Patient‐specific phosphorus mobilization clearance during nocturnal and short daily hemodialysis

The kinetics of plasma phosphorus during different hemodialysis (HD) modalities are incompletely understood. We recently demonstrated that a pseudo one‐compartment kinetic model including phosphorus mobilization from various body compartments into extracellular fluids can describe intradialytic and postdialytic rebound kinetics of plasma phosphorus during conventional and short 2‐hour HD treatments. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter, the phosphorus mobilization clearance (K_M). In this report we determined K_M in patients treated by in‐center nocturnal HD (ICNHD) and short daily HD (SDHD) with low dialyzer phosphate clearance. In the ICNHD study, eight patients underwent 8‐hour HD treatments where intradialytic and postdialytic plasma samples were collected; K_M values were determined by nonlinear regression of plasma concentration as a function of time. In the SDHD study, five patients were studied during 28 treatments for approximately 3 hours. Here, K_M was calculated using only predialytic and postdialytic plasma phosphorus concentrations. Dialyzer phosphate clearances were 134 ± 20 (mean ± SD) and 95 ± 16 mL/min during ICNHD and SDHD, respectively. K_M values for the respective therapies were 124 ± 83 and 103 ± 33 mL/min, comparable to those determined previously during conventional and short HD treatments of 98 ± 44 mL/min. When results from ICNHD, SDHD, and previous HD modalities were combined, K_M was directly correlated with postdialytic body weight (r = 0.38, P = 0.025) and inversely correlated with predialytic phosphorus concentration (r = ?0.47, P = 0.005). These findings suggest that phosphorus kinetics during various HD modalities can be described by a pseudo one‐compartment model.     

Effect of a single hemodialysis session on inflammatory markers

Inflammation is a common feature of end-stage renal disease. Although there is evidence for hemodialysis (HD)-induced inflammatory process, the effect of a dialysis session on changes in inflammatory markers is still unclear. Seventeen patients of end-stage renal disease on maintenance HD along with 20 age-matched and sex-matched healthy controls were recruited after informed consent. C-reactive protein (CRP) and lipoprotein-associated phospholipase A2 (LpPLA2) activity were measured in the study and control groups. Intradialytic in CRP and LpPLA2 were studied. Comparison of pre-HD vs. the control group and predialytic and postdialytic values was performed using the Mann-Whitney U test and Wilcoxon's test, respectively. Statistical evaluation of intradialytic changes in inflammatory markers was performed using Friedman's test. Hemodialysis patients had higher CRP levels compared with controls (P=0.001). Post-HD LpPLA2 activity (n=17) was higher (P=0.039) compared with the pre-HD activity. Intradialytic changes in inflammatory markers showed a significant increase (P=0.012) in LpPLA2 activity (n=7), while no change (P=0.133) was observed in CRP levels (n=17). Evidence on the pro-inflammatory state being initiated by dialysis is provided by increased LpPLA2 activity. This may add to the atherogenic mileu and cause endothelial dysfunction in this high-risk group. Drugs that inhibit the LpPLA2 pathway have been developed and may be effective in these patients.     

Activity concentrations of ²²⁶Ra, ²³²Th and ⁴⁰K in brands of fertilisers used in Nigeria

The activity concentration of naturally occurring radionuclides ??K, 22?Ra and 232Th have been measured in different brands of fertiliser samples sold to farmers in retail markets in six commercial cities in southwestern Nigeria. Gamma ray spectroscopy was employed in the measurements of these radionuclides. The results of measurements showed that the average activity concentration of ??K in the nitrogen, phosphorus and potassium fertilisers across the cities varied from 3972.0 ± 416.9 to 5089.3 ± 111.3 Bq kg?1, 9.9 ± 7.3 to 450.6 ± 14.3 Bq kg?1 for 22?Ra, while for 232Th it varied from less than lower limit of detection to 15.1 ± 2.8 Bq kg?1. The activity concentrations of ??K, 22?Ra and 232Th in single super phosphate (SSP) fertilisers and phosphate rocks were also determined. However, high activity concentrations of 22?Ra were obtained in the SSP fertiliser and phosphate rocks and in particular, two brands of fertilisers from ITL/TAK and F & C companies. The values of the activity concentration of the radionuclides in the brands of fertilisers used in Nigeria are within the range of values reported in several other countries except ??K.     

Dialysate saving by automated control of flow rates: comparison between individualized online hemodiafiltration and standard hemodialysis

Cost reduction and quality improvement seem to be conflicting issues. However, online hemodiafiltration (oHDF) with new automatic functions offers a cost‐efficient therapy compared to hemodialysis (HD). Seven dialysis centers conducted a randomized clinical trial with cross‐over design: high‐flux HD vs. postdilutional oHDF with functions coupling both dialysate and substitution flow rates to blood flow rates. During the 6 weeks of the study, all treatment parameters remained unchanged for HD and oHDF, apart from dialysate and substitution flow rate. Treatment data were recorded during each treatment, and predialytic and postdialytic concentrations of urea were recorded at the end of each study phase. The analysis involved 956 treatments of 54 patients. The mean dialysate consumption was 123.2 ± 6.4 l for HD and 113.4 ± 14.9 l for oHDF (p < 0.0001), the mean dialysis dose was 1.42 ± 0.23 for HD and 1.47 ± 0.26 for oHDF (p < 0.0001); oHDF resulted in a lower dialysate consumption (8.0% less) and a slightly increased dialysis dose (Kt/V 3.5% higher) compared to HD. oHDF with the investigated automatic functions offers substantial savings in dialysate consumption without decreasing dialysis dose.     

A simple pharmacokinetic model of alendronate developed using plasma concentration and urine excretion data from healthy men

The study of pharmacokinetics of alendronate has been hampered by difficulties in accurately and reproducibly determining their concentrations in serum and urine. Thus, pharmacokinetic characteristics of alendronate have been described in many reports based on urinary excretion data; and plasma pharmacokinetics and the simultaneous pharmacokinetic models of alendronate in plasma and urine are not available. The aims of this study were to measure alendronate concentration in plasma and excretion in urine concurrently and to develop compartmental pharmacokinetic model using urine data. In open-label, single-dose pharmacokinetic study, 10 healthy male volunteers received oral dose of alendronate (70?mg tablet). Blood and urine alendronate concentrations were determined using validated high-performance liquid chromatography method. Non-compartmental analysis was performed using WinNonlin program (Pharsight Inc., Apex, NC). A one-compartment pharmacokinetic model was applied to describe pharmacokinetics of alendronate. A peak plasma alendronate concentration of 33.10?±?14.32?ng/mL was attained after 1.00?±?0.16?h. The cumulative amount of alendronate excreted in urine and peak excretion rate were 731.28?±?654.57?μg and 314.68?±?395.43?μg/h, respectively. The model, which included first-order absorption rate for oral dosing, showed good fit to alendronate data obtained from plasma and urine. The absorption rate constant was 2.68?±?0.95?h^–1. The elimination rate constants K_urine and K_non-ur were 0.005?±?0.004?h^?1 and 0.42?±?0.08?h^?1, respectively. The pharmacokinetics of alendronate in plasma and urine of healthy men can be predicted using one-compartment model, and thus the behavior of drug in plasma can be estimated from urinary excretion data.     

Metformin intoxication requiring dialysis

Metformin (MTF) is one of the most common oral agents used to treat diabetes mellitus. Intoxication is associated with lactic acidosis and has significant clinical consequences. We report 12 cases requiring dialytic intervention. Twelve patients were analyzed from 2005 to 2010; 10 of these patients were treated with dialysis. Conventional hemodialysis (HD) and continuous veno-venous hemodialysis treatments with bicarbonate dialysis were used, and the results were presented as mean and standard deviation. The results are as follows: 33% of the patients were male, hospital stay was 9.3 (± 12) days, average MTF dose 1.7 g/day, mortality was 25%. Baseline glomerular filtration rate for these patients was 51.5?mL/min, with an average age of 64 (± 11) years. On presentation, all had acute kidney injury with blood urea nitrogen/creatinine 75 (± 30)/8.1 (± 3.7) mg/dL, lactic acid 12.4 (± 8.1) mmol/L, pH?7.04 (± 0.19), bicarbonate 7.2 (± 4.5) mmol/L. Metformin level was 25 (± 17) μg/mL; anion gap was 28 (± 9), and serum potassium was 5.4 (± 1.3) mEq/L. Seventy percent of patients were treated with conventional HD. Patients required 4 (± 5) dialysis treatments at blood flow QB 330 (± 53), dialysis flow QD 571 (± 111) for 305 (± 122) minutes. Postdialysis, the acidosis parameters improved: bicarbonate 19.2 (± 4.1) mmol/L, lactic acid 6 (± 4) mmol/L and MTF levels decreased 8.9 (± 5.7) μg/mL. Metformin percentage removal was calculated to be 60% (± 24). No difference was found between HD and continous veno-venous hemodialysis. The only difference between survivors was the age 53 (± 7) vs. 78 (± 10) (P?相似文献   

Pharmacokinetic evaluation and antitumor activity of 2-methoxyestradiol nanosuspension

The aim of the present study was to evaluate the pharmacokinetic and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension relative to 2-ME solution both in vitro and in vivo. The pharmacokinetics of 2-ME administered either as a nanosuspension or as a solution were compared after I.V. administration to rats. In plasma, 2-ME nanosuspension exhibited a significantly (p?相似文献   

Enhanced solute removal with intermittent, in-center, 8-hour nocturnal hemodialysis

Advances in the dialysis technique and increasing urea Kt/V have not improved outcomes for end‐stage renal disease patients maintained on hemodialysis (HD) therapy. Attention has, thus, focused on enhancing solute removal via prolonged HD sessions. A reduction in the serum levels of phosphorus and β‐2‐microglobulin (B2M) with longer HD treatments has been linked to improved patient outcomes. We have shown that serum phosphorus levels are significantly lowered in patients maintained on thrice‐weekly, in‐center, 8‐hour nocturnal HD performed at a blood flow rate of 400 mL/min. The kinetics of this modality were examined. A total of 8 patients participated in the study (age 45±7 years). Serum creatinine levels decreased from 9.2±1.9 to 3.0±1.0 mg/dL at 8 hours while serum phosphorus decreased from 5.7±1.9 to 2.5±0.7 mg/dL at 8 hours. The initial decrease from predialysis values to 1 hour after the start of HD was significant for both creatinine (P<0.0001) and phosphorus (P<0.001). Serum B2M decreased from 26.8±5.5 mg/L predialysis to 14.9±7.0 mg/L at 8 hours (P<0.01). Dialysate‐side clearances of phosphorus and creatinine were 136±13 and 143±27 cm³/min, respectively. Phosphorus clearances were steadily maintained during the 8‐hour session. A total of 904±292 mg of phosphorus was removed during the 8‐hour treatment, with 501±174 mg (55%) removed during the first 4 hours and the remaining 45% continuously removed during the latter one‐half of the session. The overall calculated B2M clearance was 55.1±40.3 cm³/min using the immediate post‐B2M value and 28.4±34.2 mg/L using the 30‐minute postdialysis value for the calculation. Serum levels of phosphorus and B2M decrease dramatically during an 8‐hour session. Future studies are necessary to determine whether the enhanced solute removal with longer HD sessions translates into an improved outcome for HD patients.     

Azadirachta indica (Neem) leaf powder as a biosorbent for removal of Cd(II) from aqueous medium

A biosorbent, Neem leaf powder (NLP), was prepared from the mature leaves of the Azadirachta indica (Neem) tree by initial cleaning, drying, grinding, washing to remove pigments and redrying. The powder was characterized with respect to specific surface area (21.45 m2g(-1)), surface topography and surface functional groups and the material was used as an adsorbent in a batch process to remove Cd(II) from aqueous medium under conditions of different concentrations, NLP loadings, pH, agitation time and temperature. Adsorption increased from 8.8% at pH 4.0 to 70.0% at pH 7.0 and 93.6% at pH 9.5, the higher values in alkaline medium being due to removal by precipitation. The adsorption was very fast initially and maximum adsorption was observed within 300 min of agitation. The kinetics of the interactions was tested with pseudo first order Lagergren equation (mean k(1)=1.2x10(-2)min(-1)), simple second order kinetics (mean k2=1.34x10(-3) gmg(-1)min(-1)), Elovich equation, liquid film diffusion model (mean k=1.39x10(-2)min(-1)) and intra-particle diffusion mechanism. The adsorption data gave good fits with Langmuir and Freundlich isotherms and yielded Langmuir monolayer capacity of 158mgg(-1) for the NLP and Freundlich adsorption capacity of 18.7 Lg(-1). A 2.0 g of NLP could remove 86% of Cd(II) at 293 K from a solution containing 158.8 mg Cd(II) per litre. The mean values of the thermodynamic parameters, DeltaH, DeltaS and DeltaG, at 293 K were -73.7 kJmol(-1), -0.24 Jmol(-1)K(-1) and -3.63 kJmol(-1), respectively, showing the adsorption process to be thermodynamically favourable. The results have established good potentiality for the Neem leaf powder to be used as a biosorbent for Cd(II).     

The Decline in Residual Renal Function in Hemodialysis Is Slow and Age Dependent

Background: Persons on peritoneal dialysis and hemodialysis with preserved residual renal function experience lower mortality rates than those without. Previous studies have shown slower rates of decline of residual renal function for peritoneal dialysis (PD)(2 to 3% decrease/month), compared with hemodialysis (HD)(6 to 7% decrease/month). However, our clinical observations suggested a lower rate of decline in hemodialysis patients. Methods: We evaluated data in 174 hemodialysis patients cared for from January 2000 through October 2001. Eighty‐seven (50%) patients had at least two timed quarterly urine collections to estimate the rate of change of residual renal function over time (urea clearance, or KrU). All patients underwent thrice‐weekly hemodialysis using polysulfone dialyzers with formaldehyde reprocessing. The rate of decline of residual renal function and the effect of KrU on laboratory variables were estimated using a random effects (MIXED) model, adjusting for the effects of age, sex, race, diabetes, and dialysis vintage. Results: The mean KrU at baseline was 3.5 mL/min. Men (P < 0.001) and persons of shorter vintage (P < 0.0001) had more residual renal function at baseline. The estimated rate of decline of residual renal function was ? 0.07 mL/min/month (? 1.9% decrease/month). The rate of decline in residual renal function was unaffected by sex, race, diabetes, or vintage, although the rate of decline was significantly attenuated among older individuals (age x time interaction, P = 0.01). Serum phosphorus (P = 0.03) and the calcium x phosphorus product (P = 0.009) increased over time and were influenced by the level of residual renal function (P = 0.06 and P = 0.006, respectively). Residual renal function did not influence the rate of change of other laboratory variables. Conclusions: In an ethnically diverse cohort of hemodialysis patients, the rate of decline of residual renal function was relatively slow and age dependent, as well as consistent with values others have reported for patients on peritoneal dialysis. Universal use of biocompatible dialyzers and bicarbonate dialysate may have contributed to differences discussed in prior reports. Residual renal function attenuated the increase in calcium–phosphorus product over time. A better understanding of the determinants of the rate of decline in residual renal function, and the specific benefits afforded to patients via maintenance of residual renal function, would help to inform the debates on timing of initiation and various dosing strategies in hemodialysis.     

Effects of secondary amyloidosis on arteriovenous hemodialysis fistula outcomes and intradialytic hypotension: a case-control study

Amyloid fibrils can affect vascular structure through deposition and by causing nitric oxide depletion and increase of asymmetric dimethyl arginine. Patients with amyloidosis are prone to development of hypotension. Hypotension may also affect the maturation of arteriovenous fistula (AVF) and may set the stage for formation of thrombosis and fistula failure. Thus, we aimed to evaluate effects of secondary amyloidosis on AVF outcomes and intradialytic hypotension. This is a case‐control study which included 20 hemodialysis patients with amyloidosis and 20 hemodialysis patients without amyloidosis as control group. All patients underwent Doppler ultrasound of AVF. A thorough fistula history and baseline laboratory values along with episodes of intradialytic hypotension and blood pressure measurements were recorded. There was no difference between the groups regarding age, gender, body mass index, presence of comorbidities, hypertension, and drug use. Systolic and diastolic blood pressures were similar (119 ± 28/75 ± 17 and 120 ± 14/75 ± 10 mmHg for patients with and without amyloidosis, respectively). Intradialytic hypotension episodes were also similar. Patients with amyloidosis had significantly lower serum albumin and higher C‐reactive protein values compared to control hemodialysis patients. AVF sites and total number of created fistulas were similar in both groups. Flow rates of current functional AVFs were not different between the groups (1084 ± 875 and 845 ± 466 mL/minute for patients with and without amyloidosis, respectively, p:0.67). Patency duration of first AVF was not different between the groups. Clinical fistula outcomes and rate of intradialytic hypotension episodes were not significantly different between patients with and without secondary systemic amyloidosis.     

Inappropriately elevated endothelin‐1 plays a role in the pathogenesis of intradialytic hypertension

The aim of this study is to investigate the effects of endogenous vasoactive substances on the occurrence of intradialytic hypertension (IDH) in patients during maintenance hemodialysis. Thirty‐four maintenance hemodialysis patients were enrolled in this trial, and 17 of them were diagnosed with IDH (defined as an increase in blood pressure of at least 10 mmHg during or immediately after a hemodialysis session), while 17 age‐matched and sex‐matched controls without IDH were selected for a retrospective comparison. We collected patients' blood samples before and after a dialysis session and measured the plasma levels of N‐terminal fragment brain natriuretic peptide, renin, angiotensin‐II, aldosterone (ALD), angiotensin‐converting enzyme (ACE), endothelin‐1 (ET‐1), nitric oxide (NO), norepinephrine (NOR), and adrenomedullin. The post‐dialysis serum ET‐1 concentrations were significantly higher (4.09 ± 2.06 vs. 2.75 ± 1.34 pg/mL, P < 0.05), while the post‐dialysis ratio of NO to ET‐1 was lower (17.79 ± 5.65 vs. 24.78 ± 12.04, P < 0.05) in IDH patients compared with the control group. Post‐dialysis ALD and NOR values were significantly lower (P < 0.01) and ACE levels were significantly higher (P < 0.01) than the pre‐dialysis concentrations only in the control and not in the IDH group. All other measured factors did not differ significantly between the groups and between pre‐dialysis and post‐dialysis determinations. Compared with blood angiotensin‐II, ALD, ACE, NOR, adrenomedullin, N‐terminal fragment brain natriuretic peptide, and NO status, inappropriately elevated ET‐1 plasma concentrations may play a predominant role in the pathogenesis of IDH.     

Volume Effects of Daily Hemodialysis

Daily hemodialysis appears to be well tolerated, with hypotension rarely complicating such therapy, a finding that is the subject of this review. When daily hemodialysis utilizes a shorter treatment time, this may limit the intradialytic reduction in plasma volume. This reduction is a function of treatment time, ultrafiltration rate (UFR), and plasma refilling rate (PRR). However, daily therapy may be associated with a higher UFR and lower PRR, both of which may accentuate the fall in plasma volume. The reduced frequency of intradialytic hypotension may, in part, be related to other aspects of such therapy, such as the smaller oscillations and decreased dialytic flux of hemodynamically active solutes.     

Reducing the risk of intradialytic hypotension by altering the composition of the dialysate

Hypotension is the most common complication of outpatient hemodialysis sessions, with a reported prevalence of 4% to 31%, depending on which definition has been used and whether patients are symptomatic and nursing interventions were required. Dialysis centers which mix the dialysate in the dialysis machine have the opportunity to individualize the composition of the dialysate for patients. This permits a choice of dialysate sodium, potassium, calcium, magnesium, bicarbonate, acetate, and citrate concentrations and temperature. Studies have reported a higher intradialytic systolic blood pressure and fewer episodes of intradialytic hypotension when using a higher dialysate sodium, calcium, magnesium concentrations and lower temperature, but no clinical advantage for changing the potassium, bicarbonate, or citrate for acetate concentrations. The introduction of newer technology allowing real time measurements of plasma electrolyte concentrations will potentially allow changing the dialysate composition to reduce the risk of intradialytic hypotension without increasing the risk of positive electrolyte balances.     

We Should Strive for Optimal Hemodialysis: A Criticism of the Hemodialysis Adequacy Concept

Adequacy of hemodialysis is frequently equated with Kt/V_urea , the amount of urea clearance (K) multiplied by time (t) and divided by urea distribution volume (V). Several formulas have been developed to calculate Kt/V_urea from the pre‐ and post‐dialysis urea concentrations. In three‐times‐weekly hemodialysis, a single pool (spKt/V_urea) value of 1.3 per treatment is commonly considered to indicate adequate therapy.
Despite providing the recommended spKt/V_urea of 1.3 per treatment, short dialysis with rapid ultrafiltration is associated with multiple intradialytic and interdialytic complications. Patients experience cramps, nausea, vomiting, headaches, fatigue, hypotensive episodes during dialysis, and hangover after dialysis; patients remain fluid overloaded with subsequent poor blood pressure control, left ventricular hypertrophy, diastolic dysfunction, and high cardiovascular mortality.
According to Webster's dictionary, "optimal" means most desirable or satisfactory; "adequate" means sufficient for a specific requirement or barely sufficient or satisfactory. Optimal dialysis is the method of dialysis yielding results that cannot be further improved. New approaches, including hemeral quotidian or long nocturnal dialysis, provide opportunities to abandon the notion that adequate dialysis is "good enough" for our patients. Optimal dialysis should be our goal. Dialysis sessions should be long and frequent enough to provide excellent intra‐ and interdialytic tolerance of hemodialysis, normalization of serum calcium and phosphorus, blood pressure control, normal myocardial morphology and function, and hormonal balance, and to eliminate all, even subtle, uremic symptoms.