Dialysis Clearance Research Articles

Endogenous Markers for Estimation of Renal Function in Peritoneal Dialysis Patients

This method comparison study, conducted at the peritoneal dialysis (PD) outpatient clinic of the Department of Renal Medicine, Aarhus University Hospital, Denmark, set out to evaluate the accuracy and reproducibility of methods for estimating glomerular filtration rate (GFR) based on endogenous markers in PD patients. The 12 consecutive patients included in the study were examined twice while in a stable condition. All patients finished the study. Inclusion criteria were age 18 years or older, ability to collect 24-hour urine, and urine production greater than 300 mL in 24 hours. The methods for estimating GFR using endogenous markers included the average of urinary clearances of creatinine and urea [U-Cl(crea-urea)] and two equations using the serum concentration of cystatin C [eGFR(CysC)]. The resulting GFR estimates were compared with those obtained using urinary and corrected plasma clearances of (51)Cr-EDTA [U-Cl(EDTA) and cP-Cl(EDTA)], the corrected plasma clearance being plasma clearance minus dialysate clearance. Compared with the U-Cl(EDTA), the U-Cl(crea-urea) GFR estimate was 12% higher [95% confidence limits (CL): 3%, 21%]. Although significantly different (p = 0.01), the latter two methods showed the best agreement. The estimates obtained using the eGFR(CysC) methods were skewed from y = x compared with the estimates obtained using other methods, indicating strong bias, probably because of extrarenal elimination. The cP-Cl(EDTA) estimate was 34% (95% CL: 26%, 42%), higher than the U-Cl(EDTA) estimate (p < 0.001). The reproducibility (coefficients of variation) differed significantly between methods: cP-Cl(EDTA), 7%; U-Cl(EDTA), 14%; U-Cl(crea-urea), 18%; and both eGFR(CysC) methods, 3%. In PD patients, GFR may be estimated as U-Cl(crea-urea) when complete urine collection is performed, taking into account an overestimation of approximately 12%. The available equations for eGFR(CysC) seem to be inaccurate; further development and validation is desirable. Omitting the eGFR(CysC) methods, cP-Cl(EDTA) was the most reproducible method and might be useful in certain situations.

Multi-adaptive neural-fuzzy system as a novel predictor of in-vivo blood side dialyser urea clearance

The blood urea concentration has been used as a surrogate marker for toxin elimination in hemodialysed patients, and several indices based on it have been proposed in recent years for monitoring treatment adequacy. Measuring urea nitrogen concentrations at the inlet and outlet of dialyser is crucial to evaluate the in-vivo blood side dialyser urea clearance during hemodialysis. Although frequent measurement is needed to avoid inadequate dialysis efficiency, artificial intelligence can repeatedly perform the forecasting tasks and may be a satisfactory substitute for laboratory tests. Neuro-fuzzy technology represents a promising forecasting application in clinical medicine. In this study, two fuzzy models have been proposed to predict dialyser inlet and outlet urea concentrations in order to estimate dialyser clearance without blood sampling. The model is of multi-input single-output MISO type. Multi-adaptive neuro-fuzzy inference system MANFIS technique of fuzzy-based systems has been employed. The performance of the model is authenticated by evaluating the predicted results with the practical results obtained by conducting the confirmation experiments. The results suggest that the neuro-fuzzy technology, based on limited clinical parameters, is an excellent alternative method for accurately predicting arterial and venous urea concentrations in hemodialysis patients. The proposed model can be used for intelligent online adaptive system.

Dialyzability and Pharmacokinetics of Sitafloxacin Following Multiple Oral Dosing in Infected Hemodialysis Patients

The pharmacokinetics and dialyzability of oral sitafloxacin, a newly available quinolone, in infected intermittent hemodialysis patients have not been reported previously. Seven infected maintenance hemodialysis patients lacking residual renal function were enrolled. Sitafloxacin (50 mg after hemodialysis on the first day, on the next day and 4 h before scheduled hemodialysis session on the 3rd day) was orally administered. On the 3rd day, blood was taken from arterial and venous sides before and 2 and 4 h after session initiation. Another sampling was performed 1 h after the session and on the 5(th) day of the study. Pharmacokinetic parameters and dialyzability of sitafloxacin were evaluated. All patients exhibited improved symptoms without major problems. Drug concentrations in all arterial samples were above the MIC of targeted bacteria. Dialyzer clearance and elimination fraction were 49.9 ± 0.9 mL/min per m(2) and 53.3 ± 2.1%, respectively. Apparent half-life during dialysis session was significantly shorter than that after the session (4.0 ± 0.4 and 46.5 ± 3.6 h, during and after the session, respectively). Dialyzer clearance was positively correlated with urea reduction ratio and negatively correlated with serum albumin concentration. About 23% of the drug in the body was removed by dialysis. Rebound of the drug concentration after the dialysis was not seen. Oral dosing of this drug at 50 mg daily in maintenance hemodialysis patients provides a safe drug concentration compatible with that of healthy subjects orally receiving 100 mg daily. Because a significant amount of the drug was removed, administration might be undertaken after the dialysis session.

Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis

To evaluate the pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis (CVVHD) after intravenous administration of unadjusted dosage regimens. Two critically ill patients had eight blood samples collected during a 12 h interval on days 8 and 10 of polymyxin B therapy. Dialysate was collected every hour during the 12 h dosing interval. Polymyxin B binding in plasma was determined by rapid equilibrium dialysis. Concentrations of polymyxin B in plasma and dialysate samples were quantified using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay. Respective maximum plasma concentrations in patients 1 and 2 were 8.62 and 4.38 mg/L; total body clearances (scaled linearly by body weight) were 0.043 and 0.027 L/h/kg, respectively, of which 12.2% and 5.62% were dialysis clearance, respectively. The corresponding volumes of distribution of polymyxin B at steady state were 0.50 and 0.34 L/kg, respectively, and protein binding in pooled plasma samples was 74.1% and 48.8%, respectively. Our findings indicate that the recommended polymyxin B doses should not be reduced for patients on CVVHD.

New High-Cutoff Dialyzer Allows Improved Middle Molecule Clearance without an Increase in Albumin Loss: A Clinical Crossover Comparison in Extended Dialysis

Background: Accumulation of middle molecules is thought to have adverse effects in patients with acute kidney injury (AKI). Elimination of middle molecules by non-convective means, i.e. hemodialysis, remains difficult. The aim of the study was to investigate the removal characteristics of a new high permeability membrane in AKI patients undergoing extended dialysis (ED). Patients and Methods: We performed a prospective, crossover study comparing the EMiC2 dialyzer (1.8 m², FMC, Germany) and AV 1000S (1.8 m², FMC) in 11 critically ill patients with AKI. β₂-Microglobulin, cystatin c, creatinine, and urea were measured before and after 0.5, 5.0 and 10 h of ED. Serum reduction ratios, dialyzer clearances, and mass in the total collected dialysate were determined. Results: Dialyzer clearance of β₂-microglobulin (EMiC2: 52 ± 1.7 ml/min, AV 1000S: 41.7 ± 1.5 ml/min, p = 0.0002) and cystatin c (EMiC2: 47.2 ± 1.2 ml/min, AV 1000S: 34.2 ± 2.3 ml/min, p < 0.0001) was markedly different, as was the reduction of serum levels of β₂-microglobulin (EMiC2: 54.3 ± 3.6%, AV 1000S: 39.1 ± 4.5%, p = 0.025) and cystatin c (EMiC2: 38.9 ± 2.6%, AV 1000S: 28.0 ± 3.9%, p = 0.043). Additionally, we observed a higher total amount of these substances in the collected dialysate. There was no significant difference in the total amount of albumin eliminated per treatment. Conclusion: The new EMiC2 dialyzer enhances removal of middle molecules without an increase in albumin loss. The clinical relevance of this finding needs to be determined.

Dialysability of sugammadex and its complex with rocuronium in intensive care patients with severe renal impairment

Renal excretion is the primary route for the elimination of sugammadex. We evaluated the dialysability of sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment in the intensive care unit (ICU). Six patients in the ICU with acute severe renal impairment received general anaesthesia for transoesophageal echocardiography, to replace their tracheal tubes, or for bronchoscopy. Five of the six patients were in the ICU after cardiac/vascular surgery and one for pneumonia-induced respiratory failure. They all received rocuronium 0.6 mg kg(-1), followed 15 min later by sugammadex 4.0 mg kg(-1). Two patients were studied for two dialysis episodes and four patients for four episodes. Rocuronium and sugammadex concentrations were measured in plasma and dialysate at several time points before, during, and after high-flux dialysis. Dialysis clearance in plasma and dialysate, and reduction ratio (RR) (the extent of the plasma concentration reduction at the end of a dialysis episode when compared with before dialysis) were calculated for each dialysis episode. Dialysis episodes lasted on average 6 h. Observed RRs indicated mean reductions of 69% and 75% in the plasma concentrations of sugammadex and rocuronium, respectively, during the first dialysis episode. Reductions were around 50% during sequential dialysis episodes. On average, dialysis clearance of sugammadex and rocuronium in blood was 78 and 89 ml min(-1), respectively. Haemodialysis using a high-flux dialysis method is effective in removing sugammadex and the sugammadex-rocuronium complex in patients with severe renal impairment.

Pharmacokinetics of Aliskiren in Patients with End-Stage Renal Disease Undergoing Haemodialysis

Aliskiren represents a novel class of orally active renin inhibitors. This study analyses the pharmacokinetics, tolerability and safety of single-dose aliskiren inpatients with end-stage renal disease (ESRD) undergoing haemodialysis. Six ESRD patients and six matched healthy volunteers were enrolled in an open-label, parallel-group, single-sequence study. The ESRD patients underwent two treatment periods where 300 mg of aliskiren was administered 48 or 1 h before a standardized haemodialysis session (4 h, 1.4 m(2) high-flux filter, blood flow 300 mL/min, dialysate flow 500 mL/min). Washout was >10 days between both periods. Blood and dialysis samples were taken for up to 96 h postdose to determine aliskiren concentrations. Compared with the healthy subjects (1681 ± 1034 ng·h/mL), the area under the plasma concentration-time curve (AUC) from time zero to infinity was 61% (haemodialysis at 48 h) and 41% (haemodialysis at 1 h) higher in ESRD patients receiving single-dose aliskiren 300 mg. The maximum (peak) plasma drug concentration (481 ± 497 ng/mL in healthy subjects) was 17% higher (haemodialysis at 48 h) and 16% lower (haemodialysis at 1 h). In both treatment periods, dialysis clearance was below 2% of oral clearance and the mean fraction eliminated from circulation was 10 and 12% in period 1 and 2, respectively. Drug AUCs were similar in ESRD patients receiving aliskiren 1 or 48 h before dialysis. No severe adverse events occurred. The exposure of aliskiren is moderately higher in ESRD patients. Only a minor portion is removed by a typical haemodialysis session. Aliskiren exposure is not significantly affected by intermittent haemodialysis, suggesting that no dose adjustment is necessary in this population.

Intra-individual variability of serum hepcidin-25 in haemodialysis patients using mass spectrometry and ELISA

Measurement of serum hepcidin levels may provide a useful alternative to the current methods of determining iron status in chronic haemodialysis (HD) patients. However, the biological variability of this pivotal regulator of iron homeostasis is unclear, and the impact of inflammation, dialysis clearance and iron therapy on hepcidin variability has not been established. Two independent studies in chronic HD patients were conducted; serum hepcidin levels were measured at the start of dialysis sessions in 20 UK patients and in 43 Dutch patients by mass spectrometry (MS). Samples from UK patients were also analysed by a competitive enzyme-linked immunosorbent assay (cELISA). Coefficient of variance (CV(1)) was calculated and potential factors affecting CV(1) were also examined. The median CV(1) (inter-quartile range) was 23% (17-28) for the UK MS, 26% (17-48) for the Dutch MS and 23% (17-39) for the UK cELISA. The CV(1) was similar in those patients receiving and those not receiving regular intravenous iron. The CV(1) was not associated with the degree of inflammation. Hepcidin levels were higher following an inter-dialytic period of 3 versus 2 days (P = 0.02). These findings suggest considerable variability of serum hepcidin levels in HD patients. Inflammation and the use of iron did not impact on the degree of variability, and hepcidin levels were higher after an inter-dialytic period of 3 versus 2 days. These findings need to be taken into account in future studies assessing the utility of serum hepcidin as a guide to the use of iron or erythropoiesis-stimulating agents therapy.

Gentamicin Pharmacokinetics and Pharmacodynamics during Short-Daily Hemodialysis

Background/Aims: Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cl_dial) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing. Methods: Six anuric patients undergoing SDHD were enrolled. Patients received intravenous infusion of 2 mg/kg gentamicin on day 1 after the first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cl_dial and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cl_s) and central volume of distribution (V_c) and influence of urea removal estimates on Cl_dial were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and postdialysis as well as daily and every-other-day dosing. Results: A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cl_s and Cl_dial were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cl_s and V_c. Predialysis every-other-day regimens were as effective (C_max ≥8 mg/l and AUC_{48 h} ≥140 mg·h/l) and less toxic (C_min <2 mg/l and AUC_{48 h} <240 mg·h/l) than postdialysis regimens. Conclusions: Estimated gentamicin Cl_dial is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.

Protein-energy wasting and peritoneal function in elderly peritoneal dialysis patients

Nutritional status is important in peritoneal dialysis (PD) patients. We aimed to compare the peritoneal transport (PT) characteristics and indicators of nutritional status in elderly and non-elderly PD patients. One-hundred and four consecutive patients were divided into either the elderly (>65 years old; n = 44) or the non-elderly (≤65 years old; n = 60) group. PT was assessed via the peritoneal equilibration test, Kt/V (K dialyzer clearance of urea, t dialysis time, V volume of distribution of urea), total creatinine clearance (CrCl), and glomerular filtration rate. Subjective global assessment (SGA), serum albumin (ALB), hemoglobin, prealbumin (PA), transferrin (TF), fat-free edema-free body mass (fat-free edema-free BM), and normalized protein intake (nPNA) were determined, and were used to indicate nutritional status. Elderly PD patients had higher dialysate to plasma creatinine ratios (D/P Cr) and CrCl, but lower serum creatinine body weights, ALB, PA, TF, fat-free edema-free BM, SGA, and nPNA than the non-elderly group. Multivariate analysis indicated that, after adjusting for PD time, body weight, diabetes mellitus, age, and sex, SGA negatively correlated with D/P Cr, whereas after adjusting for PD time, diabetes mellitus, and sex, D/P Cr positively correlated with age in all patients. Protein-energy wasting and a high PT are more common in elderly than non-elderly PD patients. Nutritional status should be carefully considered when prescribing the PD dose and frequency, especially in elderly patients.

Evaluation of Vancomycin and Gentamicin Dialysis Clearance Using In Vivo and In Vitro Systems

Advances in hemodialysis (HD) techniques have increased the potential for drug removal. Quantifying drug clearance in clinical studies for all possible dialysis conditions is impractical, given the variability in dialysis conditions. The purpose of this study was to determine the dialysis clearance (CLD) of vancomycin and gentamicin using in vitro and in vivo methods and evaluate the applicability of in vitro data. In vitro dialysis was used to determine the CLD of vancomycin and gentamicin under conditions of intermittent HD (IHD) and sustained low-efficiency dialysis (SLED). Two Fresenius polysulfone dialyzers were studied: F180NR for IHD and F50 for SLED. Data were compared with in vivo CLD determined in patients with end-stage renal disease receiving IHD and from the literature for SLED. Under IHD conditions, in vitro CLD of vancomycin and gentamicin was 131 ± 3 and 154 ± 3 mL/min, respectively, and under SLED condition it was 72 ± 9 and 84 ± 11 mL/min, respectively. These values were 11–27% higher than in vivo CLD for IHD (103 ± 15 mL/min for vancomycin and 132 ± 25 mL/min for gentamicin) and SLED (63 mL/min for vancomycin and 76 ± 38 mL/min for gentamicin). There was a statistically significant difference in vancomycin clearance by IHD for the in vitro study compared with in vivo data (p = 0.012), but not for gentamicin (p = 0.18). In vitro methods overestimated in vivo CLD, but are reasonable to assist with drug regimen design if one considers the limitations.

Study of Factors Affecting Drug Extraction during Continuous Hemofiltration and Hemodiafiltration, and the Contribution of Extraction to Systemic Clearance

The aim of this study was to elucidate the factors affecting dialysis clearance and the need for additional doses of drugs during and after continuous hemofiltration (CHF) and hemodiafiltration (CHDF). We performed a literature search of MEDLINE using the terms hemofiltration OR hemodiafiltration AND pharmacokinetics to obtain the clearances of CHF and CHDF in a clinical setting. The relationships between molecular weight, the unbound fraction (fuB), ultrafiltration flow rate (UFR) and dialysis flow rate were analyzed. The need for additional doses of certain drugs was also discussed based on the ratio of dialysis and systemic clearances. The clearance of CHF for 32 reported drugs was significantly correlated with the product of fuB×UFR (r=0.841, p<0.001), and furthermore the plots obtained lay on a line of y=x. The clearance of CHDF also showed good correlation with the product of fuB×UFR (r=0.795, p<0.001), but the plots were higher than the line for y=x, suggesting that additional clearance by dialysis was not negligible. The elimination by both forms of dialysis for drugs excreted mainly via the kidneys, and with a higher fuB, was considerable. The extent of drug clearance by both CHF and CHDF is determined mainly by fuB and UFR. The ratio of dialysis clearance to systemic clearance should be estimated to determine the contribution of CHF and CHDF.

Phosphate removal model: An observational study of low‐flux dialyzers in conventional hemodialysis therapy

Precise assessing phosphate removal by hemodialysis (HD) is important to improve phosphate control in patients on maintenance HD. We reported a simple noninvasive model to estimate phosphate removal within a 4-hour HD. One hundred sixty-five patients who underwent HD 4 hours per session using low-flux dialyzers made of polysulfone (1.2 m(2)) or triacetate (1.3 m(2)) were enrolled. Blood flows varied from 180 to 300 mL/min. Effluent dialysate samples were collected during the 4-hour HD treatment to measure the total phosphate removal. Predialysis levels of serum phosphate, potassium, hematocrit, intact parathyroid hormone, total carbon dioxide (TCO(2)), alkaline phosphatase, clinical and dialysis characteristics were obtained. One hundred thirty-five observations were randomly selected for model building and the remaining 30 for model validation. Total amount of phosphate removal within the 4-hour HD was mostly 15-30 mmol. A primary model (model 1) predicting total phosphate removal was Tpo(4) = 79.6 × C(45) (mmol/L) - 0.023 × age (years) + 0.065 × weight (kg) - 0.12 × TCO(2) (mmol/L) + 0.05 × clearance (mL/min) - 3.44, where C(45) was phosphate concentration in spent dialysate measured at the 45 minute of HD and clearance was phosphate clearance of dialyzer in vitro conditions offered by manufacturer's data sheet. Since the parameter TCO(2) needed serum sample for measurement, we further derived a noninvasive model (model 2):Tpo(4) = 80.3 × C(45) - 0.024 × age + 0.07 × weight + 0.06 × clearance - 8.14. Coefficient of determination, root mean square error, and residual plots showed the appropriateness of two models. Model validation further suggested good and similar predictive ability of them. This study derived a noninvasive model to predict phosphate removal. It applies to patients treated by 4-hour HD under similar conditions.

The new dialysis method Mini-SLED is useful for dialyzing acute brain stroke patients

Hemodialysis (HD) patients are known to be a high-risk population for brain stroke. On acute phase of stroke, standard HD treatment may increase cerebral damage by changing serum and tissue osmolarity. For low clearance dialysis, CRRT, PD or low Qb HD were used but there are some complications. To dialyze these patients more safely and simply, we modified a new dialysis method, Mini-SLED (sustained low-efficiency dialysis).

Effects of Citrate Acid Concentrate (Citrasate®) on Heparin N Requirements and Hemodialysis Adequacy: A Multicenter, Prospective Noninferiority Trial

Background: Citrasate®, citric acid dialysate (CD), contains 2.4 mEq of citric acid (citrate), instead of acetic acid (acetate) as in standard bicarbonate dialysate. Previous studies suggest CD may improve dialysis adequacy and decrease heparin requirements, presumably due to nonsystemic anticoagulant effects in the dialyzer. Methods: We prospectively evaluated 277 hemodialysis patients in eight outpatient facilities to determine if CD with reduced heparin N (HN) would maintain dialyzer clearance. Subjects progressed through four study periods [baseline (B): bicarbonate dialysate + 100% HN; period 1 (P1): CD + 100% HN; period 2 (P2): CD + 80% HN; period 3 (P3): CD + 66.7% HN]. The predefined primary endpoint was noninferiority (margin –8%) of the percent change in mean dialyzer conductivity clearance between baseline and P2. Results: Subjects were 57.4% male, 41.7% white, 54.3% black, and 44.4% diabetic; mean age was 59 ± 14.4 years; mean time on dialysis was 1,498 ± 1,165 days; 65.7% had arteriovenous fistula, 19.9% arteriovenous graft, 14.4% catheters, and 27.8% used antiplatelet agents. Mean dialyzer clearance increased 0.9% (P1), 1.0% (P2), and 0.9% (P3) with CD despite heparin reduction. SpKt/V remained stable (B: 1.54 ± 0.29; P1: 1.54 ± 0.28; P2: 1.55 ± 0.27; P3: 1.54 ± 0.26). There was no significant difference in dialyzer/dialysis line thrombosis, post-HD time to hemostasis, percent of subjects with adverse events (AEs), or study-related AEs. Conclusions: CD was safe, effective, and met all study endpoints. Dialyzer clearance increased approximately 1% with CD despite 20–33% heparin reduction. Over 92% of P3 subjects demonstrated noninferiority of dialyzer clearance with CD and 33% HN reduction. There was no significant difference in dialyzer clotting, bleeding, or adverse events.

Pharmacokinetics of Ampicillin/Sulbactam in Critically Ill Patients with Acute Kidney Injury undergoing Extended Dialysis

The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t(1/2) of 2.3 hours on and 17.4 hours off dialysis. Despite its frequent use in intensive care units, there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy. The aims of this study were to evaluate the pharmacokinetics of ampicillin/sulbactam in critically ill patients with AKI undergoing extended dialysis (ED) and to establish a dosing recommendation for this treatment method. Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospective, open-label, observational pharmacokinetic study. Pharmacokinetics after a single dose of ampicillin/sulbactam (2 g/1 g) was obtained in 12 patients. Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam (2 g/1 g) was obtained in three patients. The mean dialyzer clearance for ampicillin/sulbactam was 80.1 ± 7.7/83.3 ± 12.1 ml/min. The t(1/2) of ampicillin and sulbactam in patients with AKI undergoing ED were 2.8 ± 0.8 hours and 3.5 ± 1.5 hours, respectively. There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam. Our data suggest that in patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; treatment time, 480 minutes), a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam, with one dose given after ED, should be used to avoid underdosing.

Maintaining residual renal function in patients on haemodialysis: 5-year experience using a progressively increasing dialysis regimen.

In contrast to patients treated with peritoneal dialysis, those on periodical haemodialysis (HD) do not receive programmed progressive increases in dialysis dosage, nor is residual renal function taken into account in the calculation of the total dialysis prescription; rather, only dialyser clearance is factored into the equation. In 2006, we decided to establish a progressively increasing dialysis regimen at the start of renal replacement therapy, evaluating the possibility of starting with 2 sessions of HD/week when renal clearance of urea was equal to or greater than 2.5 ml/min. This study summarises our experience during the first 5 years of application of this progressively increasing HD prescription and its repercussions on residual renal function. We included all patients who started periodical HD between 1/1/2006 and 30/9/2010 and remained on dialysis for more than three months. The follow-up period ended on 31/12/2010 (study end date). When a patient started HD, urea and creatinine clearance levels were measured based on urea and creatinine concentrations in blood samples taken before dialysis and in urine samples taken 24 hours prior to starting the first dialysis session of the week. If urea clearance was equal to or greater than 2.5 ml/min, 2 sessions of HD per week were applied, as long as the patient's clinical situation allowed for it (according to the criteria of the attending physician). Residual renal function was analysed every 2 months until diuresis was less than 100ml/day, which is considered to be basically null. We evaluated the decrease in residual renal function, calculating the rate of decrease in glomerular filtration (ml/min/month) and 24-hour diuresis (ml/month) in patients receiving 2 and 3 HD sessions per week. In January 2010, we took a cross-sectional sample, evaluating glomerular filtration and how this value was associated with various clinical and laboratory parameters in patients receiving 2 or 3 dialysis sessions per week. During the study period, 95 patients were included in the study, 41 of which (43%) started with 2 HD sessions per week, and 54 (57%) with 3 sessions per week. The mean time that patients remained on the 2HD sessions/week regimen was 11.1 ± 7.2 months (range: 2-25 months). Of the 41 patients that started with 2 HD sessions/week, 10 received a transplant while on the treatment regimen, 1 was transferred to peritoneal dialysis, 6 recovered renal function and were able to abandon dialysis treatment, 15 were switched to the 3 HD sessions/week regimen, and 9 continued on the 2 HD sessions/week regimen at the time the study ended. Of the 15 patients that were switched to the 3 HD sessions/week regimen, 4 received transplants, 3 died, and the remaining 8 continued on HD until the end of the study. A Kaplan-Meier survival analysis revealed that patients who started on the 2 HD sessions/week regimen had a greater survival rate (log-rank: 3.964; P=.04). Losses in both glomerular filtration rate and 24-hour diuresis were lower in patients on the 2 HD sessions/week regimen: 0.22 ± 0.36 ml/min/month vs 0.89 ± 1.26 ml/min/month for glomerular filtration (P=.001), and 90.59 ± 132 ml/month vs 206.23 ± 286 ml/month for 24-hour diuresis (P=.001), respectively. In the cross-sectional sample taken in January 2010, 17 patients were on the 2 HD sessions/week regimen and 47 were on the 3 HD sessions/week regimen. Serum concentrations of β2-microglobulin were significantly lower in the 2 HD sessions/week group (19.7 ± 5 vs 38.3 ± 13; P=.000). The mean haemoglobin concentration was similar between the two groups, with a significantly lower dose required of erythropoietin in patients on the 2 HD sessions/week regimen (7058 ± 3749 units/week vs 12 553 ± 10 826 units/week; P=.037). In select populations, the start of HD can be administered on a progressively increasing dosage, starting with two sessions/week. In our experience, this is a safe prescription that probably contributes to preserving residual renal function.

An Experimental, Simplified Method for Intradialytic Cardiac Output Measurement

Hypotension during hemodialysis (HD) is a frequent and troublesome treatment complication. A decrease in the cardiac output (CO) due to an imbalance in the rates of fluid ultrafiltration vs. tissue reabsorption is a major cause of such episodes; thus, routine repeated measurements of CO during HD sessions could be of use in preventing its occurrence. We tested an experimental method (EXP) for measuring CO during HD using hardware already supplied with current Gambro dialysis machines. In 12 HD patients, CO was measured twice during dialysis by injecting a small (2 mL) bolus of highly concentrated saline into the patient's bloodstream and measuring the subsequent increase in dialysate conductivity using the Diascan technology. CO was calculated with the Stewart-Hamilton method using the area under the conductivity curve, measured dialysate flow rate, and dialyzer clearance. Compared with ultrasound hemodilution measurements, the EXP showed no bias and limits of agreement of ±34.6%. The intradialytic trend correlated well between the two methods (r(2) = 0.63, concordance rate 100%). We propose that with further development and refining, reliable measurements of CO could be performed easily during routine HD treatment using this new methodology.

In vitro Characterization of Oritavancin Clearance from Human Blood by Low-Flux, High-Flux, and Continuous Renal Replacement Therapy Dialyzers

Oritavancin is an investigational lipoglycopeptide antibiotic under clinical development for the treatment of gram-positive bacterial infections. The impact of hemodialysis on plasma concentrations of oritavancin is unknown and may be important in making dosage adjustments in such patients. The present study sought to determine the clearance of oritavancin from human blood by various commercially available dialyzers in an in vitro hemodialysis model. Three types each of low-flux (Dicea 130, F6, and Polyflux 14L) and high-flux (Revaclear, Exeltra 150, and Optiflux F160NR) dialyzers and one type of continuous renal replacement therapy (CRRT) dialyzer (Prismaflex M100) were studied. Heparinized human blood containing oritavancin (200 mg/L) was circulated from a reservoir to the dialyzers and back to the reservoir. Fresh dialysate was pumped through the dialyzers in a countercurrent manner. Blood samples from each side of the dialyzers and contaminated dialysate samples were collected at periodic intervals. Oritavancin levels were analyzed by a liquid chromatography/mass spectrometry method with a limit of quantification of 12.5 ng/mL and plasma clearances of oritavancin were calculated. The mean dialytic clearance of oritavancin was insignificant for each of the low-flux, high-flux and CRRT dialyzers. Clinically significant amounts of oritavancin were not detected in dialysate during any of the experimental dialysis sessions. The clearance of oritavancin from human blood by the dialyzers used in this study is insignificant. Further clinical studies would be required before making changes in dosage of oritavancin in hemodialysis patients.

Reliability of 51Cr-EDTA plasma and urinary clearance as a measure of residual renal function in dialysis patients

Purpose: In dialysis patients, longer survival is associated with a higher residual renal function. Randomized controlled trials are conducted to clarify how residual renal function can be preserved. However, existing methods for measuring residual renal function are uncertain and there is a need for establishing a standard for measurements of glomerular filtration rate (GFR) in dialysis patients. Methods: 51Cr-EDTA clearances in plasma, urine, and dialysate were evaluated in a sample of 12 hemodialysis and 12 peritoneal dialysis patients. The patients’ condition was generally stable, and all patients were investigated twice within 4–10 days. Results: Plasma clearances of 51Cr-EDTA for all patients ranged between 2.1 and 30.8 mL/min/1.73m2, whereas urinary 51Cr-EDTA clearances ranged from 0.7–20.0 mL/min/1.73m2. This difference was statistically significant (p < 0.001). Week-to-week reproducibility expressed as coefficients of variation were below or equal to 10% for plasma clearances and 13% for urinary clearances in hemodialysis patients and 14% in peritoneal dialysis patients. Conclusions: This study demonstrated a difference between 51Cr-EDTA plasma and urinary clearances in dialysis patients. Plasma clearance of 51Cr-EDTA had the best reproducibility. For repeated measurements as in clinical prospective trials, we recommend 51Cr-EDTA plasma clearance based on blood sampling at 5 + 24 hours with subtraction of 51Cr-EDTA dialysate clearance in peritoneal dialysis patients. Further studies are needed to corroborate our findings.