Development of in-vitro pulsatile flow generator for evaluating the performance of hemodialysis catheters.

Hemodialysis (HD) using an HD catheter is performed widely on renal failure patients. The catheter was evaluated using the recirculation ratio in pre-clinical status, which is a crucial index indicating its performance. However, pre-clinical in-vivo experiments have limitations: high cost, and ethical issues. Hence, computational and in-vitro methods have been developed as alternatives. However, computational methods require fluid dynamic knowledge, whereas in-vitro experiments are complicated and expensive. In this study, we developed a pulsatile flow generator to mimic blood flow achieving cost effectiveness and user convenience. The device used iterative learning control, achieving blood flow in the superior and inferior vena cava within a 3.3% error. Furthermore, the recirculation ratios were measured based on two insertion directions and two different external pipe materials to evaluate the catheter regarding patients' posture and blood vessel stiffness. The results provide a better understanding of cardiovascular device performance without complicated and costly pre-clinical tests.

Salvage treatment of forearm arteriovenous fistula with small caliber inflow distal artery by percutaneous transluminal angioplasty.

BACKGROUND: Dysfunctional distal arteriovenous fistulas (AVFs) with small caliber distal inflow arteries theoretically require percutaneous transluminal angioplasty (PTA) throughout the entire arterial length. However, in clinical practice, whole distal inflow arterial PTA is not frequently performed due to concerns about possible arterial rupture. Therefore, we investigated the safety and efficacy of this procedure at our center, comparing it with the standard venous PTA. METHODS: From March 2017 to December 2022, 48 cases of distal AVF salvaged by whole distal inflow arterial PTA were assigned into a treatment group and 121 cases of distal AVF salvaged by venous standard PTA not involving the whole inflow artery were assigned into a control group. These two groups were then compared. RESULTS: Those in the treatment group (who received whole distal inflow arterial PTA) were older than those in the control group (mean age, 69 vs 59 years, p < 0.001). Otherwise, differences between the two groups were unremarkable. After the salvage treatment, primary patency seemed to decrease in the treatment group with whole distal inflow arterial PTA compared to the control group with conventional PTA, although such decrease was not significant (p = 0.072). However, primary assisted patency and secondary patency were comparable between the two groups (p = 0.350 and p = 0.590, respectively). And in the treatment group, only one arterial dissection occurred, which was successfully managed with balloon tamponade so that no distal AVF was abandoned due to complications following whole distal inflow arterial PTA. CONCLUSION: Whole distal inflow arterial PTA is an effective and safe option for distal AVF salvage with a narrowed inflow artery, frequently refractory to conventional venous PTA.

Safety and durable patency of tunneled hemodialysis catheter inserted without fluoroscopy.

BACKGROUND: A tunneled hemodialysis (HD) catheter is preferred due to its lower incidence of infection and malfunction than non-tunneled ones. For safer insertion, fluoroscopic guidance is desirable. However, if the patient is unstable, transfer to the fluoroscopy may be impossible or inappropriate. METHODS: From June 2019 to September 2022, 81 tunneled HD catheter insertion cases performed under ultrasound guidance without fluoroscopy and 474 cases with fluoroscopy in our institutional HD catheter cohort were retrospectively compared. RESULTS: Immediate complications, later catheter-associated problems, including infections and catheter dysfunction, were comparable between the two groups (p = 0.20 and p = 0.37, respectively). The patency of tunneled catheters inserted without fluoroscopy was comparable to the patency of tunneled catheters inserted with fluoroscopic guidance (p = 0.90). CONCLUSION: Tunneled HD catheter insertion without fluoroscopy can be performed safely and has durable patency compared to the insertion with fluoroscopy. Therefore, this method can be considered for the selected unstable patients (e.g., ventilator care) in the intensive care unit.

Prediction of intradialytic hypotension using pre-dialysis features-a deep learning-based artificial intelligence model.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning-based artificial intelligence (AI) model to predict IDH using pre-dialysis features. METHODS: Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost). RESULTS: IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. CONCLUSIONS: Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Evaluation of outcomes with permanent vascular access in an elderly Korean population based on the National Health Insurance Service database.

INTRODUCTION: As nearly half of patients with end-stage kidney disease (ESKD) who initiate hemodialysis (HD) are over 65 years old (commonly defined as elderly), the fistula first strategy is controversial even in HD patients ≥65 years. METHODS: In Korea's National Health Insurance Service database from 2008 to 2019, 41,989 elderly (≥ 65 years) HD patients were retrospectively reviewed to identify their clinical characteristics and outcomes. Vascular access (VA) patencies, risk factors associated with patencies and patient survival between arteriovenous fistula (AVF) and arteriovenous graft (AVG) were compared. RESULTS: Elderly AVF group (n = 28,467) had superior primary, primary assisted, and secondary patencies than elderly AVG group (n = 13,522) (all p values are <0.001). Patient survival was also better in the elderly AVF group than in the elderly AVG (p < 0.001). In multivariate Cox regression analyses for diverse outcomes, AVG (vs. AVF) was identified as a risk factor for all-cause mortality (adjusted hazard ratio [HR]: 1.307; 95% confidence interval [CI]: 1.272-1.343; p < 0.001), primary patency (adjusted HR: 1.745; 95% CI: 1.701-1.790; p < 0.001), primary-assisted patency (adjusted HR: 2.163; 95% CI: 2.095-2.233; p < 0.001), and secondary patency (adjusted HR: 3.718; 95% CI: 3.533-3.913; p < 0.001). CONCLUSION: Our study demonstrated that as a permanent VA for HD, AVF should be strongly considered in elderly (≥ 65 years) ESKD Korean patients. The age limit for AVF creation in ESKD patients should be adjusted more upward.

Modeling of Fabry disease nephropathy using patient derived human induced pluripotent stem cells and kidney organoid system.

OBJECTIVES: To explore the possibility of kidney organoids generated using patient derived human induced pluripotent stem cells (hiPSC) for modeling of Fabry disease nephropathy (FDN). METHODS: First, we generated hiPSC line using peripheral blood mononuclear cells (PBMCs) from two male FD-patients with different types of GLA mutation: a classic type mutation (CMC-Fb-001) and a non-classic type (CMC-Fb-003) mutation. Second, we generated kidney organoids using wild-type (WT) hiPSC (WTC-11) and mutant hiPSCs (CMC-Fb-001 and CMC-Fb-003). We then compared alpha-galactosidase A (α-GalA) activity, deposition of globotriaosylceremide (Gb-3), and zebra body formation under electromicroscopy (EM). RESULTS: Both FD patients derived hiPSCs had the same mutations as those detected in PBMCs of patients, showing typical pluripotency markers, normal karyotyping, and successful tri-lineage differentiation. Kidney organoids generated using WT-hiPSC and both FD patients derived hiPSCs expressed typical nephron markers without structural deformity. Activity of α-GalA was decreased and deposition of Gb-3 was increased in FD patients derived hiPSCs and kidney organoids in comparison with WT, with such changes being far more significant in CMC-Fb-001 than in CMC-Fb-003. In EM finding, multi-lammelated inclusion body was detected in both CMC-Fb-001 and CMC-Fb-003 kidney organoids, but not in WT. CONCLUSIONS: Kidney organoids generated using hiPSCs from male FD patients might recapitulate the disease phenotype and represent the severity of FD according to the GLA mutation type.

Blood Pressure Control in Patients with Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease. Blood pressure (BP) control can reduce the risks of cardiovascular (CV) morbidity, mortality, and kidney disease progression. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have suggested the implementation of a more intensive BP control with a target systolic BP (SBP) of <120 mmHg based on the evidence that the CV benefits obtained is outweighed by the kidney injury risk associated with a lower BP target. However, an extremely low BP level may paradoxically aggravate renal function and CV outcomes. Herein, we aimed to review the existing literature regarding optimal BP control using medications for DKD.

Relationships between monocyte count to high-density lipoprotein cholesterol ratio and cardiovascular outcomes in patients commencing dialysis.

OBJECTIVE: High monocyte to high-density lipoprotein cholesterol ratio (MHR) is known to be a risk factor for cardiovascular (CV) complications. We aimed to evaluate the relationship between MHR and CV outcomes in patients commencing dialysis. METHODS: The medical records of patients who started maintenance dialysis between January 2006 and July 2017 were reviewed. The primary outcomes were all-cause mortality and overall CV mortality and the secondary outcomes were CV event-free survival and the incidence of CV complications. RESULTS: Five hundred ninety-seven patients were enrolled and allocated to low- or high-MHR groups. All-cause mortality did not differ between the groups during a mean follow-up period of 3.9 years. In addition, overall CV mortality did not differ between the groups. However, CV event-free survival was significantly lower in the high-MHR group than in the low-MHR group (47.5% vs. 59.0%). Multivariate Cox regression analysis showed that high MHR was an independent predictor of CV events (HR 1.886, 95% CI 1.015-3.505). CONCLUSION: High MHR at the time of initiation of dialysis may represent a useful predictor of CV complications.

Development of donepezil-induced hypokalemia following treatment of cognitive impairment.

Donepezil is a cholinesterase inhibitor used extensively to treat Alzheimer disease. The increased cholinergic activity is associated with adverse effects, therefore gastrointestinal symptoms, including nausea, vomiting, and diarrhea, are common. Hypokalemia is a rare adverse event that occurs in less than 1% of donepezil-treated patients. Although hypokalemia of mild and moderate grade does not present serious signs and symptoms, severe hypokalemia often results in prolonged hospitalization and mortality. Herein, we report a case of hypokalemia developed after the initiation of donepezil therapy for cognitive impairment.

Development of New Hemodialysis Catheter Using Numerical Analysis and Experiments.

A hemodialysis (HD) catheter, especially one with a symmetric tip design, plays an important role in the long-term treatment of patients with renal failure. It is well known that the design of the HD catheter has a considerable effect on blood recirculation and thrombus formation around it, which may cause inefficiencies or malfunctions during HD. However, hemodynamic analyses through parametric studies of its designs have been rarely performed; moreover, only comparisons between the existing models have been reported. In this study, we numerically analyzed the design of the HD catheter's side hole and distal tip for evaluating their effects on hemodynamic factors such as recirculation rate (RR), shear stress, and blood damage index (BDI). The results indicated that a larger side hole and a nozzle-shaped distal tip can significantly reduce the RR and shear stress around the HD catheter. Furthermore, based on these hemodynamic insights, we proposed three new HD catheter designs and compared their performances with existing catheters using numerical and in vitro methods. These new designs exhibited lower RRs and BDI values, thus providing better performance than the existing models. These results can help toward commercialization of more efficient HD catheters.

Role of Renal Replacement Therapy During the Peri-Transplant Period of Heart Transplantation.

BACKGROUND Heart transplantation (HT) is the most useful treatment modality for heart failure. Although several studies have reported the impact of acute kidney injury (AKI) on clinical outcomes after transplantation, little is known about the impact of peri-transplant renal replacement therapy (RRT) on clinical outcomes. We compared the clinical outcomes according to RRT use status among patients with AKI during the peri-transplant period. MATERIAL AND METHODS The medical records of 21 patients who underwent HT from January 2006 to May 2019 were reviewed. We assessed the heart failure cause, comorbidities, immunosuppressant type, requirement for extracorporeal membrane oxygenation, AKI incidence, and cardiac and renal functions over time. The patients were divided into 3 groups: those without AKI (non-AKI group, n=6), those who underwent perioperative RRT (RRT group, n=10), and those who did not undergo RRT (non-RRT group, n=5). RESULTS The most common cause of HT was dilated cardiomyopathy (52.4%). Fifteen patients (71.4%) experienced AKI during the peri-transplant period. Among them, 9 (90%) in the RRT group underwent continuous RRT and only 1 (10%) underwent intermittent hemodialysis. Until 6 months after HT, the renal function of the RRT group was worse than that of the non-RRT group (estimated glomerular filtration rate 44.2 vs. 69.2 mL/min/1.73 m2, P=0.015), but the differences dissipated by 9 months. Finally, all patients, even in the RRT group, withdrew from dialysis. CONCLUSIONS RRT during the peri-transplant period in HT may be a good bridge therapy for renal function recovery in patients with cardiorenal AKI.

Comparison of vascular access patency and patient survival between native arteriovenous fistula and synthetic arteriovenous graft according to age group.

INTRODUCTION: Arteriovenous fistula (AVF) is historically known to be the ideal option for vascular access (VA) for hemodialysis compared with arteriovenous graft (AVG). However, this approach has been recently questioned in the aging population because of their poor vessel quality and multiple comorbidities. METHODS: Data from a total of 2200 patients from the VA category of The Catholic Medical Center nephrology registry from March 2009 to February 2017 were analyzed. We compared VA patency and patient survival between two groups, AVF and AVG, according to age. FINDINGS: Compared with the AVG group, survival benefit in the AVF group continued even in patients ≥80 years. In the whole population, all the primary patency (PP), primary-assisted patency (PAP), and secondary patency (SP) measures were superior in the AVF group. With regard to subgroups, PP was comparable between the two groups in patients ≥65 years, whereas PAP and SP were superior in the AVF group even in septuagenarian patients who are from 70 to 79 years old. In patients ≥80 years, all the patency measures were comparable between the two groups. When the separate comparison of lower-arm AVF (or upper-arm AVF) and AVG, lower-arm AVF failed to demonstrate its superiority in any kind of patency in septuagenarian patients compared with AVG, whereas upper-arm AVF demonstrated its superiority in PAP and SP in septuagenarian patients. However, even upper-arm AVF failed to demonstrate its superiority in any kind of patency in patients ≥80 years. DISCUSSION: Arteriovenous fistula if using upper-arm vessel showed the superior VA patency up to septuagenarian patients, whereas, in HD patients ≥80 years, AVF and AVG were comparable in VA patency.

Quantified Vascular Calcification at the Dialysis Access Site: Correlations with the Coronary Artery Calcium Score and Survival Analysis of Access and Cardiovascular Outcomes.

Vascular calcification is a major contributor to mortality in end-stage renal disease (ESRD) patients. In this study, we investigated whether there was a correlation between the coronary artery calcium score (CACS) and the vascular calcification score (VCS), and whether higher VCS increased the incidence of interventions and major adverse cardiac and cerebrovascular events (MACCE). ECG-gated CT, including vascular access and the coronary vessel, was taken. CACS and VCS were calculated by the Agatston method. A comparison of CACS and survival analysis according to VCS groups was performed. Using a cutoff of VCS = 500, 77 patients were divided into two groups. The vintage was significantly older in the higher VCS group. The median CACS was higher in the higher VCS group (21 [0, 171] vs. 552 [93, 2430], p < 0.001). The hazard ratio (HR) for interventions and MACCEs in the higher VCS group increased by 3.2 and 2.3, respectively. Additionally, a longer duration of hemodialysis and higher magnesium levels (>2.5 mg/dL) showed lower HRs for interventions (<1). We quantified VCS and found that it was associated with the CACS. Additionally, higher VCS increased the risk of access interventions and MACCE. VCS of the access site may be suggested as a biomarker to predict ESRD patients.

Central venous disease in hemodialysis patients.

Central venous disease (CVD) is difficult to treat and often resistant to treatment. In CVD, hemodialysis vascular access should sometimes be abandoned, or in serious cases, the patient's life may be threatened. Therefore, prevention is ideal. However, as the prevalence of chronic kidney disease (CKD) has increased steadily with population aging, CKD patients with a peripherally inserted central catheter (PICC) are encountered frequently. PICCs can cause CVD, and the basilic vein, which is regarded as the important last option for native arteriovenous fistula (AVF) creation in end-stage renal disease (ESRD) patients, is destroyed frequently after its use as the entry site of PICC. The most well-established risk factors for CVD are a history of central venous catheter (CVC) insertion and its duration of use. Therefore, to reduce the incidence of CVD, catheterization in the central vein (CV) should be minimized, along with its duration of use. In this review, we will first explain the basic territories of the CV and introduce its pathophysiology, clinical features, and advanced treatment options. Finally, we will emphasize prevention of CVD.

The effect of vascular access type on intra-access flow volume during hemodialysis.

INTRODUCTION: Previous studies have revealed that vascular access resistance is constant during hemodialysis, but differs according to vascular access type. It is possible that intra-access flow volume (Qac) variation during hemodialysis may also differ according to vascular access type. We conducted this study to investigate whether there are differences in Qac according to vascular access type during hemodialysis. METHODS: A total of 58 lower-arm arteriovenous fistula, 14 lower-arm arteriovenous graft, 27 upper-arm arteriovenous fistula, and 45 upper-arm arteriovenous graft cases were studied. Three consecutive Qac values (at 30, 120, and 240 min after the start of hemodialysis) were measured in each patient by the ultrasound dilution technique. Variations in Qac over time were analyzed using repeated measures analysis of variance and multivariate regression analyses, to assess the impact of different factors on Qac variation. RESULTS: The repeated measures analysis of variance revealed that a significant interaction exists between time and vascular access type (p < 0.001). This suggests that vascular access type affects Qac change (%) variation over time during hemodialysis. In a multivariate analysis, mean arterial pressure change during hemodialysis (p = 0.009), access type (p < 0.001), and access location (p < 0.001) were independent variables causing Qac change variation. CONCLUSION: This study showed that there is a significant difference in Qac variation according to vascular access type during hemodialysis and that arteriovenous graft (vs arteriovenous fistula) and the lower-arm location (vs upper arm) were associated with a decrease in Qac during hemodialysis. This suggests that consideration of vascular access type is required to minimize Qac variation during hemodialysis.

Exchange over the guidewire from non-tunneled to tunneled hemodialysis catheters can be performed without patency loss.

PURPOSE: The exchange from a non-tunneled hemodialysis catheter to a tunneled one over a guidewire using a previous venotomy has been reported to be safe. However, some concerns that it may increase infection risk prevent its clinical application. This approach seems particularly useful for acute kidney injury patients requiring initial renal replacement therapy, in whom we frequently worry about the choice of non-tunneled versus tunneled catheters. MATERIALS AND METHODS: From March 2012 to February 2016, 88 cases to receive the over-the-guidewire exchange method from a non-tunneled to a tunneled catheter and 521 cases to receive de novo tunneled catheter placement from the hemodialysis vascular access cohort were compared retrospectively. RESULTS: The immediate complication, later catheter dysfunction requiring replacement, and infection rates were comparable between the two groups. Newly placed tunneled catheter survival in the over-the-guidewire exchange group was comparable with survival in the de novo tunneled catheter group (p = 0.24). In addition, when we compared the same two methods among only intensive care unit patients; they remained similar (p = 0.19). CONCLUSION: An exchange with the over-the-guidewire method from a non-tunneled to a tunneled catheter was comparable to a de novo catheter placement technique. Therefore, this method should be viewed more favorably and should especially be considered for acute kidney injury patients.

Extracellular Superoxide Dismutase Attenuates Renal Oxidative Stress Through the Activation of Adenosine Monophosphate-Activated Protein Kinase in Diabetic Nephropathy.

AIMS: Oxidative stress plays a crucial role in the pathogenesis of diabetic nephropathy (DN). We evaluated whether extracellular superoxide dismutase (EC-SOD) has a renoprotective effect through activation of adenosine monophosphate-activated protein kinase (AMPK) in diabetic kidneys. RESULTS: Human recombinant EC-SOD (hEC-SOD) was administered to 8-week-old male C57BLKS/J db/db mice through intraperitoneal injection once a week for 8 weeks. Renal SOD3 expression was suppressed in db/db mice, which was significantly enhanced by hEC-SOD treatment. hEC-SOD improved albuminuria, mesangial expansion, and interstitial fibrosis in db/db mice. At the molecular level, hEC-SOD increased phosphorylation of AMPK, activation of peroxisome proliferative-activated receptor γ coactivator 1α (PGC-1α), and dephosphorylation of forkhead box O transcription factor (FoxO)1 and FoxO3a. The protective effects of hEC-SOD were attributed to enhanced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased expression of NAD(P)H dehydrogenase 1 and heme oxygenase-1. Consequently, hEC-SOD recovered from systemic and renal inflammation and apoptosis, as reflected by the decreases of serum and renal monocyte chemoattractant protein-1 and tumor necrosis factor-α levels and increases of BCL-2/BAX ratio in diabetic kidney. hEC-SOD also improved oxidative stress and resulted in increased renal and urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane levels in db/db mice. In cultured human glomerular endothelial cells, hEC-SOD ameliorated apoptosis and oxidative stress caused by high glucose exposure through activation of AMPK and PGC-1α and dephosphorylation of FoxOs. INNOVATION: These findings demonstrated for the first time that EC-SOD can potentially ameliorate hyperglycemia-induced oxidative stress, apoptosis, and inflammation through activation of AMPK and its downstream pathways in diabetic kidneys. CONCLUSIONS: EC-SOD is a potential therapeutic target for treatment of type 2 DN through intrarenal AMPK-PGC-1α-Nrf2 and AMPK-FoxOs signaling. Antioxid. Redox Signal. 28, 1543-1561.

Identification of a Novel GLA Mutation (L206 P) in a Patient with Fabry Disease.

We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease.