Artificial Kidney Research Articles

Ex vivo evaluation of the blood compatibility of mixed matrix haemodialysis membranes

The patients with end stage kidney disease need haemodialysis therapies, using an artificial kidney. Nevertheless, the current therapies cannot remove a broad range of uremic toxins compared to the natural kidney. Adsorption therapies, using sorbent-based columns, can improve the clearance of uremic toxins, but the sorbent particles often require polymeric coatings to improve their haemocompatibility leading to mass transfer limitations and to lowering of their performance.Earlier, we have developed a dual layer Mixed Matrix fiber Membrane (MMM) based on polyethersulfone/polyvinylpyrrolidone (PES/PVP) polymer blends. There, the sorbent activated carbon particles are embedded in the outer membrane layer for achieving higher removal whereas the inner blood contacting selective membrane layer should achieve optimal blood compatibility. In this work, we evaluate in detail the haemocompatibility of the MMM following the norm ISO 10993–4. We study two generations of MMM having different dimensions and transport characteristics; one with low flux and no albumin leakage and another with high flux but some albumin leakage. The results are compared to those of home-made PES/PVP single layer hollow fiber and to various control fibers already applied in the clinic. Our results show that the low flux MMM successfully avoids contact of blood with the activated carbon and has good haemocompatibility, comparable to membranes currently used in the clinic. Statement of SignificanceHaemodialysis is a life-sustaining extracorporeal treatment for renal disease, however a broad range of uremic toxins cannot still be removed. In our previous works we showed that a double layer Mixed Matrix Membrane (MMM) composed of polyethersulfone/polyvinylpyrrolidone and activated carbon can achieve higher removal of uremic toxics compared to commercial haemodialysers. In this work we evaluate the haemocompatibility profile of the MMM in order to facilitate its clinical implementation. The lumen particle-free layer of the MMM successfully avoids the contact of blood with the poorly blood-compatible activated carbon. Moreover, thanks to the high amount of polyvinylpyrrolidone and to the smoothness of the lumen layer, the MMM has very good haemocompatibility, comparable to membranes currently used in the clinic.

Lightweight Proof of Game (LPoG): A Proof of Work (PoW)'s Extended Lightweight Consensus Algorithm for Wearable Kidneys.

In healthcare, interoperability is widely adopted in the case of cross-departmental or specialization cases. As the human body demands multiple specialized and cross-disciplined medical experiments, interoperability of business entities like different departments, different specializations, the involvement of legal and government monitoring issues etc. are not sufficient to reduce the active medical cases. A patient-centric system with high capability to collect, retrieve, store or exchange data is the demand for present and future times. Such data-centric health processes would bring automated patient medication, or patient self-driven trusted and high satisfaction capabilities. However, data-centric processes are having a huge set of challenges such as security, technology, governance, adoption, deployment, integration etc. This work has explored the feasibility to integrate resource-constrained devices-based wearable kidney systems in the Industry 4.0 network and facilitates data collection, liquidity, storage, retrieval and exchange systems. Thereafter, a Healthcare 4.0 processes-based wearable kidney system is proposed that is having the blockchain technology advantages. Further, game theory-based consensus algorithms are proposed for resource-constrained devices in the kidney system. The overall system design would bring an example for the transition from the specialization or departmental-centric approach to data and patient-centric approach that would bring more transparency, trust and healthy practices in the healthcare sector. Results show a variation of 0.10 million GH/s to 0.18 million GH/s hash rate for the proposed approach. The chances of a majority attack in the proposed scheme are statistically proved to be minimum. Further Average Packet Delivery Rate (ADPR) lies between 95% to 97%, approximately, without the presence of outliers. In the presence of outliers, network performance decreases below 80% APDR (to a minimum of 41.3%) and this indicates that there are outliers present in the network. Simulation results show that the Average Throughput (AT) value lies between 120 Kbps to 250 Kbps.

Ultrasensitive and Highly Selective Graphene-Based Field-Effect Transistor Biosensor for Anti-Diuretic Hormone Detection.

Nephrogenic diabetes insipidus (NDI), which can be congenital or acquired, results from the failure of the kidney to respond to the anti-diuretic hormone (ADH). This will lead to excessive water loss from the body in the form of urine. The kidney, therefore, has a crucial role in maintaining water balance and it is vital to restore this function in an artificial kidney. Herein, an ultrasensitive and highly selective aptameric graphene-based field-effect transistor (GFET) sensor for ADH detection was developed by directly immobilizing ADH-specific aptamer on a surface-modified suspended graphene channel. This direct immobilization of aptamer on the graphene surface is an attempt to mimic the functionality of collecting tube receptors in the ADH biosensor. This aptamer was then used as a probe to capture ADH peptide at the sensing area which leads to changes in the concentration of charge carriers in the graphene channel. The biosensor shows a significant increment in the relative change of current ratio from 5.76 to 22.60 with the increase of ADH concentration ranging from 10 ag/mL to 1 pg/mL. The ADH biosensor thus exhibits a sensitivity of 50.00 µA· with a limit of detection as low as 3.55 ag/mL. In specificity analysis, the ADH biosensor demonstrated a higher current value which is 338.64 µA for ADH-spiked in phosphate-buffered saline (PBS) and 557.89 µA for ADH-spiked in human serum in comparison with other biomolecules tested. This experimental evidence shows that the ADH biosensor is ultrasensitive and highly selective towards ADH in PBS buffer and ADH-spiked in human serum.

Simulating nephron ion transport function using activated wafer electrodeionization

Current approaches for treating patients with end stage renal disease include hemodialysis and peritoneal dialysis, both of which are diffusion-based treatments that require a dialysate solution. The native kidney has separate filtration (glomerulus) and transport (nephron) capabilities. Although artificial methods for simulating glomerular function using membrane ultrafiltration have been proposed, there are no known technologies for simulating the ion transport functions of the nephron. Here we have created a synthetic nephron using activated wafer electrodeionization (AWEDI). AWEDI incorporates mesh electrodes within an electrodeionization wafer, allowing ion selectivity and transport rate to be modulated independently. We demonstrate the capabilities of AWEDI with several physiologically relevant ions which mimic the fine control of ion transport by the kidney. Furthermore, by integrating our AWEDI technology with ultrafiltration, nanofiltration, and reverse osmosis modules, the possibility of incorporating AWEDI technology in an artificial kidney is demonstrated.

A Novel Flexible Ureteroscope with Omnidirectional Bending Tip Using Joystick-Type Control Unit (URF-Y0016): Initial Validation Study in Bench Models.

Purpose: The conventional flexible ureteroscope has limited access into the lower calix and often causes biomechanical stress to surgeons. Recently, a novel flexible ureteroscope with an omnidirectional bending tip with a joystick-type control unit (URF-Y0016; Olympus, Japan) was developed. We verified the operability and ergonomics of the URF-Y0016 compared with that of the conventional flexible ureteroscope (URF-P6) in bench models. Materials and Methods: Twenty-five medical students with no experience in performing ureteroscopic manipulation were randomly assigned to URF-Y0016 and URF-P6 leading groups in a crossover study. The task was performed using a simple model as an exploratory experiment and an artificial kidney model as an evaluation experiment. We compared the task completion times of both groups, while the factors influencing task completion time were entered into a multivariate model. The ergonomics of endourology were compared using a validated questionnaire. Results: The task completion time in the URF-Y0016 group was significantly shorter than in the URF-P6 group (p < 0.001). The URF-Y0016 group showed no difference in task completion time between each renal calix, whereas in the URF-P6 group the task completion time in the lower calix was significantly longer than that in other calices (p < 0.001). In multivariate analysis, the model of flexible ureteroscope used significantly influenced the task completion time (p < 0.001). The ergonomics of the URF-Y0016 group were significantly better than those of the URF-P6 group (p = 0.001). Conclusions: URF-Y0016 may offer benefits in ureteroscopy performance over the conventional flexible ureteroscope.

Fabrication of a porous polymer membrane enzyme reactor and its enzymatic kinetics study in an artificial kidney model

A porous polymer membrane-based d-amino acid oxidase (DAAO) reactor was developed that mimicked enzymatic activity in a renal ischemia model. Using glycidyl methacrylate as a biocompatible reactive monomer, poly(styrene-glycidyl methacrylate) was synthesized via a reversible addition fragment chain transfer polymerization technique. The prepared porous polymer membrane was used as a support to effectively immobilize DAAO. Compared to DAAO modified on nonporous polymer membrane and free DAAO in solution, the constructed porous polymer membrane-based DAAO enzyme reactor displayed 3-fold and 19-fold increase in enzymolysis efficiency, respectively. In addition, a chiral ligand exchange capillary electrophoresis system for DAAO was used to study DAAO enzymatic kinetics with d,l-methionine as the substrate. The proposed porous polymer membrane-based enzyme reactor showed excellent performance both on reproducibility and stability. Moreover, the enzyme reactor was successfully applied to mimic DAAO activity in a renal ischemia model. These results demonstrated that the enzyme could be efficiently immobilized onto a porous polymer membrane as an enzyme reactor and has great potential in mimicking the enzymatic activity in kidney.

Evaluation of the Usage of Erythropoietin in Patients with End-Stage Chronic Kidney Disease Dialysis Cycle in Hanoi Nephrology Hospital

Treatment and control of anemia plays an important role in improving the quality and effectiveness of artificial kidney. The study was conducted on 61 patients who met the selection and were not included in the excluded criteria group. Collecting data from medical records using retrospective, descriptive, vertical follow-up method for 6 months. Data were processed using Microsoft Excel Office 2010 and R. The results showed that patients used both EPO alpha and EPO beta simultaneously. Rate of usage’s EPO beta accounted for 23%, alpha EPO was 77%. Lyophilized form (EPO alpha) is most commonly used. Starting from T3, Hb. averages treat. There were no abnormalities in blood pressure, white blood cell, platelets, and electrolytes.&#x0D; Keywords&#x0D; Hanoi Kidney Hospital, EPO (erythropoietin), Hb, efficacy and safety.&#x0D; References&#x0D; [1] L.A. Szczech, W. Harmon, T.H. Hostetter et al, World Kidney Day 2009: Problem and Challenges in the Emering Epidemic of Kidney Disease, J Am Soc Nephrol 20 (2009) 453-455. https://doi.org/10.1681/ASN.2009010041.[2] D.T. Gilbertson, J. Liu et al, Projecting the Number of Patient with End Stage Renal Disease in the United States to the Year 2015, J Am Soc Nephrol 16 (2005) 3736-3741. https://doi.org/10.1681/ASN.2005010112.[3] A.E. Gaweda, G.R. Aronoff et al, Individualized anemia management reduces hemoglobin variability in hemodialysis patients, J Am Soc Nephrol 25(1) (2014) 159-66. https://doi.org/10.1681/ASN.2013010089.[4] Do Thi Thu Hien, Evaluation of the usage of erythropoietin in the treatment of anemia in patients with chronic renal failure on dialysis at Thai Binh Provincial General Hospital, Master of Pharmacy thesis, Hanoi University of Pharmacy, 2015 (in Vietnamese).[5] Trieu Thi Tuyet Van, Evaluation of the usage of erythropoietin in the treatment of anemia in patients with chronic renal failure on dialysis at the artificial kidney department - Bach Mai Hospital, Master of Pharmacy thesis, Hanoi University of Pharmacy, 2009 (in Vietnamese).[6] Nguyen Thi Uyen, Investigating the effectiveness and safety of Erythropoietin use in dialysis patients at artificial kidney monotherapy Sanit Paul Hospital, Graduation thesis of Pharmacist, Hanoi University of Pharmacy, 2016 (in Vietnamese).[7] Bui Thi Tam, Evaluation the effectiveness of anemia treatment with Erythropoietin in patients with chronic renal failure receiving dialysis at Dien Bien Provincial General Hospital, Graduation thesis of Pharmacist Specialist 2, Hanoi University of Pharmacy, 2011 (in Vietnamese).[8] Drug Administration of Vietnam - Ministry of health, Official dispatch number 4764/QLD-ĐK, 2014 (in Vietnamese).[9] The Vietnam Urology &amp; Nephrology Association, Guidelines for treatment of anemia in chronic kidney disease, The Vietnam Urology &amp; Nephrology Association, 2013 (in Vietnamese).[10] KDIGO, KDIGO 2012 Clinical practice guideline for the evaluation and management of chronic kidney disease, Kidney International Supplement, 2013, pp.1-150.[11] Lam Thanh Vung, Study on the characteristics of anemia and the effectiveness of Erythropoietin β combination with intravenous iron in patients with chronic renal dialysis by dialysis, Thesis Specialized level 2 Medical and Pharmaceutical University, Hue University, 2013.&#x0D;

Hollow fiber membranes for long-term hemodialysis based on polyethersulfone-SlipSkin™ polymer blends

Hemodialysis (HD) therapy is of vital importance for patients with end stage renal disease (ESRD), when there is no donor organ available for transplantation to replace their malfunctioning kidneys. In contrast to healthy kidneys which work continuously and remove a broad range of toxins, during HD, patients’ blood is cleansed three times a week for 4 h and not all uremic toxins are removed. For achieving long-term and/or continuous therapies, including wearable artificial kidneys, one requires membranes with long-term blood compatibility and high fouling resistance. Most membranes currently used in the clinic are made by blending of hydrophobic polymers, such as polysulfone (PSu) or polyethersulfone (PES), with hydrophilic additives, such as polyvinylpyrrolidone (PVP). Studies however, have shown that PVP could leach out from the membranes, especially during prolonged therapy leading to membrane fouling and/or complications to patients.Here, we develop hollow fibers with no additive leaching, by blending PES with small amounts of SlipSkin™ (SS). The latter, a random copolymer consisting of N-vinylpyrrolidone (NVP) and N-butylmethacrylate (BMA), has very good blood compatibility. The developed fibers can achieve high removal of a range of uremic toxins (creatinine and protein-bound uremic toxins) combined with excellent fouling resistance.

A Ninhydrin-Type Urea Sorbent for the Development of a Wearable Artificial Kidney.

The aim of this study is to develop polymeric chemisorbents with a high density of ninhydrin groups, able to covalently bind urea under physiological conditions and thus potentially suitable for use in a wearable artificial kidney. Macroporous beads are prepared by suspension polymerization of 5-vinyl-1-indanone (vinylindanone) using a 90:10 (v/v) mixture of toluene and nitrobenzene as a porogen. The indanone groups are subsequently oxidized in a one-step procedure into ninhydrin groups. Their urea absorption kinetics are evaluated under both static and dynamic conditions at 37 °C in simulated dialysate (urea in phosphate buffered saline). Under static conditions and at a 1:1 molar ratio of ninhydrin: urea the sorbent beads remove ≈0.6-0.7 mmol g-1 and under dynamic conditions and at a 2:1 molar excess of ninhydrin ≈0.6 mmol urea g-1 sorbent in 8 h at 37 °C, which is a step toward a wearable artificial kidney.

Galerkin Approach for the Study of Urea Concentration Distribution in Artificial Kidney in Hemodialysis

Hemodialysis is the process of purifying the blood which removes the waste product such as urea from blood through the semi-permeable membrane of dialyzer. In dialyzer, the rate of blood flow velocity is maintained around five times less than the dialyzed flow velocity during hemodialysis. The study focuses on the urea concentration distribution in the blood during dialysis using partial differential equation of diffusion process developed by J. N. Kapur, assuming blood is Newtonian, and laminar flow. The solution of urea concentration is obtained using Galerkin approximation method associated with appropriate boundary conditions.

HUBUNGAN TINGKAT KECEMASAN DENGAN KUALITAS TIDUR PADA PASIEN YANG MENJALANI HEMODIALISIS DI RUMAH SAKIT KHUSUS GINJAL RASYIDA MEDAN

Hemodialysis is the process of removing metabolic waste substances, other toxic substances through a dialiser that functions as an artificial kidney. Hemodialysis or dialysis is the transfer of the patient's blood from his body which occurs in disfusion and ultrafiltration. This study aims to determine the relationship between the level of anxiety and sleep quality in patients undergoing hemodialysis at Rasyida Kidney Special Hospital Medan. This research design used analytical survey with cross sectional approach. The sampling technique was accidental sampling, a sample of 75 respondents. The data used are primary data by distributing questionnaires, secondary data, and tertiary data while the data analysis used is univariate analysis and bivariate analysis with Chi-Square test. The results of this study with stastic test showed that the p-value result was 0.033 (&lt;α 0.05), so there was a relationship between the level of anxiety and the quality of sleep of patients undergoing hemodialysis in the Rasyida Kidney Special Hospital Medan. The conclusions in this study indicate that there is a significant correlation between the level of anxiety and sleep quality in patients undergoing hemodialysis in Medan Renalida Kidney Special Hospital. It is recommended for patients to control anxiety so that sleep quality will be better and recommended to health workers especially hemodialysis nurses to further enhance the knowledge of patients who increase hemodialysis by providing education/health education related to the effects and complications of hemodialysis.

BACTERIAL CONTAMINATION OF DIALYSIS WATER AND DIALYSATE AT MUKALLA ARTIFICIAL KIDNEY CENTER IN MUKALLA CITY - HADHRAMAUT - YEMEN: RATE OF CONTAMINATION AND SENSITIVITY OF BACTERIAL ISOLATES TO ANTIBIOTICS

Water treatment systems are a vital factor in dialysis therapy and precise control of hemodialysis water bacteriological quality is predominantly important in order to assurance a better quality of life of the hemodialysis patients. The purpose of this study was to detect the level of contamination in hemodialysis water and dialysate by bacteria in Mukalla Artificial Kidney Center and investigate the antimicrobial resistance patterns of isolated bacteria. Forty eight samples of water and dialysate were assembled weekly over a period of 3 months from 4 points. Bacteriological analysis of samples was carried out then antimicrobial susceptibilities patterns of isolated bacteria were concluded by disk diffusion method. The mean of total count of bacteria for dialysis water and dialysate were higher than the recommended values (100 CFU/ ml). The isolated bacteria which colonized the hemodialysis systems were mostly Gram-negative bacilli as Pseudomonas sp., Serratia sp., Citrobacter sp. and Enterobater sp. In general, most of the isolated bacteria were poorly responsive to antibiotics. In conclusion: Dialysis water and dialysate not passed to meet the bacteriological provisions for hemodialysis. To reduce the hazard of contaminants for hemodialysis patients, a sufficient system for water treatment, disinfection of hemodialysis system, and bacteriological contamination monitoring of the water and dialysate are necessary.&#x0D; Peer Review History: &#x0D; UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.&#x0D; Received file &#x0D; &#x0D; Average Peer review marks at initial stage: 6.0/10&#x0D; Average Peer review marks at publication stage: 8.5/10&#x0D; Reviewer(s) detail:&#x0D; Name: Dr. Maya Shaaban Eissa Hussein&#x0D; Affiliation: Egyptian Russian University, Egypt&#x0D; E-mail: maya-shaaban@hotmail.com&#x0D; &#x0D; Name: Dr. Ali Abdullah A. Al-Mehdar&#x0D; Affiliation: University of Basrah, Iraq&#x0D; E-mail: asia_abdullah65@yahoo.com&#x0D; Comments of reviewer(s): &#x0D; &#x0D; Similar Articles:&#x0D; EXPLOSION OF HEPATITIS B AND C VIRUSES AMONG HEMODIALYSIS PATIENTS AS A RESULT OF HEMODIALYSIS CRISIS IN YEMEN&#x0D; PREVALENCE AND GENOTYPING OF HEPATITIS C VIRUS IN HEMODIALYSIS PATIENTS AND EVALUATION OF HCV-CORE ANTIGEN TEST IN SCREENING PATIENTS FOR DIALYSIS IN SANA'A CITY, YEMEN

Coating of MPC polymer to improve hemocompatibility of implantable artificial kidney

Coating of MPC polymer to improve hemocompatibility of implantable artificial kidney

Dialysis-specific factors and incident atrial fibrillation in hemodialysis patients

Background Atrial fibrillation (AF) is common in end-stage renal disease patients. Besides the traditional risk factors, we aimed to find dialysis-specific factors for developing incident AF. Methods From March 2017 to August 2018, we retrospectively reviewed all outpatient-based prevalent hemodialysis patients in our artificial kidney room, and they were followed up until August 2019. Dialysate calcium concentration (3 versus 2.5 mEq/L), time length (4 versus 3.5 h), frequency (thrice weekly versus twice weekly), dialyzer size (effective surface area of 1.4 m2 versus 1.8 m2), membrane permeability (high flux versus low flux), ultrafiltration rate (mL/kg/hour), and blood flow rate (mL/min) were evaluated. Results Among a total of 84 patients, 15 (17.9%) had newly detected AF with a follow-up period of 21 (13.3–24) months. By performing multivariate Cox regression analysis, blood flow rate (mL/min) and ultrafiltration rate (mL/kg/h) were considered significant factors for developing incident AF (adjusted hazard ratio [HR], 0.977; p = 0.011 and adjusted HR, 1.176; p = 0.013, respectively), while dialysis bath, time length, and frequency, dialyzer size, and membrane type were not considered significant factors. Ultrafiltration cutoff rate of 8.6 mL/kg/h was the best predictive factor for incident AF (area under the curve-receiver operating characteristic [AUC-ROC], 0.746; p < 0.005), while blood flow rate was not considered a significant factor for incident AF in ROC analysis (AUC-ROC, 0.623; p = 0.126). Ultrafiltration rate was largely dependent on interdialytic weight gain (p < 0.005, linear-by-linear association). Conclusion Higher ultrafiltration rate was associated with incident AF in hemodialysis patients.

Phenylglyoxaldehyde-Functionalized Polymeric Sorbents for Urea Removal from Aqueous Solutions.

For realization of a wearable artificial kidney based on regeneration of a small volume of dialysate, efficient urea removal from dialysate is a major challenge. Here a potentially suitable polymeric sorbent based on phenylglyoxaldehyde (PGA), able to covalently bind urea under physiological conditions, is described. Sorbent beads containing PGA groups were obtained by suspension polymerization of either styrene or vinylphenylethan-1-one (VPE), followed by modification of the aromatic groups of poly(styrene) and poly(VPE) into PGA. It was found that PGA-functionalized sorbent beads had maximum urea binding capacities of 1.4–2.2 mmol/g and removed ∼0.6 mmol urea/g in 8 h at 37 °C under static conditions from urea-enriched phosphate-buffered saline, conditions representative of dialysate regeneration. This means that the daily urea production of a dialysis patient can be removed with a few hundred grams of this sorbent which, is an important step forward in the development of a wearable artificial kidney.

Hemodialysis

Hemodialysis

Regenerating re-absorption function of proximal convoluted tubule using microfluidics for kidney-on-chip applications

Human kidney is a sophisticated organ with 1 Million nephrons arranged in subtle form. Kidney has the most failure cases in the world compared to the rest of the body organs. Kidney failure is a severe problem, where cardiac blood output is not filtered. Dialysis is one available substitute for kidney failure, which seems to help the patient incompletely. There is a great necessity for a device (artificial kidney) that can be implanted into the body to resume the kidney function. In replicating kidney function there are many potential challenges, which must be addressed for faithful regeneration. This paper primarily focuses on regenerating the proximal convoluted tubule (PCT) size dependent re-absorption, mimicking this function using microfluidics is not reported earlier. Different structural changes in the design have been adopted and the accomplishments are discussed. It is observed that the total flow (the total of flow through all 1000 channels) in straight is 0.4 × 10−16 m3/s, in the diagonal channel is 0.4 × 10−16 m3/s, in step is 0.32 × 10−16 m3/s and in serpentine is 0.38 × 10−16 m3/s. The size-dependent re-absorption of solutes, proteins, and urea with the help of array of channels has been achieved. The dimensions of the main tubule and channel are selected to replicate cell–cell interactions. The re-absorption rate obtained is around 48%, which is closely reaching the PCT re-absorption rate. The increase in the number of channels shows increase in re-absorption rate. The novelty of reported work lies in regenerating the human kidney proximal tubule cell function of size and shape dependent re-absorption using microfluidics technology. The proposed device performance proves its prevalence in kidney-on-chip applications.

The Artificial Kidney Initiation in Kidney Injury 2 (AKIKI2): study protocol for a randomized controlled trial

BackgroundThe Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”).Methods/designThis is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation.Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l).The primary outcome will be the number of RRT-free days at day 28.One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects.DiscussionThe AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019.Trial registrationClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.

Winning the War on Kidney Disease: Perspective from the American Society of Nephrology.

Nephrology is unique. Having saved the lives of millions of people with kidney failure and advocated successfully for the federal government to cover every American on dialysis, the specialty now faces challenges that obstruct advances in care and innovation. More than one half of Americans who

Circuit Hemodynamics and Circuit Failure During Continuous Renal Replacement Therapy.

To study hemodynamic changes within continuous renal replacement therapy circuits and evaluate their relationship with continuous renal replacement therapy longevity. Analysis of downloaded variables recorded by continuous renal replacement therapy machines during multiple episodes of clinical care. Tertiary ICU in Melbourne, Australia. Cohort of 149 ICU patients: 428 episodes of continuous renal replacement therapy. None. Indices of continuous renal replacement therapy function representing 554,991 minutes were assessed including blood flow, access pressure, effluent pressure, prefilter pressure, and return pressure. We defined three patterns of artificial kidney failure: early (≤ 12 hr), intermediate (> 12-24 hr), and late (> 24 hr) in 35%, 31%, and 34% of circuits, respectively. Mean access pressure in late artificial kidney failure was 7.5 mm Hg (7.1-7.9 mm Hg) less negative than early failing circuits and pressures demonstrated lower variability in such late failing circuits. Access dysfunction, defined as access pressure less than or equal to -200 mm Hg occurred in the first 4 hours in 118 circuits (27%) which had a shorter (median [interquartile range]) life at 12.9 hr [5.5-21.3 hr]) hours than access dysfunction-free circuits (18.8 hr [10.1-33.4 hr]; p < 0.0001). Multivariate analysis found the first occurrence of access dysfunction (as a time-varying covariate) was independently associated with increased hazard of subsequent failure (hazard ratio, 1.75; 1.36-2.26). Classification and regression tree analysis of summary pressure indices in the first 2 hours confirmed minimum access pressure to be a significant predictor, as well as indices of transmembrane pressure and return pressure. A pressure-based predictor correctly identified early and late failing circuits (86.2% and 93.6% specificity, respectively). Access dysfunction is a predictor of continuous renal replacement therapy circuit failure. Future monitoring of continuous renal replacement therapy hemodynamics may facilitate remedial actions to improve circuit function.