Comparison of modeled versus reported phosphate removal and modeled versus postdialysis serum phosphate levels in conventional hemodialysis.

BACKGROUND: We compared predictions of phosphate removal by a 2-pool kinetic model with measured phosphate removal in spent dialysate as reported by others. METHODS: Twenty-six studies were identified that reported phosphate removal in 35 groups of patients. In almost all studies, patients were dialyzed for close to 4 h (range 3 to 6 h). For each study, group mean values of predialysis serum phosphate, body size, dialyzer K0 A urea, blood and dialysate flow rates, and session lengths were input into the kinetic model. Predictions of group mean phosphate removal and postdialysis serum phosphate were compared with reported measured values. RESULTS: Mean (by patient group) predicted phosphate removal was 931 ± 170 mg/treatment, somewhat higher (p < 0.001) than the reported measured value, 900 mg ± 287. The ratio of predicted/measured removal averaged 1.15 ± 0.427. In 5/35 patient groups (3/26 studies) the predicted/measured phosphate removal was greater than 1.50. If these groups were excluded, the mean measured phosphate removal was 990 mg versus 966 predicted, with a ratio of predicted/measured removal averaging 0.993. Measured group mean postdialysis serum phosphate values (reported in 25/35) were 2.64 ± 0.54, not significantly different from predicted (2.60 ± 0.24 mg/dl, p = NS). CONCLUSIONS: For conventional 4-h dialysis treatments, phosphate removal and postdialysis serum phosphate values predicted by a 2-pool kinetic model are similar to reported measured values.

Residual Renal Phosphate Clearance in Patients Receiving Hemodialysis or Hemodiafiltration.

OBJECTIVES: 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. METHODS: We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100 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. RESULTS: 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). CONCLUSIONS: 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 is <300 mL/day.

Comparison of measured vs kinetic-model predicted phosphate removal during hemodialysis and hemodiafiltration.

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.

The Predialysis Serum Sodium Level Modifies the Effect of Hemodialysis Frequency on Left-Ventricular Mass: The Frequent Hemodialysis Network Trials.

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.

Equations to Estimate the Normalized Creatinine Generation Rate (CGRn) in 3/Week Dialysis Patients With or Without Residual Kidney Function.

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.

Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements.

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.

The TiME Trial: A Fully Embedded, Cluster-Randomized, Pragmatic Trial of Hemodialysis Session Duration.

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.

Modeled Daily Ingested, Absorbed and Bound Phosphorus: New Measures of Mineral Balance in Hemodialysis Patients.

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.

Intradialytic hypotension and splanchnic shifting: Integrating an overlooked mechanism with the detection of ischemia-related signals during hemodialysis.

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.

Changes in Total Protein Concentration Due to Fluid Removal During and Shortly after Hemodialysis.

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.

A two-pool kinetic model predicts phosphate concentrations during and shortly following a conventional (three times weekly) hemodialysis session.

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 <3.0 mg/dL (0.97 mmol/L). There was a large scatter and standard deviation among patients, and whether aberrant values represent a patient-specific phenomenon is unclear. Conclusions: A modified two-pool model using a slightly expanded distal compartment and a dynamically varying intercompartmental clearance, depending on the intradialysis phosphorus concentration, can be used to predict serum phosphorus level during and shortly after dialysis, in patients following a conventional three times per week dialysis prescription.

Prediction equation for calculating residual kidney urea clearance using urine collections for different hemodialysis treatment frequencies and interdialytic intervals.

Background: The 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. Methods: The 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. Results: The residual kidney urea clearance estimating equation predicted a KRU that matched the one computed by formal modeling within 5% in >98% 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%. Conclusions: The 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. Keywords: chronic hemodialysis, clearance, guidelines, hemodialysis, predialysis.

Eliminating the need for routine monthly postdialysis serum urea nitrogen measurement: A method for monitoring Kt/V and normalized protein catabolic rate using conductivity determined dialyzer clearance.

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.

Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

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.

Creatinine generation from kinetic modeling with or without postdialysis serum creatinine measurement: results from the HEMO study.

BACKGROUND: A convenient method to estimate the creatinine generation rate and measures of creatinine clearance in hemodialysis patients using formal kinetic modeling and standard pre- and postdialysis blood samples has not been described. METHODS: We used data from 366 dialysis sessions characterized during follow-up month 4 of the HEMO study, during which cross-dialyzer clearances for both urea and creatinine were available. Blood samples taken at 1 h into dialysis and 30 min and 60 min after dialysis were used to determine how well a two-pool kinetic model could predict creatinine concentrations and other kinetic parameters, including the creatinine generation rate. An extrarenal creatinine clearance of 0.038 l/kg/24 h was included in the model. RESULTS: Diffusive cross-dialyzer clearances of urea [230 (SD 37 mL/min] correlated well (R2 = 0.78) with creatinine clearances [164 (SD 30) mL/min]. When the effective diffusion volume flow rate was set at 0.791 times the blood flow rate for the cross-dialyzer clearance measurements at 1 h into dialysis, the mean calculated volume of creatinine distribution averaged 29.6 (SD 7.2) L], compared with 31.6 (SD 7.0) L for urea (P < 0.01). The modeled creatinine generation rate [1183 (SD 463) mg/day] averaged 100.1 % (SD 29; median 99.3) of that predicted in nondialysis patients by an anthropometric equation. A simplified method for modeling the creatinine generation rate using the urea distribution volume and urea dialyzer clearance without use of the postdialysis serum creatinine measurement gave results for creatinine generation rate [1187 (SD 475) mg/day; that closely matched the value calculated using the formally modeled value, R2 = 0.971]. CONCLUSIONS: Our analysis confirms previous findings of similar distribution volumes for creatinine and urea. After taking extra-renal clearance into consideration, the creatinine generation rate in dialysis patients is similar to that in nondialysis patients. A simplified method based on urea clearance and urea distribution volume not requiring a postdialysis serum creatinine measurement can be used to yield creatinine generation rates that closely match those determined from standard modeling.

Hemodialysis Treatment Time: As Important as it Seems?

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.

Hemodialysis Ultrafiltration Rate Targets Should Be Scaled to Body Surface Area Rather than to Body Weight.

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.

Assessing the Adequacy of Small Solute Clearance for Various Dialysis Modalities, with Inclusion of Residual Native Kidney Function.

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.

Renal Replacement Therapy and Incremental Hemodialysis for Veterans with Advanced Chronic Kidney Disease.

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.