Patient-selected media and knowledge of risk to kidneys of nonsteroidal anti-inflammatory drugs.

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause community-acquired acute kidney injury, especially in high-risk populations. Both the U.S. Food and Drug Administration (FDA) medication guide and over-the-counter labeling vaguely describe kidney risks of NSAIDs and do not provide information for patients to evaluate their risk for kidney problems. The purpose of this study was to use a mobile application to evaluate the impact of patient choice of media delivering NSAID avoidance education on patient knowledge about kidney risks associated with NSAIDs. DESIGN: Prospective cohort study. The mobile application was used to deliver either a redesigned FDA medication guide or a video focused on NSAID risks (selected by the patient), followed by patient knowledge questions (PKQs) and a kidney risk assessment. SETTING AND PARTICIPANTS: One hundred fifty adult primary care patients in southeast Michigan. MAIN OUTCOME MEASURES: The primary outcome was the score on 5 NSAID PKQs between the media selected. Secondary outcomes included characterization of media choice among different demographic and NSAID kidney risk groups. The relationship between kidney risk assessment and self-reported NSAID avoidance behavior also was evaluated. RESULTS: The majority of participants (72.7%) chose to review print material. Those that chose print had significantly higher PKQ scores (5 total points) compared with participants who selected the video: mean scores 4.2 ± 0.9 with print and 3.8 ± 1.0 with video (P = 0.034). Older patients (>65 years) had significantly lower PKQ scores compared with other age groups. Forty-four percent of individuals (n = 66) reported current NSAID use, and 65% stated that they would avoid NSAIDs after the selected education material. CONCLUSION: Scores for questions related to NSAID kidney risk knowledge were higher among participants who chose print compared with video education material. Education regarding NSAID kidney risks encouraged patients to limit their use. Targeted education may be beneficial in high-risk (e.g., older) patients and should be further studied.

Imipenem/Relebactam Ex Vivo Clearance during Continuous Renal Replacement Therapy.

(1) Purpose of this study: determination of adsorption and transmembrane clearances (CLTM) of imipenem and relebactam in ex vivo continuous hemofiltration (CH) and continuous hemodialysis (CHD) models. These clearances were incorporated into a Monte Carlo Simulation (MCS), to develop drug dosing recommendations for critically ill patients requiring continuous renal replacement therapy (CRRT); (2) Methods: A validated ex vivo bovine blood CH and CHD model using two hemodiafilters. Imipenem/relebactam and urea CLTM at different ultrafiltrate/dialysate flow rates were evaluated in both CH and CHD. MCS was performed to determine dose recommendations for patients receiving CRRT; (3) Results: Neither imipenem nor relebactam adsorbed to the CRRT apparatus. The CLTM of imipenem, relebactam, and urea approximated the effluent rates (ultrafiltrate/dialysate flow rates). The types of hemodiafilter and effluent rates did not influence CLTM except in a dialysis flow rate of 1 L/h and 6 L/h in the CHD with relebactam (p < 0.05). Imipenem and relebactam 200 mg/100 mg every 6 h were sufficient to meet the standard time above the MIC pharmacodynamic targets in the modeled CRRT regimen of 25 kg/mL/h. (4) Conclusions: Imipenem and relebactam are not removed by adsorption to the CRRT apparatus, but readily cross the hemodiafilter membrane in CH and CHD. Dosage adjustment of imipenem/relebactam is likely required for critically ill patients receiving CRRT.

Lipoteichoic Acid as a Potential Noninvasive Biomarker of Biofilm in Dialysis Access.

Tunneled central venous catheters (TCVCs) are colonized by Gram-positive organisms and form biofilm. Lipoteichoic acid (LTA) is a Gram-positive cell wall component that can be measured in serum. The purpose of this pilot study was to characterize LTA concentrations in hemodialysis (HD) patients with TCVCs compared to other access types and to evaluate biofilm morphology and microbiology in TCVCs removed by clinical decision. The study enrolled patients with TCVCs (18), grafts (19), and fistulas (18). Blood samples were collected before HD, at 30 minutes, 2 hours, and end of HD. Catheters removed by clinical decision were evaluated by scanning electron microscopy (SEM) for biofilm morphology, and portions of the catheter were cultured. LTA was detectable in all samples and concentrations increased significantly in all access types during HD (p < 0.05 for all comparisons). Patients with TCVCs that had a >30% increase in LTA concentration from baseline also had the greatest rate of increase (slope) compared to grafts and fistulas (p = 0.03 and p = 0.04, respectively). Catheters removed by clinical decision (n = 7) and examined by SEM had deposition of fibrin. Cultures revealed polymicrobial colonization. TCVCs had the highest rate of increase of LTA during HD. Further studies to determine the source of LTA in patients with AVG and AVF are warranted.

Impact of hemodialysis on the concentrations of sodium and potassium during infusion of sodium thiosulfate using an In Vitro hemodialysis model.

INTRODUCTION: The purpose of this study was to evaluate the impact of hemodialysis on the concentrations of sodium and potassium in the blood when a 25 g dose of sodium thiosulfate injection is infused over 60 minutes in combination with hemodialysis. METHODS: Sodium thiosulfate (25 g) was prepared by diluting 100 mL of 250 mg/mL Sodium Thiosulfate Injection with 800 mL of 5% dextrose. This was added to the circulating blood surrogate solution at a rate of 15 mL/minute using an infusion pump of an in vitro model of dialysis machine. Serial samples were collected before the administration of the sodium thiosulfate solution, after 15 minutes, 30 minutes, and 60 minutes of infusion from pre-and post-dialyzer ports in both the dialysate circuit and the extracorporeal circuit. FINDINGS: The concentration of sodium thiosulfate in pre-dialyzer and post-dialyzer samples of the circulating blood surrogate solution peaked at 30 minutes and 15 minutes, respectively and then remained relatively unchanged during the remainder of the infusion. Mean sodium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 103.2 ± 12.2, 114.2 ± 18.8, 117.2 ± 7.5, 93.5 ± 5.9 at 0, 15, 30, and 60 minutes, respectively (p = 0.248). Mean potassium concentrations (mEq/L) in the circulating blood surrogate solution collected after exposure to a dialyzer were 1.4 ± 0.3, 1.6 ± 0.3, 1.5 ± 0.1, 1.2 ± 0.1 at 0, 15, 30, and 60 minutes, respectively (p = 0.365). Sodium and potassium concentrations in dialysate increased marginally after exposure to the dialyzer. DISCUSSION: Our study demonstrates that neither potassium nor sodium accumulated in circulating blood surrogate solution when a dose of sodium thiosulfate was infused in conjunction with hemodialysis.

Quantification of Lipoteichoic Acid in Hemodialysis Patients With Central Venous Catheters.

Hemodialysis patients with central venous catheters (CVCs) have chronic systemic inflammation, the source of which may be related to intraluminal bacterial biofilm. There is currently no non-invasive method to adequately evaluate intraluminal biofilm. Lipoteichoic acid (LTA) is a Gram-positive bacterial cell wall component that is spontaneously shed. The purpose of this study was to determine whether LTA could be quantified in biological samples and to evaluate potential relationships to markers of inflammation. Heparin-locked catheter aspirate was drawn from both the arterial and venous ports of each CVC prior to dialysis initiation. Venous blood from the dialysis circuit was collected 30 min after dialysis initiation. LTA was quantified in aspirate and plasma. Key markers of inflammation (interleukin-6, and hepcidin) and endothelial dysfunction (soluble vascular endothelial cadherin) were also determined in plasma samples. Catheter aspirate and systemic blood samples were obtained from 40 hemodialysis patients. The median (range) duration of catheter use was 130 (20-1635) days. Unexpectedly, median (range) plasma LTA concentrations (ng/mL) were significantly higher than catheter aspirate LTA concentrations [3.93 (0.25-15) vs. 2.38 (0.1-8.1), respectively, p = 0.01] in the majority (70%) of patients. Area under the receiver operator characteristic (ROC) curve showed good potential prognostic value of catheter aspirate LTA predicting systemic LTA concentrations with an area under the curve of 0.815 (95% CI, 0.68-0.95). A significant correlation was found between LTA and serum ferritin (r = 0.32, p = 0.04), however, there were no significant correlations between LTA and the other inflammation biomarkers assessed. LTA is quantifiable in aspirate and plasma of hemodialysis patients with CVCs and warrants further investigation to determine potential clinical application to intraluminal biofilm evaluation.