Tag Archives: #hemodialysis

Artificial Intelligence System Can Help Prevent Anemia in Patients Undergoing Hemodialysis (Medicine)

Scientists developed a decision support system that relies on expert opinion to prevent anemia in patients with kidney disease

Anemia, a condition characterized by the lack of healthy red blood cells in the body, is common in patients with chronic kidney disease who need to undergo routine hemodialysis (a process that helps to “clean” the blood when the kidneys don’t function well). Thus, red blood cell-stimulating agents (called “erythropoiesis-stimulating agents” or ESAs) and iron supplements (ISs) are administered as part of this process. But, complications can arise if the patients have an altered iron metabolism or poor response to medications. Moreover, the medications tend to be expensive and impose a heavy financial burden on public health. Thus, with such patients currently on the rise but not enough physicians suitably trained to administer treatment, additional support systems with smart decision-making capabilities are highly sought after. One option is to turn to artificial intelligence (AI), which seems promising but demands a large dataset and is not practical owing to diverse health conditions of patients.

So, can something be done to improve the situation? In a recent study published in the International Journal of Medical Sciences, medical researchers from Japan tried to find the answer. They came up with a new approach: instead of making the AI learn from the complex physiology of the patient’s body, they opt for a prediction model based on the decisions of experienced physicians. Assistant Professor Toshiaki Ohara from Okayama University, Japan, the lead scientist on the study, explains, “We got the idea while contemplating the thought process of seasoned physicians. After all, they do not calculate detailed values of vital reactions in a patient’s body when deciding dosages, which means prediction models based on biochemistry are not necessary.”

The researchers started off by collecting clinical data at two hospitals in Japan and then preparing two datasets for each hospital: one for training their model and the other for testing and validating its predictions. Simultaneously, they recorded the dosage directions of physicians at both hospitals and considered responses for the two medications used during hemodialysis: ESAs and ISs.

Based on these, they constructed an AI-based model called an “artificial-intelligence-supported anemia control system” (AISACS), which received a total of five inputs (four items of blood examination and dosage history) and churned out dosage direction probabilities for the two medications as outputs. In addition, to make the training process more efficient, they compensated for the time lag between blood examination and dosage decisions by using “data rectification” to match the decision dates with the examination dates.

To the researchers’ delight, AISACS showed a high prediction accuracy with correct classification (directions matching those of physicians) rates of 72%-87%. But what was even more interesting was that it provided “clinically appropriate” classifications at even higher rates (92%-97%). These were directions that didn’t match those of physicians (and were sometimes provided ahead of them) but were still considered appropriate from a medical viewpoint.

With these results, researchers are hopeful about AISAC’s future prospects. “By preventing anemia, our system can help alleviate the burdens on physicians and medical insurance systems. Moreover, it has the potential to share the knowledge and experiences related to medications,” comments an excited Dr. Ohara.

Hopefully, this new AI-based approach provides some hope to both patients undergoing hemodialysis and physicians treating them.

Featured image: AISACS received a total of five inputs and churned out dosage direction probabilities for erythropoiesis-stimulating agents and iron supplements. It was noted that AISACS sometimes produces “clinically appropriate” directions that are different from those of physicians. © 2021 Okayama University


Reference: Ohara T, Ikeda H, Sugitani Y, Suito H, Huynh VQH, Kinomura M, Haraguchi S, Sakurama K. Artificial intelligence supported anemia control system (AISACS) to prevent anemia in maintenance hemodialysis patients. Int J Med Sci 2021; 18(8):1831-1839. doi:10.7150/ijms.53298. Available from https://www.medsci.org/v18p1831.htm


Provided by Okayama University

Researchers Develop DNA Origami-based Aptamer Nanoarray for Potent and Reversible Anticoagulation in Hemodialysis (Medicine)

Anticoagulation in the extracorporeal circuit is one of the major challenges in safe and effective hemodialysis treatment. Heparin-like compounds are widely used in clinical hemodialysis procedures. But they still have a range of undesirable side effects and carry a risk of post-treatment bleeding.

Fig. 1: Design of an aptamer-functionalized DNA origami nanoarray for anticoagulation in hemodialysis. a Schematic illustration of the construction of the aptamer-loaded nanoarray by DNA origami, and the specific binding and inhibition of thrombin. Single-stranded M13mp18 DNA (M13) is folded by annealing with staple strands and capture strands (staple + capture) to form a rectangular DNA origami. Two types of thrombin-binding aptamers, TBA15 and HD22, are loaded onto the DNA origami by hybridization with capture sequences (blue and red) that extend from the surface of the rectangular DNA template (DNA Aptarray). The Aptarray can specifically and efficiently bind thrombin molecules, inhibiting coagulation. b Schematic representation of the utilization of the DNA Aptarray for efficient anticoagulation in hemodialysis. Fresh human blood from healthy donors along with the Aptarray is pumped via mechanical roller pump to a dialysis column (Dialyzer) through the closed extracorporeal circuit, while the dialysate flows through the device and then discarded. Aptarray captures thrombin molecules and efficiently inhibits their catalytic activities, eliciting robust anticoagulatory effects in the ex vivo extracorporeal hemodialysis circuit.
© Zhao et al.

A series of aptamers against thrombin have been screened by systematic evolution of ligands by exponential enrichment (SELEX) technique. These aptamers can directly recognize and inhibit thrombin molecules, while the binding to thrombin can be neutralized through the hybridization of complementary oligonucleotides (antidotes). Several nanoscale anticoagulants based on aptamer-nanoparticle assembly have been reported.  

Recently, a research team led by Prof. DING Baoquan from the National Center for Nanoscience and Technology of the Chinese Academy of Sciences reported a nanoscale anticoagulant aptamer array based on self-assembled DNA origami technology. The study was published in Nature Communications.  

The researchers constructed an anticoagulant aptamer nanoarray on rectangular DNA origami nanostructure. Two different thrombin-binding aptamers were assembled through DNA-hybridization with pre-designed capture sequences on the addressable origami surface. 

The optimized aptamer pattern on DNA origami was found to be necessary for thrombin binding. The origami-aptamer nanoarray initiated thrombin-recognition and activity inhibition, exhibiting enhanced anticoagulation in human plasma, fresh whole blood and a murine model.  

In a dialyzer-containing extracorporeal circuit that mimicked clinical hemodialysis, the researchers found that the nanoarray can prolong the circulation time, effectively preventing thrombosis formation. The nanoarray is antidote nucleotides-controlled and immunologically inert in healthy mice.  

Besides, the versatility of the origami-based nanoarray strategy could be further employed to fabricate multiple aptamers that inhibit pro-coagulant proteases in the coagulation pathway for multi-step prevention of blood clotting.  

This DNA origami platform opens a new avenue to bring a safe and effective anticoagulant for the extracorporeal treatment of renal failures and other diseases. 

Reference: Zhao, S., Tian, R., Wu, J. et al. A DNA origami-based aptamer nanoarray for potent and reversible anticoagulation in hemodialysis. Nat Commun 12, 358 (2021). https://www.nature.com/articles/s41467-020-20638-7 https://doi.org/10.1038/s41467-020-20638-7

Provided by Chinese Academy of Sciences

Low Blood Pressure During Hemodialysis May Indicate Peripheral Vascular Disease (Medicine)

Using a large nationwide registry of patients receiving maintenance hemodialysis, this study published in the American Journal of Kidney Diseases found that higher frequency of low blood pressure episodes during hemodialysis was associated with a higher incidence of diagnosed peripheral arterial disease.

Peripheral artery disease (PAD) is a condition characterized by progressive atherosclerotic narrowing or occlusion of the arteries, particularly to the lower extremities. PAD often goes undiagnosed in patients with kidney failure who may not experience traditional symptoms of claudication. It is plausible that sudden reductions in blood pressure as occurs during intradialytic hypotension (IDH) could reduce limb perfusion and lead to more PAD events or exacerbate PAD symptoms. Using a large nationwide registry of hemodialysis patients and the electronic health records of a large dialysis provider, researchers found that more frequent IDH was associated with a higher incidence of recognized PAD.

These results suggest that patients with more frequent IDH warrant careful examination for PAD such as foot examinations or other diagnostic evaluations.

Reference: Eun Young Seong, Sai Liu, Sang Heon Song, Wolfgang C. Winkelmayer, Maria E. Montez-Rath, Tara I. Chang, “Intradialytic Hypotension and Newly Recognized Peripheral Artery Disease in Patients Receiving Hemodialysis”, AJKD, 2020. https://www.ajkd.org/article/S0272-6386(20)31138-0/fulltext https://doi.org/10.1053/j.ajkd.2020.10.012

Provided by National Kidney Foundation

Non-invasive Electrolyte Levels’ Measuring Method Can Prevent Sudden Cardiac Death (Medicine)

Researchers from Kaunas University of Technology (KTU), Lithuania came up with the idea on how to measure fluctuating blood potassium levels non-invasively, through electrocardiogram.

Researchers from Kaunas University of Technology (KTU), Lithuania came up with the idea on how to measure fluctuating blood potassium levels non-invasively, through electrocardiogram. The researchers claim that their method may become a digital biomarker in the future for managing electrolyte levels. This would be a huge step towards preventing potentially life-threatening conditions among people who suffer from chronic kidney disease.

©KTU

Electrolytes and especially potassium, are paramount in the conduction of the heart’s cells. When electrolytes are too low or too high, the heart cannot contract normally, leading to dangerous arrhythmias and potentially sudden cardiac death.

“Electrolyte levels are kept within the healthy range by the kidneys. However, the patients with the last stage of chronic kidney disease, who have no renal function left, rely on hemodialysis to keep their electrolyte levels regulated. This means that they are prone to electrolyte imbalance in a 2-day-long hiatus between hemodialysis sessions”, explains Ana Rodrigues, researcher at KTU Biomedical Engineering Institute, one of the authors of the invention.

According to Rodrigues, with today’s aging society, it is estimated that the number of people requiring hemodialysis will markedly increase within 10 years. As people age, so do their kidneys. Research shows that up to 50 percent of seniors over the age of 75 can have kidney disease.

Abnormal electrolyte levels disturb the heart’s natural rhythm; such abnormalities can be reflected in the electrocardiogram. However, identifying electrolyte imbalance using an electrocardiogram is difficult due to confounding factors that mask these expected changes. The task becomes particularly complicated if electrolyte levels start to fluctuate beyond normal, but not reaching levels that require immediate medical attention.

The method proposed by the team of KTU researchers, tackles the problem through mathematical models that enable to quantify subtle changes that are not visible to the naked eye at the early stages of electrolyte imbalance. The method allows to spot potassium – the most arrhythmogenic electrolyte – induced changes in a certain part of the electrocardiogram.

“The initial results are promising. Our method may become a digital biomarker in the future for the management of electrolyte levels”, says Rodrigues.

Researchers in Lithuania came up with the idea which would allow measuring electrolyte balance noninvasively at home through an electrocardiogram. ©KTU

The method proposed by KTU researchers allows detecting abnormal potassium levels before the onset of life-threatening arrhythmias. Patients could then start hemodialysis sooner, decreasing the chance of hospitalization and even premature death.

Usually, in order to detect the changes in electrolyte balance, a blood sample would be drawn from a patient. However, blood samples are not routinely requested and cannot be drawn outside a clinical environment. Thus, researchers in Lithuania came up with the idea which would allow measuring electrolyte balance noninvasively at home through an electrocardiogram.

“Noninvasive monitoring of electrolyte levels is a very novel concept and is now in its infancy stages. Our paper is one of the first papers published on the topic and, to the best of our knowledge, the first to investigate potassium fluctuations in ambulatory settings between hemodialysis sessions”, says Rodrigues.

The research is the outcome of the close collaboration between KTU, Lithuanian University of Health Sciences (LSMU) and the University of Zaragoza, Spain.

At the moment, clinical studies involving 17 patients have been completed. The researchers are planning on continuing clinical trials with more patients in order to validate their findings. Their next goal is to create an algorithm that would include measuring different electrolyte levels, such as calcium.

Later on, the algorithm could be integrated into wearable wrist-worn device capable of acquiring electrocardiograms. Every once in a while, the patient would record a short electrocardiogram signal (roughly 2-min long) using their fingers, and the system would register the electrolyte levels. If electrolytes were at an alarming level, the clinic would be notified, and the patient would be instructed accordingly.

References: A. S. Rodrigues et al., “Noninvasive Monitoring of Potassium Fluctuations During the Long Interdialytic Interval,” in IEEE Access, vol. 8, pp. 188488-188502, 2020.
doi: 10.1109/ACCESS.2020.3031471 http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=9225155&isnumber=8948470

Provided by Kaunas University of Technology

Minimally Invasive Ellipsys System Creates Fused, Permanent Vascular Access For Dialysis (Medicine)

A new case report published in the Journal of Vascular Surgery provides one of the first known opportunities to directly visualize the permanent and fused connection (anastomosis) that is created with the minimally invasive Ellipsys® Vascular Access System. The Ellipsys System, made by Avenu Medical, creates a type of dialysis access known as a percutaneous arteriovenous fistula (pAVF) for patients with end-stage renal disease (ESRD) who require hemodialysis.

© A. Mallios et al.

“This is the first published report of direct visualization of a matured pAVF created with the Ellipsys System,” said lead author Alexandros Mallios, MD, a vascular surgeon at Paris Saint-Joseph Hospital in Paris, France. “It was an amazing opportunity that provided first hand proof of the permanent, fused vessel anastomosis made possible by this revolutionary technology.”

Hemodialysis requires access to the patient’s bloodstream, which is often created by establishing a permanent connection between an artery and a vein in the arm known as an arteriovenous fistula (AVF). Traditionally, fistulas are created during an open surgical procedure by suturing the artery and vein together. In contrast, the Ellipsys System uses a small needle puncture and catheter to percutaneously establish an AVF without an implant or suture, leaving the vessels and tissue around the fistula undisturbed.

The subject of the case report was an 80-year-old male diabetic ESRD patient who had a pAVF created with the Ellipsys System 6 months prior. He was evaluated for decreasing blood flow (unrelated to his fistula) and required surgical intervention, which provided the opportunity to visualize the matured Ellipsys pAVF up close. According to Dr. Mallios, the lack of sutures or other foreign bodies made the fusion look “remarkably natural.”

Dr. Mallios has published numerous studies showing the ability of the Ellipsys System to easily and safely create durable vascular access for ESRD patients. In July 2020, he reported one-year follow-up results of 234 Ellipsys patients, the largest study of any pAVF technique to date. Published in JVS, the study reported no adverse events and 96 percent of patients still had fully functioning fistulas with strong blood flow after a year. That “patency rate” is higher than published rates for surgically created fistulas, which average about 60% after one year.

In April 2020, JVS published a case report by Dr. Mallios that featured a 3-D rendering of the Ellipsys pAVF on the cover of the publication. Dr. Mallios also co-authored two recent papers in the Journal of Vascular Access that discussed patient eligibility for Ellipsys and the similarities between an Ellipsys pAVF and a surgical AVF, the current standard of care.

Recently published long-term Ellipsys data showed a functional patency rate of 92 percent at two years. The study also found high levels of patient satisfaction with the procedure.

Cleared by the FDA in 2018 for patients with end-stage renal disease, Ellipsys is the first significant innovation in AVF creation in over 50 years. It transforms a complex surgery into a minimally invasive procedure that can be performed in a hospital outpatient setting, ambulatory surgery center or physician’s office. Since 2015, nearly 3,000 patients worldwide have undergone the Ellipsys procedure.

Medtronic recently announced its plan to acquire Avenu Medical for the Ellipsys percutaneous fistula creation technology. Terms of the deal were not disclosed.

Video 1: Perioperative view of the percutaneously created Ellipsys anastomosis between the proximal radial artery and perforating vein of the elbow.
Video 2: Ligated percutaneous arteriovenous fistula anastomosis.

References: Alexandros Mallios,  William C. Jennings, “Percutaneously created sutureless anastomosis”, Journal Of Vascular Surgery, Volume 6, ISSUE 4, P498-499, 2020. DOI: https://doi.org/10.1016/j.jvscit.2020.05.015 http://dx.doi.org/10.1016/j.jvscit.2020.05.015

Provided by Dowling and Dennis PR