8,073 research outputs found

    Disease severity adversely affects delivery of dialysis in acute renal failure

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    Background/Aims: Methods of intermittent hemodialysis (IHD) dose quantification in acute renal failure (ARF) are not well defined. This observational study was designed to evaluate the impact of disease activity on delivered single pool Kt/V-urea in ARF patients. Methods: 100 patients with severe ARF (acute intrinsic renal disease in 18 patients, nephrotoxic acute tubular necrosis in 38 patients, and septic ARF in 44 patients) were analyzed during four consecutive sessions of IHD, performed for 3.5-5 h every other day or daily. Target IHD dose was a single pool Kt/V-urea of 1.2 or more per dialysis session for all patients. Prescribed Kt/V-urea was calculated from desired dialyzer clearance (K), desired treatment time (t) and anthropometric estimates for urea distribution volume (V). The desired clearance (K) was estimated from prescribed blood flow rate and manufacturer's charts of in vivo data obtained in maintenance dialysis patients. Delivered single pool Kt/V-urea was calculated using the Daugirdas equation. Results: None of the patients had prescription failure of the target dose. The delivered IHD doses were substantially lower than the prescribed Kt/V values, particularly in ARF patients with sepsis/septic shock. Stratification according to disease severity revealed that all patients with isolated ARF, but none with 3 or more organ failures and none who needed vasopressive support received the target dose. Conclusion: Prescription of target IHD dose by single pool Kt/V-urea resulted in suboptimal dialysis dose delivery in critically ill patients. Numerous patient-related and treatment-immanent factors acting in concert reduced the delivered dose. Copyright (C) 2007 S. Karger AG, Basel

    Application of Cystatin C Reduction Ratio to High-Flux Hemodialysis as an Alternative Indicator of the Clearance of Middle Molecules

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    Background/Aims: Although high-flux (HF) dialyzers with enhanced membrane permeability are widely used in current hemodialysis (HD) practice, urea kinetic modeling is still being applied to indicate the adequacy of both low-flux (LF) and HF HD. In comparison with urea (molecular weight, 60 Da) and ??2-microglobulin (??2MG, 12 kDa), cystatin C (CyC, 13 kDa) is a larger molecule that has attractive features as a marker for assessing solute clearance. We postulated that CyC might be an alternative for indicating the clearance of middle molecules (MMs), especially with HF HD. Methods: Eighty-nine patients were divided into LF and HF groups. Using single pool urea kinetic modeling, the urea reduction ratio (URR) and equilibrated Kt/Vurea (eKt /Vurea) were calculated. The serum CyC concentrations were measured using particle-enhanced immunonephelometry. As indices of the middle molecular clearance, the reduction ratios of ??2MG and CyC were calculated. Results: The ??2MG reduction ratio (??2MGRR) and CyC reduction ratio (CyCRR) were higher in the HF group compared to the LF group. However, the URR and eKt/Vurea did not differ between the two groups. The CyCRR was significantly correlated with the eKt/Vurea and ??2MGRR (r = 0.47 and 0.69, respectively, both p < 0.0001). Conclusions: Compared to the LF dialyzer, the HF dialyzer removed CyC and ??2MG more efficiently. Unlike the ??2MGRR, the CyCRR was correlated with the eKt/Vurea and ??2MGRR. This study suggests a role for the CyCRR as an alternative indicator of the removal of MMs

    Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study

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

    Urea rebound - some disadvantages of urea kinetic modeling

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    PURPOSE: The objectives of the present study are to determine the average urea rebound by examining the urea concentrations immediately after completion of hemodialysis (HD) and comparing these results to urea concentrations taken 30 min after the procedure (equilibrated values), to assess how the delivered dialysis dose changes when URR and Kt/V are calculated using each of these two values and to evaluate the significance of these differences and the reliability of the indicators in use.MATERIAL AND METHODS: The study covered 30 end-stage renal failure (ESRF) patients, 16 males and 14 females on chronic HD at a mean age of 43.90±10.63 years and average duration of dialysis treatment of 6.90±3.75 years. Average urea values were calculated for each patient using data from three consecutive monthly examinations taken immediately and 30 min after HD in order to determine the mean urea rebound percentage.RESULTS: Mean urea values in samples taken immediately and 30 min after HD showed statistically significant differences (p<0.05). Equilibrating urea concentration led to an average increase of 17.7% at the 30 min after HD. There was a statistically significant difference (p<0.05) between the calculated single pool Kt/V (1.23±0.11) and equilibrated Kt/V (1.17±0.18) as well as concerning mean URR values calculated by using non-equilibrated and equilibrated post dialysis urea (65.3±1.18% and 6.67±2.4%, respectively).CONCLUSION: Calculation of URR and single pool model of Kt/V for assessment of dialysis adequacy in ESRF patients on chronic HD results in overestimation of the delivered dialysis dose. These values differ statistically significantly from those when accounting for urea rebound. URR and Kt/Vsp indicators do not possess the necessary reliability as means to evaluate the delivered dialysis dose.Scripta Scientifica Medica 2013; 45(1): 71-74

    Kinetic Modeling and Adequacy of Dialysis

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

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    Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients.BackgroundAn 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.MethodsIonic 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 (Upwt2′). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and Upwt2′ (VID) are similar to those determined by the “gold standard” DDQ method (VDDQ). Eighty-two anuric hemodialysis patients were studied.ResultsVDDQ was 26.3 ± 5.2 L; VID was 26.5 ± 4.8 L. The (VID–VDDQ) difference was 0.2 ± 1.6 L, which is not statistically significant (P = 0.242). Anthropometric volume (VA) calculated using Watson equations was 33.6 ± 6.0 L. The (VA–VDDQ) difference was 7.3 ± 3.3 L, which is statistically significant (P < 0.001).ConclusionAnthropometric-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

    Effect of dialysate temperature on central hemodynamics and urea kinetics

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    Effect of dialysate temperature on central hemodynamics and urea kinetics. Use of cool dialysate is associated with increased intradialytic blood pressure, but the hemodynamic mechanism is unknown. Whether changes in dialysate temperature affect muscle blood flow, which may the alter the degree of urea compartmentalization, also is unknown. We measured hemodynamics and blood and dialysate-side urea kinetic indices in nine hemodialysis patients during two cool (35.0°C) versus two warm (37.5°C) dialysate treatments. The % change in mean arterial pressure was different when using the cool (+6.5 ± 9.7 mm Hg) versus the warm (-13.4 ± 3.6) dialysate (P < 0.01), despite comparable amounts of fluid removal. Percent changes in cardiac output were similar with the two dialysates, and thus the blood pressure effect was due primarily to changes in total peripheral resistance (%ΔTPR, cool +26 ± 13.6, warm +8.6 ± 14.5; P < 0.02). During cool dialysate use tympanic membrane temperature changed by -0.51 ± 0.23°C, whereas body temperature increased by 0.52 ± 0.14°C during use of warm dialysate. Measured urea recovery normalized to the predialysis urea nitrogen concentration was similar with the two treatments: cool 31.3 ± 0.039 liter-1; warm 29.7 ± 0.021; P = NS. In a second study, post-dialysis urea rebound values from 15 seconds to 30 minutes, expressed as the percent of the post-dialysis SUN, were similar after the two treatments: cool 11.79 ± 1.4; warm 12.21 ± 2.27, P = NS. The results suggest that increased blood pressure associated with use of cool dialysate is due to an increased TPR, and that this alteration in hemodynamics has no clinically important effects on either the amount of urea removal or the extent of post-dialysis urea rebound

    Hemodialysis in children: general practical guidelines

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    Over the past 20 years children have benefited from major improvements in both technology and clinical management of dialysis. Morbidity during dialysis sessions has decreased with seizures being exceptional and hypotensive episodes rare. Pain and discomfort have been reduced with the use of chronic internal jugular venous catheters and anesthetic creams for fistula puncture. Non-invasive technologies to assess patient target dry weight and access flow can significantly reduce patient morbidity and health care costs. The development of urea kinetic modeling enables calculation of the dialysis dose delivery, Kt/V, and an indirect assessment of the intake. Nutritional assessment and support are of major importance for the growing child. Even if the validity of these “urea only” data is questioned, their analysis provides information useful for follow-up. Newer machines provide more precise control of ultrafiltration by volumetric assessment and continuous blood volume monitoring during dialysis sessions. Buffered bicarbonate solutions are now standard and more biocompatible synthetic membranes and specific small size material dialyzers and tubing have been developed for young infants. More recently, the concept of “ultrapure” dialysate, i.e. free from microbiological contamination and endotoxins, has developed. This will enable the use of hemodiafiltration, especially with the on-line option, which has many theoretical advantages and should be considered in the case of maximum/optimum dialysis need. Although the optimum dialysis dose requirement for children remains uncertain, reports of longer duration and/or daily dialysis show they are more effective for phosphate control than conventional hemodialysis and should be considered at least for some high-risk patients with cardiovascular impairment. In children hemodialysis has to be individualized and viewed as an “integrated therapy” considering their long-term exposure to chronic renal failure treatment. Dialysis is seen only as a temporary measure for children compared with renal transplantation because this enables the best chance of rehabilitation in terms of educational and psychosocial functioning. In long term chronic dialysis, however, the highest standards should be applied to these children to preserve their future “cardiovascular life” which might include more dialysis time and on-line hemodiafiltration with synthetic high flux membranes if we are able to improve on the rather restricted concept of small-solute urea dialysis clearance

    Towards Intensified Protein Refolding and Purification on Size Exlusion Chromatography: Fundamental Studies and Mathematical Modelling

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    For industrial recombinant-protein processes, protein refolding and purification are crucial steps towards the recovery of considerable numbers of active and safe therapeutic products. In this thesis, intensification strategies for protein refolding and purification processes are explored. Development of an intensified process aims at simultaneous optimization of process performance indicators, namely: refolding yield, product purity, volumetric productivity and solvent consumption which in turn decrease the cost and time constraints to market. The first strategy investigated related to multivariable experimental work using size exclusion chromatography (SEC) as a refolding method and a denatured/reduced model protein (lysozyme). SEC was selected due to its potential for refolding of higher concentrations of protein compared to conventional refolding methods used currently in industry. The investigated variables were protein loading concentration, refolding buffer composition including pH, sodium chloride salt and ʟ-arginine, aggregation prevention additive, concentrations. The interplay of these process variables was studied and it was shown when ʟ-arginine is used, over the experimental space, the effects of pH and protein loading concentration on refolding yield are insignificant. This observation introduced the possibility of manipulating pH in a wider range without concerns for protein aggregation; for instance, to adjust the redox potential of the buffer without the need for costly redox couple chemicals to assist reformation of disulfide bridges in oxidative refolding of the protein. The results also provide more experimental evidence on the mechanism of aggregation prevention by ʟ-arginine. Secondly an experimentally-verified model of oxidative protein refolding on SEC was developed, with the goal of high-throughput process screening and optimization using the aforementioned model. Model development involved exploration of methods to find characteristic information on short-lived refolding kinetic species and lysozyme oxidative refolding kinetic schemes and constants under the two studied refolding environments, namely with and without ʟ-arginine additive. It was shown that ʟ-arginine prevents aggregation without considerable impact on the kinetics of lysozyme oxidative refolding. Finally, SEC in a multi-column continuous simulated moving bed configuration (SMB-SEC) was evaluated to fully exploit the potential of SEC for intensified protein refolding and purification. This configuration offers several advantages compared to single-column operation, including increased productivity per unit mass of solid phase, lower solvent consumption, and less diluted products, provided that operation parameters are screened and tuned for simultaneous optimization of process performance indicators. In this phase of the project, the effect of scale-up was predicted and considered for modifying and utilizing single-column model towards design/operation of a SMB-SEC. This thesis presents a framework for protein refolding and purification process development and optimization, including reduced cost of chemicals, improving the refolding yield, high-throughput measurements of parameters and finding a suitable reaction scheme of refolding and aggregation for mathematical model development applicable to both single-column and multi-column continuous operations, and defining appropriate process performance indicators for optimized operation of SMB-SEC
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