AIP Conference Proceedings 2344, 050020 (2021); https://doi.org/10.1063/5.0047542 2344, 050020
© 2021 Author(s).
Recent updates in artificial kidney
technology: Potential parsing for universal coverage burden of chronic kidney disease in Indonesia
Cite as: AIP Conference Proceedings 2344, 050020 (2021); https://doi.org/10.1063/5.0047542 Published Online: 23 March 2021
Prasandhya Astagiri Yusuf, Anindya Pradipta Susanto, Alda Zerlina Amelia, Dandy Permana Supandi, Septhendy, Muhammad Hanif Nadhif, Muhammad Satrio Utomo, and Agus Rizal Ardy Hariandy Hamid
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Recent Updates in Artificial Kidney Technology: Potential Parsing for Universal Coverage Burden of Chronic Kidney
Disease in Indonesia
Prasandhya Astagiri Yusuf
1,2,a), Anindya Pradipta Susanto
1,2, Alda Zerlina Amelia
3, Dandy Permana Supandi
3, Septhendy
3, Muhammad Hanif Nadhif
1,2,
Muhammad Satrio Utomo
1,2,4, and Agus Rizal Ardy Hariandy Hamid
51Department of Medical Physics, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta 10340, Indonesia
2Medical Technology Cluster, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta 10340, Indonesia
3Undergraduate Program, Faculty of Medicine, Universitas Indonesia, Indonesia, Jl. Salemba Raya No. 6, Jakarta 10340, Indonesia
4Research Center for Metallurgy and Material, Indonesia Institute of Science (LIPI),Banten 15310, Indonesia
5Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, Jakarta 10340, Indonesia
a)Corresponding author: prasandhya.a.yusuf@ui.ac.id
Abstract. Chronic Kidney Disease has high mortality and financial burden. It was the third most catastrophic and expensive disease protected by universal coverage. The growth of medical technology gives hope to solve this hardship potentially.
This paper aims to review current and future developments of artificial kidney technologies from different aspects. The scoops are popularity, cost-effectiveness, liters of dialysate needed, portability, safety issues, adverse effect reports, quality of life, the availability, and the number of professional medical workers needed to operate the device. The currently available treatments such as hemodialysis, peritoneal dialysis, and kidney transplantation have its benefits and challenges.
Peritoneal dialysis gives a better quality of life and more cost-effective, however, it has the highest dropout ratio. The future artificial kidneys, such as the wearable artificial kidney, automated wearable artificial kidney, and implantable artificial kidney, offer solutions to overcome the existing challenges. Although the new technologies have not yet reached the Indonesian market, the potential benefits are high in helping chronic kidney disease patients – by offering simplicity, accessibility, reachability, and affordability of the treatment.
Keywords: Artificial kidney; Chronic kidney disease; Medical technology.
INTRODUCTION
The Global Burden of Disease in 2015 study estimated that 1.2 million people with chronic kidney disease (CKD) died. Due to difficult access to dialysis, 2.3 – 7.1 million people died from end-stage kidney disease [1]. High-income countries spent more than 2% - 3% of the annual healthcare financial plan for end-stage kidney disease treatments.
The increments in prevalence were associated with the presence of universal health coverage (Jaminan Kesehatan Nasional or JKN) by the Indonesian government.CKD patients were thought to be assisted financially by the universal coverage so that more patients may have more access to the treatment and more prolonged survival. However, further studies are needed to validate this assumption. A population of CKD patients has always been used as one of the examples that patients under universal healthcare coverage could access extended and costly non-communicable
specialistic care. It was of importance to mention because, previously, access to this type of care was complicated and costly, especially for people with middle and low income [2]. Presumably speaking, with a monthly JKN premium of around $10, CKD patients might have an opportunity to access of dialysis treatments, which may reach the price of approximately $600 per month using a private payment, despite the possibly tiresome administration. However, due to the subsidy policy inherited in the JKN spirit, the payment of the CKD treatments might be reduced to the 60 folds of the original out-of-pocket expenditure.
This scheme looks beneficial for patients. Unfortunately, financially speaking, this type of scheme, at the same time, might also be a burden for government spending. It was reported that the JKN program has suffered badly from the cost overrun, which was more than $2.3 billion in 2019, resulting in a question of the financial sustainability of this program. The poor promotive-preventive program and catastrophic diseases were blamed as the root cause of the excessive spending. Based on the data from 2014 to 2016, CKD was listed as the third most catastrophic disease in terms of the highest treatment cost spending, amounting from 2.90% to 4.35% of the total cost. The first and the second highest in the list were ischemic heart disease and cancer, respectively.
According to the World Health Organization (WHO), the swift development of medical technology was believed to be one of many practical solutions to tackle healthcare challenges in the universal coverage system and countries with low resource settings. Regarding the CKD treatments, artificial kidneys (i.e., hemodialysis and peritoneal dialysis), manifested from biomedical engineering expertise, were expected to model the performance and functionalities of a kidney more accurately. This type of technology has been around for many decades and has proven helping millions of patients. After significantly expansive innovations of the artificial kidney, especially with cutting- edge technological developments, this technology was expected to tackle the third global burden of disease.
Despite the advantages that artificial kidneys may provide, reviews mentioning the technical aspects and opportunity outlook of artificial kidneys are still limited. This type of review is even more difficult to find when talking with the context of Indonesia and the applied universal health coverage.
This study aims to evaluate the current CKD treatments in Indonesia and state of the art on artificial kidney technology, as well as their potential benefits to alleviate the CKD burden in the setting of the Indonesian universal health coverage (JKN). In the following paragraphs, three prospective portable devices, including wearable artificial kidneys (WAK), automated wearable artificial kidneys (AWAK), and implantable artificial kidneys (IAK), are discussed.
CURRENT CKD TREATMENTS IN INDONESIA
Based on the Indonesian Renal Registry data, the most popular CKD treatment in Indonesia in 2018 is hemodialysis (HD), reaching 132,142 patients or equivalent with 98% of overall CKD patients [3]. This report was consistent with a similar pattern observed in other developing countries. Although the outcomes of CKD patients treated with HD or peritoneal dialysis (PD) were generally similar, the choice of treatments depended on the preference or resource availability. This figure, nonetheless, kept increasing from the previous years. Most of the HD patients (90%) received treatment funding from the universal coverage.
Hemodialysis is a blood filtering method that utilizes a pumping machine outside the body and thin hollow fibers, the so-called dialyzers [4]. The HD process typically takes approximately 4-6 hours and is performed 2-3 times a week at a dialysis center. To perform a dialysis service, a health provider must have at least a kidney and hypertension specialist as a supervisor, internal medicine specialist, hemodialysis-certified general practitioner, 3 skilled nurses for every 4 hemodialysis machines, an electromedical technician, and an administrator. As documented in the Indonesian Renal Registry Team Report (2018), there were around 11,531 HD machines, operated by 5,336 HD-certified nurses in Indonesia. Nevertheless, they were mostly concentrated in Java Island and bigger cities. The escalation of HD patients was in accordance with the enhancement of HD units and facilities in Indonesia, alongside with the implementation of national coverage, the so-called JKN. A significant increment of patients who underwent HD treatments was recorded from 77,892 (2017) to 132,142 (2018) [5].
Peritoneal dialysis (PD) is also a filtering method that the process occurs inside the patient's peritoneal cavity.
Peritoneum has very good blood circulation so that it is good to be a natural filter membrane. There are two kinds of peritoneal dialysis: continuous ambulant peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD).
In contrast to hemodialysis, CAPD and kidney transplantation still need empowerment in the resource field. CAPD is not as popular as hemodialysis so that it requires more awareness among dialysis patients and health workers. There are less skilled nurses and doctors for CAPD than nurses dedicated to hemodialysis. Kidney transplantations are hampered due to the kidney donor shortage, as well as the distribution of skilled surgeons around Indonesia.
The new number of patients with CAPD in 2006 increased almost five times the number of patients in 2002.
However, some of them dropped out of the treatment. Reasons for this may be due to infections, catheter issues, ultrafiltration incompetence, and death. In 2017, the number of HD units in Indonesia was still higher than the number of patients that used the PD treatment, even though patients that used the PD treatment were more scattered than in 2009 [3].
The cost needed for HD and PD treatments in Indonesia is relatively high. The mean cost needed for HD patients in a 1-year treatment was USD 8,926 (IDR 133.9 million), while the mean treatment cost for PD patients in a 1-year treatment was USD 5,446 (IDR 81.7 million) [6]. To achieve a good quality of life, HD patients needed about USD 193 (IDR 2.9 million), while PD patients needed USD 61 (IDR 0.91 million). This situation demonstrated that PD treatments were more cost-effective than HD treatments.
PD treatments in diabetic patients with end-stage renal disease were correlated to the increased mortality risk [7].
An earlier study showed that the risk of death and survival rate of CAPD patients and HD patients was not significantly different [8]. However, in terms of quality of life, PD patients got a higher score in many aspects than HD patients [9].
In Indonesia, any form of organ transplantation has to obey the Ministry of Health Regulation (Number 38), 2016.
Kidney transplantations are only done in limited numbers of approved hospitals, which were annually evaluated by the National Transplantation Committee. The hospital's requirements are the accreditation, competencies of human resources, and facilities of the hospital. Kidney transplantations in Indonesia have been done since 1977 and were pioneered by Sidabutar at Cipto Mangunkusumo Hospital, the so-called RSCM. In 2013, RSCM had more than 50 kidney transplantation surgeries, including for children. The survival rate of patients increased since this alternative was applied. Kidney transplantation surgeries require multi-disciplinary professionals so that the cost would be quite expensive, about USD 23,333 (IDR 350 million) for each surgery with no complications. Fortunately, this cost might be claimed and listed as one of the treatments covered by the JKN scheme.
In 2018, there were 66.433 patients with CKD who needed renal replacement therapies. On the other hand, only 108 patients (0.16%) underwent kidney transplantation from living donors [5]. Sadly, the demands for kidney transplantation are still increasing, whereas Indonesia lacked organ donors. Several problems were still faced in implementing kidney transplantations in Indonesia, such as government policies, human resources, funding issues, donor availabilities, and cultural acceptance [10]. The three latter factors impacted the limited number of organ transplant donors since cadaveric organs were still taboo and controversial among recipients. Moreover, the implementation of deceased donor kidneys still faced hitch from various entities. The embodiment was necessary to prepare until the national regulation of deceased donor kidneys is set up [11]. Furthermore, the World Health Organization (WHO) also prohibited organ transplant tourism, which might lead the patients to seek a donor only from their own countries [12]. In Indonesia, the specific organization that facilitates the donor-recipient organ has not been formed, and it takes more effort for one who needs it.
FUTURE OF CKD TREATMENTS WITH WEARABLE MEDICAL DEVICES
To overcome the limitation of kidney donors and hospitalized patients, the refinement and improvement of artificial kidney technology are required. Currently, this type of technology was still being developed in the past years.
The latest innovation dwelled on the cheaper treatments, simpler mechanisms, and home-based therapies since several existing technological outputs, e.g. hemodialysis and peritoneal dialysis, still faced challenges from the perspective of the patients. Therefore, further options of artificial kidney technology were still aspired to actualize the simplicity, accessibility, reachability, and affordability, making sure that the artificial kidney is accessible to everyone, and giving lots of options for every requirements and conditions [13,14].
Currently, the in-center procedure is the only available option for CKD treatments. However, the procedure limits patient activity due to hours of bedside treatment. The advancement of medical technology brings wearable medical devices for CKD into reality to improve patients' quality of life. The device can perform continuous treatment and tackles the burden of size and weight, as well as the need for line power and liters of water. Currently, there are three ongoing developments of the wearable artificial kidney, such as Wearable Artificial Kidney (WAK), Automated Wearable Artificial Kidney (AWAK or WAK PD), and Implantable Artificial Kidney (IAK). While all three are still in the clinical or preclinical trial phase, these highly efficient devices have a promising solution for future CKD treatment, especially under universal health coverage (see Figure 1).
FIGURE 1.Schematic figure of artificial kidney devices.
Wearable Artificial Kidney (WAK)
Wearable Artificial Kidney (WAK) by Wearable Artificial Organs Inc. is a portable HD-based renal replacement therapy device. Blood is pumped through a catheter, anticoagulated with heparin, and then proceeds to a 2-channel pump which propels blood and dialysate alternately. The alternate flow generates positive and negative trans- membrane pressure in 60 to 70 oscillations per minute. The blood then proceeds to a bubble detector before entering the patient. The device cuts the need for 140 liters dialysate in the conventional HD to only 6 liters [15].
Automated Wearable Artificial Kidney (AWAK)
Automated Wearable Artificial Kidney (AWAK) by AWAK Technologies Pte, LTD, uses PD as a fundamental principle - using 1 to 1.5 L of dialysate injection into the peritoneal cavity. However, its system uses dialysate regeneration as a measurement of minimizing fluid requirements. About 500 mL of dialysate is drained every 7.5 minutes. The dialysate will be pumped through sorbents to remove waste, filtered, degassed, supplemented with electrolytes and glucose before being returned to the peritoneal cavity. According to Gura et al. this technology might also be used for patients with end-stage renal diseases [16].
Implantable Artificial Kidney (IAK)
Implantable Artificial Kidney Implantable Artificial Kidney (IAK) by Vanderbilt University and the University of California, San Francisco utilizes tissue engineering and silicon nanotechnology to mimic the kidney’s work mechanism. It consists of two main components, the HemoCartridge as the filter and the BioCartridge, which latter contains cultured renal tubule cells. The device needs to be implanted and connected to the artery, so the need to pump is negated. The toxic waste is concentrated into a small amount of urine like liquid and flowed to the bladder. About 2-4 L of waste is excreted daily [15].
COMPARISON BETWEEN THE CURRENT AND FUTURE ARTIFICIAL KIDNEY DEVICES
The comparison between different artificial kidney devices is summarized in Table 1. Treatments for an end-stage renal disease that have already been applied in Indonesia were mainly HD and PD. From total dialysis patients in 2017, HD treatment dominated with 98% proportion [3]. Comparing the two, PD is more cost-effective in 1-year treatment [6], PD patients also have a better quality of life [9]. Both have safety issues that need to be taken care of [15], however, the dropout rate was relatively higher in PD [3].
Regarding the kidney implant, ethics and financial issues should not be a burden since renal replacement therapy had been done since 1977 [17]. Besides, the JKN coverage on the cost of dialysis and kidney transplantation opens more accessibility for the respective patients.
As for the future artificial kidneys, WAK and AWAK are the only portable devices that have been tested on humans. IAK is still in the preclinical phase so that there is no clinical-phase trial evidence. A clinical trial of 24-hours usage of WAK was conducted in 2016 in the United States. A total of seven patients were observed. In 24 hours, two patients experienced mild muscle cramps, one patient experienced nausea, one patient experienced diarrhea the following day of the WAK treatment. One patient whose white blood cell count was elevated before WAK treatment was given a single prophylactic antibiotics IV and experienced moderate malaise after WAK treatment. Five patients had premature ventricular contractions, but no episodes of sustained ventricular or atrial arrhythmia. No serious adverse event was reported [18].
AWAK, on the other hand, underwent the first in-human study between March 2016 to October 2018 in Singapore.
A total of 15 prevalent PD patients were observed, one patient was excluded from the study due to having no valid therapies. The most common adverse event was abdominal discomfort (73%), which was mostly resolved by draining the dialysate or bowel movement. No serious adverse event was reported [19].
WAK was found to be effective in filtering waste as well as regenerating sorbents, with no cases of uremic solute saturation. No significant clotting was observed in six of the seven patients. Over the 24 hours study, the value of serum electrolytes, hematologic indices, and hemodynamic parameters were observed and comparing it with the baseline after dialysis shows similar values. Meanwhile, AWAK PD therapy showed stable values for serum sodium, potassium, and bicarbonate, and solute clearance that were similar to conventional PD [18].
Both WAK and AWAK, although have been clinically tested, are still not marketed currently, so no information regarding the cost is available [15,18]. However, the developer of WAK believes that the costs of using WAK will be less than the current standard hemodialysis system. A 2014 report by ECRI Institute suggests that WAK will cost 3040% less than conventional dialysis if it incorporates remote monitoring systems. Information regarding the costs of AWAK, however, is not available.
On top of HD, PD, and kidney transplantation, new technological approaches, such as WAK and AWAK, are projected as alternatives once launched in the market. However, the two devices must comply with the clinical and technical requirements. To prepare for device distributions in Indonesia, the potential distributors will need to educate health workers and provide some training in cooperation with the ministry of health. The distributor also needs to inform their product to patients and the market in cooperation with health providers. IAK is not recommended yet since it has not been made to clinical trials. Nevertheless, this does not hold up Indonesia to do clinical trials of this device. Local clinical trials provide more accurate data due to similarities in race and culture.
TABLE 1. Comparison between different Artificial Kidney Devices.
Aspect Artificial Kidney Devices
HD PD WAK AWAK IAK Ref
Popularity
(patients) 132,142 1,737 N/A N/A N/A [3]
Cost
(USD/year) USD 8,926 USD 5,446 USD 5,356 -
6,248* N/A N/A [3]
Dialysate
(liters) 140 N/A 6 1-1.5 N/A [15]
Mobility/
Portability
Stationary due to connection to HD
machines Limited mobility Portable with battery-powered
Portable with battery-
powered Implanted [15,20]
Duration for intended use
3-5 hours, 2-3
times a week N/A 24 hours
continuously
24 hours continuously
24 hours
continuously [15]
Safety Issues
Access-related (e.g. clotting), Infection control,
machine error
Poor hygiene and infection control
Dislodgment issues, accidental disconnection,
poor aseptic
Clogging, N/A [15]
Adverse
Effect N/A N/A Mild muscle
cramping, nausea, diarrhea
Abdominal
discomfort N/A [15]
Quality of
life Lower than PD Higher than HD
Higher than conventional HD based on
RTSQ (p < 0.001)
N/A N/A [9]
Availability
11,531 machines, but not HD centers
are not evenly distributed
Dialysate are supplied through limited distributor
N/A
(clinical trial) N/A (clinical trial)
N/A (preclinical
trial) [5]
Professional medical workers
5,336 trained
nurses Not needed Not needed Not needed
Need training for
surgery [3]
HD = Hemodialysis, PD = Peritoneal Dialysis, WAK = Wearable Artificial Kidney, AWAK = Automated Wearable Artificial Kidney, IAK = Implantable Artificial Kidney, N/A = not available, RTSQ = Renal Treatment Satisfaction Questioner,
*) estimated value. This paper uses an exchange rate of 1 USD = 15,000 IDR according to the assumption of the 2019 National Budget.
CONCLUSION
Comparing the existing options of CKD treatments in Indonesia, PD seems more recommended because it gives a better quality of life and more cost-effective. To prepare homecare treatment with PD, proper education for the patient’s family or caregiver is very essential. PD works at home where health workers are not present, thus the patient’s family or caregiver needs to know at least about the procedure (machine operation and schedule), hygiene, and health workers to contact if an unexpected thing happens. This is very essential to decrease the dropout ratio of PD patients.
Considering the escalation of HD units and PD facilities in Indonesia, Indonesia is highly expected to adapt to new technology for CKD treatments. Portable devices, such as WAK and AWAK, allow for patients' mobility, which may increase the quality of life of the patients and reduce doctor’s visits. To provide affordable WAK and AWAK devices in Indonesia, two approaches might be considered. The first approach is the use of a commercial power bank as a power source [21], considering the low cost, availability, and portability. The second approach is the local production of dialysate, which may eliminate customs and logistic cost. Meanwhile, to improve the robustness, WAK and AWAK devices may feature real-time monitoring and adaptive features using an internet-of-things (IoT) platform [22] and a control system [23], respectively.
ACKNOWLEDGMENTS
This report is a final output of an Artificial Organ & Physiological Engineering module for Undergraduate Medical Students at the Faculty of Medicine, Universitas Indonesia. The elective module aims on introducing the latest medical technology for future physicians. The report is partially funded by Hibah PUTI 2020 Universitas Indonesia. Authors thank Yasmina Z. Syadza for her help in designing the figure.
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