The European Kidney Health Alliance (EKHA) and the Decade of the KidneyTM.

The European Kidney Health Alliance (EKHA) is an advocacy organization that defends the case of the kidney patients and the nephrological community at the level of the European Union (EU), and from there, top to bottom, also at the national level of the EU member states and the EU-associated countries. The Decade of the KidneyTM is a global initiative launched by the American Association of Kidney Patients (AAKP) to create greater awareness and organize patient demands for long overdue innovation in kidney care. This article describes the medical and patient burden of kidney disease, the history of EKHA, its major activities and tools for policy action, and the need for innovation of kidney care. We then describe the Decade of the KidneyTM initiative, the rationale behind why EKHA joined this activity to emanate parallel action at the European side, the novel professionalized structure of EKHA, and its immediate targets. The final aim is to align all major stakeholders for an action plan on kidney disease comparable to Europe's successful Beating Cancer Plan, with the additional intent that the EKHA model is applied also by the respective national kidney-related societies to create a broad mobilization at all levels. The ultimate aims are that the EU considers chronic kidney disease (CKD) as a major health and health-economic problem, to consequently have CKD included as a key health research target by the European Commission, and to improve quality of life and outcomes for all kidney patients.

The European Green Deal and nephrology: a call for action by the European Kidney Health Alliance.

The world faces a dramatic man-made ecologic disaster and healthcare is a crucial part of this problem. Compared with other therapeutic areas, nephrology care, and especially dialysis, creates an excessive burden via water consumption, greenhouse gas emission and waste production. In this advocacy article from the European Kidney Health Alliance we describe the mutual impact of climate change on kidney health and kidney care on ecology. We propose an array of measures as potential solutions related to the prevention of kidney disease, kidney transplantation and green dialysis. For dialysis, several proactive suggestions are made, especially by lowering water consumption, implementing energy-neutral policies, waste triage and recycling of materials. These include original proposals such as dialysate regeneration, dialysate flow reduction, water distillation systems for dialysate production, heat pumps for unit climatization, heat exchangers for dialysate warming, biodegradable and bio-based polymers, alternative power sources, repurposing of plastic waste (e.g. incorporation in concrete), registration systems of ecologic burden and platforms to exchange ecologic best practices. We also discuss how the European Green Deal offers real potential for supporting and galvanizing these urgent environmental changes. Finally, we formulate recommendations to professionals, manufacturers, providers and policymakers on how this correction can be achieved.

Wearable and implantable artificial kidney devices for end-stage kidney disease treatment: Current status and review.

BACKGROUND: Chronic kidney disease (CKD) is a major cause of early death worldwide. By 2030, 14.5 million people will have end-stage kidney disease (ESKD, or CKD stage 5), yet only 5.4 million will receive kidney replacement therapy (KRT) due to economic, social, and political factors. Even for those who are offered KRT by various means of dialysis, the life expectancy remains far too low. OBSERVATION: Researchers from different fields of artificial organs collaborate to overcome the challenges of creating products such as Wearable and/or Implantable Artificial Kidneys capable of providing long-term effective physiologic kidney functions such as removal of uremic toxins, electrolyte homeostasis, and fluid regulation. A focus should be to develop easily accessible, safe, and inexpensive KRT options that enable a good quality of life and will also be available for patients in less-developed regions of the world. CONCLUSIONS: Hence, it is required to discuss some of the limits and burdens of transplantation and different techniques of dialysis, including those performed at home. Furthermore, hurdles must be considered and overcome to develop wearable and implantable artificial kidney devices that can help to improve the quality of life and life expectancy of patients with CKD.

Comparison between Speckle Plethysmography and Photoplethysmography during Cold Pressor Test Referenced to Finger Arterial Pressure.

Speckle Plethysmography (SPG) and Photoplethysmography (PPG) are different biophotonics technologies that allow for measurement of haemodynamics. As the difference between SPG and PPG under low perfusion conditions is not fully understood, a Cold Pressor Test (CPT-60 s full hand immersion in ice water), was used to modulate blood pressure and peripheral circulation. A custom-built setup simultaneously derived SPG and PPG from the same video streams at two wavelengths (639 nm and 850 nm). SPG and PPG were measured at the right index finger location before and during the CPT using finger Arterial Pressure (fiAP) as a reference. The effect of the CPT on the Alternating Component amplitude (AC) and Signal-to-Noise Ratio (SNR) of dual-wavelength SPG and PPG signals was analysed across participants. Furthermore, waveform differences between SPG, PPG, and fiAP based on frequency harmonic ratios were analysed for each subject (n = 10). Both PPG and SPG at 850 nm show a significant reduction during the CPT in both AC and SNR. However, SPG showed significantly higher and more stable SNR than PPG in both study phases. Harmonic ratios were found substantially higher in SPG than PPG. Therefore, in low perfusion conditions, SPG seems to offer a more robust pulse wave monitoring with higher harmonic ratios than PPG.

On the potential of wearable bioimpedance for longitudinal fluid monitoring in end-stage kidney disease.

Bioimpedance spectroscopy (BIS) has proven to be a promising non-invasive technique for fluid monitoring in haemodialysis (HD) patients. While current BIS-based monitoring of pre- and post-dialysis fluid status utilizes benchtop devices, designed for intramural use, advancements in micro-electronics have enabled the development of wearable bioimpedance systems. Wearable systems meanwhile can offer a similar frequency range for current injection as commercially available benchtop devices. This opens opportunities for unobtrusive longitudinal fluid status monitoring, including transcellular fluid shifts, with the ultimate goal of improving fluid management, thereby lowering mortality and improving quality of life for HD patients. Ultra-miniaturized wearable devices can also offer simultaneous acquisition of multiple other parameters, including haemodynamic parameters. Combination of wearable BIS and additional longitudinal multiparametric data may aid in the prevention of both haemodynamic instability as well as fluid overload. The opportunity to also acquire data during interdialytic periods using wearable devices likely will give novel pathophysiological insights and the development of smart (predicting) algorithms could contribute to personalizing dialysis schemes and ultimately to autonomous (nocturnal) home dialysis. This review provides an overview of current research regarding wearable bioimpedance, with special attention to applications in end-stage kidney disease patients. Furthermore, we present an outlook on the future use of wearable bioimpedance within dialysis practice.

Camera-Derived Photoplethysmography (rPPG) and Speckle Plethysmography (rSPG): Comparing Reflective and Transmissive Mode at Various Integration Times Using LEDs and Lasers.

Background: Although both speckle plethysmography (SPG) and photoplethysmography (PPG) examine pulsatile changes in the vasculature using opto-electronics, PPG has a long history, whereas SPG is relatively new and less explored. The aim of this study was to compare the effects of integration time and light-source coherence on signal quality and waveform morphology for reflective and transmissive rSPG and rPPG. Methods: (A) Using time-domain multiplexing, we illuminated 10 human index fingers with pulsed lasers versus LEDs (both at 639 and 850 nm), in transmissive versus reflective mode. A synchronized camera (Basler acA2000-340 km, 25 cm distance, 200 fps) captured and demultiplexed four video channels (50 fps/channel) in four stages defined by illumination mode. From all video channels, we derived rPPG and rSPG, and applied a signal quality index (SQI, scale: Good > 0.95; Medium 0.95−0.85; Low 0.85−0.8; Negligible < 0.8); (B) For transmission videos only, we additionally calculated the intensity threshold area (ITA), as the area of the imaging exceeding a certain intensity value and used linear regression analysis to understand unexpected similarities between rPPG and rSPG. Results: All mean SQI-values. Reflective mode: Laser-rSPG > 0.965, LED-rSPG < 0.78, rPPG < 0.845. Transmissive mode: 0.853−0.989 for rSPG and rPPG at all illumination settings. Coherent mode: Reflective rSPG > 0.951, reflective rPPG < 0.740, transmissive rSPG and rPPG 0.990−0.898. Incoherent mode: Reflective all <0.798 and transmissive all 0.92−0.987. Linear regressions revealed similar R2 values of rPPG with rSPG (R2 = 0.99) and ITA (R2 = 0.98); Discussion: Laser-rSPG and LED-rPPG produced different waveforms in reflection, but not in transmission. We created the concept of ITA to investigate this behavior. Conclusions: Reflective Laser-SPG truly originated from coherence. Transmissive Laser-rSPG showed a loss of speckles, accompanied by waveform changes towards rPPG. Diffuse spatial intensity modulation polluted spatial-mode SPG.

Father of Artificial Organs - The story of medical pioneer Willem J. Kolff (1911-2009).

This biography of serial inventor and medical doctor Willem J. ("Pim") Kolff is written by scientific/historical journalist Herman Broers. The book provides an objective and multi-perspective account of the life and work of Dr. Kolff, who put an undisputed mark on the history of organ-replacement devices by secretly inventing the first clinically functioning hemodialysis machine (in a Nazi-occupied Holland) and later in the United States leading the team that realized the first implantable fully artificial heart. Besides offering a solid historical account, the book also describes the present revival of innovation in the artificial kidney field and contains valuable lessons for a broad variety of readers. Suitable for an audience ranging from medical professionals interested in technology & technologists interested in medicine, to patients & their families, as well as policy makers & research funding parties. The review of this scientific/historic book was composed using the recommendations of Gupta for book reviews of scientific and technical books. Additionally, the reviewer team, composed of a biomedical engineer, a dialysis patient, and a nephrologist, tried to distil some lessons that may be learned from the book.

Probing expert opinions on the future of kidney replacement therapies.

Patients with kidney failure can only survive with some form of kidney replacement (transplant or dialysis). Unfortunately, innovations in kidney replacement therapy lag behind many other medical fields. This study compiles expert opinions on candidate technologies for future kidney replacement therapies. A worldwide web-based survey was conducted with 1566 responding experts, identified from scientific publications on kidney (renal) replacement therapy, indexed in the Web of Science Core Collection (period 2014-2019). Candidate innovative approaches were categorized in line with the Kidney Health Initiative roadmap for innovative kidney replacement therapies. Most respondents expected a revolution in kidney replacement therapies: 68.59% before 2040 and 24.85% after 2040, while 6.56% expected none. Approaches anticipated as most likely were implantable artificial kidneys (38.6%) and wearable artificial kidneys (32.4%). A majority of experts expect that kidney replacement therapies can be significantly improved by innovative technologies.

Wearable health devices and personal area networks: can they improve outcomes in haemodialysis patients?

Digitization of healthcare will be a major innovation driver in the coming decade. Also, enabled by technological advancements and electronics miniaturization, wearable health device (WHD) applications are expected to grow exponentially. This, in turn, may make 4P medicine (predictive, precise, preventive and personalized) a more attainable goal within dialysis patient care. This article discusses different use cases where WHD could be of relevance for dialysis patient care, i.e. measurement of heart rate, arrhythmia detection, blood pressure, hyperkalaemia, fluid overload and physical activity. After adequate validation of the different WHD in this specific population, data obtained from WHD could form part of a body area network (BAN), which could serve different purposes such as feedback on actionable parameters like physical inactivity, fluid overload, danger signalling or event prediction. For a BAN to become clinical reality, not only must technical issues, cybersecurity and data privacy be addressed, but also adequate models based on artificial intelligence and mathematical analysis need to be developed for signal optimization, data representation, data reliability labelling and interpretation. Moreover, the potential of WHD and BAN can only be fulfilled if they are part of a transformative healthcare system with a shared responsibility between patients, healthcare providers and the payors, using a step-up approach that may include digital assistants and dedicated 'digital clinics'. The coming decade will be critical in observing how these developments will impact and transform dialysis patient care and will undoubtedly ask for an increased 'digital literacy' for all those implicated in their care.

Optimizing Indocyanine Green Fluorescence Angiography in Reconstructive Flap Surgery: A Systematic Review and Ex Vivo Experiments.

Background. Indocyanine green angiography (ICGA) offers the potential to provide objective data for evaluating tissue perfusion of flaps and reduce the incidence of postoperative necrosis. Consensus on ICGA protocols and information on factors that have an influence on fluorescence intensity is lacking. The aim of this article is to provide a comprehensive insight of in vivo and ex vivo evaluation of factors influencing the fluorescence intensity when using ICGA during reconstructive flap surgery. Methods. A systematic literature search was conducted to provide a comprehensive overview of currently used ICGA protocols in reconstructive flap surgery. Additionally, ex vivo experiments were performed to further investigate the practical influence of potentially relevant factors. Results. Factors that are considered important in ICGA protocols, as well as factors that might influence fluorescence intensity are scarcely reported. The ex vivo experiments demonstrated that fluorescence intensity was significantly related to dose, working distance, angle, penetration depth, and ambient light. Conclusions. This study identified factors that significantly influence the fluorescence intensity of ICGA. Applying a weight-adjusted ICG dose seems preferable over a fixed dose, recommended working distances are advocated, and the imaging head during ICGA should be positioned in an angle of 60° to 90° without significantly influencing the fluorescence intensity. All of these factors should be considered and reported when using ICGA for tissue perfusion assessment during reconstructive flap surgery.

Optimizing the image of fluorescence cholangiography using ICG: a systematic review and ex vivo experiments.

BACKGROUND: Though often only briefly described in the literature, there are clearly factors that have an influence on the fluorescence intensity, and thereby the usefulness of the technique. This article aims to provide an overview of the factors influencing the fluorescence intensity of fluorescence imaging with Indocyanine green, primarily focussed on NIRF guided cholangiography. METHODS: A systematic search was conducted to gain an overview of currently used methods in NIRF imaging in laparoscopic cholecystectomies. Relevant literature was searched to gain advice on what methods to use. Ex vivo experiments were performed to assess various factors that influence fluorescence intensity and whether the found clinical advices can be confirmed. RESULTS: ICG is currently the most widely applied fluorescent dye. Optimal ICG concentration lies between 0.00195 and 0.025 mg/ml, and this dose should be given as early as achievable-but maximum 24 h-before surgery. When holding the laparoscope closer and perpendicular to the dye, the signal is most intense. In patients with a higher BMI and/or cholecystitis, fluorescence intensity is lower, but NIRF seems to be more helpful. There are differences between various marketed fluorescence systems. Also, no uniform method to assess fluorescence intensity is available yet. CONCLUSIONS: This study identified and discussed several factors that influence the signal of fluorescence cholangiography. These factors should be taken into account when using NIRF cholangiography. Also, surgeons should be aware of new dyes and clinical systems, in order to benefit most from the potential of NIRF imaging.

Automated Spectroscopic Tissue Classification in Colorectal Surgery.

BACKGROUND: In colorectal surgery, detecting ureters and mesenteric arteries is of utmost importance to prevent iatrogenic injury and to facilitate intraoperative decision making. A tool enabling ureter- and artery-specific image enhancement within (and possibly through) surrounding adipose tissue would facilitate this need, especially during laparoscopy. To evaluate the potential of hyperspectral imaging in colorectal surgery, we explored spectral tissue signatures using single-spot diffuse reflectance spectroscopy (DRS). As hyperspectral cameras with silicon (Si) and indium gallium arsenide (InGaAs) sensor chips are becoming available, we investigated spectral distinctive features for both sensor ranges. METHODS: In vivo wide-band (wavelength range 350-1830 nm) DRS was performed during open colorectal surgery. From the recorded spectra, 36 features were extracted at predefined wavelengths: 18 gradients and 18 amplitude differences. For classification of respectively ureter and artery in relation to surrounding adipose tissue, the best distinctive feature was selected using binary logistic regression for Si- and InGaAs-sensor spectral ranges separately. Classification performance was evaluated by leave-one-out cross-validation. RESULTS: In 10 consecutive patients, 253 spectra were recorded on 53 tissue sites (including colon, adipose tissue, muscle, artery, vein, ureter). Classification of ureter versus adipose tissue revealed accuracy of 100% for both Si range and InGaAs range. Classification of artery versus surrounding adipose tissue revealed accuracies of 95% (Si) and 89% (InGaAs). CONCLUSIONS: Intraoperative DRS showed that Si and InGaAs sensors are equally suited for automated classification of ureter versus surrounding adipose tissue. Si sensors seem better suited for classifying artery versus mesenteric adipose tissue. Progress toward hyperspectral imaging within this field is promising.

Differentiation between nerve and adipose tissue using wide-band (350-1,830 nm) in vivo diffuse reflectance spectroscopy.

BACKGROUND: Intraoperative nerve localization is of great importance in surgery. In certain procedures, where nerves show visual resemblance to surrounding adipose tissue, this can be particularly challenging for the human eye. An example of such a delicate procedure is thyroid and parathyroid surgery, where iatrogenic injury of the recurrent laryngeal nerve can result in transient or permanent vocal problems (0.5-2.0% reported incidence). A camera system, enabling nerve-specific image enhancement, would be useful in preventing such complications. This might be realized with hyperspectral camera technology using silicon (Si) or indium gallium arsenide (InGaAs) sensor chips. METHODS: As a first step towards such a camera, we evaluated the performance of diffuse reflectance spectroscopy by analysing spectra collected during 18 thyroid and parathyroid resections. We assessed the contrast information present in two different spectral ranges, for respectively Si and InGaAs sensors. Two hundred fifty three in vivo, wide-band diffuse reflectance spectra (350-1,830 nm range, 1 nm resolution) were acquired on 52 tissue spots, including nerve (n = 22), muscle (n = 12), and adipose tissue (n = 18). We extracted 36 features from these spectroscopic data: 18 gradients and 18 amplitude differences at predefined points in the tissue spectra. Best distinctive feature combinations were established using binary logistic regression. Classification performance was evaluated in a cross-validation (CV) approach by leave-one-out (LOO). To generalize nerve recognition applicability, we performed a train-test (TT) validation using the thyroid and parathyroid surgery data for training purposes and carpal tunnel release surgery data (10 nerve spots and 5 adipose spots) for classification purposes. RESULTS: For combinations of two distinctive spectral features, LOO revealed an accuracy of respectively 78% for Si-sensors and 95% for InGaAs-sensors. TT revealed accuracies of respectively 67% and 100%. CONCLUSIONS: Using diffuse reflectance spectroscopy we have identified that InGaAs sensors are better suited for automated discrimination between nerves and surrounding adipose tissue than Si sensors.

Coordinating efforts to optimize next-generation kidney replacement therapies: the European Kidney Health Alliance Work Group 'Breakthrough Innovation'.

Chronic kidney disease (CKD) is one of the fastest growing health problems, set to become the fifth global death cause by 2040. Factors contributing to this fast growth include increased survival from other diseases (cancer, cardiovascular disease, diabetes, etc.), population aging, lack of early CKD diagnosis tools, insufficient CKD awareness within healthcare systems, limited therapeutic armamentarium to prevent CKD progression and limitations of currently available kidney replacement therapies (KRTs). The European Kidney Health Alliance (EKHA) and the American Association of Kidney Patients joined forces within the Decade of the KidneyTM framework to address these issues. We report on the rationale and vision of the EKHA Work Group 'Breakthrough Innovation' which aims to disrupt the existing innovation paradox on KRT. We discuss how the concepts of international technological roadmapping and coopetition may leverage breakthrough KRT technologies, and present a map of the kidney innovation playing field, driven by patient advocacy groups.

Comparing Remote Speckle Plethysmography and Finger-Clip Photoplethysmography with Non-Invasive Finger Arterial Pressure Pulse Waves, Regarding Morphology and Arrival Time.

OBJECTIVE: The goal was to compare Speckle plethysmography (SPG) and Photoplethysmography (PPG) with non-invasive finger Arterial Pressure (fiAP) regarding Pulse Wave Morphology (PWM) and Pulse Arrival Time (PAT). METHODS: Healthy volunteers (n = 8) were connected to a Non-Invasive Blood Pressure (NIBP) monitor providing fiAP pulse wave and PPG from a clinical transmission-mode SpO2 finger clip. Biopac recorded 3-lead ECG. A camera placed at a 25 cm distance recorded a video stream (100 fps) of a finger illuminated by a laser diode at 639 nm. A chest belt (Polar) monitored respiration. All signals were recorded simultaneously during episodes of spontaneous breathing and paced breathing. ANALYSIS: Post-processing was performed in Matlab to obtain SPG and analyze the SPG, PPG and fiAP mean absolute deviations (MADs) on PWM, plus PAT modulation. RESULTS: Across 2599 beats, the average fiAP MAD with PPG was 0.17 (0-1) and with SPG 0.09 (0-1). PAT derived from ECG-fiAP correlated as follows: 0.65 for ECG-SPG and 0.67 for ECG-PPG. CONCLUSION: Compared to the clinical NIBP monitor fiAP reference, PWM from an experimental camera-derived non-contact reflective-mode SPG setup resembled fiAP significantly better than PPG from a simultaneously recorded clinical transmission-mode finger clip. For PAT values, no significant difference was found between ECG-SPG and ECG-PPG compared to ECG-fiAP.

Near-Infrared Spectral Similarity between Ex Vivo Porcine and In Vivo Human Tissue.

BACKGROUND: In vivo diffuse reflectance spectroscopy provides additional contrast in discriminating nerves embedded in adipose tissue during surgery. However, large datasets are required to achieve clinically acceptable classification levels. This study assesses the spectral similarity between ex vivo porcine and in vivo human spectral data of nerve and adipose tissue, as porcine tissue could contribute to generate large datasets. METHODS: Porcine diffuse reflectance spectra were measured at 124 nerve and 151 adipose locations. A previously recorded dataset of 32 in vivo human nerve and 23 adipose tissue locations was used for comparison. In total, 36 features were extracted from the raw porcine to generate binary logistic regression models for all combinations of two, three, four and five features. Feature selection was performed by assessing similar means between normalized features of nerve and of adipose tissue (Kruskal-Wallis test, p < 0.05) and for models performing best on the porcine cross validation set. The human test set was used to assess classification performance. RESULTS: The binary logistic regression models with selected features showed an accuracy of 60% on the test set. CONCLUSIONS: Spectral similarity between ex vivo porcine and in vivo human adipose and nerve tissue was present, but further research is required.

Portable, wearable and implantable artificial kidney systems: needs, opportunities and challenges.

Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate. Dialysate recycling systems based on sorbents have great potential for such regeneration. Novel dialysis membranes composed of polymeric or inorganic materials are being developed to improve the removal of a broad range of uraemic toxins, with low levels of membrane fouling compared with currently available synthetic membranes. To achieve more complete therapy and provide important biological functions, these novel membranes could be combined with bioartificial kidneys, which consist of artificial membranes combined with kidney cells. Implementation of these systems will require robust cell sourcing; cell culture facilities annexed to dialysis centres; large-scale, low-cost production; and quality control measures. These challenges are not trivial, and global initiatives involving all relevant stakeholders, including academics, industrialists, medical professionals and patients with kidney disease, are required to achieve important technological breakthroughs.

Enabling Robust Radar-Based Localization and Vital Signs Monitoring in Multipath Propagation Environments.

OBJECTIVE: Over the last two decades, radar-based contactless monitoring of vital signs (heartbeat and respiration rate) has raised increasing interest as an emerging and added value to health care. However, until now, the flaws caused by indoor multipath propagation formed a fundamental hurdle for the adoption of such technology in practical healthcare applications where reliability and robustness are crucial. Multipath reflections, originated from one person, combine with the direct signals and multipaths of other people and stationary objects, thus jeopardizing individual vital signs extraction and localization. This work focuses on tackling indoor multipath propagation. METHODS: We describe a methodology, based on accurate models of the indoor multipaths and of the radar signals, that enables separating the undesired multipaths from desired signals of multiple individuals, removing a key obstacle to real-world contactless vital signs monitoring and localization. RESULTS: We also demonstrated it by accurately measure individual heart rates, respiration rates, and absolute distances (range information) of paired volunteers in a challenging real-world office setting. CONCLUSION: The approach, validated using a frequency-modulated continuous wave (FMCW) radar, was shown to function in an indoor environment where radar signals are severely affected by multipath reflections. SIGNIFICANCE: Practical applications arise for health care, assisted living, geriatric and quarantine medicine, rescue and security purposes.