of

Background Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study. Methods Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance. Results Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models. Conclusion In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction. Electronic supplementary material The online version of this article (10.1186/s12882-018-0951-0) contains supplementary material, which is available to authorized users.

Each year approximately 13,000 Veterans transition to maintenance dialysis, mostly in the traditional form of thrice-weekly hemodialysis from the start. Among >6000 dialysis units nationwide, there are currently approximately 70 Veterans Affairs (VA) dialysis centers. Given this number of VA dialysis centers and their limited capacity, only 10% of all incident dialysis Veterans initiate treatment in a VA center. Evidence suggests that, among Veterans, the receipt of care within the VA system is associated with favorable outcomes, potentially because of the enhanced access to healthcare resources. Data from the United States Renal Data System Special Study Center "Transition-of-Care-in-CKD" suggest that Veterans who receive dialysis in a VA unit exhibit greater survival compared with the non-VA centers. Substantial financial expenditures arise from the high volume of outsourced care and higher dialysis reimbursement paid by the VA than by Medicare to outsourced providers. Given the exceedingly high mortality and abrupt decline in residual kidney function (RKF) in the first dialysis year, it is possible that incremental transition to dialysis through an initial twice-weekly hemodialysis regimen might preserve RKF, prolong vascular access longevity, improve patients' quality of life, and be a more patient-centered approach, more consistent with "personalized" dialysis. Broad implementation of incremental dialysis might also result in more Veterans receiving care within a VA dialysis unit. Controlled trials are needed to examine the safety and efficacy of incremental hemodialysis in Veterans and other populations; the administrative and health care as well as provider structure within the VA system would facilitate the performance of such trials.

Author(s): Obi, Yoshitsugu; Kalantar-Zadeh, Kamyar; Streja, Elani; Daugirdas, John T | Abstract: BackgroundThe purpose of the study was to explore the precision of an equation designed to estimate residual kidney urea clearance (KRU) from interdialytic urine collection data and pre-hemodialysis (HD) serum urea nitrogen (SUN) in different hemodialysis treatment schedules.MethodsThe generalizability of the proposed equation was tested in 32 731 HD treatments where urine was collected prior to a dialysis session, mostly for 24 h but sometimes longer, in patients being dialyzed 1-4 times/week.ResultsThe residual kidney urea clearance estimating equation predicted a KRU that matched the one computed by formal modeling within 5% in g98% of sessions analyzed. The errors in estimated versus modeled KRU for interdialytic intervals (IDIs) of 2, 3, 4 and 7 days, were 1.6 ± 1.5%, -0.4 ± 1.6%, 0.9 ± 1.6%, and 1.5 ± 1.2%, respectively. Percent errors were similar for schedules of 1-4/week with the exception of urine collection during the 2-day interval of a 2:5-day twice-weekly schedule; here error averaged 5.0 ± 1.2%. Use of the average of the SUN values at the start and end of the collection period overestimated modeled KRU by 11.3 ± 4.5%, whereas an equation suggested by others underestimated modeled KRU by -9.9 ± 3.4%.ConclusionsThe equation tested predicts values for KRU that are similar to those obtained from formal urea kinetic modeling, with percent errors that only rarely exceed 5%. It gives relatively precise results for a wide range of HD treatment schedules, IDIs and urine collection periods.Keywordschronic hemodialysis, clearance, guidelines, hemodialysis, predialysis.

Hemodialysis treatment time and Kt/V can both be considered to be primary measures of hemodialysis adequacy, because when either goes to zero, mortality is certain in patients without residual kidney function. Treatment time is important, but it needs to be adjusted based on surface-area-normalized Kt/V, residual kidney function, and expected ultrafiltration rate. Rescaling dose of dialysis measured as Kt/V to body surface area prevents ultrashort dialysis in small patients, women, and children with minimal residual kidney function. Most if not all of the observational studies of associations between outcome and dialysis session length are probably confounded by dose targeting bias. Once adequate Kt/V (taking into account body surface area) has been provided, adequate dialysis time probably is most relevant in terms of limiting the need for a high fluid removal rate. The latter may adversely impact survival by causing recurrent ischemia to cardiovascular and other tissues. There is little high-quality evidence at this time to support a minimum 4-hour treatment time for all patients, regardless of body size, solute removal, or residual kidney function. On the other hand, there is little evidence that prolonging weekly treatment time up to 24 hours per week is harmful. The final decision regarding treatment time is best individualized, based on patient acceptability and experience, residual kidney function, body surface-area-normalized Kt/V, and expected ultrafiltration rate.

The association between higher ultrafiltration rates and poor outcomes in hemodialysis patients has received increased attention, to the point that various regulatory entities are considering adding ultrafiltration rate as a quality measure to be monitored and controlled. Most of the discussion to date has focused on ultrafiltration rate scaled to body weight, or more correctly, body mass (ml/hour per kg). One outcome study suggests that ultrafiltration rate might best be not scaled at all to body size, as modestly higher ultrafiltration rate in very small-size patients may be associated with some survival benefit, probably via increased dietary intake. Outcomes studies also suggest that the risk of exceeding a weight-scaled ultrafiltration target may be magnified in very large patients, and that body weight-scaled ultrafiltration targets in such patients should be set a lower level. Here, we present an analysis, based on physiological hemodynamic arguments, that it would be better to scale ultrafiltration rate to body surface area rather than to body mass. Whatever ultrafiltration rate is scaled to, attempts to restrict ultrafiltration rate by limiting interdialytic weight gain in small, possibly malnourished patients, should be done cautiously, to prevent an inadvertent lowering of intake of calories and dietary protein.

Both urine volume and residual kidney clearances are known to increase over the course of an interdialytic interval. However, no strategy has been proposed for adjusting data from an interdialytic urine collection to a weekly value for urine flow rate or residual kidney urea clearance. Data from a reanalysis of published results allows a proposal for such an adjustment, which assigns a relative value to each dialysis day of the week based on its distance from a preceding hemodialysis treatment. The strategy also identifies which urine collection periods and interdialytic intervals give results that should be most representative of weekly average values.

Background Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established. Methods To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients. Results The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care. Conclusions Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.

In the most simple analysis, a patient's hematocrit during hemodialysis will rise when the rate of ultrafiltration exceeds the rate at which the fluid is mobilized from extravascular spaces; the greater the rise in hematocrit, the lower blood volume is and the more likely intradialytic hypotension (IDH) is to occur. A secondary mechanism of IDH may be due to sudden shift of blood volume away from the heart under conditions of borderline cardiac filling. A substantial portion of blood volume resides in the splanchnic venous system. During the early part of dialysis, a centripetal shift of red cells from this anatomical region to the central circulation has been documented to occur. The magnitude of this shift is unpredictable, and it may depend on the level of splanchnic vasoconstriction predialysis. The amount of splanchnic shift may also be reduced in patients with autonomic dysfunction. Once this central shift in blood volume has occurred, it can be reversed during further ultrafiltration due to ischemia-induced release of vasodilatory molecules that cause dilation of upstream splanchnic arterioles; this causes increased transmission of arterial pressure to the splanchnic veins, acutely increasing their capacity. The increased splanchnic venous capacity may cause a sudden shift of blood away from the central circulation to fill these veins under conditions where cardiac filling has already been reduced. The result can be severe IDH due to insufficient cardiac filling and cardiac output. One fruitful preventive approach might be to continuously monitor the blood or dialysate for the sudden appearance of such ischemia-related molecules or other signals which may herald not only dialysis hypotension but tissue stunning, warning that the fluid removal rate should be immediately reduced.

Background: Control of predialysis serum phosphorus in hemodialysis patients is challenging. We explored the utility of a novel kinetic phosphorus modeling program. Methods: As part of a quality assurance program, urea kinetic modeling results were combined with those from phosphorus kinetic modeling to compute modeled daily ingested phosphorus (DIP) and components making up this metric, including absorbed, bound, and nonabsorbed, nonbound phosphorus. Results: In 182 hemodialysis patients, DIP averaged 1,089 ± 348 mg/day in men and 934 ± 292 in women (p < 0.002) and correlated substantially with body weight. DIP/kg bodyweight (12.8 ± 3.40 mg/kg) was not significantly different between the sexes. Prescribed equivalent binder dose (EBD) was 4.98 ± 3.61 and 4.53 ± 3.02 g/day in men and women, respectively (p NS). Protein catabolic rate (PCR) was significantly higher in men (64.4 ± 18) g/day vs. women (48.2 ± 15.6, p < 0.001), and the DIP/PCR ratio was 17.4 ± 4.81 in men vs. 20.1 ± 5.76 in women (p < 0.001). Presence of residual kidney function was associated with a lower prescribed EBD dose (4.08 ± 2.62 vs. 5.38 ± 3.81 g/day, p < 0.01). Self-reported poor binder compliance was associated with higher DIP or DIP/kg as well as higher prescribed EBD. In anuric patients, DIP/kg was increased in patients consuming diets with high phosphate additive content and those reporting poor compliance with the prescribed dose of phosphate binders. Conclusions: The combination of urea kinetic and phosphorus modeling can be used to estimate measures related to phosphorus intake. High DIP/PCR or DIP/kg body weight values in anuric patients suggest consumption of a diet high in phosphorus additives or noncompliance with the prescribed amount of phosphorus binders.

Many dialysis machines can compute dialyzer sodium clearances at multiple time points during a dialysis treatment using conductivity. For a given treatment, the average dialyzer sodium clearance (K), when combined with treatment time (t), and the estimated urea distribution volume (V, usually based on either anthropometry or bioimpedance), can be used to estimate Kt/V, an important measure of hemodialysis adequacy. While this conductivity-derived value for Kt/V correlates moderately with Kt/V calculated from predialysis and postdialysis serum urea nitrogen (SUN) values (urea reduction ratio, URR), the ultrafiltration volume, and session length it is, unfortunately, not sufficiently accurate to replace URR-based Kt/V. Here we underline the potential utility of an alternative method to estimate Kt/V (a variant of a technique originally proposed by Gotch and Levin and their colleagues) using conductivity-derived sodium clearance (K) that does not require routine measurement of the postdialysis SUN but which should closely track Kt/V computed in the usual fashion. The increased accuracy with the new method is explained by the use of a patient-specific value of V, which is an average value calculated from several dialysis sessions where both conductivity dialyzer clearance and predialysis and postdialysis SUN have been measured. Once this patient-specific conductivity/URR-based value for V has been determined, it can be used to calculate Kt/V for subsequent treatments in which conductivity-based dialyzer clearances are measured, but around which predialysis and postdialysis SUN values have not been obtained. (If the predialysis SUN values for such a subsequent treatment are also measured, then a normalized protein catabolic rate that closely tracks the value from conventional urea modeling, can also be determined.) By reducing the number of postdialysis SUN measurements needed to monitor hemodialysis adequacy this new method of estimating Kt/V by conductivity should save staff time and laboratory costs, increase patient and staff safety, and decrease error rates associated with improper postdialysis blood sampling technique.

A thorough understanding of renal physiology, and in particular acid-base physiology, is essential for an understanding of nephrology. Difficulties in both teaching and learning this material are major impediments to attracting medical trainees into nephrology. Approaches to teaching renal physiology include collaborative learning, computer-based learning and laboratory-based learning. Computer-based learning applications are becoming increasingly popular and can be useful, but are most successful when they incorporate interactive components. Students also note that the presence of a live instructor remains desirable. Some concepts of renal and in particular acid-base physiology can be taught using structured self-experimentation, a practice with a long tradition that possibly should be revitalized.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for all stages of chronic kidney disease (CKD) and related complications since 1997. The 2015 update of the KDOQI Clinical Practice Guideline for Hemodialysis Adequacy is intended to assist practitioners caring for patients in preparation for and during hemodialysis. The literature reviewed for this update includes clinical trials and observational studies published between 2000 and March 2014. New topics include high-frequency hemodialysis and risks; prescription flexibility in initiation timing, frequency, duration, and ultrafiltration rate; and more emphasis on volume and blood pressure control. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research.

Background: Changes in plasma volume during hemodialysis are complex and have been shown to depend on the rate of fluid removal and the degree of fluid overload. We examined changes in total protein concentration during and shortly after a dialysis treatment in archived data from the HEMO study. Methods: During follow-up months 4 and 36 of the HEMO study, additional blood samples were obtained during a typical dialysis session at 30 and 60 min after dialysis. In 315 studies from 282 patients where complete data were available, we calculated the concentration change in total protein and compared it to the modeled change in both total body water and extracellular fluid space as derived from 2-pool urea kinetic modeling. Results: The mean postdialysis modeled urea volume (V) was 31.1 ± 6.18 L. Mean fluid removal was 2.76 ± 1.27 kg, over a session length of 207 ± 28 min. The ratio of predialysis V to postdialysis V averaged 1.090 ± 0.040. The mean TP ratios (post/pre) at 0, 30, and 60 min postdialysis averaged 1.121 ± 0.070 (SD), 1.091 ± 0.090, and 1.091 ± 0.086. The dialysate to serum sodium gradient, studied in a different group of treatments where this information was available, had no impact on these findings, nor did the length of the interdialytic interval. Conclusions: On average, after equilibration, the change in plasma volume due to fluid removal is similar to the modeled change in total body water (urea space), irrespective of dialysate to serum sodium gradient. This supports previous observations that during dialysis with ultrafiltration, plasma volume contracts to a lesser degree than the interstitial volume and that some fluid may be removed from spaces other than the extracellular fluid.

The control of serum phosphorus by dialysis is made difficult by the fact that intradialytic blood levels tend to be low, and because phosphorus is removed almost exclusively from the plasma during its passage through the dialyzer. The most practical way to increase phosphorus removal is to extend dialysis time, although attention to dialysis efficiency (surface area, advanced membrane, and higher blood and dialysate flow rates) also plays a role. Benefits of hemodiafiltration in helping control serum phosphorus have been claimed, but not found in all studies. Because serum phosphorus levels tend to plateau during the later parts of a dialysis session, extending weekly dialysis time is of greater benefit for phosphorus removal than for urea removal. Increasing dialysis frequency also probably has a small benefit. It appears that 18-30 hours of dialysis per week are required to obviate the need for phosphorus binders. Several promising models of phosphorus kinetics are under development. These may help predict the change in treatment on serum phosphorus levels, but their ability to do so has not yet been critically assessed.

Removal of small molecular weight solutes shows a strong relationship to hemodialysis outcomes. In contrast, survival with high-flux dialysis or hemodiafiltration is only slightly better than with low-flux hemodialysis. Despite laboratory evidence regarding toxicity of protein-bound uremic solutes, few data exist showing that increased removal of this class of molecules impacts outcomes. In the FHN trials, there was no effect of frequent dialysis, including frequent and long dialysis, on nutrition or control of anemia, outcomes expected to be sensitive to uremic toxin removal; the main benefit appeared to be better volume control. Scaling of hemodialysis dose to total body water may not be optimal. Kt/V scaling to body surface area and use of a continuous measure such as standard Kt/V reduces the likelihood of underdialysis of small patients, including children, and women. Minimum hemodialysis time may best be considered in respect to ultrafiltration rate, and a maximum target ultrafiltration rate unscaled to body size may be optimal. Intensive, extended dialysis may cause adverse effects to residual kidney function, and more information needs to be collected to better understand how urine volume modifies dose requirements, and how to maximize the chances of preserving residual kidney function.

Background Few data are available regarding the long-term mortality rate for patients receiving nocturnal home hemodialysis. Study Design Posttrial observational study. Setting & Participants Frequent Hemodialysis Network (FHN) Nocturnal Trial participants who consented to extended follow-up. Intervention The FHN Nocturnal Trial randomly assigned 87 individuals to 6-times-weekly home nocturnal hemodialysis or 3-times-weekly hemodialysis for 1 year. Patients were enrolled starting in March 2006 and follow-up was completed by May 2010. After the 1-year trial concluded, FHN Nocturnal participants were free to modify their hemodialysis prescription. Outcomes & Measurements We obtained dates of death and kidney transplantation through July 2011 using linkage to the US Renal Data System and queries of study centers. We used log-rank tests and Cox regression to relate mortality to the initial randomization assignment. Results Median follow-up for the trial and posttrial observational period was 3.7 years. In the nocturnal arm, there were 2 deaths during the 12-month trial period and an additional 12 deaths during the extended follow-up. In the conventional arm, the numbers of deaths were 1 and 4, respectively. In the nocturnal dialysis group, the overall mortality HR was 3.88 (95% CI, 1.27-11.79; P =0.01). Using as-treated analysis with a 12-month running treatment average, the HR for mortality was 3.06 (95% CI, 1.11-8.43; P =0.03). Six-month running treatment data analysis showed an HR of 1.12 (95% CI, 0.44-3.22; P =0.7). Limitations These results should be interpreted cautiously due to a surprisingly low (0.03 deaths/patient-year) mortality rate for individuals randomly assigned to conventional home hemodialysis, low statistical power for the mortality comparison due to the small sample size, and the high rate of hemodialysis prescription changes. Conclusions Patients randomly assigned to nocturnal hemodialysis had a higher mortality rate than those randomly assigned to conventional dialysis. The implications of this result require further investigation.

In women, children, and smaller adults, dialysis adequacy targets based solely on Kt/V might result not only in shorter treatments with inadequate fluid removal and undesirably rapid ultrafiltration rates, but also in less than optimal removal of small and middle molecular weight solutes if fractional removal is considered in relation to body surface area. The outcomes evidence for this is not definitive, but is suggested by a prespecified secondary analysis of the randomized HEMO trial results, and is supported by observational data. Also, there is evidence from normal renal physiology that in healthy humans of different body size, glomerular filtration rate (GFR) scales more closely to body surface area than to total body water. With these factors in mind, time on HD may need to be greater than that predicted by standard KT/V measurements to maximize survival in women and in smaller patients.

The association of adult height with mortality has been extensively investigated in the general population, but little is known about this relationship among dialysis patients. We explored the relationship between height and mortality in a retrospective cohort study of 1,171,842 adults who began dialysis in the United States from 1995 to 2008 and were followed until December 31, 2010. We evaluated height-mortality associations in sex-specific quintiles of increasing height (Q1–Q5) using multivariable Cox regression models adjusted for demographics, comorbid conditions, lifestyle and disability indicators, socioeconomic status, and body weight. For men, compared with the referent quintile (Q1

Measurement of small molecule clearance remains important in the clinical care of patients requiring long-term dialysis. Many patients maintain a significant degree of residual native kidney function and may have nontraditional schedules with or without combined dialysis modalities. In this review, we examine and outline methods for comparing small molecule clearances among various dialysis prescriptions and modalities, with inclusion of residual kidney urea clearance.

An international group of around 50 nephrologists and scientists, including representatives from large dialysis provider organisations, formulated recommendations on how to develop and implement quality assurance measures to improve individual hemodialysis patient care, population health and cost effectiveness. Discussed were methods thought to be of highest priority, those clinical indicators which might be most related to meaningful patient outcomes, tools to control treatment delivery and the role of facilitating computerized expert systems. Emphasis was given to the use of new technologies such as measurement of online dialysance and ways of assessing fluid status. The current evidence linking achievement of quality criteria with patient outcomes was reviewed. This paper summarizes useful processes and quality measures supporting quality assurance that have been agreed across the expert panel. It also notes areas where more understanding is required.

Residual kidney urea clearance in dialysis patients typically is calculated as the per minute excretion of urea nitrogen, obtained during the 24-48 hour collection period that usually ends just prior to a dialysis session, divided by the time-averaged serum water urea nitrogen concentration during the collection period. This concentration is difficult to estimate unless a formal kinetic modeling program is being used. We used a urea kinetic modeling program to derive an equation to estimate the time-averaged serum water concentration during urine collection periods of various lengths collected during various interdialytic intervals, for 3/week or 2/week dialysis schedules. The equation to predict time-averaged serum water urea nitrogen concentration during the collection period was a function of the ratio of the duration of the predialysis collection period to the duration of the interdialytic interval during which the collection was accomplished, as well as the urea reduction ratio and predialysis serum urea nitrogen concentration of the dialysis session immediately following the end of the collection period.

The protein catabolic rate normalized to body size (PCRn) often is computed in dialysis units to obtain information about protein ingestion. However, errors can manifest when inappropriate modeling methods are used.We used a variable volume 2-pool urea kinetic model to examine the percent errors in PCRn due to use of a 1-pool urea kinetic model or after omission of residual urea clearance (Kru).When a single-pool model was used, 2 sources of errors were identified. The first, dependent on the ratio of dialyzer urea clearance to urea distribution volume (K/V), resulted in a 7% inflation of the PCRn when K/V was in the range of 6 mL/min per L. A second, larger error appeared when Kt/V values were below 1.0 and was related to underestimation of urea distribution volume (due to overestimation of effective clearance) by the single-pool model. A previously reported prediction equation for PCRn was valid, but data suggest that it should be modified using 2-pool eKt/V and V coefficients instead of single-pool values. A third source of error, this one unrelated to use of a single-pool model, namely omission of Kru, was shown to result in an underestimation of PCRn, such that each ml/minute Kru per 35 L of V caused a 5.6% underestimate in PCRn.Marked overestimation of PCRn can result due to inappropriate use of a single-pool urea kinetic model, particularly when Kt/V1.0 (as in short daily dialysis), or after omission of residual native kidney clearance.

BACKGROUND The extent to which anemia management is facilitated by more frequent hemodialysis (HD) is controversial. We hypothesized as a preselected outcome that patients receiving HD six times (6×) compared with three times (3×) per week would require lower doses of erythropoietin-stimulating agents (ESA) and/or achieve higher blood hemoglobin (Hb) concentrations. METHODS Subjects enrolled in the Frequent Hemodialysis Network (FHN) daily and nocturnal trials were studied. As the primary outcome for anemia, the dose of ESAs was recorded at 4-month intervals and the monthly dose of intravenous iron (IV Fe) was reported. Serum iron, transferrin saturation and ferritin were measured at baseline and then at 4-month intervals, whereas Hb concentration was measured monthly. RESULTS There was no significant treatment effect in the 6× versus 3× treatment groups on logESA dose or the ratio of log of ESA dose to Hb concentration in either trial. In the daily trial, Hb concentrations increased significantly in the 6× versus 3× group, at Month 12 compared with baseline (0.3 g/dL; 95% CI: 0.05-0.58, P

Background Previous studies have suggested that a conventional two-pool model cannot be used to predict intradialysis and early postdialysis phosphorus concentrations. Methods A conventional two-pool urea model was modified by increasing the distal compartment volume from two-thirds to three times the total body water and by the use of a dynamically variable intercompartmental phosphorus clearance during dialysis. The phosphate solver model parameters were derived from an examination of the results in the literature, and fine-tuned using a training set (F4) of 415 Hemodialysis (HEMO) Study patients studied during a dialysis session where phosphorus was measured at 4 months of follow-up. Validation was done in a group of 380 different HEMO Study patients plus 9 from the original F4 group, who were evaluated at 36 months of follow-up. Results The model predicted measured median early (1 h) intradialysis, end-dialysis and 30-min postdialysis serum phosphorus levels in the test and validation datasets with little apparent bias, including the highest and lowest deciles of predialysis serum phosphorus. The model tended to underestimate slightly intradialysis serum phosphorus when predialysis serum phosphorus was

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition.

Substantial activation of platelets can occur in the course of hemodialysis. Platelet surface markers show evidence of platelet degranulation. Some activation occurs due to exposure of blood to the roller pump segment and microbubbles may play a role. Platelet activation seems to be reduced with reused dialyzers or with those containing synthetic versus cellulosic membranes. Nevertheless, a substantial degree of platelet activation can be demonstrated with polysulfone and other synthetic membranes; the amount of activation may differ substantially among polysulfone membranes, depending on the manufacturer and the polyvinylpyrrolidone content. Platelet–platelet and platelet–leukocyte aggregates have been detected in the dialyzer blood outflow line and the consequences of these to the microcirculation are unknown. Typically, the platelet count decreases slightly during the first hour of dialysis, but mostly returns to initial values by the end of dialysis. A number of chronic hemodialysis patient cases have been reported in which a marked decrease in platelet count (50% or more) during dialysis was observed, resulting in mild degrees of predialysis thrombocytopenia. In only one case was the decrease in platelet count associated with bleeding. Dialyzer hypersensitivity symptoms are infrequently associated with a fall in platelet count. Most recent cases of dialysis-associated thrombocytopenia have been with polysulfone membranes, especially polysulfone membranes sterilized by electron beam. The exact cause of these reactions remains unknown.

More frequent hemodialysis sessions and longer session lengths may offer improved phosphorus control. We analyzed data from the Frequent Hemodialysis Network Daily and Nocturnal Trials to examine the effects of treatment assignment on predialysis serum phosphorus and on prescribed dose of phosphorus binder, expressed relative to calcium carbonate on a weight basis. In the Daily Trial, with prescribed session lengths of 1.5-2.75 hours six times per week, assignment to frequent hemodialysis associated with both a 0.46 mg/dl decrease (95% confidence interval [95% CI], 0.13-0.78 mg/dl) in mean serum phosphorus and a 1.35 g/d reduction (95% CI, 0.20-2.50 g/d) in equivalent phosphorus binder dose at month 12 compared with assignment to conventional hemodialysis. In the Nocturnal Trial, with prescribed session lengths of 6-8 hours six times per week, assignment to frequent hemodialysis associated with a 1.24 mg/dl decrease (95% CI, 0.68-1.79 mg/dl) in mean serum phosphorus compared with assignment to conventional hemodialysis. Among patients assigned to the group receiving six sessions per week, 73% did not require phosphorus binders at month 12 compared with only 8% of patients assigned to sessions three times per week (P

A number of relevant issues regarding whether to start dialysis or manage an older patient with conservative therapy and whether to start hemodialysis or peritoneal dialysis are covered in other chapters of this handbook. This chapter is limited to the question of what sort of hemodialysis or peritoneal dialysis prescription we should write for an older patient, once the decision has been made to manage their advanced symptomatic kidney disease with chronic renal replacement therapy.

PurposeAn empirically-derived equation to estimate hemodialysis treatment variable-volume single-pool Kt/V, where Kt/V = −ln(R-GFAC × t) + (4−3.5 × R) × UFV/W, was published in 1993 ( 1 ) and quickly became a standard tool for the estimation of dialysis dose. We aim to find a theoretical basis for this equation.MethodsA mathematical derivation is used to find the connection between Kt/V and modeled urea concentrations.ResultsThere is a theoretical basis for the empirical structure of the estimating equation, but the estimation of the effect of ultrafiltration on Kt/V can be improved. Finally, we show that the accuracy of the formula may be suboptimal for some extreme dialysis schedules and propose a new equation that is more robust across atypical dialysis prescriptions.ConclusionsThe currently used Kt/V estimating equation has a sound theoretical basis and an improved version is proposed that can maintain accuracy with a broader range of fluid removal.