Urea Clearance Research Articles

Serum \u03b22-microglobulin as a predictor of residual kidney function in peritoneal dialysis patients

BackgroundWhile clinical guidelines recommend that residual kidney function (RKF) is measured in peritoneal dialysis (PD) patients, 24-h urine collection is cumbersome and prone to errors. We wished to determine whether an equation using serum β2-microglobulin (β2M) could prove of clinical benefit in estimating RKF and identifying patients who could start PD with incremental prescriptions.MethodsWe measured serum β2M in consecutive PD outpatients recently starting dialysis with continuous ambulatory PD (CAPD) or automated PD (APD), attending a single tertiary hospital for their routine clinical visit. RKF was defined as the mean of 24-h urine clearances of creatinine and urea. An equation estimating RKF (eRKF) was generated based on serum β2M levels on a randomly selected modelling group.ResultsWe included 511 patients, of whom 351 in the modelling group and 150 in the validation group. Mean age was 58.7 ± 15.8, 307 (60.0%) were men and median RKF value was 4.5 (2.4–6.5) mL/min/1.73 m2. In the validation group, an equation based on β2M, creatinine, urea, age and gender showed minimal bias of − 0.1 mL/min/1.73 m2 to estimate RKF. Area under the receiving operator characteristic curve was 0.915 to detect RKF ≥ 2 mL/min/1.73 m2.ConclusionAn equation based on serum β2M concentration would not be able to replace 24-h urine collection as the standard of care when an exact measurement of RKF is required. However, it could prove useful in identifying patients suitable for an incremental PD prescription and for monitoring RKF in individuals unable to reliably collect urine.Graphic abstract

Amphiphilic poly(lactic acid) membranes with low fouling and enhanced hemodiafiltration

Hemocompatible membranes were obtained by blending of poly(lactic acid) PLA with 3 different amphiphilic block copolymers, poly(methyl methacrylate)-b-poly(2-acryloamido-2-methyl-1-propanesulfonic acid) (PA), poly(methyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PH) and poly(methyl methacrylate)-b-poly(2-dimethylamino ethyl methacrylate) (PD). These membranes presented a promising balance between middle-size molecules convective transport and desirable proteins retention. Copolymers segregation to the membrane surface was confirmed by X-ray photoelectron spectroscopy (XPS). Contact angle decreases from 79.6° for pure PLA membrane to 73.9° to 61.0° for the membrane containing the amphiphilic block copolymers, which leads to an increase in anti-fouling properties and water flow through the membranes. All membranes exhibited hemocompatibility and non-hemolyzing properties. PLA/PH blend membranes presented the highest urea (94.7% and 72.5%) and lysozyme (54.2% and 40.5%) clearance with Bovine Serum Albumin (BSA) retention between 90 and 91 %. PLA/PA exhibited the highest BSA retention (99.3%) with moderated urea (80.2%) and lysozyme (17.4%) clearance. Thus, the proper combination of amphiphilic copolymer with PLA will allow fine-tuning the middle-molecule toxin separation with high retention of large desirable proteins through the membranes.

Association between Dialysis Adequacy and Cognition in Patients with Peritoneal Dialysis.

ObjectiveCognition of peritoneal dialysis patients is influenced by various factors including dialysis adequacy such as fractional urea clearance (Kt/V) and relative overhydration (RelOH). This study aimed to discover the potential contribution of dialysis adequacy to cognitive function in patients undergoing peritoneal dialysis. MethodsFifty-nine patients undergoing peritoneal dialysis were recruited. Demographic information, comorbidities, and clinical lab findings were retrospectively collected, and dialysis adequacy was determined by the Kt/V and RelOH calculation. Cognition and depression were measured with Digit Symbol Substitution Test, Hopkins Verbal Learning Test, Wechsler memory scale (spatial span), Wisconsin Card Sorting Test, and Beck’s depression inventory. Partial correlation test was used to explore the correlation of dialysis adequacy with cognitive function. ResultsRelOH showed significant correlation with some of the Wisconsin Card Sorting test results. The categories achieved showed negative correlation (r=-0.32, p=0.02) and trials to complete first category showed positive correlation (r=0.31, p=0.02) with RelOH. Other tasks showed no significant correlation with RelOH. Kt/V. ConclusionOur study demonstrates that peritoneal dialysis adequacy, measured by RelOH, seems to be significantly correlated with the occurrence of cognitive impairment. The outcome suggests that RelOH may have the potential to clarify the role of cognitive impairment in peritoneal dialysis patients.

Rate of decline in residual kidney function pre and post peritoneal dialysis initiation: A post hoc analysis of the IDEAL study.

BackgroundResidual kidney function (RKF) is associated with improved survival and quality of life in dialysis patients. Previous studies have suggested that initiation of peritoneal dialysis (PD) may slow RKF decline compared to the pre-dialysis period. We sought to evaluate the association between PD initiation and RKF decline in the Initiating Dialysis Early And Late (IDEAL) trial.MethodsIn this post hoc analysis of the IDEAL randomized controlled trial, PD participants were included if results from 24-hour urine collections had been recorded within 30 days of dialysis initiation, and at least one value pre- and one value post-dialysis commencement were available. The primary outcome was slope of RKF decline, calculated as mean of urinary creatinine and urea clearances. Secondary outcomes included slope of urine volume decline and time from PD initiation to anuria.ResultsThe study included 151 participants (79 early start, 72 late start). The slope of RKF decline was slower after PD initiation (-2.69±0.18mL/min/1.73m2/yr) compared to before PD (-4.09±0.33mL/min/1.73m2/yr; change in slope +1.19 mL/min/1.73m2/yr, 95%CI 0.48–1.90, p<0.001). In contrast, urine volume decline was faster after PD commencement (-0.74±0.05 L/yr) compared to beforehand (-0.57±0.06L/yr; change in slope -0.18L/yr, 95%CI -0.34—-0.01, p = 0.04). No differences were observed between the early- and late-start groups with respect to RKF decline, urine volume decline or time to anuria.ConclusionsInitiation of PD was associated with a slower decline of RKF compared to the pre-dialysis period.

Lamellar perfusion and energy metabolism in a preferential weight bearing model.

Supporting limb laminitis (SLL) is suspected to be caused by lamellar ischaemia as a consequence of increased mechanical load. Examine the effects of prolonged preferential weight bearing (PWB) on lamellar perfusion and metabolism. In vivo experiment. Microdialysis probes were inserted in the lamellar and sublamellar dermis of one forelimb in 13 Standardbred horses. In six horses, a platform shoe (contralateral forelimb) was used to induce increased load on the microdialysis-instrumented forelimb (PWB). The remaining seven horses were controls (CON). All horses were housed in stocks with limb weight distribution logged continuously for 92hours. Microdialysate was collected and analysed every 4hours for glucose, lactate, pyruvate, and lactate to pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar perfusion. Data were analysed using a mixed-effects linear regression model. Median [IQR] load on the microdialysis-instrumented limb was equivalent to 38.7%bwt. [37.3-40.3] in PWB and 27.3%bwt. [26.6-28] in CON. Limb offloading frequency increased in CON (P<.001) but not PWB (P=.2). Lamellar microdialysate glucose decreased in PWB (P<.001) and CON (P=.004), however, the rate of decrease was higher in PWB (P=.007). Lamellar L:P increased in PWB (P<.001) and peaked at 196 [79-656], whereas L:P did not change over time in CON (P=.6) and peaked at 42 [41-49]. Lamellar urea clearance decreased in PWB (P<.001) but not in CON (P=.3). Sublamellar L:P and urea clearance did not change over time in either group (P>.05). The PWB model may not be representative of naturally occurring SLL. Evidence of lamellar ischaemia (increased L:P and decreased urea clearance) was detected exclusively in the lamellar dermis of PWB feet subjected to persistently increased load. Lamellar ischaemia is a consequence of increased mechanical load and likely contributes to the development of SLL.

The lacking equation that estimates the protein catabolic rate in patients on once-weekly haemodialysis.

The normalized protein catabolic rate (PCRn) is one of the key indices derived from the urea kinetic model (UKM) in haemodialysis (HD) patients. Ideally, it should be assessed using the double pool UKM (KDOQI clinical practice guidelines, AIKD, 2015), as the web-based software Solute-Solver (SS) does (Daugirdas et al., AJKD, 2009). Simple formulae exist to compute PCRn for patients on thrice- or twice-weekly HD schedule, but not for patients on once-weekly HD schedule (1HD/wk). Aim of the present technical note was to introduce the lacking equation that estimates PCRn in the 1HD/wk regimen. Data of a single HD session associated to monthly UKM studies were retrieved from the electronic database of our dialysis unit for 80 historical patients on 1HD/wk regimen. The UKM parameters, as calculated with SS, were used in a subgroup of 40 randomly selected patients (group 1) to build-up a multiple regression model of PCRn. The latter was used to predict PCRn (PCRnPred) values in the cohort of the remaining 40 patients (group 2). The Bland-Altman plot was used to analyse the agreement between PCRnPred and the paired "observed" (PCRnObs) values, as measured with SS. The following equation was established by means of the multiple regression analysis: PCRn =-0.46 + 0.01 × C0 + 0.09 × eKt/V + 3.94 × Kru/V, where C0 is pre-dialysis blood urea nitrogen concentration, eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. The PCRnPred values were 0.99 ± 0.24g/kg/day; the PCRnObs values were 0.96 ± 0.23g/kg/day (mean difference 0.03 ± 0.05g/kg/day). Their difference at the Bland-Altman analysis ranged from -0.08 to + 0.13g/kg/day. Finally, a nomogram was drawn: it can be used to estimate not only PCRn from Kru/V and C0, but also C0 as a function of Kru/V and PCRn. The equation here introduced allows a simple and accurate estimate of PCRn in patients on once-weekly HD regimen. The availability of the nomogram relating C0 to PCRn and Kru/V could be a further step to make safer and safer the once-weekly HD regimen. The following equation was established by means of the multiple regression analysis [Formula: see text] where PCRn is the normalized protein catabolic rate (PCRn), C0 is pre-dialysis blood urea nitrogen concentration (BUN), eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. A nomogram relating pre-dialysis BUN to PCRn and Kru/V could be drawn: it can be used to estimate not only PCRn from Kru/V and pre-dialysis BUN, but also pre-dialysis BUN as a function of Kru/V and PCRn.

Differences between Holstein dairy cows in renal clearance rate of urea affect milk urea concentration and the relationship between milk urea and urinary nitrogen excretion

Urine and fecal excretions from cattle contribute to global nitrogen (N) emissions. The milk urea nitrogen (MUN) concentration in dairy cows is positively correlated with urinary urea N (UUN) emissions, and both decline with the reduction in crude protein intake. However, MUN concentration may differ between individual cows despite feeding the same ration. Thus, we hypothesized that due to differences in endogenous N utilization cows with high MUN concentration excrete more UUN than cows with a low MUN concentration. The objective of the present study was to elucidate N partitioning and urea metabolism in dairy cows with divergent MUN concentrations fed two planes of crude protein. Twenty Holstein dairy cows with high (HMU; n = 10) and low (LMU; n = 10) milk urea concentrations were fed two isocaloric diets with a low (LP) and normal (NP) crude protein level. Methane and ammonia emissions were recorded in respiration chambers. Feed intake, feces and urine excretions and milk yield were recorded for four days and subsamples were analyzed for total N and N-metabolites. A carbon-13 labeled urea bolus was administered intravenously followed by a series of plasma samplings. Total N and UUN excretions and ammonia emissions from excreta were lower on the LP diet, however, methane emissions, urinary N excretions and ammonia emissions were comparable between groups. Although plasma and salivary urea concentrations, urea pool size and urea turnover were higher, HMU cows had lower renal urea clearance rates. Additionally, HMU cows had lower renal clearance rates for creatinine, uric acid and creatine and excreted less uric acid (on the LP diet only) and creatine with urine. In conclusion, contrary to our hypothesis, HMU cows did not excrete more UUN than LMU cows. The lower urinary creatine excretion of HMU cows suggests that these animals have a lower environmental nitrogen footprint.

Effects of methanolic leaf extract of Pterocarpus santalinoides on the recovery from gentamicin-induced nephrotoxicity in albino rats

This study evaluated the effects of methanolic leaf extract of Pterocarpus santalinoides (MLEPS) on the recovery from gentamicin-induced nephrotoxicity in albino rats. Fresh leaves of P. santalinoides were collected, dried, pulverized, and extracted by cold maceration technique using 80% methanol. Thirty male albino rats randomly assigned into six groups (A–F) of five rats each were used for the study. Nephrotoxicity was induced in groups A–E by intra-peritoneal administration of gentamicin (GM) once a day at 100 mg/kg for 10 days. Thereafter, the nephropathic (NP) rat groups (A–E) were used to assess the therapy with MLEPS. Group A was given drinking water (negative control). Groups B, C, and D were treated orally with MLEPS at 125, 250, and 500 mg/kg, respectively. Group E was treated orally with silymarin at 200 mg/kg (positive control). Group F was not treated with GM and MLEPS (normal control). Parameters measured relating to kidney function were serum creatinine and urea concentrations, urine protein level, and 24-h water consumption. All the parameters were significantly (p 0.05) to that of the group F (normal control) rats on days 5 and 10 PTWE, though it was not significantly (p > 0.05) different from the untreated control (group A). Urine protein levels of rats treated with 500 mg/kg MLEPS (group D) were lower and comparable to that of rats treated with silymarin (group E). Also, treatment with MLEPS at 250 and 500 mg/kg led to amelioration of renal tubular necrosis in the NP rats. It was concluded that treatment with MLEPS at 500 mg/kg significantly improved recovery time from GM-induced kidney damage in rats, based on the enhancement of creatinine and urea clearance from blood, reduction of protein loss in urine, and amelioration of histological lesions.

Evaluation of Residual Kidney Function during Once-Weekly Incremental Hemodialysis

Background: The initial once-weekly administration of incremental hemodialysis to patients with residual kidney function (RKF) has recently attracted considerable interest. Methods: The aim of our study was to assess the performance of a series of different methods in measuring serum urea nitrogen and serum Cr (sCr) RKF in patients on once-weekly hemodialysis (1WHD). Evaluations were carried out by means of 24-h predialysis urine collection (Kr-24H) or 6-day inter-dialysis collection (Kr-IDI) and estimation of glomerular filtration rate based on (KrSUN + KrsCr)/2 for the purpose of identifying a simple reference calculation to be used in assessing RKF in patients on 1WHD dialysis. Ninety-five urine samples were collected from 12 1WHD patients. A solute solver urea and Cr kinetic modeling program was used to calculate residual urea and Cr clearances. Mann-Whitney U test, Pearson’s correlation coefficient (R), and linear determination coefficient (R²) were used for statistical analysis. Results: 1WHD patients displayed a mean KrSUN-IDI of 4.5 ± 1.2 mL/min, while KrSUN-24H corresponded to 4.1 ± 0.9 mL/min, mean KrsCr-IDI to 9.1 ± 4.0 mL/min, and KrsCr 24H to 8.9 ± 4.2 mL/min, with a high regression between IDI and 24-h clearances (for IDI had R² = 0.9149 and for 24H had R² = 0.9595). A good correlation was also observed between KrSUN-24H and (KrSUN + KrsCR/2) (R² = 0.7466, p < 0.01. Discussion: Urine collection over a 24-h predialysis period yielded similar results for both KrSUN and KrsCr compared to collection over a longer interdialytic interval (KrSUN + KrsCr)/2 could be applied to reliably assess RKF in patients on 1WHD. Conclusion: The parameters evaluated are suitable for use as a routine daily method indicating the commencement and continued use of the 1WHD Incremental Program.

Achieving dialysis adequacy: A global perspective.

Dialysis adequacy is conventionally quantified as net urea clearance. Single pool (sp) Kt/Vurea remains the best studied measure of dialysis adequacy globally. Other measures such as fluid status control, anemia correction, and mineral metabolism are monitored variably. Increasing use of hemodiafiltration across Europe and many parts of Japan and Australia is predicated on studies showing better patient survival with middle molecule clearance. Apart from local clinical practice guidelines, the income level and public health policy of a country determine quality of dialysis services. Among developed nations, small solute clearance adequacy targets are achieved with high frequency. In the United States, dialysis adequacy target is met by focussing on high blood flow rates and large dialyzer size, sometimes at the cost of session time. In Japan, Australia, and Germany, session length is given importance. Dialysis adequacy reporting is restricted and inconsistent in developing nations. The Gulf Cooperation Council countries, Russia and Malaysia, respectively, are close to achieving dialysis adequacy target (spKt/Vurea ≥1.2) universally in their dialysis populations. Patient-reported outcomes are typically measured only in developed countries. Patient survival on dialysis, partly linked to dialysis adequacy, varies greatly around the world, with Japan having the best survival rates. Until the development of better markers of dialysis adequacy, universal consistency in reporting of conventional parameters with a focus on patient-reported measures should be endeavored.

A faster decline of residual kidney function and erythropoietin stimulating agent hyporesponsiveness in incident hemodialysis patients.

Erythropoietin stimulating agents (ESA) hyporesposiveness has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of decline of residual kidney function (RKF) on ESA hyporesposiveness has not been adequately elucidated among patients receiving HD. The associations of RKF decline with erythropoietin resistance index (ERI; average weekly ESA dose [units])/post-dialysis body weight [kg]/hemoglobin [g/dL]) were retrospectively examined across four strata of annual change in RKF (residual renal urea clearance [KRU] < -3.0, -3.0 to <-1.5, -1.5 to <0, ≥0 mL/min/1.73 m2 per year; urinary volume < -600, -600 to<-300, -300 to <0, ≥0 mL/day per year) using logistic regression models adjusted for clinical characteristics and laboratory variables in 5239 incident HD patients in a large US dialysis organization between 1 January 2007 and 31 December 2011. The median values of the annual change in KRU and urinary volume were -1.2 (interquartile range [IQR]: -2.8 to 0.1) mL/min/1.73 m2 per year and -250 (IQR: -600 to 100) mL/day per year. A faster KRU decline in the first year of HD was associated with higher odds for ESA hyporesponsiveness: KRU decline of <-3.0, -3.0 to <-1.5, and -1.5 to <0/min/1.73 m2 per year were associated with adjusted odds ratios (OR) of 2.07 (95% confidence interval [CI]: 1.66-2.58), 1.54 (95%CI: 1.28-1.85), and 1.26 (95%CI: 1.07-1.49), respectively (reference: ≥0 mL/min/1.73 m2 per year). These associations were consistent across strata of baseline KRU, age, sex, race, diabetes, congestive heart failure, hemoglobin, and serum albumin. Sensitivity analyses using urinary volume as another index of RKF showed consistent associations. A faster RKF decline during the first year of dialysis was associated with ESA hyporesponsiveness and low hemoglobin levels among incident HD patients.

Adequacy of hemodialysis in acute kidney injury: Real-time monitoring of dialysate ultraviolet absorbance vs. blood-based Kt/Vurea.

Current guidelines recommend monitoring the adequacy of hemodialysis (HD) treatments in patients with acute kidney injury (AKI). Blood-based methods for calculating urea such as reduction ratio (URR) and single-pool Kt/Vurea (spKt/Vurea) require pre- and post-HD blood urea nitrogen (BUN) measurements. This study aims to compare real-time monitoring of urea clearance using dialysate ultraviolet absorbance (UV) with laboratory-measured spKt/Vurea. We conducted a single-center, retrospective study among hospitalized patients with AKI, who required intermittent hemodialysis (IHD). Those patients whose dialysis dose was simultaneously monitored by spKt/Vurea and UV-absorbance (UV-spKt/Vurea) were included in the study. The statistical correlation between both methods was assessed by means of the Pearson moment product correlation, Mann-Whitney U-test and Bland-Altman analysis of agreement. Thirty patients with AKI were evaluated. There was no statistical difference between the mean spKt/Vurea calculated by traditional methods and the mean UV-spKt/Vurea. (1.37 ± 0.37 vs. 1.28 ± 0.36, P = 0.12, CI: 95%). A Pearson moment correlation analysis revealed a close agreement between both methods (r = 0.79, P < 0.001). Furthermore, Bland-Altman analysis showed that >95% of the data points were confined within the upper and lower levels of agreement. In this pilot study of patients with AKI, UV-spKt/Vurea correlated with standard blood-based spKt/Vurea and may be a useful tool to monitor dialysis adequacy. Larger studies evaluating multiple UV and blood-based measurements per patient and a more diverse AKI population are needed to confirm this initial observation.

Is It Time for Precision Dialysis?

In 2015, President Obama announced funding for precision medicine to augment personalized medicine, which has been described as “the right treatment for the right patient in the right place at the right time.” Patients with ESKD experience high symptom burden and mortality, necessitating more

In-Vitro Study of Polysulfone-polyethylene glycol/chitosan (PEG-PSf/CS) Membranes for Urea and Creatinine Permeation

High concentrations of creatinine and urea in the blood can be removed by dialysis using semipermeable membranes that are selective for certain species and hold other species through diffusion processes. This ability requires a membrane that has an active side, which functions as a targeted species identifier. The membrane must be biocompatible because the membrane will be in direct contact with the body’s biological systems. The membrane material that is made must be acceptable to the blood system so that there is no rejection from the body and have a large contact area to obtain an effective diffusion process. For this reason, a hollow fiber membrane (HFM) is needed. One of the synthetic polymers used as the base material for HFM is PSf. PSf has mechanical strength, heat resistance, and is easily formed into HFM. However, PSf has disadvantages such as lack of active side and less compatible with blood due to its hydrophobic properties. Modification using PEG and chitosan will reduce the hydrophobicity of the PSf. Membrane results were analyzed the physical, chemical, and transportability for urea and creatinine. The results of functional group characterization by FTIR show that the modification reaction was successfully carried out on polysulfone to produce PEG-PSf/CS. The modification succeeded in making the PSf membrane more hydrophilic, as evidenced by a decrease in the contact angle from 69.4° (PSf) to 53° (PEG-PSf/CS). Water uptake capability increases to 609%, and membrane porosity increases porosity increased from 72 to 83%. The water flux is also increased. Creatinine clearance ability increases from 0.09 mg/dl to 0.25 mg/dL. Urea clearance ability increases from 2.3 mg/dL to 3.07 mg/dL. The SEM image showed that the modification makes the membranes more porous.

Utility of serum beta-trace protein as a tool for estimating residual kidney function in peritoneal dialysis patients.

Beta-trace protein (BTP) is a novel marker for residual kidney function (RKF) without need for urinary collection. We aimed to examine its utility as a tool for estimating RKF in incident peritoneal dialysis (PD) patients. This was a post hoc analysis of incident PD patients from the balANZ trial cohort. The outcomes evaluated were trends of serum BTP concentration with time, factors associated with change in BTP using mixed-effect multilevel linear regression and correlation of BTP with mean urinary urea and creatinine clearances (measured glomerular filtration rate (GFR)). Performances of two BTP-derived equations (Shafi-Eqn and Steubl-Eqn) to estimate GFR were evaluated by reporting bias (median difference between estimated and measured GFR), precision (interquartile range of median bias), accuracy (±2 mL/min of measured GFR) and P30 (percentage estimates within 30% of measured GFR) with confidence intervals (CIs) generated by bootstrapping 2000 replicates. The agreement between BTP-estimated GFR and measured GFR was also plotted graphically on Bland-Altman analysis. The study included 161 PD patients. BTP concentration increased with dialysis vintage and was inversely correlated with measured GFR (r = -0.64). Larger increases in BTP were associated with longer PD vintage and higher dialysate glucose exposure. Biases of BTP-estimated GFRs (Shafi-Eqn and Steubl-Eqn) were 1.2 mL/min/1.73 m2 (95% CI 1.0-1.3 mL/min/1.73 m2) and 0.4 mL/min/1.73 m2 (95% CI 0.2-0.6 mL/min/1.73 m2), respectively. Both BTP-estimated GFRs had poor precision (3.2 mL/min/1.73 m2 (95% CI 2.9-3.5 mL/min/1.73 m2) and 2.8 mL/min/1.73 m2 (95% CI 2.5-3.2 mL/min/1.73 m2), respectively) and accuracy of estimates (55% (95% CI 52-60%) and 59% (95% CI 55-63%), respectively). The mean difference of BTP-estimated GFR (Shafi-Eqn and Steubl-Eqn) and measured GFR were -1.14 mL/min/1.73 m2 and -0.42 mL/min/1.73 m2, respectively, with large limit of agreement on Bland-Altman plot. Serum BTP level was inversely related to RKF but neither BTP-estimated GFR equations were sufficiently accurate for routine use in PD patients.

Impact of incremental versus conventional initiation of haemodialysis on residual kidney function: study protocol for a multicentre feasibility randomised controlled trial

IntroductionPreserving residual kidney function (RKF) may be beneficial to patients on haemodialysis (HD) and it has been proposed that commencing dialysis incrementally rather than three times a week may preserve...

Comparison of Clinical Performance of VectorFlow and Palindrome Symmetric-Tip Dialysis Catheters: A Multicenter, Randomized Trial

PurposeTo compare clinical performance of 2 widely used symmetric-tip hemodialysis catheters. Materials and MethodsPatients with end-stage renal disease initiating or resuming hemodialysis were randomized to receive an Arrow–Clark VectorFlow (n = 50) or Palindrome catheter (n = 50). Primary outcome was 90-d primary unassisted catheter patency. Secondary outcomes were Kt/V ([dialyzer urea clearance × total treatment time]/total volume of urea distribution), urea reduction ratio (URR), and effective blood flow (QB). ResultsPrimary unassisted patency rates with the VectorFlow catheter at 30, 60, and 90 d were 95.5% ± 3.3, 87.2% ± 7.3, and 80.6% ± 9.8, respectively, compared with 89.1% ± 6.2, 79.4% ± 10.0, and 71.5% ± 12.6 with the Palindrome catheter (P = .20). Patients with VectorFlow catheters had a mean Kt/V of 1.5 at 30-, 60-, and 90-day time points, significantly higher than the mean Kt/V of 1.3 among those with Palindrome catheters (P = .0003). URRs were not significantly different between catheters. Catheter QB rates exceeded National Kidney Foundation–recommended thresholds of 300 mL/min at all time points for both catheters and were similar for both catheters (median, 373 mL/min). Catheter failure, ie, poor flow rate requiring guide-wire exchange or removal, within the 90-day primary outcome occurred in 3 VectorFlow subjects and 5 Palindrome subjects (P = .72). Infection rates were similar, with 0.98 infections per 1,000 catheter days for VectorFlow catheters compared with 2.62 per 1,000 catheter days for Palindrome catheters (P = .44). ConclusionsThe 90-day primary patency rates of Palindrome and VectorFlow catheters were not significantly different, and both achieved sustained high QB through 90 day follow-up. However, dialysis adequacy based on Kt/V was consistently better with the VectorFlow catheter versus the Palindrome.

Sodium copper chlorophyllin attenuates adenine-induced chronic kidney disease via suppression of TGF-beta and inflammatory cytokines.

The present study was designed to evaluate the effect of sodium copper chlorophyllin (SCC) in adenine-induced chronic kidney disease (CKD). CKD was induced in male Wistar rats by feeding 0.3% w/w adenine diet for 28 days. After induction, animals were treated with sodium copper chlorophyllin at dose 2.7, 5.4, and 10.8 mg/kg for the next 28 days. The biochemical and urines parameters like creatinine, blood urea nitrogen (BUN), albumin, total protein creatinine clearance, urea clearance, and glomerular filtration rate were assessed on days 0, 14, and 28. Plasma TGF-β1, COX-2, and IL-6 levels were assessed. Various oxidative stress parameters and TGF-β1 expression were determined in the kidney. Histopathology of the kidney was studied with different stains. Sodium copper chlorophyllin-treated animals showed a significant reduction in urine output and relative kidney weight. The treatment with sodium copper chlorophyllin significantly improved kidney function by normalizing biochemical and urine parameters. Treatment with SCC significantly reduced circulatory inflammatory mediators-TGF-β1, COX-2, and IL-6. Additionally, the treatment also significantly reduced oxidative stress and TGF-β1 expression in kidney tissues. Histopathology studies showed inhibition in the kidney damage due to the treatment of SCC. The sodium copper chlorophyllin treatment attenuated adenine-induced chronic kidney disease in rats.

P1248DOES INCREMENTAL HAEMODIALYSIS PRESERVE NATIVE KIDNEY FUNCTION? A MULTI-CENTRE FEASIBILITY RANDOMISED CONTROL TRIAL

Abstract Background and Aims Incremental HD is a method of individualising haemodialysis (HD) dose according to level of residual renal function(RRF) such that as RRF reduces, HD dose is upwardly adjusted. Retrospective data suggest potential benefit of this approach in preserving RRF, a key predictor of survival for dialysis patients. Method A randomised, intention-to-treat, multi-centre trial was designed to determine the feasibility of a future definitive trial of incremental HD to establish if this approach preserves RRF. The trial was designed to estimate effect size of potential benefit in terms of RRF. 55 patients with RRF urea clearance≥3ml/min/1.73m2 BSA and within 3 months of starting HD were randomised across 4 UK dialysis centres to either conventional 3x weekly HD for 3.5-4 hours or incremental HD. The incremental HD protocol involved initiation of HD 2x weekly after randomization and upward adjustment of HD frequency and time as RRF was lost. In the conventional HD arm, patients were dialysed to ensure Standard Kt/VDialysis&amp;gt;2.0. In the incremental HD arm, patients were dialysed to ensure Standard Kt/VDialysis+Standard Kt/VResidual Renal Function&amp;gt;2.0 so both groups were dialysed to the same urea clearance target, except that urea clearance incorporated RRF in the incremental HD arm. Follow up was for 6 months (primary outcome data) but secondary outcome data will be for 12m. Patients were withdrawn for transplant, dialysis modality change or for patient choice. The primary outcome was rate of change of RRF in the first 6 months after randomization (effect size of intervention). Recruitability, retainability, protocol adherence and rate of adverse events were also measured as a primary objective. As a secondary outcome, we determined proportion of patients with urea clearance≥2 and ≥3ml/min /1.73m2 BSA at the 6 month time point. Impact of dialysis treatment was measured using questionnaire-based assessments at baseline and 6 months. Results 26 patients were randomised to standard HD and 29 to incremental HD. Baseline demographics including age, weight, haemoglobin, blood pressure, Charleson Comorbidity Index, were not significantly different between study arms. Baseline residual renal urea clearance was 5.1 ± SD 1.8 ml/min/1.73m2 BSA in the standard HD arm and 5.72 ± SD 2.49 in the incremental HD arm. 6 months, residual renal urea clearance reduced to 2.68±SD 1.73 in the standard HD arm and 3.80±SD 1.85 in the incremental arm. In the first 6 months, 3 patients recovered to dialysis independence (standard arm=1, incremental arm=2). Slope of RRF was not significantly different between two arms (p=0.39). The proportion of patients with significant urea clearance&amp;gt;2ml/min/1.73m2 BSA at 6 months was significantly higher in the incremental HD arm (92%) compared to the standard HD arm (65%), p=0.032. Rate of major adverse cardiac events, fluid overload, hyperkalaemia, vascular access events, deaths and infections did not differ significantly between groups. There were 2 deaths in the standard HD arm (in 4025 patient days) versus 1 in the incremental HD arm in the first 6 months(4666 patient days). There was no significant difference in Clinical Frailty Score, Montreal Cognitive Assessment score, depression score (PHQ-9), Quality of Life (EQ-5D-5L) and Illness Intrusiveness Rating Scale between groups at baseline and 6m time points. Conclusion Rate of loss of RRF (slope) was not significantly different between incremental HD and standard HD arms but incremental HD was associated with significantly higher probability of retaining urea clearance&amp;gt;2ml/min/1.73m2. There was no evidence of any clinical detrimental effect of incremental HD in terms of mortality, fluid overload or hyperkalaemic events. Incremental HD does not appear to be harmful and may confer a small benefit to preservation of residual renal function. A definitive study is required to define clinical benefits further.

P1423INCREASED BLOOD FLOW RATE IN HIGH-FLUX HAEMODIALYSIS - IS IT RELEVANT FOR PHOSPHORUS REMOVAL IN HAEMODIALYSIS PATIENTS?

Abstract Background and Aims High-flux haemodialysis (HD), beside other uremic solutes harmful for patients, controls the level of phosphorus, major factor for HD-related morbidity and mortality. First line in phosphorus control in HD patients is dietary phosphorus intake reduction, whereas its’ removal is undervalued by hemodialysis. The primary objective was to analyse whether change in the rate of blood flow is relevant in phosphorus removal in HD patients. Second objective was to evaluate other variables impacted by higher blood flow rates. Method Retrospective study was conducted enrolling 80 patients from a single center in a period of 12 months. In the first six months, all patients were on lower blood flow rate (LBFR group) than the same patient group was switched to a higher blood flow rate in the following six months (HBFR group). Demographic, clinical and laboratory variables were collected and intra/inter-patient group analysis was performed. Results Forty-seven patients were male, and 41.3% were female. Mean age of the study population was 61.2±13.47 years (males 60.3±13.38, females 62.4±13.68). Mean dialysis vintage was 63.31±66.57 months. The average real blood flow rate in LBFR group was 290.75±19.65 ml/min (median 285.34 ml/min), 344.87±9.12 ml/min in HBFR group (median 339 ml/min), p=0.0002. The level of phosphorus in LBFR group was 1.52±0.03 mmol/L, and 1.45±0.04 in HBFR group, p=0.007. Other variables that significantly showed improvement following the increase of blood flow rate were eKT/V (p=0.0006), urea clearance (p=0.02) and transferrin saturation (p=0.04). The level of post-HD urea (p=0.02) and body surface area (p=0.04) were decreased. Weekly EPO dosage decrease in HBFR group (p=0.02) was not correlated with increased iron sucrose administration (LBFR group 59.99±36.18 mg/wk, HBFR group 65.8±28.7, p=0.45). There were no significant changes related to cardiac function; systolic (p=0.44) and diastolic pressure (p=0.36), mean arterial (p=0.43) and pulse pressure (p=0.26) remained in reference range. Also, the average dose of calcium-based phosphate binders did not change significantly (p=0.34). Conclusion This study showed that increased blood flow rate in HD patients reduces phosphorus and EPO consumption, improves urea clearance without significant impact on cardiac function and calcium overload with calcium-based phosphate binders.