Supplementary Material for: Chronic Kidney Disease Causes Disruption of Gastric and Small Intestinal Epithelial Tight Junction

<b><i>Background:</i></b> Integrity of the tight junction (TJ) which seals the gap between the epithelial cells of the gastrointestinal tract is critical in preventing the entry of the microbial toxins, antigens, and other harmful products in the subepithelial tissues and the internal milieu. By enabling the absorption of these products, impairment of the intestinal epithelial barrier leads to local and systemic inflammation. We have recently found depletion of the key protein constituents of colonic epithelial TJ in animals with chronic kidney disease (CKD). Postmortem studies have revealed the presence of inflammation throughout the gastrointestinal tract in uremic humans. This observation suggests that uremia may cause disruption of the epithelial barrier in all segments of the gastrointestinal tract including the stomach, jejunum, and ileum. The present study was undertaken to explore this possibility. <b><i>Methods:</i></b> Sprague-Dawley rats were randomized to CKD or control groups. The CKD group was subjected to 5/6 nephrectomy while the control group underwent a sham operation. The animals were observed for 10 weeks at which time they were euthanized and their stomachs, jejunums, and ileums were removed and processed for measurement of TJ proteins. <b><i>Results:</i></b> The CKD rats showed marked azotemia, systemic oxidative stress, and marked depletion of the key protein constituents of the epithelial TJ (claudin-1, occludin, and ZO1) in the stomach, jejunum, and ileum. <b><i>Conclusions:</i></b> The present study extends the earlier finding of uremia-induced disruption of colonic epithelial TJ by documenting the involvement of the stomach, jejunum, and ileum as well

Supplementary Material for: Patiromer Decreases Serum Potassium and Phosphate Levels in Patients on Hemodialysis

<p><b><i>Background:</i></b> Persistent hyperkalemia (serum potassium (K) ≥5.5 mEq/l) is a common condition in hemodialysis (HD) patients, is associated with increased mortality, and treatment options are limited. The effect of patiromer, a gastrointestinal K binder, on serum K was examined in HD patients. <b><i>Methods:</i></b> Six hyperkalemic HD patients (5 anuric) were admitted to clinical research units for 15 days (1 pretreatment week and 1 patiromer treatment week) and they received a controlled diet with identical meals on corresponding days of pretreatment and treatment weeks. Phosphate (P) binders were discontinued on admission. Patiromer, 12.6 g daily (divided 4.2 g TID with meals), was started on the Monday morning following the last pretreatment week blood sampling. Serum and 24-hour stool samples were collected daily. <b><i>Results:</i></b> Mean ± SE serum K decreased (maximum change per corresponding day, 0.6 ± 0.2 mEq/l, p = 0.009) and fecal K increased 58% on patiromer compared with the pretreatment week. During the pretreatment week, 69.0, 47.6, and 11.9% of patients' serum K values were ≥5.5, ≥6.0, and ≥6.5 mEq/l, respectively. This was reduced to 38.1% (p = 0.009), 11.9% (p < 0.001), and 2.4% (p = 0.2) on patiromer. Following P binder discontinuation, the long interdialytic interval mean ± SE serum P numerically increased from 5.8 ± 0.4 to 7.0 ± 0.5 mg/dl (p = 0.06). On patiromer, P decreased from 7.0 ± 0.5 to 6.2 ± 0.5 mg/dl (p = 0.04). While on patiromer, fecal P numerically increased by 112 ± 72 mg/day (17%; p = 0.1792; range -148 to 344 mg/day). No patient discontinued patiromer because of adverse events (AEs); none had serious AEs. <b><i>Conclusions:</i></b> In 6 hyperkalemic HD patients, patiromer decreased serum K and P levels and increased fecal K.</p

Supplementary Material for: Mild renal function impairment and long-term outcomes in patients with three-vessel coronary artery disease: a cohort study

Background: Limited data are available on the long-term impact of mild renal dysfunction (eGFR 60-89 ml/min/1.73m2) in patients with three-vessel coronary disease (3VD). Methods: A total of 5,272 patients with 3VD undergoing revascularization were included and were categorized into 3 groups: normal renal function (eGFR ≥90 ml/min/1.73m2, n=2352), mild renal dysfunction (eGFR 60-89, n=2501) and moderate renal dysfunction (eGFR 30-59, n=419). Primary endpoint was all-cause death. Secondary endpoints included cardiac death and major adverse cardiac and cerebrovascular events (MACCE), a composite of death, myocardial infarction and stroke. Results During the median 7.6-year follow-up period, 555 (10.5%) deaths occurred. After multivariable adjustment, patients with mild and moderate renal dysfunction had significantly higher risks of all-cause death (adjusted HR: 1.36, 95% CI 1.07-1.70; adjusted HR 2.06, 95% CI 1.53-2.78, respectively) compared with patients with normal renal function. patients after coronary artery bypass grafting (CABG) had a lower rate of all-cause death and MACCE than those undergoing percutaneous coronary intervention (PCI) in the normal and mild renal dysfunction group, but not in the moderate renal dysfunction group. Results were similar after propensity score matching. Conclusions In patients with 3VD, even mild renal impairment was significantly associated with a higher risk of all-cause death. The superiority of CABG over PCI diminished in those with moderate renal dysfunction. Our study alerts clinicians to the early screening of mild renal impairment in patients with 3VD and provides real-world evidence on the optimal revascularization strategy in patients with renal impairment

Supplementary Material for: Association of Intravenous Tirofiban with Functional Outcomes in Acute Ischemic Stroke Patients with Acute Basilar Artery Occlusion Receiving Endovascular Thrombectomy

Introduction: The aim of this study was to test the hypothesis that intravenous tirofiban improves functional outcomes without promoting the risk of intracranial hemorrhage (ICH) in stroke secondary to basilar artery occlusion (BAO) receiving endovascular thrombectomy. Methods: Patients with acute BAO stroke who were treated with endovascular thrombectomy and had tirofiban treatment information were derived from “BASILAR”: a nationwide, prospective registry. All eligible patients were divided into tirofiban and no-tirofiban groups according to whether tirofiban was used intravenously. The primary endpoint was the 90-day severity of disability as assessed by the modified Rankin scale score. Safety outcomes were the frequency of ICH and mortality. Results: Of 645 patients included in this cohort, 363 were in the tirofiban group and 282 were in the no-tirofiban group. Thrombectomy with intravenous tirofiban reduced the 90-day disability level over the range of the modified Rankin scale (adjusted common odds ratio, 2.08; 95% confidence interval (CI), 1.45–2.97; p p p = 0.004) and symptomatic ICH (4.8% vs. 10.1%; p = 0.01) in the tirofiban group was significantly lower than that in the no-tirofiban group. Conclusions: In patients with acute BAO stroke who underwent endovascular treatment, intravenous tirofiban might be associated with favorable outcome, reduced mortality, and a decreased frequency of ICH