Effect of nephrostomy sheath size on renal pelvic pressure during endoscopic combined intrarenal surgery: artificial kidney model study.

BACKGROUND: This study aimed to evaluate the intrarenal pelvic pressure in endoscopic combined intrarenal surgery using an artificial kidney model. METHODS: An artificial kidney model was created using the Urovac evacuator™. Four sizes of nephrostomy sheaths (MIP-L: 25/26 Fr, MIP-M: 16.5/17.5 Fr, MIP-S: 11/12 Fr, MIP-XS: 8.5/9.5 Fr) and two sizes of ureteral access sheaths (12/14 Fr and 10/12 Fr) were installed into the model. For each combination of nephrostomy and ureteral access sheath, renal pelvic pressure was measured with and without insertion of the retrograde flexible ureteroscope. Irrigation from the nephroscope was adjusted to 40-160 mmHg using an automatic irrigation device, and the irrigation of the ureteroscope was by spontaneous dripping at 80 cmH2O. Conditions were measured six times, and the renal pelvic pressure was compared in different conditions. RESULTS: Without ureteroscope insertion through the ureteral access sheath, the renal pelvic pressure never exceeded 30 mmHg. Meanwhile, when the ureteroscope was inserted, the renal pelvic pressure increased as the nephrostomy sheath and ureteral access sheath became narrower and as the irrigation pressure increased. Intrarenal pelvic pressure exceeded 30 mmHg when the irrigation pressure was increased in 12/14 Fr ureteral access sheath when MIP-XS was used, and in 10/12 Fr ureteral access sheath when MIP-XS and MIP-S were used. CONCLUSIONS: The use of a thin nephrostomy sheath in endoscopic combined intrarenal surgery can lead to increased intrarenal pelvic pressure. Although our results are from an artificial kidney model, special care is suggested to be required when using a retrograde flexible ureteroscope simultaneously in treatment of patients.

Haemodialysis machine designation for patients with chronic Hepatitis B virus: A practice and attitudes survey of Australian renal healthcare workers.

BACKGROUND: To reduce the risk of viral transmission, guidelines recommend the use of designated haemodialysis machines and patient isolation for patients with chronic hepatitis B virus (HBV). These practices are without a strong evidence base, and may no longer be necessary in the setting of heat disinfection programs and standard precautions. METHODS: An online cross-sectional survey was developed for renal clinicians across Australia and New Zealand to explore infection prevention policy concerning patients with chronic HBV in haemodialysis units. We sought to determine whether psychosocial and cultural impacts might result from the mandatory use of machine designation and patient isolation practices, as perceived by multidisciplinary healthcare workers with experience working with this patient population. RESULTS: Sixty-seven responses from 27 health districts across all states of Australia and one New Zealand district were received. Most respondents were from urban areas (65%), and were nurses (87%). 50% of health districts reported using designated machines, while 32% isolate patients. Lack of necessary resources limited the use of designated machines (57%), and patient isolation (78%). Respondents not routinely using these precautions were more likely to express concerns regarding patient psychosocial wellbeing and cultural appropriateness. Overall, 30% of respondents expressed concerns regarding the cultural appropriateness of these recommendations. CONCLUSION: We demonstrate wide variation in haemodialysis infection prevention and control policy and practice with regards to managing patients with chronic HBV. While use of standard precautions and machine disinfection are consistently applied, resource availability and concerns for patient psychosocial wellbeing limit adherence to international guidelines.

In vitro comparison of simulated intrapelvic pressure in an artificial kidney model during retrograde intrarenal surgery among various single-use ureteroscopes.

OBJECTIVES: This study compares intrapelvic pressure (IPP) during retrograde intrarenal surgery with various single-use flexible ureteroscopes (f-URS) in an artificial kidney model. METHODS: We created an artificial kidney model with a pressure sensor using a bladder evacuation device. The model was completely closed and the only backflow was on the side of the ureteroscope inside the ureteral access sheath (UAS). We tested five single-use f-URSs (LithoVue, Wiscope, PU3022A, PU3033A, and AXIS) with six different types of UAS (9.5/11.5-14/16 Fr). Using the automatic irrigation system, 30 s of irrigation was performed at various pressures (40-180 mmHg) and steady-state IPP was recorded. IPP was compared between the five single-use f-URSs. IPP cutoff value was determined at 30 mmHg. The diameter of the endoscope tip and the curved and shaft parts were also measured and recorded. RESULTS: The diameters of all parts were significantly different between single-use f-URSs. The maximum IPP tended to be higher in ureteroscopes with larger diameters of the proximal parts (curved part/shaft part). In LithoVue and Uscope PU3022A f-URSs, the maximum IPP did not exceed 30 mmHg when UAS ≥12/14 Fr was used. In AXIS and Wiscope f-URSs, it did not exceed the cutoff value when the UAS ≥11/13 Fr was used. In Uscope PU3033A f-URS, it did not exceed 30 mmHg when the UAS ≥10/12 Fr was used. CONCLUSIONS: Maximum IPP tended to be higher in f-URSs with larger diameters of the proximal part and the appropriate size of the UAS differed between various single-use f-URSs.

An early artificial implantable kidney prototype demonstrates short-term viability in a porcine model without immunosuppression.

Dialysis remains an imperfect treatment for over two million patients with renal failure worldwide. This bioreactor may lead to the completely implantable, continuous filtration system they need.

Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m2 and 140-165 mL/min/m2, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.

Bisphenol A and Bisphenol S in Hemodialyzers.

Bisphenol A (BPA)-based materials are used in the manufacturing of hemodialyzers, including their polycarbonate (PC) housings and polysulfone (PS) membranes. As concerns for BPA's adverse health effects rise, the regulation on BPA exposure is becoming more rigorous. Therefore, BPA alternatives, such as Bisphenol S (BPS), are increasingly used. It is important to understand the patient risk of BPA and BPS exposure through dialyzer use during hemodialysis. Here, we report the bisphenol levels in extractables and leachables obtained from eight dialyzers currently on the market, including high-flux and medium cut-off membranes. A targeted liquid chromatography-mass spectrometry strategy utilizing stable isotope-labeled internal standards provided reliable data for quantitation with the standard addition method. BPA ranging from 0.43 to 32.82 µg/device and BPS ranging from 0.02 to 2.51 µg/device were detected in dialyzers made with BPA- and BPS-containing materials, except for the novel FX CorAL 120 dialyzer. BPA and BPS were also not detected in bloodline controls and cellulose-based membranes. Based on the currently established tolerable intake (6 µg/kg/day), the resulting margin of safety indicates that adverse effects are unlikely to occur in hemodialysis patients exposed to BPA and BPS quantified herein. With increasing availability of new data and information about the toxicity of BPA and BPS, the patient safety limits of BPA and BPS in those dialyzers may need a re-evaluation in the future.

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.

Daily practice evaluation of the paediatric set of a next-generation long-term haemodialysis machine.

BACKGROUND: From 2006 to 2020, 24% of children starting haemodialysis in France weighed < 20 kg. Most new-generation long-term haemodialysis machines do not propose paediatric lines anymore but Fresenius has validated two devices for use in children above 10 kg. Our aim was to compare the daily use of these two devices in children < 20 kg. METHODS: Retrospective single-center evaluation of daily practice with Fresenius 6008® machines, and low-volume paediatric sets (83 mL), as compared to 5008® machines with paediatric lines (108 mL). Each child was treated randomly with both generators. RESULTS: A total of 102 online haemodiafiltration sessions were performed over 4 weeks in five children (median body weight 12.0 [range 11.5-17.0] kg). Arterial aspiration and venous pressures were maintained respectively over - 200 mmHg and under 200 mmHg. For all children, blood flow and volume treated per session were lower with 6008® vs. 5008® (p < 0.001), median difference between the two devices being 21%. In the four children treated in post-dilution mode, substituted volume was lower with 6008® (p < 0.001, median difference: 21%). Effective dialysis time was not different between the two generators; however, the difference between total duration of session and dialysis effective time was slightly higher (p < 0.05) with 6008® for three patients, due to treatment interruptions. CONCLUSION: These results suggest that children between 11 and 17 kg should be treated with paediatric lines on 5008® if possible. They advocate for modification of the 6008 paediatric set to decrease resistance to blood flow. The possibility to use 6008® with paediatric lines in children below 10 kg deserves further studies.

Automated adjustment of dialysate sodium by the hemodialysis monitor: Rationale, implementation, and clinical benefits.

Prescribing dialysate sodium is the responsibility of the physician, but there are currently no clear guidelines for this prescription. Furthermore, there is quite frequently a significant difference between prescribed and measured dialysate sodium. Several arguments, both theoretical and experimental, suggest that dialysate sodium should be adjusted individually in such a way as to result in a decreasing sodium profile that takes into account the patient's predialytic natremia. The generalization in clinical routine of this strategy requires the integration into the hemodialysis monitor of software making the machine capable to automatically adjust the dialysate sodium at each session. The only three such softwares that have been integrated into hemodialysis machines for routine clinical use are discussed. All three work with conductivity measurements as a surrogate for sodium concentrations. Although there are only a few publications on the use of these softwares in clinical practice, they appear to result in improved intradialytic tolerance to the dialysis treatment, better control of hypertension, and reduced thirst, leading to decreased interdialytic weight gain.

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.

[Review of Leachable Substances in Hemodialyzer].

With the rapid development of my country's hemodialysis industry, the application of hemodialysis machines has become more and more extensive, but at the same time, the quality control technology of hemodialysis machines is not perfect. Especially for a wide range of leachable substances in dialyzers, there are few studies and detection methods. This study first briefly describes the development of hemodialyzers, and then expounds the common types of leachables, extraction methods, and chromatography and mass spectrometry conditions. It is summarized that the research plan of leachable substances is to determine the type first, then formulate the extraction plan, and then establish the detection method. Finally, we look forward to the research prospects of hemodialyzer leachables, and point out that with the deepening and extensive development of research, it can further promote the healthy development of the hemodialyzer industry.

A first proof-of-concept for the non-invasive, time-efficient measurement of the plasma sodium concentration for individualized dialysis.

Dialysis-induced changes in plasma sodium concentration may cause undesirable side effects. To prevent these, the sodium content in dialysis fluid has to be individualized based on the patient's plasma sodium concentration. In this paper, we describe a simple conductivity based method for measuring the plasma sodium concentration. The method is based on performing a bypass during which the residual volume on the dialysate side of the dialyzer at least partially adopts the sodium concentration on the blood side. The conductivity at dialysate outlet of the dialyzer after the end of bypass corresponds to the sodium concentration. We show that already 14 s of bypass are sufficient to subsequently measure a conductivity that correlates with the blood-side sodium concentration. Thus, the short bypass method allows a time saving of 88% compared to the long bypass of 120 s. In vitro experiments with bovine blood show that plasma sodium concentration can be non-invasively and time-efficiently measured during dialysis. Bland Altman analysis reveals a bias of 0.28 mmol/l and limits of agreement of -3.17 and 3.74 mmol/l for the long bypass. For the short bypass, bias is 0.09 mmol/l and limits are -3.90 and 4.08 mmol/l. Since the method presented is based on established conductivity cells, no additional sensors are required, so that the method could be easily implemented in dialysis machines. In future, performing a bypass at the beginning of a treatment may be used to adjust the composition of dialysis fluid individually for each patient.

Zirconium cyclosilicate: An oral sorbent for potassium, four decades in the making.

HemoCleanse collaborated with Dr. John Sherman and Union Carbide in the 1980s to develop a cation exchanger with high selectivity for potassium and ammonium, for use in a wearable artificial kidney. Synthetic zeolites had unexpected solubility in this application but by 2000, UOP (a sister company of Union Carbide) had developed zirconium cyclosilicate (SZC). HemoCleanse performed early animal studies of SZC as an oral sorbent. These showed remarkable binding characteristics. HemoCleanse then obtained the license for SZC for medical applications, helped to form ZS Pharma, and collaborated in further animal studies and clinical trials. AstraZeneca purchased ZS Pharma in 2015, and SZC (Lokelma®) has now become an effective treatment for hyperkalemia in patients with kidney failure and cardiac conditions.

Artificial Kidney Capsule Packed with Mesenchymal Stem Cell-Laden Hydrogel for the Treatment of Rhabdomyolysis-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has emerged as a major public health problem affecting millions of people worldwide without specific and satisfactory therapies due to the lack of an effective delivery approach. In the past few decades, hydrogels present infinite potential in localized drug delivery, while their poor adhesion to moist tissue and isotropic diffusion character always restrict the therapeutic efficiency and may lead to unwanted side effects. Herein, we proposed a novel therapeutic strategy for AKI via a customizable artificial kidney capsule (AKC) together with a mesenchymal stem cell (MSC)-laden hydrogel. Specifically, an elastic capsule owning an inner chamber with the same size and shape as the kidney is designed and fabricated through three-dimensional (3D) modeling and printing, serving as an outer wrap for kidney and cell-laden hydrogels. According to the in vitro experiment, the excellent biocompatibility of gelatin-based hydrogel ensures viability and proliferation of MSCs. In vivo mice experiments proved that this concept of AKC-assisted kidney drug delivery could efficiently reduce epithelial cell apoptosis and minimize the damage of the renal tubular structure for mice suffering AKI. Such a strategy not only provides a promising alternative in the treatment of AKI but also offers a feasible and versatile approach for the repair and recovery of other organs.

Improved hemocompatibility of polysulfone hemodialyzers with Endexo® surface modifying molecules.

Anticoagulation therapy is widely used to reduce clotting during hemodialysis (HD), but may cause adverse effects in end-stage kidney disease patients. A new hemodialyzer with a membrane modified by surface modifying molecule was developed to improve hemocompatibility that aimed to reduce the need for anticoagulation during dialysis treatments. We compared membrane surface characteristics and in vitro hemocompatibility of the new hemodialyzer to the standard polysulfone (PSF) hemodialyzer membrane. Scanning electron microscopy, contact angle measurement (68° ± 3° test vs. 41.6° ± 6° control), and X-ray photoelectron spectrometry measurement for fluorine atomic % (7.4% ± 0.4% test vs. not detectable control), showed that the membrane surface was modified with surface modifying macromolecule (SMM1) but maintained membrane structure and surface hydrophilicity. Zeta potential of the blood-contacting surface showed that the absolute surface charge was reduced at neutral pH (-3.3 mV ± 1.1 mV test vs. -15.6 mV ± 1.0 mV control). Platelet count reduction was significantly less for the SMM1-modified dialyzer (40.88% ± 21.89%) compared to the standard PSF dialyzer (62.62% ± 34.13%), along with Platelet Factor 4 (1824.10 ng/ml ± 436.26 ng/ml test vs. 2479.00 ng/ml ± 852.96 ng/ml control). These studies demonstrate the successful incorporation of SMM1 into the new hemodialyzer with the expected results. Our in vitro experiments indicate that the SMM1-modified hemodialyzers could improve hemocompatibility compared to standard PSF hemodialyzers and have the potential to minimize the patient's anticoagulant requirements during HD. Additional research with SMM1 additives incorporated into the entire dialysis circuit and use in a clinical settings are required to confirm these promising findings.

Survival of infants treated with CKRT: comparing adapted adult platforms with the Carpediem™.

BACKGROUND: The most severely ill neonates and infants with AKI who need kidney replacement therapy have had to rely upon peritoneal dialysis, or adaptations of veno-venous continuous kidney replacement therapy (CKRT) devices for adults. Data from the Prospective Pediatric CRRT (ppCRRT) registry observed children < 10 kg had a lower survival rate than children > 10 kg (44% vs. 64%, p < 0.001). A CKRT device designed specifically for small children could improve outcomes. The Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM™) is specifically dedicated to providing CKRT for newborns and small infants. METHODS: We performed a retrospective cohort analysis comparing patient severity of illness and outcomes between the ppCRRT and CARPEDIEM registries, involving 6 Italian pediatric intensive care units. Thirty-eight subjects from the CARPEDIEM registry and 84 subjects from the ppCRRT registry < 10 kg were screened for comparison. We compared patient outcomes with a weight-matched cohort (< 5 kg) of 34 patients from the CARPEDIEM registry and 48 patients from the ppCRRT registry. RESULTS: The ppCRRT subjects had higher rates of vasoactive medication at CKRT initiation. Survival to CKRT termination was higher for CARPEDIEM subjects (33/34 vs. 21/48, p < 0.0001). Multivariable logistic regression showed that CARPEDIEM registry cohort was the only variable to retain an association with survival to CKRT discontinuation. CONCLUSIONS: We suggest children receiving CKRT using CARPEDIEM have excellent survival. Our data should be interpreted with caution given the retrospective comparison across two eras more than a decade apart.

Flow Dynamic Analysis by Contrast-Enhanced Imaging Techniques of Medium Cutoff Membrane Hemodialyzer.

INTRODUCTION: Medium cutoff (MCO) membranes represent an interesting innovation in the field of hemodialysis. Given the correlation between large (PM >25 kDa) middle molecules (LMM) and clinical outcomes, the possibility to broaden the spectrum of solutes removed in hemodialysis with MCO membranes introduces a new perspective for end-stage kidney disease patients. Due to low diffusion coefficients of LMM, the use of convection is required to maximize extracorporeal clearance. High convective rates are achieved with high-flux membranes in hemodiafiltration, a technique not available in the US. In case of the MCO membrane, remarkable clearances of LMM are achieved combining the permeability of the membrane with a significant amount of internal convection. The mechanism of filtration-backfiltration inside the dialyzer enables effective removal of LMM in a technique called expanded hemodialysis (HDx). Given such theoretical explanation, it is important to demonstrate the blood and ultrafiltration rheology inside the MCO dialyzer. METHOD: This study for the first time describes flow dynamic parameters and internal cross-filtration, thanks to specific radiology and nuclear imaging techniques. RESULTS: Flow dynamic analysis of the blood and dialysate compartment confirms excellent distribution of velocities and an excellent matching of blood and dialysate. Average blood flow velocity allows for wall shear rates adequate to avoid protein stagnation at the blood membrane interface and increase in blood viscosity. Cross-filtration analysis demonstrates a remarkable filtration/backfiltration flux reaching values >30 mL/min at a blood flow of 300 mL/min and zero net filtration. CONCLUSION: The MCO dialyzer Theranova 400 appears to have a design optimized to perform expanded hemodialysis (HDx).