Direct Dialysis Quantification Research Articles

TO015INTRADIALYTIC ON-LINE MULTICOMPONENT TOTAL REMOVED SOLUTE MONITORING IN SPENT DIALYSATE BY A NOVEL MINIATURIZED OPTICAL SENSOR

Abstract Background and Aims Urea is the most commonly exploited marker of dialysis adequacy. Plenty of other uremic retention solutes with a deleterious effect on morbidity and mortality of uremic patients accumulate in ESKD patients [1]. Commonly, the uremic solutes are divided into three physicochemical types [2] with the representative markers urea, uric acid (UA),indoxyl sulfate (IS), and β2-Microglobulin (B2M). Optical monitoring of the uremic marker molecules has been proposed [3]. Despite being cumbersome as a clinical routine, direct dialysis quantification from total dialysate collection (TDC) is as the ‘gold standard’ for measuring the total amount of uremic solutes removed [4]. A robust and compact optical on-line dialysis monitoring device is a step closer to automatic assessment of removal of uremic toxins in dialysis. The aim of this study was to evaluate intradialytic on-line multicomponent Total Removed Solute (TRS) monitoring in the spent dialysate by a novel miniaturized optical sensor during hemodialysis (HD) and hemodiafiltration (HDF) with different settings. Method Ten ESKD patients (6 male and 4 female, 60.2±16.8 years) on chronic HDF were enrolled into the study (fistula N=9, graft N=1). For each patient 5 midweek dialysis sessions (length 240min, HD: N=1, Qb=200ml/min, Qd=300ml/min, 1,5m2; HDF: N=4, Qb≥300ml/min, Qd≥500ml/min, Vsubst≥15l, 1,8m2 and 2,2m2) were included. Spent dialysate from the drain was monitored on-line by a miniaturized sensor prototype (Optofluid Technologies OÜ, Estonia). For the reference, the samples from the spent dialysate drain tube of the HD machine were taken as 7, 60, 120 and 180min after the start and at the end of the session (240min). The concentrations of urea and B2M in dialysate were determined in the clinical laboratory. Concentration of IS and UA was determined utilizing the HPLC. TRS values were calculated using the tank weight and the lab or optical tank solute concentrations. t-test was used to determine significant differences between the methods (P≤0.05). Results The laboratory and optical TRS values were 489±112mM and 512±87mM for urea (R2=0.870), 4232±712µM and 4331±756µM for UA (R2=0.985), 230±47mg and 231±40mg for B2M (R2=0.906), 606±339µM and 616±321µM for IS (R2=0.969) (Fig. 1), being not statistically different for any uremic solutes. The reason for higher correlation for UA and IS is direct measurements of UA and IS by the optical sensor whereas urea and B2M are estimated indirectly. Conclusion Novel miniaturized optical sensor successfully carried out intradialytic on-line multicomponent TRS monitoring for the uremic solutes urea, UA, B2M and IS in the spent dialysate.

A new technique for low-volume continuous sampling of spent dialysate: a validation study.

The measure of hemodialysis (HD) adequacy recommended nowadays by most guidelines, Kt/V-urea, presents significant drawbacks. Direct dialysis quantification (DDQ) through total dialysate collection (TDC), considered the gold standard measure of HD adequacy, is cumbersome, which precludes its widespread use in clinical practice. The present study aims to validate a low-volume continuous sampling of spent dialysate (CSSD). Cross-sectional study carried out at a university hospital. Throughout 4-h hemodialysis sessions, urea removal was measured by three DDQ methods: TDC, CSSD, and fractional sampling of dialysate (FSD). The primary outcome was the comparison between the total mass of urea removed measured by TDC and the dialysate sampling techniques. The comparison between urea distribution volume (UDV) estimated by anthropometric method and through DDQ was a secondary outcome. The analysis was done through linear regression and Bland-Altman concordance method. Twenty HD sessions were studied. The mean amount of urea collected in TDC and calculated from the 40-mL sample of CSSD were 33.70 ± 11.70g and 33.90 ± 11.70g, respectively [r 0.96, p < 0.0001; bias - 0.2 (95% CI - 1.8 to 1.4); limits of agreement - 6.8 to 6.4]. The anthropometric measure, when compared with DDQ method, underestimated UDV in patients with smaller body size. This new simple, inexpensive, and small volume CSSD technique can provide accurate information about the total amount of solutes removed by hemodialysis.

Precise Quantitative Assessment of the Clinical Performances of Two High-Flux Polysulfone Hemodialyzers in Hemodialysis: Validation of a Blood-Based Simple Kinetic Model Versus Direct Dialysis Quantification.

Highly permeable dialysis membranes with better design filters have contributed to improved solute removal and dialysis efficacy. However, solute membrane permeability needs to be well controlled to avoid increased loss of albumin that is considered to be detrimental for dialysis patients. A novel high-flux dialyzer type (FX CorDiax; Fresenius Medical Care) incorporating an advanced polysulfone membrane modified with nano-controlled spinning technology to enhance the elimination of a broader spectrum of uremic toxins has been released. The aim of this study was to compare in the clinical setting two dialyzer types having the same surface area, the current (FX dialyzer) and the new dialyzer generation (FX CorDiax), with respect to solute removal capacity over a broad spectrum of markers, including assessment of albumin loss based on a direct dialysis quantification method. We performed a crossover study following an A1-B-A2 design involving 10 patients. Phase A1 was 1 week of thrice-weekly bicarbonate hemodialysis with the FX dialyzer, 4 h per treatment; phase B was performed with a similar treatment regimen but with a new FX CorDiax dialyzer and finally the phase A2 was repeated with FX dialyzer as the former phase. Solute removal markers of interest were assessed from blood samples taken before and after treatment and from total spent dialysate collection (direct dialysis quantification) permitting a mass transfer calculation (mg/session into total spent dialysate/ultrafiltrate). On the blood side, there were no significant differences in the solute percent reduction between FX CorDiax 80 and FX 80. On the dialysate side, no difference was observed regarding eliminated mass of different solutes including β2 -microglobulin (143.1 ± 33.6 vs. 138.3 ± 41.9 mg, P = 0.8), while the solute mass removal of total protein (1.65 ± 0.51 vs. 2.14 ± 0.75 g, P = 0.04), and albumin (0.41 ± 0.21 vs. 1.22 ± 0.51 g, P < 0.001) were significantly less for FX CorDiax 80 compared to the FX 80 dialyzer. The results of this cross-over study indicate that the new FX CorDiax dialyzer has highly effective removal of middle molecules, without any concomitant increase in total protein and albumin loss. The clinical relevance and potential benefit of this finding needs to be determined.

Ranking of factors determining potassium mass balance in bicarbonate haemodialysis.

One of the most important pathogenetic factors involved in the onset of intradialysis arrhytmias is the alteration in electrolyte concentration, particularly potassium (K(+)). Two studies were performed: Study A was designed to investigate above all the isolated effect of the factor time t on intradialysis K(+) mass balance (K(+)MB): 11 stable prevalent Caucasian anuric patients underwent one standard (∼4 h) and one long-hour (∼8 h) bicarbonate haemodialysis (HD) session. The latter were pair-matched as far as the dialysate and blood volume processed (90 L) and volume of ultrafiltration are concerned. Study B was designed to identify and rank the other factors determining intradialysis K(+)MB: 63 stable prevalent Caucasian anuric patients underwent one 4-h standard bicarbonate HD session. Dialysate K(+) concentration was 2.0 mmol/L in both studies. Blood samples were obtained from the inlet blood tubing immediately before the onset of dialysis and at t60, t120, t180 min and at end of the 4- and 8-h sessions for the measurement of plasma K(+), blood bicarbonates and blood pH. Additional blood samples were obtained at t360 min for the 8 h sessions. Direct dialysate quantification was utilized for K(+)MBs. Direct potentiometry with an ion-selective electrode was used for K(+) measurements. Study A: mean K(+)MBs were significantly higher in the 8-h sessions (4 h: -88.4 ± 23.2 SD mmol versus 8 h: -101.9 ± 32.2 mmol; P = 0.02). Bivariate linear regression analyses showed that only mean plasma K(+), area under the curve (AUC) of the hourly inlet dialyser diffusion concentration gradient of K(+) (hcgAUCK(+)) and AUC of blood bicarbonates and mean blood bicarbonates were significantly related to K(+)MB in both 4- and 8-h sessions. A multiple linear regression output with K(+)MB as dependent variable showed that only mean plasma K(+), hcgAUCK(+) and duration of HD sessions per se remained statistically significant. Study B: mean K(+)MBs were -86.7 ± 22.6 mmol. Bivariate linear regression analyses showed that only mean plasma K(+), hcgAUCK(+) and mean blood bicarbonates were significantly related to K(+)MB. Again, only mean plasma K(+) and hcgAUCK(+) predicted K(+)MB at the multiple linear regression analysis. Our studies enabled to establish the ranking of factors determining intradialysis K(+)MB: plasma K(+) → dialysate K(+) gradient is the main determinant; acid-base balance plays a much less important role. The duration of HD session per se is an independent determinant of K(+)MB.

Inorganic Phosphorus Homeostasis during the First Hour of Dialysis

Background/aim: Hyperphosphatemia is a well-recognized complication of chronic kidney disease, and phosphorus kinetics during hemodialysis (HD) remains a vague area of investigation. We studied the inorganic phosphorus homeostasis during the first hour of an HD session. Materials/methods: Twelve patients were studied twice, in two consecutive HD sessions. Total (TPR), extracellular (EPR), and intracellular (IPR) phosphorus mass removal was determined using the direct dialysate quantification (DDQ) method. Alterations of serum inorganic phosphorus (sP), erythrocyte intracellular phosphorus (PERY), and 2,3-diphosphoglycerate (2,3-DPG) concentrations were measured before HD initiation and at 1, 2, 3, 4, 5, 10, 30, and 60 min. Results: The contribution of IPR to TPR was negative in the first 10 min of both HD sessions (–27.2 ± 6.5 and −26.4 ± 58 mmol, respectively, p = ns) while the contribution of the IPR to TPR increased as the time elapsed. Intracellular phosphorus and 2,3-DPG remained almost unchanged during the 60 min of HD session. Conclusions: Unchanged PERY concentration during the first hour of an HD session does not reject the hypothesis of a simultaneous efflux and influx of phosphorus from/to intracellular compartment.

Renal Replacement Therapy in Acute Renal Failure: Which Index is Best for Dialysis dose Quantification?

The "delivered dose" of dialysis may significantly affect the outcome of acute renal failure (ARF) patients requiring dialysis. Our study aimed to elucidate which dose quantification method offers an appropriate parameter to compare different treatments in ARF patients. Six sustained low-efficiency daily dialysis (SLEDD), and 7 continuous venovenous hemofiltration (CVVH) patients with a prescribed Kt/V of 1.0 were studied during a single treatment. CVVH was studied over the first 24 hours after initiation. SLEDD was performed for 6-12 h. Solute clearance (K) was determined by direct dialysate quantification (DDQ). The single-pool Kt/V (spKt/V), equilibrated Kt/V (eqKt/V), equivalent renal urea clearance (EKRc), and solute removal index (SRI) were calculated. There were no significant differences at enrollment between the SLEDD and the CVVH groups in any patient characteristics except for the serum creatinine levels. The prescribed Kt/V of both groups was similar (SLEDD, 0.9+/-0.22; CVVH, 1.10+/-0.12, p=NS). The EKRc, which is used to verify kinetic equivalence among patients treated with differing renal replacement therapies (RRT), was higher in CVVH (15.7 in SLEDD; 27.4 in CVVH, p<0.0001), despite the fact that there was no difference between the delivered spKt/V for the SLEDD (1.05+/-0.40) and the CVVH (1.10+/-0.11) groups. The values for SRIurea (0.61 in SLEDD; 1.04 in CVVH, p=0.001), SRIcreatinine (0.55 in SLED; 1.02 in CVVH, p<0.0001), and SRIphosphate (1.81 in SLED; 3.60 in CVVH, p=0.03) were higher in CVVH. The EKRc is calculated assuming a steady state, which is an incorrect assumption in ARF patients with hypercatabolism. The SRI calculated using direct dialysate effluent quantification appears to be more reliable as an index of the dialysis dose compared to other methods in ARF patients. However, the use of the dialysate-side SRI is limited by the difficulty of dialysate effluent collection.

Do different haemodialysis regimen interfere with genomic damage in patients with end-stage-renal disease?

Continuous renal replacement therapies have practical and theoretical advantages compared with conventional intermittent hemodialysis in hemodynamically unstable or severely catabolic patients with acute renal failure (ARF). Sustained low-efficiency dialysis (SLED) is a hybrid modality introduced July 1998 at the University of Arkansas for Medical Sciences that involves the application of a conventional hemodialysis machine with reduced dialysate and blood flow rates for 12-hour nocturnal treatments. Nine critically ill patients with ARF were studied during a single SLED treatment to determine delivered dialysis dose and the most appropriate model for the description of urea kinetics during treatment. Five patients were men, mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 28.9 and mean weight was 92.5 kg. Kt/V was determined by the reference method of direct dialysate quantification (DDQ) combined with an equilibrated postdialysis plasma water urea nitrogen (PUN) concentration and four other methods that were either blood or dialysate based, single or double pool, or model independent (whole-body kinetic method). Solute removal indices (SRIs) were determined from net urea removal and urea distribution volume supplied from DDQ (reference method) and by mass balance using variables supplied from blood-based formal variable-volume single-pool (VVSP) urea kinetic modeling. Equivalent renal urea clearances (EKRs) were calculated from urea generation rates and time-averaged concentrations for PUN based on weekly mass balance with kinetic variables supplied by either DDQ (reference method) or formal blood-based VVSP modeling. Mean Kt/V determined by the reference method was 1.40 and not significantly different when determined by formal VVSP modeling, DDQ using an immediate postdialysis PUN, or the whole-body kinetic method. Correction of single-pool Kt/V by a Daugirdas rate equation did not yield plausible results. Mean SRI and EKR by the reference methods were 0.61 and 24.8 mL/min, respectively, and not significantly different when determined by blood-based methods. A single-pool urea kinetic model adequately described intradialytic PUN profiles, indicating that SLED was associated with minimal urea disequilibrium. This was supported by the parity between hemodialyzer and whole-body urea clearances, and the mean postdialytic urea rebound of 4.1% (P = 0.13 versus zero). Additional prospective studies are needed in this setting to define the optimal method for dialysis quantification, targets for azotemic control, and optimal modality of renal replacement therapy. In conclusion, SLED delivers a high dose of dialysis with minimal associated urea disequilibrium and can be quantified by Kt/V, SRI, and EKR from blood-based methods using single-pool urea kinetic models. © 2002 by the National Kidney Foundation, Inc.

Direct Dialysis Quantification: Investigation of the Impact of Dialysate Preservation Techniques on Solute Assays

Aims: Urease-producing microorganisms may lower urea nitrogen (UN) during dialysate-side dosing. We investigated the impact of 3 proven preservatives (acetic acid, ceftazidime, thimerosal) on UN concentration, and the concentrations of creatinine (CR) and β₂-microglobulin (β₂M). Methods: The UN, CR and β₂M concentrations were assayed in 3 separate aliquots from 20 spent dialysate samples (ceftazidime, 125 mg/l, or 1% thimerosal, 1 ml/l, vs. control). The β₂M concentration was assayed in 10 further spent dialysate collections (concentrated glacial acetic acid, 5 ml/l, vs. control). Solute concentrations were compared with the concordance correlation coefficient (r_c). Results: Ceftazidime and thimerosal had little effect on the concentrations of UN and CR (r_c >0.97). For the β₂M concentration, agreement remained good (r_c >0.96) for ceftazidime and thimerosal (although the former tended to lower concentrations) but acetic acid was less optimal (r_c = 0.893). Conclusions: Ceftazidime and thimerosal may be used as dialysate preservatives without affecting the UN or CR concentrations. Thimerosal is to be preferred when studying β₂M. Acetic acid produces unacceptable inaccuracy when measuring β₂M.

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients

An adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance. Ionic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (U(pwt2')). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and U(pwt2') (V(ID)) are similar to those determined by the "gold standard" DDQ method (V(DDQ)). Eighty-two anuric hemodialysis patients were studied. V(DDQ) was 26.3 +/- 5.2 L; V(ID) was 26.5 +/- 4.8 L. The (V(ID)-V(DDQ)) difference was 0.2 +/- 1.6 L, which is not statistically significant (P= 0.242). Anthropometric volume (V(A)) calculated using Watson equations was 33.6 +/- 6.0 L. The (V(A)-V(DDQ)) difference was 7.3 +/- 3.3 L, which is statistically significant (P < 0.001). Anthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples.

Urea kinetics during sustained low-efficiency dialysis in critically ill patients requiring renal replacement therapy

Continuous renal replacement therapies have practical and theoretical advantages compared with conventional intermittent hemodialysis in hemodynamically unstable or severely catabolic patients with acute renal failure (ARF). Sustained low-efficiency dialysis (SLED) is a hybrid modality introduced July 1998 at the University of Arkansas for Medical Sciences that involves the application of a conventional hemodialysis machine with reduced dialysate and blood flow rates for 12-hour nocturnal treatments. Nine critically ill patients with ARF were studied during a single SLED treatment to determine delivered dialysis dose and the most appropriate model for the description of urea kinetics during treatment. Five patients were men, mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 28.9 and mean weight was 92.5 kg. Kt/V was determined by the reference method of direct dialysate quantification (DDQ) combined with an equilibrated postdialysis plasma water urea nitrogen (PUN) concentration and four other methods that were either blood or dialysate based, single or double pool, or model independent (whole-body kinetic method). Solute removal indices (SRIs) were determined from net urea removal and urea distribution volume supplied from DDQ (reference method) and by mass balance using variables supplied from blood-based formal variable-volume single-pool (VVSP) urea kinetic modeling. Equivalent renal urea clearances (EKRs) were calculated from urea generation rates and time-averaged concentrations for PUN based on weekly mass balance with kinetic variables supplied by either DDQ (reference method) or formal blood-based VVSP modeling. Mean Kt/V determined by the reference method was 1.40 and not significantly different when determined by formal VVSP modeling, DDQ using an immediate postdialysis PUN, or the whole-body kinetic method. Correction of single-pool Kt/V by a Daugirdas rate equation did not yield plausible results. Mean SRI and EKR by the reference methods were 0.61 and 24.8 mL/min, respectively, and not significantly different when determined by blood-based methods. A single-pool urea kinetic model adequately described intradialytic PUN profiles, indicating that SLED was associated with minimal urea disequilibrium. This was supported by the parity between hemodialyzer and whole-body urea clearances, and the mean postdialytic urea rebound of 4.1% (P = 0.13 versus zero). Additional prospective studies are needed in this setting to define the optimal method for dialysis quantification, targets for azotemic control, and optimal modality of renal replacement therapy. In conclusion, SLED delivers a high dose of dialysis with minimal associated urea disequilibrium and can be quantified by Kt/V, SRI, and EKR from blood-based methods using single-pool urea kinetic models.

Artificial intelligence: A new approach for prescription and monitoring of hemodialysis therapy

The effect of dialysis on patients is conventionally predicted using a formal mathematical model. This approach requires many assumptions of the processes involved, and validation of these may be difficult. The validity of dialysis urea modeling using a formal mathematical model has been challenged. Artificial intelligence using neural networks (NNs) has been used to solve complex problems without needing a mathematical model or an understanding of the mechanisms involved. In this study, we applied an NN model to study and predict concentrations of urea during a hemodialysis session. We measured blood concentrations of urea, patient weight, and total urea removal by direct dialysate quantification (DDQ) at 30-minute intervals during the session (in 15 chronic hemodialysis patients). The NN model was trained to recognize the evolution of measured urea concentrations and was subsequently able to predict hemodialysis session time needed to reach a target solute removal index (SRI) in patients not previously studied by the NN model (in another 15 chronic hemodialysis patients). Comparing results of the NN model with the DDQ model, the prediction error was 10.9%, with a not significant difference between predicted total urea nitrogen (UN) removal and measured UN removal by DDQ. NN model predictions of time showed a not significant difference with actual intervals needed to reach the same SRI level at the same patient conditions, except for the prediction of SRI at the first 30-minute interval, which showed a significant difference (P = 0.001). This indicates the sensitivity of the NN model to what is called patient clearance time; the prediction error was 8.3%. From our results, we conclude that artificial intelligence applications in urea kinetics can give an idea of intradialysis profiling according to individual clinical needs. In theory, this approach can be extended easily to other solutes, making the NN model a step forward to achieving artificial-intelligent dialysis control. © 2001 by the National Kidney Foundation, Inc.

Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy

The replacement of renal function for critically ill patients is procedurally complex and expensive, and none of the available techniques have proven superiority in terms of benefit to patient mortality. In hemodynamically unstable or severely catabolic patients, however, the continuous therapies have practical and theoretical advantages when compared with conventional intermittent hemodialysis (IHD). We present a single center experience accumulated over 18 months since July 1998 with a hybrid technique named sustained low-efficiency dialysis (SLED), in which standard IHD equipment was used with reduced dialysate and blood flow rates. Twelve-hour treatments were performed nocturnally, allowing unrestricted access to the patient for daytime procedures and tests. One hundred forty-five SLED treatments were performed in 37 critically ill patients in whom IHD had failed or been withheld. The overall mean SLED treatment duration was 10.4 hours because 51 SLED treatments were prematurely discontinued. Of these discontinuations, 11 were for intractable hypotension, and the majority of the remainder was for extracorporeal blood circuit clotting. Hemodynamic stability was maintained during most SLED treatments, allowing the achievement of prescribed ultrafiltration goals in most cases with an overall mean shortfall of only 240 mL per treatment. Direct dialysis quantification in nine patients showed a mean delivered double-pool Kt/V of 1.36 per (completed) treatment. Mean phosphate removal was 1.5 g per treatment. Mild hypophosphatemia and/or hypokalemia requiring supplementation were observed in 25 treatments. Observed hospital mortality was 62.2%, which was not significantly different from the expected mortality as determined from the APACHE II illness severity scoring system. SLED is a viable alternative to traditional continuous renal replacement therapies for critically ill patients in whom IHD has failed or been withheld, although prospective studies directly comparing two modalities are required to define the exact role for SLED in this setting.

Quantitation of dialysis: historical perspective.

This article is an attempt to provide a historical perspective to the ongoing attempts to quantify dialysis therapy. It is immediately apparent that motivated chemists, physicists, engineers, mathematicians, and other scientists from all over the world have greatly aided this effort. Dialysis, described by Graham in 1861, was furthered by Abel et al. and Hass before World War I. Willem Kolff attempted to evaluate mass removed and Alwall used a solute extraction ratio. However, the concept of "clearance" and "dialysance" awaited the studies of Wolf et al. in 1951. This classic work describes most of the information concerning actual dialyzer performance known today. A. S. Michaels provided the equations leading to the KoA/Ro/A concept in 1966 which only very recently required updating. The interaction of diffusion and convection is complex and was studied by Villarroel in 1977 and recently by Jaffrin. L. W. Henderson studied and described hemofiltration and hemodiafiltration from 1967-1975. Efforts to relate the patient's outcome to the dialyzer's performance have been difficult and ongoing since 1971; the Babb-Scribner Square meter-hour (which included the expression "Kt/V"); the Kopp et al. Liter-Kilogram concept; 1972 Kjellstrand clearance * time/kg or Liter. A NIH sponsored conference on the Adequacy of Dialysis in Monterey, California in March of 1974 was focused somewhat on the "middle molecule" theory of uremic toxicity, but contained a presentation by Sargent and Gotch on the possibilities of urea kinetic modeling. They developed iterative computer programs to obtain the best estimates of the required variables. At about this same time, Teschan, Ginn et al. published a series of neurofunctional tests and EEG power spectra analyses which most convincingly showed that dialysis two times a week was inadequate, and that dialysis delivered three times a week at urea clearance equal to body water volume was required to normalize these abnormalities: a major contribution! The National Cooperative Dialysis Study reported in Kidney International, 1983, was either misunderstood or ignored by most practitioners. The mechanistic analysis of the study by Gotch and Sargent appeared in 1985 and indicated that at adequate protein intake a Kt/V >0.8 yielded better patient survival. In 1982 Malchesky reported the Direct Dialysis Quantification (DDQ) based on calculations from the total mass removed in the dialysate. Although cumbersome, it avoids many errors including the effect of hematocrit and other factors on dialyzer clearance and many consider it to be "the gold standard." The 1990s were characterized by the development of many simple logarithmic equations to estimate Kt/V and eKt/V suitable for spreadsheets which could be used for CQI by individual units. These are primarily by J. T. Daugirdas and coworkers, Smye and Tattersall. In 1991 the Urea Reduction Ratio (URR) was introduced by Lowrie, who in 1999 suggested that Kt and V (as indicator of lean body mass) were independent predictors of survival. Peritoneal dialysis: Although performed before and immediately after World War II, almost all of the basic quantification mechanistics and data are found in the publications of S. T. Boen (1964). New quantifiers, the Mass Transport Area Coefficient (MTAC) or Pyle-Popovich model, the Henderson-Nolph, and Garred models, were compared by Waniewski. Gotch announced a PD modeling program which suggested that a weekly PKt/V at 2.1 was needed to supply the same urea removal as a Kt/V of 3.6, but warned that both were sensitive to decreased time.

A fractional dialysate collection method to estimate solute removal in continuous venovenous hemodialysis

Fractional direct dialysis quantification (fDDQ), whereby a known proportion of dialysate effluent is sampled, can reliably estimate total solute removal in intermittent hemodialysis (IHD). Our study aimed to develop and test the technique in continuous venovenous hemodialysis (CVVHD). Twenty dialysate collections (mean duration 23.5 hours, range 17.25 to 26.6) were performed in 12 patients on CVVHD. An infusion pump diverted 10% of the total effluent volume to the fractional collection (fc), the remainder being channeled into the bulk collection (bc). Both fc and bc were collected on ice and assayed for urea nitrogen (UN) and creatinine (Cr). Actual solute removal (ASR) was calculated from the measured effluent volume and solute concentrations of the fc and bc. Estimated solute removal (ESR) was calculated from the product of the fc solute concentration and effluent volume. All fc/bc samples in 15 out of 20 collections underwent gram stain and aerobic/anaerobic culture. Bland-Altman analyses suggested good agreement between ASR and ESR [absolute values of percentage differences: 95% CI = 1.73, 5.17% (UN); 1.88, 4.31% (Cr)]. Favorable concordance correlation coefficients confirmed this [rc = 0.995 (UN), 0.997 (Cr)] and were apparently unaffected by heavy pseudomonal growths in 4 out of 7 culture positive collections [rc = 0.997 (UN), 0.997 (Cr); culture negative (N = 8), rc = 0.996 (UN), 0.997 Cr)]. fDDQ, using 24-hour, pump-assisted, cooled fractional dialysate sampling reliably estimates total solute removal and provides a practical alternative to total dialysate collection in assessing delivered dialysis dose.

Use of iohexol to quantify hemodialysis delivered and residual renal function: Technical Note

Classically, urea (molecular wt = 60) is used to determine the urea reduction ratio (URR) or clearance, based on volume of distribution (Kt/V). These methods are subject to many errors. The purpose of this study was to determine whether iohexol (Io; molecular wt = 821) could be used instead of urea and provide better information as well as middle molecule clearance data. Ten hemodialysis (HD) patients were evaluated. All were dialyzed for three hours, and a single bolus of 100 ml of Io was injected immediately post-HD. For direct dialysis quantification (DDQ), the spent dialysate was collected in a drum, and urea and iodine (I) determined immediately prior to, at the end of, and 30 minutes post-HD. As routinely used, DDQ measures clearance directly rather than estimates the levels. Calculated Kt/V urea (1.21+/-0.05) significantly overestimated DDQ Kt/V urea (0.78+/-0.04, P < 0.001) whereas calculated and DDQ Kt/V Io were similar (1.44+/-0.10 vs. 1.36+/-0.05). The URR and iohexol reduction ratio (IoRR) were also different (0.63+/-0.02 vs. 0.69+/-0.02; P < 0.002) with a urea but not Io rebound (URR30 min 0.59+/-0.02, P < 0.05). Calculated urea clearance (C(urea)), 247+/-21 ml/min, significantly overestimated DDQ C(urea) (157+/-10 ml/min P < 0.001). Calculated CIo and DDQ CIo, however, were similar (109+/-8 vs. 104+/-7 ml/min). Total body clearance (TBC) in six anuric subjects was 2.5+/-0.3 ml/min, and in four oliguric subjects was 5.2+/-0.5 ml/min. In 10 additional patients, direct urine measurements demonstrated a non-renal clearance (NRC) of 2.97+/-0.18 ml/min, which was 4.0+/-0.3% of body wt. Use of this factor allowed an estimation of residual renal function (RRF) that accurately reflected measured RRF (1.32+/-0.53 vs. 1.42+/-0.55 ml/min) A single injection of Io can be used to determine Kt/V, RR, and RRF without rebound or the inconvenience of urine collection. It may also represent middle molecule clearance better than urea kinetics, and may serve as a superior method for determining HD delivered and dialysis adequacy.

Mass Balance Index: An Index for Adequacy of Dialysis and Nutrition

Determining adequacy of dialysis has remained a problem for the nephrologist despite the results of the National Cooperative Dialysis Study published more than 20 years ago. Urea Kinetics Modelling (UKM) which requires computer data entry is time-consuming for the dialysis staff but is the only method that has been rigorously studied. Furthermore, it is unclear today what value of Kt/V represents ideal dialysis; the technique is subject to a number of errors associated with estimation of dialyser clearance (K) and volume of distribution of urea (V) but it is useful for calculating protein catabolic rate (PCR). Methods that use urea reduction ratios (URR) is widely used because it is simpler but not always accurate and suffer from an inability to calculate PCR. Direct dialysis quantification (DDQ) can overcome a number of these problems but it is too cumbersome for routine use. Simpler methods to determine dialysateside kinetics have the advantage of solving a number of these problems and also facilitate the calculation of PCR to determine the patient's nutritional state. In our study we have demonstrated that by taking two dialysate samples at the beginning and at the end of dialysis (2-DSM), it is possible to determine total urea removal (TUR) which is equivalent to DDQ. By taking blood samples after dialysis and before the next dialysis, it is possible to calculate the total urea generated (TUG). The ratio of TUR/TUG will provide an index of dialysis which places emphasis on removal of solute that has accumulated in the inter-dialytic interval thus re-establishing a state of equilibrium. We refer to this index as the Mass Balance Index (MBI). The MBI is also useful in helping to identify those patients whose PCR is inadequate since the mean MBI for patients with an nPCR <0.8 was 0.93 +/- 0.03 vs 1.08 +/- 0.02 in those with a PCR >0.8. In these two groups of patients the Kt/V was not significantly different, 1.49 +/- 0.07 vs 1.53 +/- 0.06, p -0.64. We suggest that the emphasis for adequacy of dialysis should shift away from Kt/V to maintaining a state of equilibrium by removing the solutes that accumulate between dialysis and by identifying those patients with an inadequate PCR.

Kinetic Modeling of "Go Slow" Dialysis in Acute Renal Failure.

Go slow" dialysis is a gentle, intermittent hemodialysis therapy for acute renal failure patients, with advantages compared to slow, continuous therapies. It employs a recirculating closed dialysate circuit. A two-pool urea kinetic model is elaborated to determine kinetic parameters from blood and dialysate concentrations. This will allow quantification of the therapy. Variable clearance is included to accurately describe the kinetic process. The model is tested in an acute renal failure patient. Solute removals, as determined from direct dialysis quantification and by the model, are comparable. Variable clearance is not required to determine the kinetic parameters, because the constant mean clearance delivers equal results. The dialysis dose, as defined, allows comparison with chronic renal therapies. It requires solute removal determined from dialysate sampling and time-averaged concentration (TAC) from the urea kinetic modeling. In the test patient, dialysis dose is lower compared to standard thrice-weekly therapies because of its lower efficiency and higher TAC, a result of his highly catabolic state.

Quantitating Dialysis using two Dialysate Samples: A Simple, Practical and Accurate Approach for Evaluating Urea Kinetics

Urea kinetics is now widely used to determine the adequacy of dialysis. Several simplified formulae are currently in use but only a few have been accepted into clinical practice because of their simplicity and ease of calculation. A recent analysis of these formulae showed that for the same set of blood urea values the calculated Kt/V can range from 1.0 to 1.5. We have developed a new dialysate-based method (2DSM) to estimate the urea kinetic parameters using dialysate and blood samples taken at the beginning and at the end of dialysis. The total urea removed (TUR) was calculated from the geometric mean of the two dialysate samples, dialysate flow rate and the duration of dialysis. The Watson formula was used to determine the volume of distribution of urea. A comparison of the 2DSM and the direct dialysate quantification (DDQ) method showed the following results (mean +/- sd, n = 52): for total urea removal (TUR) 697 +/- 32 vs 722 +/- 37 mmol (p = 0.6, r2 = 0.928, y = 101 + 0.83 x, mean difference 25 +/- 76 mmol, see Bland-Altman plot), dialysate urea concentration (Durea) 5.55 +/- 0.25 vs 5.75 +/- 0.29 mmol/l (p = 0.6, r2 = 0.928, y = 0.8 + 0.82 x, mean difference 0.2 +/- 0.6 mmol, see Bland-Altman plot), dialyser clearance (K) 232 +/- 4.4 vs 235 +/- 5.6 ml/min (p = 0.54), Kt/V 1.42 +/- 0.04 vs 1.51 +/- 0.04 (p = 0.21), volume of distribution of urea (Vd) 40.14 +/- 1.04 vs 38.74 +/- 1.2 L, (p = 0.38), and PCR 64.6 +/- 2.6 vs 68.1 +/- 3.1 g/day. We have developed a simple method of determining dialysate-based urea kinetics which requires two dialysate samples, one at the beginning and one at the end of dialysis and a blood sample at the midpoint of dialysis. TUR can be calculated using the dialysate flow rate and the dialysis duration and once this is known all the other kinetic parameters can be calculated.

Fractional direct dialysis quantification: A new approach for prescription and monitoring hemodialysis therapy

We describe a new methodology, fractional direct dialysis quantification (FDDQ) utilizing the Fresinius Dialysate Sampling Module (DSM), for quantitating total solute removal during hemodialysis (HD). Our data demonstrate that this technique and Direct Dialysis Quantification (DDQ) yield virtually identical results. FDDQ, however, obviates the practical obstacles that have limited the applicability of DDQ. We discuss the theoretical and practical advantages of this methodology, as compared to urea kinetic modeling (UKM) with Kt/V, for prescribing and monitoring dialysis therapy. FDDQ provides reliable and accurate quantitative data of dialysis function and protein catabolic rate (PCR) independent of questionable theoretical assumptions and parameters required for UKM with Kt/V. It is simple to comprehend and apply. It permits easy comparison of standard and rapid high efficiency dialyses. It also facilitates the quantitative comparison of HD and continuous therapies (peritoneal dialysis and various types of continuous hemofiltration). FDDQ permits the use of other solutes, in place of or in addition to urea, for the quantitation of HD. Because of its simplicity and probable low cost, it can be used with each HD session. It will thus provide accurate data on delivered versus prescribed therapy. These features should permit more accurate monitoring and lead to a clearer understanding of the relationship of outcomes versus delivered dialysis dose, and consequently more effective adjustment of dialysis therapy.

Establishing a dialysis therapy/patient outcome link in intensive care unit acute dialysis for patients with acute renal failure

The aim of this study was to describe a relationship between intensive care unit (ICU) patient acuity, delivered dialysis dosing, and patient mortality from newly acquired acute renal failure (ARF) requiring dialytic support. A prospectively collected ICU ARF registry formed the basis for data comparison. All data was verified. Eight hundred forty-four ICU patients were identified who met biochemical or clinical criteria of ARF and required first-time dialytic support. An acute dialysis scoring system was established using 23 independent variables identified with univariant analysis, and reduced to eight variables with multiple regression analysis in 512 patients. These eight variables were assigned a weighted score derived from their odds ratio, and the scoring system was than validated prospectively to either registry data not involved in the generation of the system (n = 148), or double-blinded score assignment at time of first dialysis (n = 130). Several established scoring systems were also appliedto the database for external comparison. Dialysis dosing was analyzed using either direct dialysate quantification or blood side urea kinetics once appropriate formulae were identified from paired blood/dialysate results. Using our database and four published ARF acuity/predictive models (Lohr, Cioffi, Bullock, Acute Physiology and Chronic Health Evaluation [APACHEii]), outcome predictions were grossly inaccurate. Application of the Cleveland Clinic Foundation (CCF) ARF acuity score showed highly predictable outcomes when compared using the Lemeshow, Hosmer goodness-of-fit statistics, and highly reproducible results in both the prospective database and double-blinded prospective clinical trials. When comparing dialytic support techniques received (intermittent dialysis v continuous therapies), the CCF scoring system remained highly predictive of mortality. When one compares dose of delivered dialysis to patients with ARF in the ICU setting, there seems to be no effect on outcome at the two ends of the scoring system. Those with very low (<4) and very high (>15) CCF scores had survivals of 78% and 0%, respectively, regardless of the dose of dialysis. Patients with intermediate scores seemed to be the most effected by dialysis dose delivery, with higher delivery (>58% urea reduction ratio for intermittent hemodialysis; <45 mg/dL time-averaged concentration of urea (TAC UREA) for continuous renal replacement therapy [CRRT]) associated with a significant reduction in mortality when compared with the same CCF scoring quartile with low-dialysis dose delivery. While underlying patient comorbidity has a significant effect on survival in ARF, the dose of delivered dialysis also seems to play a major role in patients with moderated levels of severity. Methods that allow a higher delivered dialysis dose to this group of patients will be rewarded with improved patient outcome.