Search

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. [ABSTRACT FROM AUTHOR]

Uremic toxins (UTs) generally accumulate in patients developing end-stage renal disease (ESRD). Although some kinds of UTs cause early death after starting hemodialysis (HD), it remains unknown whether the degree of excessive accumulation of various UTs is associated with worsening of prognosis. We retrospectively conducted this cohort study consisting of adult patients developing ESRD who initiated HD at the National Center for Global Health and Medicine from 2010 to 2019. We created a new uremic score, which was defined as the aggregate score of the following variables reflecting uremic state: elevated blood urea nitrogen, β2-microglobulin, and anion gap before starting HD. The primary outcome was early mortality within 1-year after HD commencement. The hazard ratio (HR) and 95% confidence interval (CI) for a one-point increase in uremic score was calculated with Cox proportional hazard models adjusted by baseline conditions. We included 230 participants, 16 of whom experienced the primary outcome of early mortality after HD commencement. Uremic score was significantly associated with the primary outcome (crude HR: 1.91, 95% CI 1.16–3.14; adjusted HR: 4.19, 95% CI 1.79–9.78). Our novel uremic score, reflecting accumulation of specific UTs, more precisely predicts early mortality after HD commencement. [ABSTRACT FROM AUTHOR]

Motor functions are deteriorated by aging. Some conditions may magnify this deterioration. This study examined whether hemodialysis (HD) process would negatively impact gait and balance beyond diabetes condition among mid-age adults (48–64 years) and older adults (65+ years). One hundred and ninety-six subjects (age = 66.2 ± 9.1 years, body-mass-index = 30.1 ± 6.4 kg/m2, female = 56%) in 5 groups were recruited: mid-age adults with diabetes undergoing HD (Mid-age HD+, n = 38) and without HD (Mid-age HD−, n = 40); older adults with diabetes undergoing HD (Older HD+, n = 36) and without HD (Older HD−, n = 37); and non-diabetic older adults (Older DM−, n = 45). Gait parameters (stride velocity, stride length, gait cycle time, and double support) and balance parameters (ankle, hip, and center of mass sways) were quantified using validated wearable platforms. Groups with diabetes had overall poorer gait and balance compared to the non-diabetic group (p < 0.050). Among people with diabetes, HD+ had significantly worsened gait and balance when comparing to HD− (Cohen's effect size d = 0.63–2.32, p < 0.050). Between-group difference was more pronounced among older adults with the largest effect size observed for stride length (d = 2.32, p < 0.001). Results suggested that deterioration in normalized gait speed among HD+ was negatively correlated with age (r = −0.404, p < 0.001), while this correlation was diminished among HD−. Interestingly, results also suggested that poor gait among Older HD− is related to poor ankle stability, while no correlation was observed between poor ankle stability and poor gait among Older HD+. Using objective assessments, results confirmed that the presence of diabetes can deteriorate gait and balance, and this deterioration can be magnified by HD process. Among HD− people with diabetes, poor ankle stability described poor gait. However, among people with diabetes undergoing HD, age was a dominate factor describing poor gait irrespective of static balance. Results also suggested feasibility of using wearable platforms to quantify motor performance during routine dialysis clinic visit. These objective assessments may assist in identifying early deterioration in motor function, which in turn may promote timely intervention. [ABSTRACT FROM AUTHOR]