Impact Of Renal Function Research Articles

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): <45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups <45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group <45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p<0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p<0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p<0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR <45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR <45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p<0.001). Between group differences in eGFR changes were statistically significant (adjusted p<0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR <45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR <45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

The impact of renal function on clinical outcomes of patients with cancer-associated isolated distal deep vein thrombosis: Insights from the ONCO DVT study

BackgroundThe multicenter, open-label, randomized clinical trial ONCO DVT compared 3-month and 12-month edoxaban treatment regimens for isolated distal deep vein thrombosis (DVT) and suggested potential benefits of prolonged edoxaban treatment in terms of thrombotic risk. However, the risk-benefit balance of prolonged edoxaban treatment in patients with renal function remains unclear. ObjectivesTo compare the safety and efficacy of 3-month and 12-month edoxaban treatment regimens in patients with cancer-associated isolated distal DVT and different renal functions. MethodsThis pre-specified subgroup analysis of the ONCO DVT study included 601 patients divided into subgroups according to renal function using a 50 mL/min creatinine clearance (Ccr) cutoff. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) and VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months. ResultsAmong the 601 patients, 131 (21.8 %) comprised the renal dysfunction subgroup. The primary endpoint occurred in 6 (9.7 %) and 1 (1.4 %) patients in the 3-month and 12-month edoxaban groups in the renal dysfunction subgroup, respectively, and in 16 (6.6 %) and 2 (0.9 %) patients in the no renal dysfunction subgroup, respectively. The major secondary endpoint occurred in 9 (14.5 %) and 7 (10.1 %) patients in the 12-month and 3-month edoxaban groups in the renal dysfunction subgroup, and in 13 (5.3 %) and 21 (9.3 %) patients in the no renal dysfunction subgroup, respectively. ConclusionsA 12-month edoxaban regiment was superior to a 3-month treatment in terms of thrombotic risk irrespective of renal function. A higher bleeding risk was not identified in patients with renal dysfunction who received prolonged edoxaban treatment.

Imeglimin: A Clinical Pharmacology Review.

Imeglimin (PXL008, EMD-387008, Twymeeg®) is a first-in-class novel oral hypoglycemic agent, launched in Japan, for the treatment of type 2 diabetes mellitus. Its mechanism of action targets mitochondrial bioenergetics to ameliorate insulin resistance and to enhance β-cell function. This review summarizes the properties underlying the pharmacokinetic profile of imeglimin, a small cationic drug belonging to the tetrahydrotriazine chemical class, with a complex mechanism of absorption involving an active transport through organic cation transporters (OCTs). Imeglimin absorption decreases when dose increases due to the saturation of the active uptake transport. Post absorption, imeglimin is rapidly and primarily distributed to organs and tissues, and has a half-life ranging from 9.03 to 20.2h. Plasma protein binding of imeglimin is low, which explains the rapid distribution to the organs observed in all species. Imeglimin is excreted unchanged in urine, indicating a low extent of metabolism. Imeglimin is a substrate of multidrug and toxic compound extrusion (MATE)2-K and a substrate and inhibitor of OCT1, OCT2, and MATE1. Clinical drug-drug interaction studies confirmed the absence of relevant clinical interaction with substrates or inhibitors of these transporters. Overall, the drug-drug interaction potential of imeglimin is low. Its pharmacokinetics profile has also been characterized in special populations, showing no influence of mild and moderate hepatic impairment but an impact of renal function on imeglimin renal clearance. Dosage adjustment is thus required in moderately and severely renally impaired patients. Imeglimin pharmacokinetics was shown to be insensitive to ethnicity and food intake and to have no effect on QTcF interval.

The Impact of Renal Function on Liver Cirrhosis among Patients in Wasit Governorate, Iraq

In Al-Kut city's AL-Zahraa general hospital, this study was carried out.for individuals with liver cirrhosis to evaluate their serum levels of ALT, AST, GGT, ALP, urea, creatinine, T.Protien, Albumin, and Bilirubin. The 50 patients ranged in age from 20 to 60, with 29 male and 21 female individuals.Based on the patient's medical history and physical examination, liver cirrhosis was determined to affect both sexes of the patient. The 30 control groups were drawn from the medical personnel and family of those who did not exhibit any indications or symptoms of renal liver disease or kidney diseases. With ages ranging from 22 to 66, there were 20 men and 10 women. Eight to fourteen hours following the patients' overnight fasts, blood samples were obtained. The research reveals the following. Serum ALT, AST and GGT concentrations in liver cirrhosis patients were found to be significantly increased compared with control group (P<0.01).Serum Bilirubin (Total) and direct Bilirubin concentrations in liver cirrhosis patients were found to be significantly high compared with control group (P<0.5), (P<0.01) respectively. Serum Albumin concentrations in liver cirrhosis patients were found to be no significantly lower compared with control group (P>0.5). Serum Total protein concentrations in liver cirrhosis patients were found to be no significantly lower compared with control group (P≤0.5).Serum Alkaline phosphatase (ALP) concentrations in liver cirrhosis patients were found to be significantly increased compared with control group (P<0.01).Serum urea, creatinine, Uric acid and ammonia level concentrations in liver cirrhosis patients were found to be significantly high compared with control group (P<0.01).

Meropenem PK/PD Variability and Renal Function: "We Go Together".

Meropenem is a carbapenem antibiotic widely employed for serious bacterial infections. Therapeutic drug monitoring (TDM) is a strategy to optimize dosing, especially in critically ill patients. This study aims to show how TDM influences the management of meropenem in a real-life setting, not limited to intensive care units. From December 2021 to February 2022, we retrospectively analyzed 195 meropenem serum concentrations (Css). We characterized patients according to meropenem exposure, focusing on the renal function impact. A total of 36% (n = 51) of the overall observed patients (n = 144) were in the therapeutic range (8-16 mg/L), whereas 64% (n = 93) required a meropenem dose modification (37 patients (26%) underexposed; 53 (38%) overexposed). We found a strong relationship between renal function and meropenem concentrations (correlation coefficient = -0.7; p-value < 0.001). We observed different dose-normalized meropenem exposure (Css/D) among renal-impaired (severe and moderate), normal, and hyperfiltrating patients, with a median (interquartile range) of 13.1 (10.9-20.2), 7.9 (6.1-9.5), 3.8 (2.6-6.0), and 2.4 (1.6-2.7), respectively (p-value < 0.001). Meropenem TDM in clinical practice allows modification of dosing in patients inadequately exposed to meropenem to maximize antibiotic efficacy and minimize the risk of antibiotic resistance, especially in renal alterations despite standard dose adaptations.

The Impact of Renal Function on Hepatic Encephalopathy Following TIPS Placement for Refractory Ascites.

The impact of renal function on hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement for refractory ascites is poorly understood. We investigated the role of renal function on HE following TIPS placement. A retrospective study was performed for patients undergoing TIPS for refractory ascites from 2007-2019. Patients were stratified by GFR at time of TIPS placement and by whether they were on hemodialysis (HD). Chronic kidney disease (CKD) stage 3 or higher was defined as pre-TIPS GFR < 60 for at least 3 months. Logistic regression analyses were used to identify the role of GFR and CKD at time of TIPS placement on HE within 60 days post TIPS placement. Among 201 TIPS patients for refractory ascites (61% male; mean age 59.1), 78 (39%) patients were in CKD, and 16 (21%) were on HD. Mean GFR at time of TIPS placement was 62.7 ± 28.2 for all non-HD patients (n = 185). Compared with the GFR ≥ 90 group, GFR < 30 or HD (OR, 3.56; 95%CI, 1.19-10.7; p = 0.023) and CKD (OR, 2.52; 95%CI, 1.40-4.53; p = 0.002) at time of TIPS placement were significant predictors of post-TIPS placement HE within 60 days. GFRs between 30-60 and 60-90 were not significant predictors. In TIPS patients for recurrent ascites, patients with acutely impaired renal function or chronic renal dysfunction were at an increased risk for HE after TIPS.

The impact of renal function on the three-year outcomes in patients with myocardial infarction with nonobstructive coronary arteries

BackgroundDue to limited data availability, we compared the 3-year outcomes of patients with acute myocardial infarction (AMI) and nonobstructive coronary arteries (MINOCA) and those with obstructive coronary arteries (MIOCA) according to renal function. MethodsFrom a final cohort of 10,774 patients with AMI were classified into 2 groups: the chronic kidney disease (CKD) group (estimated glomerular filtration rate <60 mL/min/1.73 m2, 2,854 patients; MINOCA, 123; MIOCA, 2,731) and the non-CKD group (7,920 patients; MINOCA, 256; MIOCA, 7,664). The primary outcome was the 3-year all-cause death rate, and the secondary outcomes included cardiac death (CD), non-CD death (NCD), recurrent myocardial infarction (MI), and any revascularization. ResultsIn both the CKD and non-CKD groups, the adjusted in-hospital mortality, 3-year all-cause death, CD, and recurrent MI rates were similar between the MINOCA and MIOCA groups, but the adjusted 3-year any revascularization rates were significantly higher in the MIOCA group than in the MINOCA group. Characteristically, in the CKD group, the adjusted 3-year NCD rate (P = 0.032) was higher in the MINOCA group than in the MIOCA group, and sepsis was the main cause of NCD in this group. In both the MINOCA and MIOCA groups, all-cause death and NCD were significantly higher in the CKD group than in the non-CKD group. ConclusionsRegardless of renal function, the MINOCA and MIOCA groups had comparable mortality rates. However, patients with MINOCA and CKD had higher NCD rates. Close monitoring of renal function and enhanced strategies are required to reduce mortality in patients with MINOCA.

Impact of Renal Function on the Prognosis of Patients Receiving Atezolizumab/Bevacizumab Combination Therapy and Lenvatinib Monotherapy for Unresectable Hepatocellular Carcinoma

Introduction: Several studies have reported kidney injury caused by immune checkpoint inhibitors, and proteinuria caused by vascular endothelial growth factor inhibitors for unresectable hepatocellular carcinoma (u-HCC). We investigated the relationship between renal function and prognosis in patients with u-HCC receiving atezolizumab and bevacizumab (AB) and lenvatinib (LEN) therapy. Methods: Fifty-one patients who received AB and 50 patients who received LEN therapy were included. We analyzed prognostic factors related to the overall survival (OS), and characteristics related to renal function. Results: In patients with AB therapy, OS was shorter in patients with baseline proteinuria of 1+ or higher, as assessed by urine dipstick test, compared to those with –/± (p = 0.024). There were many cases with two or more drugs with a high risk of renal dysfunction (p = 0.019) in patients with 1+ or higher. Furthermore, OS was shorter in the group with estimated glomerular filtration rate (eGFR) grade deterioration without urinary protein-creatinine ratio (UPCR) of 2 g/g·Cre or higher than in the other groups (p = 0.027). In the group where eGFR worsened without an increase in UPCR, there were many cases with a daily salt intake of 10 g or more (p = 0.027), three or more drugs with a high risk of renal dysfunction (p = 0.021), and a history of arteriosclerosis (p = 0.021). On the other hand, in patients with LEN therapy, OS tends to be shorter in patients with proteinuria of ± or higher, compared to those without (p = 0.074). There were many cases with a daily salt intake of 10 g or more in patients with ± or higher (p = 0.002). Conclusion: In patients receiving AB and LEN therapy, baseline proteinuria was associated with OS. Renal function deterioration without proteinuria was associated with a poor prognosis in AB therapy. Excessive salt intake, preexisting atherosclerotic disease, and drug with a high risk of renal dysfunction were risk factors for renal deterioration.

Impact of renal function on Ticagrelor-induced antiplatelet effects in coronary artery disease patients.

Chronic renal failure (CKD) is associated with the presence of increased platelet reactivity and lower clinical benefit of clopidogrel. Ticagrelor has a more favorable pharmacodynamic and pharmacokinetic profile compared to clopidogrel, which has translated into better clinical outcomes in patients with acute coronary syndrome (ACS). We conducted a prospective mechanistic cohort study in order to investigate the impact of renal failure on the pharmacokinetics and pharmacodynamics of ticagrelor in patients with acute ACS. Patients were divided into two groups based on their estimated renal clearances (eGFR≥60mL/min and eGFR<60mL/min). Platelet function was determined using the VerifyNow system at baseline, after the ticagrelor loading dose and at discharge. In addition, levels of ticagrelor and its active metabolite (AR-C124910XX) were determined in the first hour after loading dose. 48 patients were recruited (eGFR≥60mL/min: 35 and eGFR<60mL/min: 13). There were no significant differences between the groups in terms of platelet inhibition after the loading or after 7days of treatment (p=0.219). However, the levels of ticagrelor and its active metabolite were lower in subjects with normal renal function than in CKD, especially at 4 (p=0.02 and 0.04 respectively) and 6h of loading (p=0.042 and 0.08 respectively). No differences in platelet inhibition were observed after treatment with ticagrelor in patients with different renal function, although patients with renal impairment showed higher levels of ticagrelor and AR-C124910XX after 4h of the loading dose.

Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping

The chemotherapeutic agent 5-fluorouracil (5-FU) is catabolized by dihydropyrimidine dehydrogenase (DPD), the deficiency of which may lead to severe toxicity or death. Since 2019, DPD deficiency testing, based on uracilemia, is mandatory in France and recommended in Europe before initiating fluoropyrimidine-based regimens. However, it has been recently shown that renal impairment may impact uracil concentration and thus DPD phenotyping. The impact of renal function on uracilemia and DPD phenotype was studied on 3039 samples obtained from three French centers. We also explored the influence of dialysis and measured glomerular filtration rate (mGFR) on both parameters. Finally, using patients as their own controls, we assessed as to what extent modifications in renal function impacted uracilemia and DPD phenotyping. We observed that uracilemia and DPD-deficient phenotypes increased concomitantly to the severity of renal impairment based on the estimated GFR, independently and more critically than hepatic function. This observation was confirmed with the mGFR. The risk of being classified 'DPD deficient' based on uracilemia was statistically higher in patients with renal impairment or dialyzed if uracilemia was measured before dialysis but not after. Indeed, the rate of DPD deficiency decreased from 86.4% before dialysis to 13.7% after. Moreover, for patients with transient renal impairment, the rate of DPD deficiency dropped dramatically from 83.3% to 16.7% when patients restored their renal function, especially in patients with an uracilemia close to 16 ng/ml. DPD deficiency testing using uracilemia could be misleading in patients with renal impairment. When possible, uracilemia should be reassessed in case of transient renal impairment. For patients under dialysis, testing of DPD deficiency should be carried out on samples taken after dialysis. Hence, 5-FU therapeutic drug monitoring would be particularly helpful to guide dose adjustments in patients with elevated uracil and renal impairment.

LBODP034 Metformin Associated Lactic Acidosis, Rare But Real

Abstract Background Metformin has been widely used as a first-line agent to treat type 2 diabetes mellitus. Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e. g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). Case description We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM admitted to the emergency department with a history of dehydration due to diarrhea and complicated by acute renal failure Our patient is a 57-year-old female with a medical history of DM on metformin 1000 mg twice daily, hypertension, hyperlipidemia, and hypothyroidism who presented to the hospital with a concern of altered mental status. Upon presentation, the patient could not provide much history, but her daughter confirmed that she was in her normal state of health until 2 weeks ago when she started complaining of knee pain and stated that she was taking ibuprofen 600 mg every 8 hours for pain with good response. Later, 2 days prior to her presentation she started having severe nausea, vomiting, weakness and was noted to be confused so she was brought to the emergency department. Upon arrival the patient's blood pressure was noted to be 104/50, GCS 15, rest of the vitals were within normal. Potassium was 5.5(3.4 - 5.3 mmol/L), bicarbonate 5(22 - 33 mmol/L), creatinine 10.2(0.4 - 1.1 mg/dL) compared to normal creatinine 6 months ago, GFR&amp;lt;5(&amp;gt;59 ml/min/1.73 sq meters, anion gap 41(4-16), PH 6.7(7.33 - 7.43), After resuscitation, her severe acidemia persisted despite aggressive intervention with volume resuscitation and vasopressors, leading to the initiation of renal replacement therapy. After multiple dialysis treatments, her severe acidemia resolved and creatinine improved back to baseline after which she was discharged home in stable condition. Conclusion The reported incidence of lactic acidosis in clinical practice has proved to be very low (&amp;lt;10 cases per 100,000 patient-years). This literature-based review provides an update on the impact of renal function and other conditions (cirrhosis, sepsis, or hypoperfusion) on metformin plasma levels and the risk of MALA in patients with type 2 diabetes. As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment to minimize the potential for toxic metformin levels and MALA. Presentation: No date and time listed

Impact of Renal Function on Short-Term Outcome After Reperfusion Therapy in Patients With Ischemic Stroke.

A high and low estimated glomerular filtration rate (eGFR) could affect outcomes after reperfusion therapy for ischemic stroke. This study aimed to determine whether renal function based on eGFR affects mortality risk in patients with ischemic stroke within 6 months following reperfusion therapy. This prospective registry-based cohort study included 2266 patients who received reperfusion therapy between January 2000 and September 2019 and were registered in the SECRET (Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy) study or the Yonsei Stroke Cohort. A high and low eGFR were based on the Chronic Kidney Disease Epidemiology Collaboration equation and defined, respectively, as the 5th and 95th percentiles of age- and sex-specific eGFR. Occurrence of death within 6 months was compared among the groups according to their eGFR such as low, normal, or high eGFR. Of the 2266 patients, 2051 (90.5%) had a normal eGFR, 110 (4.9%) a low eGFR, and 105 (4.6%) a high eGFR. Patients with high eGFR were younger or less likely to have hypertension, diabetes, or atrial fibrillation than the other groups. Active cancer was more prevalent in the high-eGFR group. During the 6-month follow-up, there were 24 deaths (22.9%) in the high-eGFR group, 37 (33.6%) in the low-eGFR group, and 237 (11.6%) in the normal-eGFR group. After adjusting for variables with P<0.10 in the univariable analysis, 6-month mortality was independently associated with high eGFR (hazard ratio, 2.22 [95% CI, 1.36-3.62]; P=0.001) and low eGFR (HR, 2.29 [95% CI, 1.41-3.72]; P=0.001). These associations persisted regardless of treatment modality or various baseline characteristics. High eGFR as well as low eGFR were independently associated with 6-month mortality after reperfusion therapy. Kidney function could be considered a prognostic factor in patients with ischemic stroke after reperfusion therapy.

Impact of Renal Function on Anti-factor Xa Activity Concentrations with Edoxaban Use in Patients with Non-valvular Atrial Fibrillation

Chromogenic anti-factor Xa activity (AXA) assay is used to measure the pharmacodynamics of factor Xa inhibitors, including edoxaban. Although AXA concentrations in patients with non-valvular atrial fibrillation using edoxaban have been reported, the impact of renal function on AXA concentrations with edoxaban use in patients with non-valvular atrial fibrillation has not been fully assessed. Trough and peak AXA concentrations were measured in 93 patients with non-valvular atrial fibrillation taking edoxaban (73.6 ± 11.2 years, 48 were male). The patients were divided into three groups: patients with moderate renal dysfunction (creatinine clearance 15-49 mL/min), mild renal dysfunction (creatinine clearance 50-95 mL/min), and normal renal function (creatinine clearance >95 mL/min). Both trough and peak AXA concentrations were assessed among the groups according to the edoxaban dose (30 or 60 mg). At a 30-mg dose, patients with moderate renal dysfunction showed significantly higher trough AXA concentrations than patients with mild renal dysfunction or normal renal function. At a 60-mg dose, patients with mild renal dysfunction showed significantly higher trough AXA concentrations than patients with normal renal function. Peak AXA concentrations were not significantly different between the groups. Creatinine clearance was significantly and negatively correlated with trough AXA concentrations at a 60-mg dose, whereas the correlation of creatinine clearance with AXA concentrations was borderline significant at a 30-mg dose. No correlation was found between creatinine clearance and peak AXA concentrations at either dose. Creatinine clearance tends to be negatively correlated with trough AXA concentrations in patients with non-valvular atrial fibrillation taking edoxaban, while renal function is not correlated with peak AXA concentrations.

Renal Function Impact in the Prognostic Value of Galectin-3 in Acute Heart Failure.

IntroductionGalectin-3 (Gal-3) is an inflammatory marker associated with the development and progression of heart failure (HF). A close relationship between Gal-3 levels and renal function has been observed, but data on their interaction in patients with acute HF (AHF) are scarce. We aim to assess the prognostic relationship between renal function and Gal-3 during an AHF episode.Materials and MethodsThis is an observational, prospective, multicenter registry of patients hospitalized for AHF. Patients were divided into two groups according to estimated glomerular filtration rate (eGFR): preserved renal function (eGFR ≥ 60 mL/min/1.73 m2) and renal dysfunction (eGFR <60 mL/min/1.73 m2). Cox regression analysis was performed to evaluate the association between Gal-3 and 12-month mortality.ResultsWe included 1,201 patients in whom Gal-3 values were assessed at admission. The median value of Gal-3 in our population was 23.2 ng/mL (17.3–32.1). Gal-3 showed a negative correlation with eGFR (rho = −0.51; p < 0.001). Gal-3 concentrations were associated with higher mortality risk in the multivariate analysis after adjusting for eGFR and other prognostic variables [HR = 1.010 (95%-CI: 1.001–1.018); p = 0.038]. However, the prognostic value of Gal-3 was restricted to patients with renal dysfunction [HR = 1.010 (95%-CI: 1.001–1.019), p = 0.033] with optimal cutoff point of 31.5 ng/mL, with no prognostic value in the group with preserved renal function [HR = 0.990 (95%-CI: 0.964–1.017); p = 0.472].ConclusionsGal-3 is a marker of high mortality in patients with acute HF and renal dysfunction. Renal function influences the prognostic value of Gal-3 levels, which should be adjusted by eGFR for a correct interpretation.

609 Prognostic role of renal function in patients with previous myocardial infarction. A study with cardiac magnetic resonance

Abstract Aims There is not strong evidence in literature about the impact of renal function on the prognosis of patients with ischaemic cardiomyopathy. Thus, the aim of the study was to investigate mild renal impairment [estimated glomerular filtration rate (eGFR): 60–89 ml/min] as an independent prognostic factor in patients with history of myocardial infarction (MI). Methods and results We studied 339 consecutive patients (65 ± 13 years old, female 13%) from 2001 and 2012 with previous MI. Patients with eGFR &amp;lt;60 ml/min were excluded. We performed cardiac magnetic resonance (CMR) in all patients to quantify left ventricular ejection fraction (LVEF), volumes, and wall motion score index (WMSI), and to measure the infarction extent by late gadolinium enhancement (LGE). Renal function was estimated by creatinine value with Cockcroft–Gault formula and patients were divided according to normal (≥90 ml/min) and reduced (60–89 ml/min) eGFR. Patients with normal eGFR were 106 (31%, 56.9 ± 10.5 years old), 233 (69%, 66.1 ± 9.9 years old) had renal impairment. During follow-up (median 3.5 years), cardiac events (cardiac death or appropriate intra-cardiac defibrillator shock) occurred in 28/233 (12%) of patients with eGFR &amp;lt;90 ml/min and in 4/106 (4%) of patients with eGFR ≥90 ml/min (P &amp;lt; 0.05). Furthermore, survival curve showed a significantly worst prognosis in patients with renal impairment (P &amp;lt; 0.03). In the group of patients with ejection fraction (EF) &amp;lt; 35% (121 patients), cardiac events were observed only in patients with eGFR &amp;lt;90 ml/min (23/99, 23%, P &amp;lt; 0.05). At multivariate stepwise analysis, age &amp;gt;65 years old, eGFR &amp;lt;90 ml/min and WMSI &amp;gt;1.7 turned out to be independent predictor of cardiac events (P &amp;lt; 0.05). Conclusions In patients with previous MI, a mild renal impairment (eGFR between 60 and 89 ml/min) was an independent predictor of prognosis, especially if combined with left ventricular disfunction.

64. Novel Biomarkers Improve Estimation of Vancomycin Clearance in Critically Ill Children

BackgroundThere are a paucity of robust population PK (popPK) models to inform vancomycin (VAN) dosing in critically ill children. The majority of published models incorporate peak/trough data and rely on flawed estimates of renal function. We sought to develop a popPK model for IV VAN in critically ill children utilizing novel plasma and urinary biomarkers.MethodsWe conducted a prospective observational study of critically ill children prescribed VAN for a suspected infection in the CHOP pediatric ICU. Children < 1 year of age and those receiving ECMO or CRRT were excluded. Five VAN samples were collected from a single dosing interval for each subject. Plasma biomarkers (creatinine [Cr], cystatin C [CysC], NGAL) and urinary biomarkers (CysC, NGAL, KIM-1, osteopontin) were collected the morning of PK sampling; urinary biomarkers were corrected for urine creatinine. Nonparametric popPK modeling was performed using Pmetrics. The impact of renal function (GFR) on VAN clearance (CL) was estimated first, comparing model performance with each biomarker (Cr and plasma CysC). The influence of age, sex, additional biomarkers, PIM3 score, and receipt of vasopressors as covariates was then assessed for relevant PK parameters.Results30 subjects completed the study. Median age was 10 years (range 1-17); 76% were male. The majority (90%) of children received VAN for suspected sepsis. PK sampling occurred at a median of 37.7 hours (range 24.6-94.8) into VAN treatment; 136 VAN samples were included. A 2-compartment model with fixed allometric scaling of 0.75 on clearances and 1 on volumes best described the data. CysC-based GFR as a covariate on VAN CL using the HOEK formula (GFR = -4.32 + (80.35/CysC)) resulted in the best model fit. Age and plasma NGAL were also informative on VAN CL in the final model (Figure 1). During model building, urinary NGAL was also associated with VAN CL (comparable to plasma NGAL) and outperformed Cr, although it was not retained in the final model.Figure 1. Final population PK model and parameter estimates. ConclusionPlasma CysC is a better renal function estimate than Cr to inform VAN clearance in critically ill children. Urinary and plasma NGAL also improved estimation of VAN CL during popPK modeling. Novel biomarkers can better describe VAN exposures in critically ill children than reliance on Cr alone.Disclosures Kevin J. Downes, MD, Merck (Individual(s) Involved: Self): Grant/Research Support Stuart L. Goldstein, MD, Bioporto (Consultant, Grant/Research Support)

Impact of Renal Function on Effectiveness and Safety Associated With Low Dose Dabigatran in Non-valve Atrial Fibrillation Patients After Catheter Ablation.

Aim: The purpose of this study is to compare the effectiveness and safety of 110 mg dabigatran in non-valve atrial fibrillation (NVAF) patients with different eGFRs.Methods: We conducted a single-center retrospective cohort study to investigate the effectiveness and safety of 110 mg dabigatran for NVAF patients between January 2017 and December 2018 based on the eGFR category.Results: A total of 560 NVAF patients who treated with 110 mg dabigatran were included for analysis. In 12 months, the Kaplan-Meier survival curves indicated that the lower eGFR subgroups were more likely to experience thrombosis, bleeding, and cumulative events earlier (P = 0.021 for thrombosis; P = 0.026 for bleeding; P = 0.001 for cumulative events). Gastrointestinal bleeding occurred more frequently in the moderate group than in other groups (6.94% in the moderate group vs. 1.54% in the mild group vs. 1.22% in the normal group, P = 0.028). By multivariate analysis, chronic kidney disease (P = 0.043; OR = 4.273, 95% CI 1.043–17.543) and diabetes mellitus (P = 0.023; OR = 2.194, 95% CI 1.114–4.323) were independent predictors of the composite endpoints. A positive linear relationship was observed between eGFR levels and occurrence rate of thrombosis and bleeding under anticoagulation patients with 110 mg dabigatran (R2 = 0.432 and R2 = 0.784, respectively).Conclusions: Impaired renal function was associated with decreased safety and increased thrombosis risks in NVAF patients taking low dose dabigatran.

Improvement of renal function prior to liver transplantation is not associated with better long-term renal outcome or survival

Introduction and objectivesSince MELD implementation renal impairment in liver transplant (LT) recipients has become of increasing importance. This is the first study evaluating the course of renal function immediately prior to LT as predictor for long-term renal and overall outcome. Patients and methodsIn this retrospective study, 226 adults undergoing LT at the University Medical Center Hamburg-Eppendorf (2011-2015) were included. The impact of renal function over a period of 3 months prior to LT compared to renal function at the day of LT on long-term renal outcome and survival was assessed. ResultsAccording to GFR at day of LT renal function improved (≥1 CKD stage) in 64 patients (28%), remained stable in 144 (64%) or deteriorated in 18 (8%). Improvement of renal function prior to LT did neither significantly affect 90-day (13% vs. 14%, p = 0.83), nor 5-year post-LT mortality (35% vs. 41%, p = 0.57). 50 patients (22%) with hepatorenal syndrome (HRS) received terlipressin prior to LT, but only 18 (37%) showed prolonged stabilization of renal function (improvement ≥1 CKD stage). Response to terlipressin did neither improve 90-day (p=1), 5-year mortality (p = 0.52) nor long-term renal function (p = 0.843). Nevertheless, need for dialysis pre-LT (59% vs. 34%, p = 0.005) and post-LT (62% vs. 17%, p<0.001) was associated with increased 5-year mortality. ConclusionsImprovement of renal function immediately prior to LT, either spontaneously or following terlipressin therapy, did neither ameliorate long-term renal outcome nor survival in LT recipients. Future studies need to clarify the impact of terlipressin in HRS on the transplant waiting time in LT candidates.

Differential impact of renal function on the diagnostic performance of resting full-cycle ratio as non-hyperemic physiological assessment

Abstract Background Fractional flow reserve (FFR) is a gold standard method to evaluate functional lesion severity in daily clinical practice. Recently, the resting full-cycle ratio (RFR) was Previous studies showed the better diagnostic performance of RFR comparing with FFR. It is well known that patients with chronic kidney disease (CKD) have poor prognosis. Therefore, we should carefully assess the functional lesion severity in CKD patients. However, it is unclear whether the diagnostic performance of RFR for detecting functional ischemia is similar regardless of the degree of renal function. The aim of this study is to compare the diagnostic performance of RFR based on renal function. Method This study was a prospectively enrolled observational study. A total of 265 consecutive patients with 373 intermediate lesions were enrolled in this study. There were classified into three groups according to renal function (Group 1: eGFR ≥60 mL/min/1.73m2; Group 2: 30 mL/min/1.73m2 ≤eGFR &amp;lt;60 mL/min/1.73m2; Group 3: eGFR &amp;lt;30mL/min/1.73m2). The RFR was measured after adequately waiting for stable condition, while FFR was measured after intravenous administration of ATP (180mcg/kg/min). The discordance between FFR and RFR were assessed the data using known cutoffs for FFR (≤0.80) and RFR (≤0.89). Results Of 373 lesions, the median age was 70.1±11.0 years. Functional significance was observed in 153 lesions (41.0%) of all lesions. RFR showed a significant correlation with FFR in each group (Group 1; r2=0.63 [p&amp;lt;0.001], Group 2: r2=0.67 [p&amp;lt;0.001], Group 3: r2=0.51 [p&amp;lt;0.001], respectively). The ROC curve analysis of RFR showed differential results for predicting functional significance (Group 1: AUC 0.88, cut-off value 0.91; Group 2: AUC 0.88, cut-off value 0.89; Group 3: AUC 0.81, cut-off value 0.83; respectively) in each group. The prevalence of discordant between RFR and FFR was significantly different among 3 groups (Group 1: 16.5%, Group 2: 19.4%, Group 3: 25.0%, respectively, p&amp;lt;0.05 for among 3 groups). Conclusion The diagnostic performance of RFR was different based on renal function. During RFR acquisition, the degree of renal function could influence concordance with FFR, and should be taken into account when interpreting RFR. Funding Acknowledgement Type of funding sources: None.

S1068 The Impact of Renal Function on Hepatic Encephalopathy Following Transjugular Intrahepatic Portosystemic Shunt Placement for Refractory Ascites

S1068 The Impact of Renal Function on Hepatic Encephalopathy Following Transjugular Intrahepatic Portosystemic Shunt Placement for Refractory Ascites