Does central venous stenosis affects the brachial artery flow volume and peripheral vascular resistive index in patients on maintenance hemodialysis? A retrospective study.

BACKGROUND: A well-functioning vascular access (VA) is crucial for the patients on maintenance hemodialysis (HD). Central venous stenosis (CVS) is a common, yet, overlooked complication of VA as its diagnosis is challenging. Moreover, its effect on the flow volume (FV) and the peripheral resistive index (RI) was not well discussed before. Despite the availability of doppler ultrasound (DUS) in most centers, direct visualization of central veins using DUS is quite difficult. METHODS: This is a retrospective single-center self-controlled cohort study that was conducted in a specialized vascular access management tertiary center in Japan and included all patients with CVS who underwent percutaneous transluminal angiography (PTA) with or without vascular stenting in the period from January 2014 to September 2022. The patients were divided according to their VA type into arteriovenous fistula (AVF), and arteriovenous graft (AVG) groups, then subdivided, according to the type of stenosis, into two subgroups: CVS, and mixed central and peripheral venous stenosis (MVS) groups. The FV and RI of the feeding artery were compared in the same procedure before and after PTA to assess the impact of the procedure itself. RESULTS: Data of 485 percutaneous transluminal angiography procedures (PTA), performed in 95 patients during the period from January 2014 to September 2022, were collected. FV and RI were significantly affected in the patients with MVS than patients with CVS. After PTA, both FV and RI were significantly improved. The improvement rate of FV and RI after PTA were significantly higher in patients with MVS than patients with CVS. However, it was difficult to determine the cut-off value to diagnose or to assess the improvement of CVS. CONCLUSION: Our findings suggest that FV and RI measurement by DUS are good tools, along with the clinical findings for assessment of CVS in certain situations.

Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial.

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

Vascular sound visualization system is useful for monitoring and surveillance of vascular access.

BACKGROUNDS: Vascular access (VA) is a lifeline for maintenance hemodialysis patients. Monitoring and surveillance of VA, therefore, play an important role for maintaining VA patency. Surveillance needs special apparatus to estimate the VA function, while, monitoring including physical examination does not usually need such devices but highly skill-dependent and qualitative. PURPOSE: We report the clinical utility in monitoring and surveillance of VA using a newly developed electronic stethoscope and vascular sound visualization application. METHODS: One hundred eight patients participated in the study. The vascular sounds were collected using the electronic stethoscope, converted into digital data, sent wirelessly to a personal computer, and then calculated. The units for the calculated intensity of the vascular sound were decibel [dB]. The intensity, however, was normalized as INDEX values ranging from 0 to 99 for practical use. Correlation between INDEX and the mean flow volume (mFV) and resistance index (RI) of brachial artery measured by Doppler ultrasound sonography were examined for VA surveillance. INDEX was continually measured at each dialysis session in ten patients who underwent the angioplasty for VA monitoring. RESULTS: INDEX significantly correlated with the mFV (coefficient of correlation value = 0.68, p < 0.001) and RI (coefficient of correlation value = -0.51, p < 0.001) of brachial artery. Using the calculated cut-off values, the accuracy of INDEX for the diagnosis of AVF dysfunction ranged from 66% to 82%. INDEX attained the peak just after the angioplasty of culprit lesions and gradually decreased from one patient to another. CONCLUSION: These results suggest that vascular sound visualization system can be useful in VA monitoring and surveillance for detecting and predicting the access stenosis.

A Prospective, Randomized Clinical Trial of Etelcalcetide in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism (the DUET Trial).

INTRODUCTION: The clinical trial on the Development of a treatment strategy for chronic kidney disease‒mineral and bone disorder by a mUltilateral mechanism of ETelcalcetide hydrochloride, or the DUET trial, was designed to determine the efficacy of etelcalcetide, an intravenous calcimimetic, for control of secondary hyperparathyroidism (SHPT). METHODS: Eligible SHPT maintenance hemodialysis patients (n = 124) were randomized (1:1:1) for inclusion in the DUET trial, a 12-week, multicenter, open-label, parallel-group study (jRCTs041180108), and assigned to either an etelcalcetide + active vitamin D group (group E+D), an etelcalcetide + oral calcium preparation group (group E+Ca), or a control group (group C). The primary endpoint was number of patients with a 50% reduction from baseline of intact parathyroid hormone (iPTH) levels, and iPTH levels ≤ 240 pg/mL at 12 weeks after start of the trial. RESULTS: The proportion of patients reaching the primary endpoint (95% confidence interval [CI]) was 90.0% (76.3%-97.2%) in group E+D, 56.8% (39.5%-72.9%) in group E+Ca, and 19.5% (8.8%-34.9%) in group C. Etelcalcetide treatment led to a significant increase in the number of patients achieving the endpoint (odds ratio, 13.4; 95% CI, 5.10-35.3) on logistic regression analysis, with iPTH, corrected serum calcium, and phosphate at baseline as covariates. Significantly more patients achieved the endpoint in group E+D compared with group E+Ca (odds ratio, 6.35; 95% CI, 1.79-22.48). There were fewer hypocalcemic visits in group E+D compared with group E+Ca (P = 0.018), yet the former group was prone to hyperphosphatemia. CONCLUSION: Etelcalcetide showed good control of iPTH for maintenance hemodialysis patients with SHPT. Active vitamin D was useful in correcting hypocalcemia, but the oral calcium preparation was superior for suppression of hyperphosphatemia.

Current state of dialysis treatment and vascular access management in Japan.

According to the data from the Japanese Society for Dialysis Therapy, the number of dialysis patients was about 330,000 at the end of 2016. The mean age of newly initiated patients was 69.4 years and that of maintenance was 68.2 years. And, diabetic nephropathy is the most common primary disease, with an incidence rate of 43.2%. These results mean that the systemic vascular condition is getting worse. In spite of these backgrounds, the patients of 97.3% were treated by hemodialysis; therefore, careful management of vascular access is essential to better maintain the condition of patients. The Dialysis Outcomes and Practice Patterns Study shows that vascular access modalities are an important factor in determining prognoses of patients and that prognosis in Japan is one of the best worldwide. In Japan, the use of arteriovenous fistulae accounts for 95% of vascular access modalities. However, a statistic by Japanese Society for Dialysis Therapy suggests that the use of arteriovenous graft has been increasing. In 2005, Japanese Society for Dialysis Therapy Guidelines recommended percutaneous transluminal angioplasty be the first choice for the treatment of vascular access stenosis. Since then, percutaneous transluminal angioplasty has become an important procedure for long-term maintenance of the morphology and function of vascular access. In Japan, approximately 60% of percutaneous transluminal angioplasty are conducted by nephrologists and urologists; in addition, arteriovenous fistulae creation procedures are also performed by them. According to my private opinion, such conditions above show that even in the absence of standardized training on vascular access management, doctors on site perform their duties in an appropriate manner. However, the problems of how we evaluate the specificity in Japan and pass it down the generations still remain.

Standard procedures of endovascular treatment for vascular access stenosis in our facility - clinical usefulness of ultrasonography.

In Japan, the number of patients receiving dialysis is 314,180 at the end of 2013 and 97% are treated with hemodialysis. And the mean age of patients and the percentage of diabetes have been increasing. For this reason, preparations of a new vascular access (VA) and its long-term maintenance have become difficult. In the guidelines by the Japanese Society for Dialysis Therapy (JSDT), endovascular treatment (ET) is positioned as the first line for VA stenosis. The procedure of ET itself is very simple. The revision of Japanese health insurance set an expensive technical fee for ET in 2012. It also added a restriction by which the claims for both technical and material fees would be denied, if the treatment was performed within 3 months after a previous treatment. This makes determination of best treatment timing more important. The functional evaluation using ultrasonography (US) is a useful monitoring index for determination of the ET timing for patients with stenosis. We investigated the cumulative relative frequency of flow volume (FV) and resistant index (RI) of brachial artery in arteriovenous graft (AVG) and arteriovenous fistula (AVF) cases with access failures. As a result, the cut-off values of FV and RI in AVG were 480 mL/min and 0.57, and in AVF were 354 mL/min and 0.61, respectively. Therefore we determine the treatment timing based on these results. Since 2012, active monitoring using US could have decreased the number of treatment patients by 100 per year. This meant that objective evaluation by US enabled treatments at a more suitable time to promote the proper use of medical expenses for EV treatment.

Effectiveness of skin perfusion pressure monitoring during surgery for an ischemic steal syndrome associated refractory ulcer.

We describe an 80-year-old man with end-stage renal disease due to type 2 diabetes who had been maintained on hemodialysis for 9 years. He developed refractory ulcers from an abraded wound in the right hand of his access arm. The arteriovenous fistula (AVF) was located between the right brachial artery and the median antecubital vein draining into the cephalic vein and the deep veins close to the elbow. The blood flow of the right brachial artery measured by using Doppler ultrasonography was 920 ml/min. On the contrary, the radial and ulnar arteries were poorly palpable near the wrist, and ultrasonography could not be performed accurately because of a high degree of calcification. The skin perfusion pressure (SPP) of the first finger on the affected side decreased to 22 mmHg. However, the SPP improved to approximately 40 mmHg upon blocking an inflow into the deep vein. According to SPP data, only a communicating branch of the deep vein was ligated, and the AVF itself was preserved. One month after surgery, the skin ulcer healed, and maintenance hemodialysis was performed by using the preserved cephalic vein for blood access.In conclusion, we successfully treated a refractory wound associated with steal syndrome, without terminating the AVF. SPP-guided surgery may be safe and effective to adjust the blood flow in patients with AVF having steal syndrome.

Comparison of clinical effectiveness between surgical and endovascular treatment for thrombotic obstruction in hemodialysis access.

PURPOSE: Endovascular treatment (ET) is widely used for thrombotic complications of vascular access (VA) for hemodialysis. We evaluated the effectiveness of both ET and surgical interventions for thrombotic complications. METHODS: We studied 533 patients who underwent surgical procedures (a total of 879 procedures) and 54 patients who received ET (a total of 156 procedures) for VA obstruction (endovascular group; group 1). The 533 patients who underwent surgical procedures were further divided into two groups: the surgical balloon-angioplasty group (the thrombus was surgically removed and the stenotic lesions were dilated by balloon angioplasty; 189 procedures; group 2) and the surgical repair group (the stenotic lesions were bypassed with additional graft diversion or creation of a new access; 690 procedures; group 3). The three groups were evaluated for VA patency. RESULTS: Using the Kaplan-Meier method, the 2-yr patency for groups 1, 2, and 3 were 11.1%, 11.5%, and 34.0% (p<0.0001). The 2-yr patency rates in patients in whom arteriovenous grafts were used were 5.9% (group 1), 9.2% (group 2), and 22.8% (group 3) (p<0.0001), whereas in patients with arteriovenous fistulae they were 33.7% (group 1), 35.7% (group 2), and 59.8% (group 3) (p=0.0005). CONCLUSIONS: A surgical approach may cause difficulty in creating a new VA, because useful access vessels are limited. Our results indicate surgical balloon-angioplasty and ET provide the same patency. ET is less invasive and can be repeated, which makes it beneficial for the patients. We concluded ET could be considered as the first-line treatment for thrombotic complications.

Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7).

BACKGROUND: Andersen-Tawil syndrome, a skeletal muscle syndrome associated with periodic paralysis and long QT intervals on the ECG, has been linked to defects in KCNJ2, the gene encoding for the inward rectifier potassium channel (I(K1).) OBJECTIVES: The purpose of this study was to examine the cellular mechanisms underlying the ECG and arrhythmic manifestations of Andersen-Tawil syndrome. METHODS: To investigate the effects of KCNJ2 loss-of-function mutations responsible for Andersen-Tawil syndrome, we used barium chloride (BaCl(2)) to inhibit I(K1) in arterially perfused wedge preparation. Transmembrane action potentials (APs) were simultaneously recorded from endocardial, midmyocardial, and epicardial cells, together with a transmural ECG. RESULTS: BaCl(2) (1 to 30 microM) produced a concentration-dependent prolongation of the QT interval, secondary to a homogeneous prolongation of AP duration of the three cell types. QT interval was prolonged without an increase in transmural dispersion of repolarization (TDR). Low extracellular potassium (2.0 mM), isoproterenol (20-50 nM), and an abrupt increase in temperature (36 degrees C-39 degrees C) in the presence of 10 microM BaCl(2) did not significantly increase TDR but increased ectopic extrasystolic activity. Early afterdepolarizations were not observed under any condition. Spontaneous torsades de pointes arrhythmias were never observed, nor could they be induced with programmed electrical stimulation under any of the conditions studied. CONCLUSION: Our results provide an understanding of why QT prolongation associated with Andersen-Tawil syndrome is relatively benign in the clinic and provide further support for the hypothesis that the increase in TDR, rather than QT interval, is responsible for development of torsades de pointes.

Detection of a radio counterpart to the 27 December 2004 giant flare from SGR 1806-20.

It was established over a decade ago that the remarkable high-energy transients known as soft gamma-ray repeaters (SGRs) are located in our Galaxy and originate from neutron stars with intense (< or = 10(15)G) magnetic fields-so-called 'magnetars'. On 27 December 2004, a giant flare with a fluence exceeding 0.3 erg cm(-2) was detected from SGR 1806-20. Here we report the detection of a fading radio counterpart to this event. We began a monitoring programme from 0.2 to 250 GHz and obtained a high-resolution 21-cm radio spectrum that traces the intervening interstellar neutral hydrogen clouds. Analysis of the spectrum yields the first direct distance measurement of SGR 1806-20: the source is located at a distance greater than 6.4 kpc and we argue that it is nearer than 9.8 kpc. If correct, our distance estimate lowers the total energy of the explosion and relaxes the demands on theoretical models. The energetics and the rapid decay of the radio source are not compatible with the afterglow model that is usually invoked for gamma-ray bursts. Instead, we suggest that the rapidly decaying radio emission arises from the debris ejected during the explosion.

Adenosine infusion inhibits adenosine-induced cardiac actions but enhances acetylcholine-induced actions in isolated dog atria.

Using isolated, blood-perfused canine atrial preparations, adenosine was continuously administered at various infusion rates into the cannulated sinus node artery. Adenosine induced negative chrono- and inotropic effects in an infusion-rate related manner. The inotropic responses to the adenosine infusion apparently faded but the chronotropic responses did not. Effects of a bolus injection of adenosine, acetylcholine (ACh), or norepinephrine and effects of intracardiac autonomic nerve stimulation (ICNS) were examined before and during the adenosine infusion. During the adenosine infusion, adenosine-induced effects were significantly reduced but ACh-induced ones were significantly potentiated, and the norepinephrine-induced effects were slightly depressed. ICNS readily induced negative and positive chrono- and inotropic responses which were blocked by atropine and propranolol. These negative responses were enhanced but positive ones were slightly but insignificantly depressed during the adenosine infusion. From these results, it is concluded that adenosine infusion (1) produces a stable continuous bradycardia but in the developed tension an initial decrease is followed by a gradual recovery response showing the fade phenomenon, (2) causes an acute desensitizing action on a subsequent bolus dose of adenosine, and (3) induces a weak antiadrenergic effect, while enhancing cholinergic effects in isolated canine atria.

Autonomic control of the location and rate of the cardiac pacemaker in the sinoatrial fat pad of parasympathetically denervated dog hearts.

INTRODUCTION: Parasympathetic activity predominates over sympathetic activity not only with respect to heart rate but also with respect to the pacemaker location in the dog heart. After we removed the parasympathetic neural elements in the sinoatrial (SA) fat pad in the right atrium, we observed that cervical vagus stimulation did not decrease the atrial rate, but it did suppress the increase in rate evoked by sympathetic stimulation. We determined whether the pacemaker rate and location were affected by presynaptic or postsynaptic mechanisms. METHODS AND RESULTS: We determined the earliest activation site by means of isochronic activation mapping of the right atrium of open chest, anesthetized dog hearts. An electrode array, which consisted of 48 unipolar electrodes, was used to record atrial activation. This array covered the three main pacemaker regions, including the SA node region. After parasympathetic nerve fibers in the SA fat pad had been denervated, vagus stimulation at 10 and 30 Hz did not decrease the heart rate, but it attenuated the increase in heart rate evoked by sympathetic stimulation or isoproterenol. Vagus stimulation at 10 Hz during sympathetic stimulation did not shift the earliest activation site from the superior pacemaker region to the SA node region in 11 of 18 experiments. However, vagus stimulation at 10 Hz during isoproterenol infusion shifted the earliest activation site to the SA node region in 11 of 13 experiments. More intense vagus stimulation during combined sympathetic stimulation or isoproterenol infusion shifted the earliest activation site to the SA node or the inferior pacemaker region in 15 of 18 and in all experiments, respectively. CONCLUSION: The results suggest that activation of parasympathetic elements not located in the SA fat pad attenuates the increase in heart rate and the shift in pacemaker location evoked by sympathetic activation. The sympathetic and parasympathetic effects interact at presynaptic and postsynaptic sites in the dog heart.

Botulinum neurotoxin A blocks cholinergic ganglionic neurotransmission in the dog heart.

There is no data about whether botulinum neurotoxin inhibits the parasympathetic ganglionic neurotransmission in the heart, although botulinum toxin as a clinical drug inhibits the release of acetylcholine at the neuromuscular junction. Therefore, we investigated whether botulinum toxin (type A) injected into the sinoatrial (SA) fat pad inhibits decreases in heart rate induced by stimulation of the preganglionic parasympathetic nerves in the heart of the anesthetized dog. Stimulation of the parasympathetic nerves in the SA fat pad (SAP stimulation) prolonged the atrial interval but not the atrioventricular (AV) interval, and cervical vagus nerve stimulation (CV stimulation) prolonged both atrial and AV intervals. After botulinum toxin (20 or 25 mouse units) was injected into the SA fat pad, it gradually inhibited the prolongation of the atrial interval evoked by SAP and CV stimulations but not the prolongation of the AV interval evoked by CV stimulation. Conditioning successive stimulation of the cervical vagus nerves accelerated the inhibition by botulinum toxin of the chronotropic response to CV stimulation. These results indicate that selective injection of botulinum toxin into the SA fat pad blocks bradycardia mediated by parasympathetic ganglionic activation in the dog heart.