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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]

Fabry disease is an X-linked lysosomal storage disease, second in prevalence after Gaucher disease. The onset of symptoms occurs in childhood or adolescence with palmo-plantar burning pains, hypo hidrosis, angiokeratomas, and corneal deposits. In the absence of diagnosis and treatment, the disease will progress to the late phase, characterized by progressive cardiac, cerebral and renal damage, and possible death. We present the case of an 11-year-old male boy who was transferred to the Pediatric Nephrology Department for palmo-plantar burning pain and end stage renal disease. Following the evaluations for the etiology of end stage renal disease we excluded the vasculitis, the neurologic diseases, extrapulmonary tuberculosis. Because of suggestive aspect at CT scan and lack of etiologic diagnosis of renal insufficiency we performed lymph node and kidney biopsy, with a surprising result for storage disease. The specific investigation confirmed the diagnosis. [ABSTRACT FROM AUTHOR]

Background and objectives: The short-term reported antibody response to SARS-COV-2 vaccination in dialysis patients is high, with a seroconversion response rate up to 97%. Data on the long-term durability of this response are scarce. Our objective was to characterize the long-term anti-spike antibody level in dialysis patients. Design, setting, participants, and measurements: In an observational study, we measured SARS-COV-2 anti-spike antibody levels in dialysis patients who completed 2 doses of the BNT162b2 mRNA SAR S-COV-2 vaccine at 1, 3 and 6 months after the second vaccine dose. We compared the response to dialysis patients who were infected with COVD-19 and to a control group of healthcare-employees. Results: One hundred and forty-two dialysis patients who had been vaccinated (ages 64 ± 11.9 years, 61% male), 33 dialysis patients who had COVID-19 infection (ages 54 ± 14.3 years, 55% male) and 104 individuals in the control group (ages 50 ± 12.2 years, 44% male) were included. The response rate in the vaccinated dialysis patients was 94%, 78% and 73% at 1, 3 and 6 months after the second vaccine dose. In the COVID-19 infected dialysis group and in the control group, the response rate remained at 100% over 6 months. The percentage of change in antibody levels between one and 6 months was −66% in the vaccinated dialysis group, −28% in the control group (p < 0.001) and +48% in dialysis patients who had been infected with COVID-19 (p < 0.001). A non-responder status at 6 months was associated with a lower albumin level. No serious adverse events following vaccination were reported. In conclusion: the initially high response rate to the BNT162b2 vaccine in dialysis patients decreases rapidly. Our results indicate that an early booster (3rd) dose, at three months after the second dose, may be advised for this population to preserve the humoral immunity. [ABSTRACT FROM AUTHOR]

Apparent treatment-resistant hypertension (ATRH) is closely related to chronic kidney disease (CKD); however, the long-term outcomes and the effects of improvement in ATRH in patients with CKD are not well understood. We evaluated the relationship between the persistence of ATRH and the progression of CKD. This cohort study enrolled 1921 patients with CKD. ATRH was defined as blood pressure above 140/90 mmHg and intake of three different types of antihypertensive agents, including diuretics, or intake of four or more different types of antihypertensive agents, regardless of blood pressure. We defined ATRH subgroups according to the ATRH status at the index year and two years later. The prevalence of ATRH at baseline was 14.0%. The presence of ATRH at both time points was an independent risk factor for end-point renal outcome (HR, 1.41; 95% CI, 1.04–1.92; p = 0.027). On the other hand, the presence of ATRH at any one of the time points was not statistically significant. In conclusion, persistent ATRH is more important for the prognosis of renal disease than the initial ATRH status. Continuous follow-up and appropriate treatment are important to improve the renal outcomes. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAA) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, possibly leading to HCV elimination by 2030 as endorsed by the World Health Organization (WHO). However, some patients belonging to the so-called unique or special populations are referred to as difficult-to-treat due to unreached sustained virological response, potential drug side effects or interactions or co-morbidities. Several years after the DAA introduction and on the basis of excellent findings in terms of efficacy and safety, some doubts arise around the exact meaning of the special population designation and whether this group of patients actually exists. The aim of this review is to discuss and analyze current evidence on the management and treatment of the so-called "unique populations". We placed particular emphasis on patients with decompensated cirrhosis, chronic kidney disease (CKD), coinfections, rare genotypes, and previous treatment failure, in order to provide physicians with an updated overview of the actual problems and needs in the current scenario. [ABSTRACT FROM AUTHOR]

End stage renal disease (ESRD) is the last stage of chronic kidney disease that requires dialysis or a kidney transplant to survive. Many studies reported a higher risk of mortality in ESRD patients compared with patients without ESRD. In this paper, we develop a model to predict postoperative complications, major cardiac event, for patients who underwent any type of surgery. We compare several widely-used machine learning models through experiments with our collected data yellow of size 3220, and achieved F1 score of 0.797 with the random forest model. Based on experimental results, we found that features related to operation (e.g., anesthesia time, operation time, crystal, and colloid) have the biggest impact on model performance, and also found the best combination of features. We believe that this study will allow physicians to provide more appropriate therapy to the ESRD patients by providing information on potential postoperative complications. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) and chronic kidney disease (CKD) are strictly related; several independent risk factors of AF are often frequent in CKD patients. AF prevalence is very common among these patients, ranging between 15% and 20% in advanced stages of CKD. Moreover, the results of several studies showed that AF patients with end stage renal disease (ESRD) have a higher mortality rate than patients with preserved renal function due to an increased incidence of stroke and an unpredicted elevated hemorrhagic risk. Direct oral anticoagulants (DOACs) are currently contraindicated in patients with ESRD and vitamin K antagonists (VKAs), remaining the only drugs allowed, although they show numerous critical issues such as a narrow therapeutic window, increased tissue calcification and an unfavorable risk/benefit ratio with low stroke prevention effect and augmented risk of major bleeding. The purpose of this review is to shed light on the applications of DOAC therapy in CKD patients, especially in ESRD patients. [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]

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. Early intervention in lupus nephritis improves prognosis. There is an association between hyperuricemia and lupus nephritis; nevertheless, the sex-specific role of uric acid in lupus nephritis remains unclear. We retrospectively analyzed 578 patients diagnosed with LN by renal biopsy. We determine the relationship of serum uric acid to progression of LN using Kaplan–Meier survival analyses and Cox proportional hazards models. The primary end point was LN progression defined as the initiation of dialysis or kidney transplantation. Men had higher mean serum uric acid levels than did women. Every 1 mg/dL increase in baseline uric acid level increased the risk of LN progression by 15.1%. The serum uric acid level was an independent risk factor for LN progression in women (hazard ratio [HR], 1.158; confidence interval [CI], 1.018–1.317; p = 0.028) but not in men (HR, 1.499; CI, 0.964–2.331; p = 0.072). Sensitivity analysis involving serum uric acid terciles generated consistent and robust results. Serum uric acid level was an independent risk factor for LN progression in women but not in men. [ABSTRACT FROM AUTHOR]

The risk of chronic kidney disease (CKD) following severe acute kidney injury (AKI) in critically ill patients is well documented, but not after less severe AKI. The main objective of this study was to evaluate the long-term incidence of CKD after non-severe AKI in critically ill patients. This prospective single-center observational three-years follow-up study was conducted in the medical intensive care unit in Bordeaux's hospital (France). From 2013 to 2015, all patients with severe (kidney disease improving global outcomes (KDIGO) stage 3) and non-severe AKI (KDIGO stages 1, 2) were enrolled. Patients with prior eGFR < 90 mL/min/1.73 m2 were excluded. Primary outcome was the three-year incidence of CKD stages 3 to 5 in the non-severe AKI group. We enrolled 232 patients. Non-severe AKI was observed in 112 and severe AKI in 120. In the non-severe AKI group, 71 (63%) were male, age was 62 ± 16 years. The reason for admission was sepsis for 56/112 (50%). Sixty-two (55%) patients died and nine (8%) were lost to follow-up. At the end of the follow-up the incidence of CKD was 22% (9/41); Confidence Interval (CI) 95% (9.3–33.60)% in the non-severe AKI group, tending to be significantly lower than in the severe AKI group (44% (14/30); CI 95% (28.8–64.5)%; p = 0.052). The development of CKD three years after non-severe AKI, despite it being lower than after severe AKI, appears to be a frequent event highlighting the need for prolonged follow-up. [ABSTRACT FROM AUTHOR]

A healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence of the benefits of physical activity and other health-related behaviors in the early-stage of CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from 1 January 2009 to 31 December 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan–Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status, and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64–0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06–1.95; p < 0.02) and 1.61 (95% CI: 1.44–1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD. [ABSTRACT FROM AUTHOR]

Background: The results have been inconsistent with regards to the impact of uric acid (UA) on clinical outcomes both in the general population and in patients with chronic kidney disease. The aim of this study was to study the influence of serum UA levels on mortality in patients undergoing continuous ambulatory peritoneal dialysis. Methods: Data on 492 patients from a single peritoneal dialysis unit were retrospectively analyzed. The mean age of the patients was 53.5 ± 15.3 years, with 52% being female (n = 255). The concomitant comorbidities at the start of continuous ambulatory peritoneal dialysis (CAPD) encompassed diabetes mellitus (n = 179, 34.6%), hypertension (n = 419, 85.2%), and cardiovascular disease (n = 186, 37.9%). The study cohort was divided into sex-specific tertiles according to baseline UA level. A Cox proportional hazard model was used to calculate hazard ratios (HRs) of all-cause, cardiovascular, and infection-associated mortality with adjustments for demographic and laboratory data, medications, and comorbidities. Results: Multivariate Cox regression analysis showed that, using UA tertile 1 as the reference, the adjusted HR of all-cause, cardiovascular, and infection-associated mortality for tertile 3 was 0.4 (95% confidence interval (CI) 0.24–0.68, p = 0.001), 0.4 (95% CI 0.2–0.81, p = 0.01), and 0.47 (95% CI 0.19–1.08, p = 0.1). In the fully adjusted model, the adjusted HRs of all-cause, cardiovascular, and infection-associated mortality for each 1-mg/dL increase in UA level were 0.84 (95% CI, 0.69–0.9, p = 0.07), 0.79 (95% CI, 0.61–1.01, p = 0.06), and 0.79 (95% CI, 0.48–1.21, p = 0.32) for men and 0.57 (95% CI, 0.44–0.73, p < 0.001), 0.6 (95% CI, 0.41–0.87, p = 0.006), and 0.41 (95% CI, 0.26–0.6, p < 0.001) for women, respectively. Conclusions: Higher UA levels are associated with lower risks of all-cause, cardiovascular and infection-associated mortality in women treated with continuous ambulatory peritoneal dialysis. [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]

Urea at post-dialysis levels induces increased ROS in a number of cell types. The aim of this study was to determine whether urea-induced production of ROS remains elevated after urea is no longer present, and, if it does, to characterize its origin and effects. Human arterial endothelial cells were incubated with 20 mM urea for two days, and then cells were incubated for an additional two days in medium alone. Maximal ROS levels induced by initial urea continued at the same level despite urea being absent. These effects were prevented by either MnSOD expression or by Nox1/4 inhibition with GKT13781. Sustained urea-induced ROS caused a persistent reduction in mtDNA copy number and electron transport chain transcripts, a reduction in transcription of mitochondrial fusion proteins, an increase in mitochondrial fission proteins, and persistent expression of endothelial inflammatory markers. The SOD-catalase mimetic MnTBAP reversed each of these. These results suggest that persistent increases in ROS after cells are no long exposed to urea may play a major role in continued kidney damage and functional decline despite reduction of urea levels after dialysis. [ABSTRACT FROM AUTHOR]