Is Hemodialysis Patient Survival Dependent upon Small Solute Clearance (Kt/V)?: If So How Can Kt/V be Adjusted to Prevent Under Dialysis in Vulnerable Groups?

Small solute clearance achieved during a single hemodialysis session has been traditionally evaluated by urea clearance, normalized for total body water (Kt/Vurea) for more than 30 years. By consensus, the target sessional KtVurea for thrice weekly treatments has been increased from 0.9 to 1.2 over the years. Although this is supported by observational studies, there is a fundamental lack of prospective studies to support this threshold target. In clinical practice achieving sessional Kt/Vurea targets are most closely followed in the US. Yet there appears to be a paradox in that by following Kt/Vurea targets in the US hemodialysis patient survival is better for men and the obese, the opposite of what is seen in the general population. Delivery of a lower dose of hemodialysis to women and smaller men can be explained by underestimation of total body water. The advent of bioimpedance techniques which can measure both body water and body composition will potentially allow a rescaling and re-evaluation of the importance of small solute clearances (Kt/Vurea) in the hemodialysis patient population.

Clearance of serum solutes by hemofiltration in dogs with severe heat stroke.

BACKGROUND: We have previously reported that hemofiltration (HF) may be an effective additional means of treating heat stroke when rapid cooling is not effective. METHODS: Dogs were assigned to a heat stroke (control) or heat stroke + hemofiltration (HF) group (n = 8 each group). After heat stroke induction, dogs in the HF group received HF for 3 h. Serum concentrations of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-6, blood urea nitrogen (BUN) and creatinine were measured at baseline and 1, 2, and 3 h after heat stroke. Clearance rates of solutes were determined 1, 2, and 3 h after the start of HF. RESULTS: Serum concentrations of all solutes tended to increase with time after heat stroke in the control group, but decreased (BUN, creatinine) or remained relatively unchanged (TNF-α, IL-6, IL-10) with time in the HF group. Concentrations of all solutes were significantly lower in the HF group compared with the control group at 2 and 3 h (P < 0.05). Clearance rates for small molecular weight solutes were high, while those for larger molecular weight solutes were low. CONCLUSION: HF prevents heat stroke-induced increases in serum cytokine concentrations and is effective for clearing small molecular weight solutes from serum, but less effective for clearing larger molecular weight solutes, including TNF-α, IL-6, and IL-10.

Clinical application of Ultracontrol®: infusion volume and use with different dialyzers.

INTRODUCTION: Recent studies indicate that the survival benefit with post-dilution on line hemodiafiltration (OL-HDF-post) are achieved if the infusion volume (Vinf) is greater than 20L per session, a goal that is not easily achieved due to hemoconcentration problems. Today we have automated techniques to achieve higher performance minimizing the number of alarms as Ultracontrol® (Ultrac). The objective in the first part of study was to evaluate the UltraC performance (expressed as the filtration fraction (FF) and Vinf) and which problems it presents, and in the second part, to study its performance with four different dialyzers. MATERIAL AND METHODS: 1st period. Nine patients were transferred to OL-HDF-post with UltraC. The first 3 months on OL-HDF all sessions were recorded and compared with hemodialysis sessions in the previous month. 2nd part: 18 patients on chronic OL-HDF-post were dialyzed for a week with each of these dialyser: FX1000, FX800, Elisio210H and Polyflux210. RESULTS: 1st period: In 3 patients, problems associated with inappropriate pressures emerged. In 3 patients there were problems associated with inadequate PTM and Psist that resolved changing to pressure control. Mean values were: maximum Qb 441 (21) (range 350-490) ml/min, Vinf 26.3 (3.3) l/session, FF 30.6 (2.5)%, KT 59.9 (5) l/session. KT increase of 12% compared to HD. 2nd part: Polyflux210 required less UltraC withdrawals than the others. Different PTM or Psist were found and determined the need for removal of the system. The KT was adequate. a) The UltraC system reaches FF of 30% with minimal alarms and Vinf higher than 20 l. b) Structural characteristics of dialysers can limit their use with UltraC although they managed to desirable KT and Vinf in a manual way.

How to optimize drug delivery in renal replacement therapy.

Drug dosing in the setting of acute kidney injury (AKI) is complicated by several factors such as pharmacokinetic changes in renal failure, inaccuracy of renal estimating equations in this setting, lack of therapeutic drug monitoring capability for most drugs, and use of extracorporeal renal replacement. Pharmacokinetic changes include decreases in protein binding and drug metabolism. Renal estimating equations most often overestimate renal clearance in AKI. Additionally, it is well recognized that some drugs are significantly cleared by extracorporeal therapy. Patients with AKI are therefore at risk for adverse outcomes of drug therapy. It has been reported that approximately half of patients with reduced renal clearance receive drug doses that are 2.5 times higher than the recommended maximum dose. To ensure efficacy and prevent toxicity, therapeutic drug monitoring is highly recommended. However, in the absence of drug monitoring, adequate concentrations can only be inferred from clinical response. A clinician must weigh the risks and benefits of possible over-dosing or under-dosing based on the therapeutic index of the drug and the clinical situation. This article will review the important factors to consider for drug dosing in patients with AKI receiving continuous renal replacement therapy and sustained low-efficiency dialysis.

[Measuring Kt by ionic dialysance is a useful tool for assessing dialysis dose in critical patients]. / La determinación del Kt por dialisancia iónica es una herramienta útil para la evaluación de la dosis de diálisis en pacientes críticos.

AIM: To evaluate the Kt assessed through ionic dializance (KtOCM) in UCI patients undergoing renal replacement therapy for acute kidney injury, comparing the results with those obtained through the urea removal rate method determined by dialyzate collection (Kturea). MATERIAL AND METHODS: 18 adult UCI staying individuals suffering from renal replacement therapy requiring oliguric acute kidney injury were included in this study. RRT consisted in intermittent or extended hemodialysis performed through a Fresenius 4008E dialysis machine equipped with an on-line clearance monitor (OCM Fresenius). The KtOCM results were provided automatically. The Spearman correlation test was used to assess the relationship between the two exploratory methods and the Student s t test to compare the results obtained by the KtOCM and the Kturea. RESULTS: 35 treatments were analyzed. There were not statistically significant differences between the results form the KtOCM and the Kturea (34.9 +/- 10.69 vs 32.78 +/- 11.31, p = NS). A remarkable association was find between both methods (r = 0.87; 95CI, 0.76-0.94; p < 0.001). CONCLUSIONS: The assessment of Kt through ionic dialyzance is a simple method to estimate the dose of dialysis in critically ill patients and is and useful tool to monitor and adjust the RRT in real time according to a target dose.

[The monitoring of dialysis dose by ionic dialysance-based Kt reveals less dialysis adequacy than the Kt/V(UREA)-based measurement in critically ill patients with acute renal failure]. / La medida de la dosis de diálisis mediante Kt por dialisancia iónica revela una menor adecuación que la medida por Kt/V(UREA) en la insificiencia renal aguda de pacientes críticos.

INTRODUCTION: Measurement of dialysis dose by methods based on urea kinetics (Kt/VUREA) are hardly applicable to critical ill patients with acute renal failure (ARF). However, it is the base of the ADQI consensus recommendation for the target minimum dose. OBJECTIVE: To evaluate the usefulness of the real-time measurement of delivered dialysis dose (Kt) by means of the ionic dialysance (KtID) in the critically ill patient and to compare adequacy of dialysis dose between KtID and traditional Kt/V(UREA). MATERIAL AND METHODS: Prospective observational study in 17 critically ill patients with ARF requiring acute hemodialysis with a predefined prescription for the study (51 measures). RESULTS: The mean delivered Kt/V(UREA) was 1.19 +/- 0.14, with 59% of the sessions with values equal or above the ADQI recommendation. On the contrary, the mean KtID values obtained was 37.6 +/- 1 l, with only 29.4% of the sessions being equal or greater than the recommended values. CONCLUSIONS: Dialysis dose monitoring by means of KtID reveals a lower degree of adequacy as compared to the traditional Kt/V(UREA) method. The dynamic character of KtID monitoring can allow the adaptation of each dialysis session ("K" and/or "t") in order to achieve the recommended dose.

Membrane designs and composition for hemodialysis, hemofiltration and hemodialfiltration: past, present and future.

Today hemodialysis is a routine outpatient treatment, not only carried out in hospitals, but more commonly in free standing units without on site medical supervision. One of the key advances that have underpinned this expansion of hemodialysis provision has been the technological advances in dialyzer membrane technology. Dialyzer membranes have undergone a sea change from collodion tubes to cellulose sheets to the modern day capillary fiber dialyzer. Improvements have not only been limited to reliability of manufacture, but also reduction in bio-incompatibility, and improved small solute clearances. However, the holy Grail remains the development of a dialyzer capable of removing middle sized azotemic retention solutes, and protein bound or lipophilic solutes.

A mathematical model of regional citrate anticoagulation in hemodialysis.

BACKGROUND/AIMS: Regional citrate anticoagulation (RCA) during hemodialysis (HD) has several advantages over heparin anticoagulation, but calcium (Ca) derangements are a major concern necessitating repeated monitoring of systemic ionized Ca (Ca(2+)). We developed a mathematical model of Ca and citrate (Ci) kinetics during RCA. METHODS: Using patient- and treatment-related parameters, including pre-HD serum Ca and protein concentrations, hematocrit, blood and dialysate flow rates, dialysate composition and access recirculation, the model computes all relevant aspects of RCA based on physicochemical, biochemical and physiological principles such as chemical Ca and Ci equilibria, transmembrane solute fluxes and Ci metabolic rate. The model was validated in 17 treatments using arterial Ci infusion, Citrasate dialysate, and no postdialyzer Ca substitution. RESULTS: Measured and predicted systemic Ca(2+) before HD was 1.08 +/- 0.06 and 1.05 +/- 0.05 mmol/l, respectively (difference -0.03 +/- 0.046, 95% confidence interval, CI, -0.055 to -0.007), and at 15 min into the treatment 1.01 +/- 0.05 and 1.02 +/- 0.05 mmol/l, respectively (difference 0.012 +/- 0.054, 95% CI -0.015 to 0.04). At 15 min, the measured and predicted predialyzer Ca(2+) was 0.33 +/- 0.06 and 0.39 +/- 0.05 mmol/l, respectively (difference 0.06 +/- 0.03; 95% CI 0.044-0.077), and the measured and predicted postdialyzer Ca(2+) was 0.7 +/- 0.05 and 0.61 +/- 0.05 mmol/l, respectively (difference -0.09 +/- 0.04; 95% CI -0.11 to -0.07). Bland-Altman analysis showed no systematic bias in these predictions. CONCLUSION: This novel model of RCA shows excellent accuracy in predicting systemic, pre- and postdialyzer Ca(2+) concentrations and may prove valuable in both research and clinical applications of RCA.

Automated regional citrate anticoagulation: technological barriers and possible solutions.

BACKGROUND: Large-scale adoption of regional citrate anticoagulation (RCA) is prevented by risks of the technique as practiced traditionally. Safe RCA protocols with automated delivery on customized dialysis systems are needed. METHODS: We applied kinetic analysis of solute fluxes during RCA to design a protocol for sustained low-efficiency dialysis (SLED) for critically ill patients. We used a high-flux hemodialyzer, a zero-calcium (Ca) dialysate, a dialysis machine with online clearance and access recirculation monitoring, and a separate optical hematocrit (Hct) sensor. Flow rates were Q(B) = 200 ml/min for blood; Q(D) = 400 ml/min for dialysate, with Na = 140 mmol/l and HCO(3) = 32 mmol/l; Q(citrate) = 400 ml/h of acid citrate dextrose A; ultrafiltration as indicated. The Q(Ca) was infused into the return blood line, adjusted hourly based on online Hct and a <24-hour-old albumin level. RESULTS: Using the SLED-RCA protocol in an anhepatic, ex vivo dialysis system, ionized Ca (iCa) was >1 mmol/l in the blood reservoir and <0.3 mmol/l in the blood circuit after citrate but before Ca infusion (Q(Ca)) with normal electrolyte composition of the blood returning to the reservoir. Clinically, SLED-RCA completely abrogated clotting, without adverse electrolyte effects. The Q(Ca) prediction algorithm maintained normal systemic iCa (0.95-1.4 mmol/l) in all patients. The high citrate extraction on the dialyzer prevented systemic citrate accumulation even in shock liver patients. Safety analysis shows that building a dialysis system for automated SLED-RCA is feasible. CONCLUSION: Using predictive Q(Ca) dosing and integrating control of the infusion pumps with the dialysis machine, SLED-RCA can be near-automated today to provide a user-friendly and safe system.

On small solute clearance and patient outcomes: evidential practice or observational trepidation?

Recent guidelines on peritoneal dialysis adequacy set a minimum target for small solute clearance at Kt/V urea 1.70. While evidence from both observational studies and randomized controlled trials (RCTs) supports such a minimum target, there continues to be debate over what role small solute clearance plays in determining patient outcome. Current ANZDATA Registry results from Australia and New Zealand add fuel to this debate by demonstrating a significant nonlinear U-shaped relationship between peritoneal small solute clearance and patient survival. The ANZDATA results indicate that patients with too low or too high peritoneal Kt/V urea may be at significant risk of death compared to those with a peritoneal Kt/V urea between 1.70 and 2.00. As these results are somewhat at odds with results from published RCTs, we will examine the level of evidence from the observational setting that is the ANZDATA Registry and contrast it against the level of evidence from RCTs, particularly the ADEMEX trial. New results from the ADEMEX study are presented as a possible explanation for the paradoxical U-shaped results seen in the ANZDATA study.

Peritoneal small solute clearance is nonlinearly related to patient survival in the Australian and New Zealand peritoneal dialysis patient populations.

BACKGROUND: The contribution of peritoneal small solute clearance per se to peritoneal dialysis (PD) patient outcomes remains uncertain. The aim of the present study was to determine whether baseline peritoneal small solute clearance predicted subsequent survival in Australian and New Zealand PD patients. METHODS: The study included all adult patients in Australia and New Zealand that commenced PD between 1 April 2002 and 31 December 2005 and had a peritoneal Kt/V (pKt/V) measurement performed within 6 months of PD commencement. Time to death and death-censored technique failure were examined by Kaplan-Meier analyses and both univariate and multivariate Cox proportional hazards models. RESULTS: pKt/V measurements were available in 2434 (63%) of the 3841 individuals that began PD treatment in Australia and New Zealand during the study period. These patients were divided into 4 groups according to their baseline pKt/V values: <1.45 (n = 599), 1.45 - 1.69 (n = 550), 1.70 - 2.00 (n = 607), and >2.00 (n = 678). Compared with the reference group (pKt/V 1.70 - 2.00), patient mortality was significantly increased in individuals with pKt/V <1.45 [adjusted hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.24 - 2.84; p = 0.003] and tended to be increased in those with pKt/V 1.45 - 1.69 (adjusted HR 1.46, 95% CI 0.96 - 2.21; p = 0.074). Importantly, higher pKt/V values (>2.00) also tended to be associated with higher mortality (adjusted HR 1.42, 95% CI 0.96 - 2.11; p = 0.079). The other independent predictors of death were lower residual renal function (RRF), older age, peripheral vascular disease, diabetes mellitus, late referral, higher peritoneal permeability, and untreated hypertension. No interaction was observed between pKt/V, RRF, and survival. Death-censored technique failure was demonstrated to be significantly worse in the pKt/V 1.45 - 1.69 group (adjusted HR 1.36, 95% CI 1.03 - 1.79; p = 0.028), older individuals, and individuals with Asian racial origin. CONCLUSIONS: Initial peritoneal Kt/V significantly and independently influences patient survival in Australian and New Zealand PD patients. Overall survival appears to be optimal in the pKt/V range 1.70 - 2.00, with poorer outcomes observed above and below these values. In particular, survival is significantly worse when the achieved pKt/V is <1.45. In addition, RRF is an important independent predictor of patient survival in the Australian and New Zealand incident PD patient populations. The results of this study should therefore draw attention to the possible danger of not delivering adequate PD dose to patients with considerable RRF.

Calcium and magnesium flux in automated peritoneal dialysis.

BACKGROUND: Calcium and magnesium balance in continuous ambulatory peritoneal dialysis (CAPD) has been extensively studied with several of the different formulations of fluid available. Calcium and magnesium balance in automated PD (APD) is less well studied and the effect on Ca and Mg flux is unknown. Data on glucose polymer solutions are also lacking. This prospective observational study was undertaken to examine mass transfer of Ca and Mg in APD patients. METHODS: 12 patients on APD were studied for two 24-hour periods using, alternately, 1.75 mmol/L and 1.25 mmol/L Ca (Dianeal PD1 and Dianeal PD4; Baxter Healthcare, Newbury, UK) 1.36% glucose-based dialysis fluid for the 9-hour overnight dialysis, followed by a 15-hour daytime dwell of glucose polymer-based fluid (icodextrin). Serum ionized Ca, serum Mg, and dialysate Ca and Mg concentrations were measured at the beginning and end of each period. Mass transfer was calculated as millimoles per exchange. RESULTS: During rapid overnight exchanges with Dianeal PD1 and PD4, mass transfer of Mg and Ca did not show significant correlations with serum levels when using PD1 fluid; however, mass transfer of Mg, but not Ca, was significantly correlated to serum levels when using PD4 fluid. During the long dwell with icodextrin, dialysate drain volume was the most significant factor determining the flux of both Ca and Mg. CONCLUSION: Mass transfer of Ca and Mg in APD patients using conventional dialysis fluid was not related to drain volume in this study, which differs to studies in CAPD. Flux of Ca and Mg during icodextrin use was found to be dependent on ultrafiltration rate and not dialysate or serum concentration.

A combined crystalloid and colloid pd solution as a glucose-sparing strategy for volume control in high-transport apd patients: a prospective multicenter study.

BACKGROUND: Evidence is accumulating that the continuous exposure to high glucose concentrations during peritoneal dialysis (PD) is an important cause of ultrafiltration (UF) failure. The cornerstone of prevention and treatment of UF failure is reduction of glucose exposure, which will also alleviate the systemic impact of significant free glucose absorption. The challenge for the future is to discover new therapeutic strategies to enhance fluid and sodium removal while diminishing glucose load and exposure using combinations of available osmotic agents. OBJECTIVES: To investigate in patients on automated PD (APD) with a fast transport pattern whether there is a glucose-sparing advantage to replacing 7.5% icodextrin (ICO) during the long dwell with a mixed crystalloid and colloid PD fluid (bimodal UF) in an attempt to promote daytime UF and sodium removal while diminishing the glucose strength of the dialysate at night. DESIGN: A 2 parallel arm, 4 month, prospective nonrandomized study. SETTING: PD units or university hospitals in 4 French and Belgian districts. RESULTS: During the 4-month intervention period, net UF and peritoneal sodium removal during the long dwell when treated by bimodal UF was about 2-fold higher than baseline (with ICO). The estimated percent change (95% confidence interval) from baseline in net daytime UF for the bimodal solution was 150% (106% - 193%), versus 18% (-7% - 43%) for ICO (p < 0.001). The estimated percent change from baseline in peritoneal sodium removal for the bimodal solution was 147% (112% - 183%), versus 23% (-2% - 48%) for ICO (p < 0.001). The estimated percent change from baseline in UF efficiency (24-hour net UF divided by the amount of glucose absorbed) was significantly higher (p < 0.001) when using the bimodal solution was 71%, versus -5% for ICO. CONCLUSION: Prescription of bimodal UF during the day in APD patients offers the opportunity to optimize the long dwell exchange in a complete 24-hour APD cycle. The current study demonstrated that a bimodal solution based on the mixing of glucose (2.6%) and icodextrin (6.8%) achieved the double target of significantly improving UF and peritoneal sodium removal by exploring a new concept of glucose-sparing PD therapy.

The kinetics of water transperitoneal transport during long-term peritoneal dialysis performed using icodextrin dialysis fluid.

INTRODUCTION: Dialysis fluid containing icodextrin is used in patients on peritoneal dialysis (PD) because of its significant ultrafiltration properties. The use of the fluid in treating patients with congestive heart failure resistant to diuretics has also been reported. OBJECTIVES: The aim of the study was to evaluate water peritoneal transport during a 16-hour dialysis exchange performed using icodextrin-containing dialysis fluid. PATIENTS AND METHODS: Eleven clinically stable patients were enrolled in the study (5 women and 6 men; mean age, 50.4 +/- 18.3 years), treated with PD for 26.9 +/- 22.4 months. Water transperitoneal transport was evaluated using a modified version of Babb-Randerson-Farrell thermodynamic model of membrane transport with human albumin marked with iodine as the marker of intraperitoneal volume. Based on blood and dialysate samples collected during the 16-hour dialysis exchange, the intraperitoneal volume of dialysate and dialysate reverse absorption were calculated. RESULTS: There were no clinical complications associated with the use of icodextrin fluid during the study. A significant increase in intraperitoneal volume of dialysate (950 ml on average) compared to the initial value was observed in the whole group at the 16th hour of the exchange. CONCLUSIONS: The study demonstrated that dialysis fluid with icodextrin ensured effective ultrafiltration during a 16-hour dialysis exchange. This indicates its potential usefulness in the treatment of patients with severe congestive heart failure with or without coexisting end-stage renal disease.

[Acetate-free on-line PHF: how to improve hyperacetatemia and haemodynamic tolerance]. / PHF on-line sin acetato: cómo mejorar la hiperacetatemia y la tolerancia hemodinámica.

SUMMARY BACKGROUND: The small quantity of acetate present in the dialysis fluid exposes patient's blood to an acetate concentration 30-40 times the physiological levels. This amount is even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient. METHODS: 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained. RESULTS: Postdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with postdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride postdialysis were higher and serum concentrations of bicarbonate pre and posthemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate. CONCLUSIONS: PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate.

Surface-area-normalized Kt/V: a method of rescaling dialysis dose to body surface area-implications for different-size patients by gender.

Dialysis is measured as Kt/V, which scales the dose (Kt) to body water content (V). Scaling dialysis dose to body surface area (S(dub)) has been advocated, but the implications of such rescaling have not been examined. We developed a method of rescaling measured Kt/V to S(dub) and studied the effect of such alternative scaling on the minimum adequacy values that might then be applied in male and female patients of varying body size. We examined anthropometric estimates of V and S (Watson vs. Dubois estimates) in 1765 patients enrolled in the HEMO study after excluding patients with amputations. An S-normalized target stdKt/V was defined, and an adequacy ratio (R) was computed for each patient as R = D/N where D = delivered stdKt/V (calculated using the Gotch-Leypoldt equation for stdKt/V) and N = the S-normalized minimum target value. In the HEMO data set, we determined the extent to which baseline (prerandomization) stdKt/V values would have exceeded such an S-based minimum target stdKt/V. The median V(wat):S(dub) ratios were significantly higher in men (21.34) than in women (18.50). The average of these (20) was used to normalize the current suggested minimally adequate value (stdKt/V > or = 2.0/week) to the S-normalized target value (stdKt/S > or = 40 L/M(2)), assuming that average modeled V = average anthropometric V. To achieve this S-normalized target, the required single-pool (sp) Kt/V was always higher in women than in men at any level of body size. For small patients (V(wat) = 25L), required stdKt/V values were 2.05 and 2.21/week for men and women, respectively, corresponding to spKt/V values of 1.31 and 1.52/session. On the other hand, large (V(wat) = 50L) male patients would need spKt/V values of only 1.0/session. Prerandomization baseline dialysis sessions in the HEMO study were found to meet such a new S-based standard in almost all (766/773) men and in 885/992 women. An analysis of scaling dose to anthropometrically estimated liver size (L) showed similar gender ratios for V(wat):L and V(wat):S(dub), providing a potential physiologic explanation underpinning S-based scaling. S-based scaling of the dialysis dose would require considerably higher doses in small patients and in women, and would allow somewhat lower doses in larger male patients. Current dialysis practice would largely meet such an S-based adequacy standard if the dose were normalized to a V(wat):S(dub) ratio of 20.