C. Mion

Protein catabolic rate over lean body mass ratio: A more rational approach to normalize the protein catabolic rate in dialysis patients

Protein catabolic rate (PCR), equivalent to dietary protein intake in stable dialysis patients, is widely accepted as a marker of their protein nutritional status. PCR is usually established from urea generation rate using urea kinetic modeling (UKM), but the normalizing factor is still a matter of controversy. By convention, PCR is expressed in grams of protein degraded daily divided by the dry body weight (BW) (nPCRBW). To be valid, this implies that dry BW is close to ideal BW and that body composition is preserved with a lean body mass (LBM) over BW ratio near 0.73. Such conditions being infrequently found in dialysis patients, it has been proposed to normalize PCR to ideal BW or to total body water, but these correction factors are not really appropriate. A more rational approach would be to express PCR as the ratio of protein degraded to the kilograms of LBM (nPCRLBM), thus offering the main advantage of directly coupling PCR to changes in protein or nitrogen reserve. In this study, we developed a combined kinetic model of urea and creatinine applied to the midweek dialysis cycle in 66 end-stage renal disease (ESRD) patients. UKM provided Kt/V and PCR, whereas creatinine kinetic modeling (CKM) was used to calculate LBM. Thirty-four patients with a preserved LBM (LBM/dry BW ratio equal to or greater than 0.70; mean ratio, 0.81 +/- 0.11) and with a dry/ideal BW ratio of 1.01 +/- 0.16 had a mean PCR of 1.14 +/- 0.30 g/kg/24 h when normalized to BW (nPCRBW) and of 1.40 +/- 0.30 g/kg/24 h when normalized to LBM (nPCRLBM). In the 32 patients with a reduced LBM (LBM/dry BW ratio, below 0.70; mean ratio, 0.60 +/- 0.09) and dry/ideal BW ratio of 1.11 +/- 0.23, the mean nPCRBW was 0.99 +/- 0.31 g/kg/24 h, whereas nPCRLBM was 1.62 +/- 0.32 g/kg/24 h. For both subgroups, Kt/V was similar, with mean values of 1.76 +/- 0.34 and 1.69 +/- 0.27. Normalizing PCR to LBM offers a double benefit: it compensates for the error induced by abnormal body composition (eg, obese patients) and permits PCR to be adjusted for the decrease in LBM that occurs with age. We propose nPCRLBM as a more rational index to express PCR in dialysis patients.

Recombinant Human Erythropoietin: 18 Months' Experience in Hemodialysis Patients

It has been shown that the regular administration of erythropoietin (EPO) permits the correction of anemia in end-stage renal failure patients. We analyzed the effect of chronic administration of EPO in 13 stable, regularly dialyzed end-stage renal failure patients over an 18-month period. The effects of EPO were evaluated according to standard criteria including clinical status, blood pressure control, hematology and biochemistry data, protein nutritional status, and dialysis efficiency. Following a 2-week control period, EPO was administered intravenously (IV) after the dialysis session according to a two-phase protocol. The first period (correction phase) consisted of a stepwise EPO dose increment, starting at 3 x 24 IU/kg/wk and doubling the dose every 14 days according to hemoglobin response in order to achieve a target hemoglobin level of approximately 11.0 g/dL (110 g/L). In the second period (maintenance phase) EPO dose was optimized to maintain the hemoglobin level between 100 and 110 g/L (10.0 and 11.0 g/dL), by adjusting either the unit dose or the frequency of injection. Anemia was corrected in all patients within 11 weeks, with EPO dose increasing from 72 to 360 IU/kg/wk. The stabilization of hemoglobin was achieved with an average EPO dose of 275 IU/kg/wk (50 to 476 IU/kg/wk). Concomitantly, a subjective and clinical improvement was noted in all patients. The dialysis efficacy remained in an acceptable range throughout the study, falling significantly (approximately 10%) through the first 3 months of treatment to stabilize at an effective urea clearance of approximately 120 L/wk. The dietary protein intake calculated from urea kinetic modeling ranged between 1.1 and 1.2 g/kg/d.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythropoietin-Induced Changes in Protein Nutrition: Quantitative Assessment by Urea Kinetic Modeling Analysis

To evaluate objectively the effects of recombinant human erythropoietin (rHuEPO) administration on nutritional status in stable dialyzed patients, we used urea kinetic modeling (UKM) analysis and dietary protein intake evaluation by dietary assessment. Fifteen patients (9 females, 6 males; mean age 46.9 +/- 15.6 years) dialyzed for 9.4 +/- 6.3 years were studied longitudinally for 18 months, consisting of a control period (6 months) and an rHuEPO treatment period (12 months). Treatment modalities based on 3 weekly sessions were hemodialysis in 12 patients (6 cuprophane, 3 cellulose acetate and 3 highly permeable membranes), hemodiafiltration in 2 patients and postdilutional hemofiltration in 1 patient. Bicarbonate buffered dialysate was used in 9 patients and acetate in 6 patients. Urea kinetic modeling using a single-pool model was performed monthly over 1-3 cycles. rHuEPO was administered intravenously at the end of dialysis according to a two-phase protocol: (1) correction of anemia by stepwise increment of rHuEPO dose, and (2) maintenance dose to keep hemoglobin at 10-11 g/dl. rHuEPO administration corrected anemia in all patients, improving their general clinical condition. Dialysis efficacy was significantly reduced (15%) after the 3rd month of rHuEPO therapy. Clearnces were restored by increasing dialysis time and/or improving dialyzer performances, and adequacy of dialysis was maintained in all patients. During the 12 months of rHuEPO therapy, the protein catabolic rate remained stable at 1.2 g/kg/24 h in spite of an increase in appetite. At the same time, dry body weight increased significantly after 9 months, and the ratio dietary protein intake/protein catabolic rate a gross estimation of nitrogen balance, increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and Microbiological Evaluation of a Postdilutional Hemofiltration System with In-Line Production of Substitution Fluid

Safety and efficacy of a recently developed hemofiltration (HF) system with in-line production of substitution fluid (GHS-10; Gambro, Lund, Sweden) based on a sterilizing filtration of acetate buffered dialysate has been evaluated in 4 patients over a 6-month period. Two patients were prematurely excluded from the study: 1 because of acetate intolerance and the other because of kidney transplantation. Two patients completed the study (240 HF sessions). Treatment adequacy was maintained in the 2 medium term treated patients according to the usual clinical and biochemical criteria and a mean exchange volume of 100-105 liters/week (30-35 liters/session three times weekly). Urea kinetic modeling analysis performed over all HF cycles gave the following results: dialysis index (urea clearance.time-on HF/urea volume space) (KT/V) approximately 1-1.1, urea time averaged concentration (UREA TAC) approximately 15-20 mmol/l, and protein catabolic rate (PCR) approximately 1.1-1.2 g/kg/day. Rare clinical adverse symptoms observed during the course of sessions were attributed to acetate intolerance. Microbiological safety was confirmed in vivo by the absence of pyrogenic reactions after 240 HF sessions (approximately 7 m3 substitution fluid infused intravenously) and in vitro by the constant absence of bacteria and/or endotoxin content limulus amaebocyte lysate (LAL) sensibility threshold 10 pg/l within the infusate produced during the sham HF sessions. The fluid mass balance obtained with the GHS-10 monitor was excellent. The electrolyte composition as judged by Na variation remained in a range of 2-3%. GHS-10 used in this study for postdilutional HF confirms that a large quantity of intravenous quality fluid may be safely produced by ultrafiltration from dialysate. It also introduced a new dimension in biocompatibility of dialysis by demonstrating that sterile dialysate may be routinely produced and used for routine dialysis.

Analysis of the Influence of the Infusion Site on Dialyser Clearances Measured in an in vitro System Mimicking Haemodialysis and Haemodiafiltration

Background: Blood flow (QB), dialysate flow (QD), and dialyser characteristics are the three major factors driving dialysis efficacy. Haemodiafiltration has added an increased convective volume to increase efficacy. We aimed to assess the influence of the infusion site of the replacement fluid in an in vitro system emulating haemodiafiltration. Methods: An in vitro system allowing us to control the dialysate temperature, concentration gradient, the flow of both dialyser sides over a range wider than that compatible with clinic, was set to evaluate the influence of the different parameters on dialysis efficacy. The total ion clearance was used as an accepted method for small molecule clearance assessment. Cellulose triacetate (CT190C, Baxter; FB170U, Nipro) and polysulfone (HF80, Fresenius) dialysers were included in the study. Dialysis as well as on-line diafiltration both with pre- and postdilutional infusion were assessed. The experimental conditions presented in this study included QD 620 and 970 ml/min. The convective flows ranged from 50 to 200 ml/min. Results: For a QD = 620 ml/min and a QB = 350 ml/min the total ion clearance ranged from 269 to 274 for HF80, from 291 to 294 for FB170 and from 294 to 302 for CT190. The variability of the measurements was very low (SD < 1%). Total ion clearance increased by 17–21% when QB was raised from 300 to 400 ml/min. Increasing QD from 420 to 970 ml/min (for QB = 350 ml/min), resulted in an increase in total ion clearance which was more marked at lower QD (from 420 to 620 ml/min) and plateaued thereafter (from 620 to 970 ml/min). Postdilutional on-line diafiltration with 100 ml/min of infusate resulted in an additional increase in total ion clearance of 5.4–8.6%. This increase was proportional to the infused volume. On the contrary, predilutional on-line diafiltration resulted in a decrease in total ion clearance which was also proportional to the infused volume (between –5.1 and –6.9% at 100 ml/min infusion volume and –9.7 to –12.9% at 200 ml/min). Conclusions: The present in vitro system provided accurate and reproducible results on dialyser clearances. Our experiments confirmed previous studies on the influence of QB and QD on dialyser efficacy. Further, they show that the proportional increase in postdilutional on-line diafiltration is lesser than that previously reported. More importantly, they also show that pre-dilution infusion in high efficiency systems results in a drop in dialyser clearance compared to dialysis alone, again proportional to the infusion rate. Thus, increasing the convective flow may increase dialysis efficacy even more than increasing QD alone. However, the choice of infusion site is crucial to obtaining this benefit in small molecule clearances.

Microbiological Aspects of the Batch Preparation of Replacement Fluid for Hemofiltration

A batch preparation system for manufacturing the replacement fluid for hemofiltration was investigated by microbiological methods. The elements of the pretreatment system of tap water (depth filters,

Effects of Haemofilter Reuse on Membrane Permeability Characteristics in Post-Dilutional Haemofiltration

The cost of post-dilutional haemofiltration (HF) is one of the major factors limiting the wider application of this technique in end stage renal disease. Reuse of the haemofilters is one of the procedures which could contribute to cost containment in HF. The method for reprocessing haemofilters presented here was shown to be safe and efficient. The restoration of the permeability characteristics of the haemofilter membrane can be monitored during each session from repeated measurements of ultrafiltration rates.