Hypertensive urgencies and emergencies

2020 ◽  
pp. 3800-3810
Author(s):  
Gregory Y.H. Lip ◽  
Alena Shantsila
Keyword(s):  
Blood Pressure ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Rare Condition ◽  
Visual Disturbance ◽  
Organ Damage ◽  
Renal Diseases ◽  
Mild Renal Impairment ◽  
Cotton Wool Spots ◽  
Hypertensive Urgencies

Hypertensive urgencies and emergencies occur most commonly in patients with previous hypertension, especially if inadequately managed. About 40% of cases have an underlying cause, most commonly renovascular disease, primary renal diseases, phaeochromocytoma, and connective tissue disorders. Hypertensive emergencies occur when severely elevated or sudden marked increase in blood pressure is associated with acute end-organ damage. Malignant phase hypertension is a rare condition characterized by very high blood pressure, with bilateral retinal haemorrhages and/or exudates or cotton wool spots, with or without papilloedema. Presentation is typically with visual disturbance, with or without headaches. Urinalysis may demonstrate proteinuria and haematuria, even in the absence of primary renal disease. Some patients with mild renal impairment at first presentation may improve, or even regain normal renal function, but this is unlikely to occur in those with more severe renal impairment at presentation.

Hypertensive urgencies and emergencies

2010 ◽  
pp. 3074-3082
Author(s):  
Gregory Y.H. Lip ◽  
D. Gareth Beevers
Keyword(s):  
Blood Pressure ◽  
Connective Tissue ◽  
Organ Damage ◽  
Renal Diseases ◽  
Connective Tissue Disorders ◽  
Renovascular Disease ◽  
End Organ Damage ◽  
Hypertensive Emergencies ◽  
Hypertensive Urgencies

Hypertensive urgencies and emergencies occur most commonly in patients with previous hypertension, especially if inadequately managed. About 40% of cases have an underlying cause, most commonly renovascular disease, primary renal diseases, phaeochromocytoma, and connective tissue disorders. Hypertensive emergencies occur when severely elevated or sudden marked increase in blood pressure is associated with acute end-organ damage....

Abstract 11267: LX4211, a Dual Inhibitor of Sodium-Glucose Cotransporters 1 and 2, Reduces Systolic Blood Pressure in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Renal Impairment

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Pablo Lapuerta ◽  
Paul Strumph ◽  
Philip Banks ◽  
Ikenna Ogbaa ◽  
Brian Zambrowicz ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Impairment ◽  
Systolic Blood Pressure ◽  
Severe Renal Impairment ◽  
Postprandial Glucose ◽  
Dual Inhibitor

Introduction: Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors target only the kidney, and they have reduced efficacy when patients with type 2 diabetes mellitus (T2DM) have renal impairment (RI). LX4211 blocks sodium and glucose absorption in the gastrointestinal tract by inhibition of SGLT1, and it enhances urinary sodium and glucose excretion in the urine through inhibition of SGLT2. The dual SGLT1/2 action of LX4211 was anticipated to reduce systolic blood pressure (SBP) in addition to improving glucose control in the setting of RI. Methods: This analysis explored the effect of LX4211 on SBP in a clinical trial of patients with T2DM and moderate to severe RI. Patients (N=31) were randomly assigned to be treated with LX4211 (400 mg, N=16) or placebo (N=15) qd for 7 consecutive days. Postprandial glucose levels after a standard high glucose meal served as the primary measure of pharmacodynamic activity. Baseline and Day 8 trough SBP measures were each an average of 3 seated assessments. Results: Mean baseline characteristics included age 66.4 years, estimated glomerular filtration rate (eGFR) 43.4 mL/min/1.73 m 2 , and SBP 130.9 mmHg. Postprandial glucose area under the curve (sampled from pre-dose to 4 hours post meal) was reduced from Baseline to Day 7 by 169.3 mg*hr/dL on LX4211 compared to placebo (p=0.003). Day 8 SBP reductions were 11.4 mmHg on LX4211 and 0.0 mmHg on placebo (p=0.045 for difference between groups). Patients with greater RI (eGFR <45 mL/min/1.73 m2) treated with LX4211 (N=6) had a 10.5 mmHg SBP reduction compared to 0.3 mmHg on placebo (N=9). The difference between seated and standing SBP did not change with LX4211 (0.0 mmHg change, Day 8 vs. Baseline). There were no reports of hypotension, hypovolemia, no serious adverse events, and no patient discontinued due to an adverse event. Mild hypoglycemia was reported in 1 LX4211 patient compared to 2 placebo patients. Conclusions: LX4211 may reduce SBP and enhance glycemic control in T2DM patients with moderate to severe RI.

scholarly journals Pharmacokinetics of Telbivudine in Subjects with Various Degrees of Renal Impairment

2007 ◽  
Vol 51 (12) ◽  
pp. 4231-4235 ◽  
Author(s):  
Xiao-Jian Zhou ◽  
Suzanne Swan ◽  
William B. Smith ◽  
Thomas C. Marbury ◽  
Gloria Dubuc-Patrick ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Normal Function ◽  
Plasma Exposure ◽  
Mild Renal Impairment ◽  
Severe Impairment ◽  
Stage Renal Disease ◽  
End Stage

ABSTRACT This study evaluates the effect of renal impairment on the pharmacokinetics of telbivudine. Thirty-six subjects were assigned, on the basis of creatinine clearance (CLCR), to 1 of 5 renal function groups with 6 to 8 subjects per group: normal renal function; mild, moderate, or severe renal impairment; or end-stage renal disease [ESRD] requiring hemodialysis. Subjects received a single oral dose of telbivudine at 600 mg (normal function and mild impairment), 400 mg (moderate impairment), or 200 mg (severe impairment and ESRD); plasma and/or urine samples were collected over a 48-h period for pharmacokinetic analyses. Telbivudine was well tolerated by all subjects. The pharmacokinetics of 600 mg of telbivudine were comparable for subjects with mild renal impairment and normal renal function. Likewise, for subjects with moderate to severe impairment, including ESRD, reduced doses from 200 to 400 mg produced plasma exposure similar to that for subjects with normal renal function. These results indicate that the pharmacokinetics of telbivudine were dependent on renal function, especially for subjects with moderate to severe renal impairment or ESRD. Apparent total plasma clearance, renal clearance (CLR), and urinary excretion of telbivudine decreased as renal function deteriorated. A linear relationship was established between CLR and CLCR. In ESRD subjects, a routine 3.5- to 4-h hemodialysis session removed telbivudine from plasma at an extraction ratio of ∼45%, representing a ∼23% reduction in total exposure. These results suggest that while no adjustment of the telbivudine dose appears necessary for subjects with mild renal impairment, dose adjustment is warranted for those with moderate to severe renal impairment or ESRD in order to achieve optimal plasma exposure.

Asymptomatic hypertension-mediated organ damage in patients with or without moderate to severe chronic kidney disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Schiavone ◽  
C Gobbi ◽  
A Ratti ◽  
G Ferrari ◽  
A Villarini ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Organ Damage ◽  
Vascular Damage ◽  
Hypertensive Patients ◽  
Severe Chronic Kidney Disease ◽  
Fundus Oculi

Abstract Introduction Moderate or severe chronic kidney disease (CKD) is regarded as high or very high risk factor in the Systematic COronary Risk Evaluation (SCORE) system, as stated in the ESC guidelines on arterial hypertension. Assessment of cardiovascular (CV) risk should be completed evaluating hypertension-mediated organ damage (HMOD). Purpose The aim of our study was to find out differences in HMOD in patients with or without moderate to severe chronic kidney disease (CKD). Methods We enrolled 80 consecutive non-diabetic hypertensive patients, divided into two groups according to the presence of impaired renal function, evaluated by estimated glomerular filtration rate (eGFR): moderate to severe CKD group (n=26 patients, eGFR &lt;60 mL/min/1.73 m2) and mild CKD - normal renal function group (n=54 patients, eGFR ≥60 mL/min/1.73 m2). A transthoracic echocardiogram was performed to evaluate cardiac HMOD. Small and large vessel damage was assessed by means of non-mydriatic digital fundus oculi examination in order to detect arteriolar narrowing using arteriolar-venular ratio (AVr), applanation tonometry to measure carotid-femoral pulse wave velocity (cfPWV) and carotid ultrasound to quantify intima-media tickness (IMT). Results Moderate to severe CKD patients appeared to be older (mean age 75.54±8.06 vs 63.38±9.62, p=0.001) and showed lower level of total and LDL cholesterol. Both groups showed abnormal values of cfPWV, but these were significantly higher in the presence of moderate to severe CKD (14.12±7.93 m/s vs 10.94±5.81 m/s, p=0.03). Abnormal AVr values were found in patients with higher grade of CKD, with statistically significant differences in the two groups (0.75±0.015 vs 0.81±0.06, p=0.00001). Carotid IMT resulted to be at the upper limit of normality in both groups (0.95±0.15 vs 0.90±0.18, p=0.35). With regard to echocardiography evaluation, left ventricular mass index (LVMi: 105.04±0.4 vs 96.35±1.7, p=0.06) and relative wall thickness (RWT: 0.43±0.02 vs 0.42±0.05, p=0.41) did not differ significantly in the two groups, with a mild trend for LVMi. Both groups showed abnormal diastolic dysfunction on average, but no differences emerged in the presence of more severe renal impairment (deceleration time 281.74±0.37 vs 256.30±0.54, p=0.08; E/A 0.86±0.03 vs 0.95±0.25, p=0.20; E/e' 7.89±2.93 vs 7.60±2.46, p=0.66). Conclusions Our study showed significant differences in HMOD in presence of moderate to severe renal impairment. Moderate to severe CKD seemed to be associated to vascular damage (hypertensive retinopathy and arterial stiffness), while no significant differences in echocardiographic markers of cardiac remodeling were found, suggesting that systemic vascular damage is more closely linked to CKD than cardiac damage. Therefore, the use of fundus oculi examination and PWV should always be considered to properly assess the target organ damage in hypertensive patients with CKD. Funding Acknowledgement Type of funding source: None

scholarly journals Impact of Renal Function on the Pharmacokinetics and Safety of Ceftolozane-Tazobactam

2014 ◽  
Vol 58 (4) ◽  
pp. 2249-2255 ◽  
Author(s):  
Myra Wooley ◽  
Benjamin Miller ◽  
Gopal Krishna ◽  
Ellie Hershberger ◽  
Gurudatt Chandorkar
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Moderate Renal Impairment ◽  
Open Label ◽  
Two Phase ◽  
Time Curve ◽  
Mild Renal Impairment ◽  
Before And After ◽  
Stage Renal Disease

ABSTRACTCeftolozane-tazobactam is a novel antipseudomonal cephalosporin with a β-lactamase inhibitor. We investigated the pharmacokinetics (PK) and safety of ceftolozane-tazobactam in subjects with various degrees of renal function. In two phase I, open-label studies, a single dose of ceftolozane-tazobactam was administered as a 1-h intravenous infusion to 24 subjects with normal, mild, or moderate renal impairment (1,000/500 mg) and six subjects with severe renal impairment (500/250 mg). Six subjects with end-stage renal disease (ESRD) received two doses of ceftolozane-tazobactam (500/250 mg each), pre- and posthemodialysis (post-HD). PK parameters were determined by noncompartmental methods. Plasma exposure to ceftolozane-tazobactam increased as renal function declined with only slightly increased exposures in subjects with mild renal impairment; the median area under the concentration-time curve from time zero to infinity (AUC0-∞) for ceftolozane and tazobactam increased 1.4- and 1.2-fold, respectively. In subjects with moderate renal impairment, the AUC0-∞increased 2.5- and 2.2-fold for ceftolozane and tazobactam, respectively. In subjects with severe renal impairment, the dose-normalized median AUC0-∞for ceftolozane and tazobactam increased 4.4- and 3.8-fold, respectively. In ESRD subjects, ceftolozane and tazobactam concentrations declined rapidly following the start of HD, with approximately 66 and 56% reductions in overall exposure based on the AUC0-∞before and after dialysis. Slight increases in exposure with mild renal impairment do not warrant a dose adjustment; however, subjects with moderate or severe renal impairment and those on HD require a decrease in the dose, a change in the frequency of administration, or both to achieve exposures within the established safety and efficacy margins of ceftolozane-tazobactam. Ceftolozane-tazobactam was well tolerated by all renal impairment groups.

Factor Xa Inhibitors

2006 ◽  
Author(s):  
Richard C. Becker ◽  
Frederick A. Spencer
Keyword(s):  
Renal Impairment ◽  
Early Stage ◽  
Severe Renal Impairment ◽  
Subcutaneous Administration ◽  
Factor Xa ◽  
Drug Clearance ◽  
Factor Xa Inhibitors ◽  
Thromboembolism Prophylaxis ◽  
Mild Renal Impairment ◽  
St Segment Elevation

The importance of factor Xa in the initiation and propagation of coagulation, as well as its pluripotential cellular properties, has been discussed previously. Considered collectively, the effects exhibited by this particular protease make it an attractive target for pharmacologic inhibition. Factor Xa inhibition can be classified and subcategorized as follows: indirect (antithrombin [AT]-dependent), nonselective (e.g., unfractionated heparin); indirect, semi-selective (e.g., low-molecular-weight heparin); indirect, selective (e.g., fondaparinux); and direct, selective (e.g., DX-9065a [in early stage of development]). Oral factor Xa inhibitors are in phase II testing. Fondaparinux (Arixtra) is a synthetic pentasaccharide that requires AT for selective fXa binding (Petitou et al., 1991). Unlike heparin compounds, fondaparinux does not inhibit thrombin directly nor does it interact with platelets (or platelet-derived proteins). After subcutaneous administration in healthy volunteers, fondaparinux was nearly 100% bioavailable, and absorption was rapid (Cmax within 2 hours) (Donat et al., 2002). Clearance is through renal mechanisms with a terminal halflife of 17 ± 3 hours (slightly longer in elderly volunteers). Overall, drug clearance is 25% lower in patients with mild renal impairment (creatinine clearance [CrCl] 50–80 mL/min), approximately 40% lower in patients with moderate renal impairment (CrCl 30–50 mL/min), and 55% lower in patients with severe renal impairment (CrCl <30 mL/min). OASIS-5, the largest trial performed to date in non-ST segment elevation acute coronary syndromes (ACS), randomized 20,078 patients to fondaparinux (2.5 mg subcuaneous once daily) or enoxaparin (1 mg/kg twice daily) for 2 to 8 days. The primary outcome (composite of death, MI, and refractory ischemia on day 9) was 5.9% and 5.8%, respectively. Major bleeding rates were 2.1% and 4.0%, respectively (hazard ratio 0.53; p<.001). By 6-month follow-up, the endpoints of death, death/MI, stroke, and composite of death/MI/stroke were significantly reduced in those receiving fondaparinux. Catheter thrombosis (during PCI) was 3-fold higher in fondaparinux-treated patients compared to those receiving enoxaparin (1.3% vs. 0.5%, respectively) (European Society of Cardiology presentation, September 2005). The clinical use of fondaparinux for venous thromboembolism prophylaxis will be discussed in Chapter 22.

scholarly journals Blood Pressure Variability and Risk for Progression of Cardiovascular and Renal Diseases in Patients with Diabetes Mellitus

2015 ◽  
Vol 22 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Sorin Ioan Zaharie ◽  
Teodora Daniela Maria ◽  
Mirela Zaharie ◽  
Maria Moţa ◽  
Eugen Moţa
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Cardiovascular Events ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Renal Diseases ◽  
Hypertensive Patients ◽  
Patients With Diabetes ◽  
Prognostic Importance

Abstract Accurate measurement of blood pressure (BP) and evaluation of global cardiovascular risk is crucial for diagnosis and treatment of hypertensive patients. When hypertension and diabetes mellitus are associated, the risk for cardiovascular events is bigger than the sum of the components. Beyond systolic and diastolic BP values as targets for antihypertensive treatment, recent guidelines recognize BP variability as an independent predictor for future cardiovascular events. 24 hours ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM) are two methods used in patient day to day life conditions for BP measurements. Increased variability of systolic and/or diastolic BP within one day (“short-term BP variability”) and also over longer periods (“long-term BP variability”) showed by ABPM and/or HBPM is associated with target-organ damage and cardiovascular events. This review is focused on the prognostic importance of BP variability in hypertensive patients with diabetes mellitus.

Abstract 021: Haplotype-Dependent Differential Regulation Of The Human AT1R Gene Is Exacerbated By Age: Effects On Tissue Inflammatory And Redox Milieu

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Anita Rana ◽  
Sudhir Jain ◽  
Nitin Puri ◽  
Brahmaraju Mopidevi ◽  
Meenakshi Kaw ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Transcriptional Regulation ◽  
Gene Expression Regulation ◽  
Artificial Chromosome ◽  
Organ Damage ◽  
Antioxidant Defenses ◽  
Renal Diseases ◽  
R Gene ◽  
Nucleotide Polymorphisms ◽  
Inflammatory Milieu

Age-associated inflammation and redox imbalance underlie etiopathogenesis of cardiovascular-renal diseases, including hypertension and end organ damage. Angiotensin II (Ang II), via activation of the AT1R, contributes to the development and progression of these pathophysiologies. We have identified two haplotype blocks of single nucleotide polymorphisms (SNPs) in the hAT 1 R gene: haplotype II (Hap II: -810A, -713G, -214C, -153G) and I (Hap I: -810T, -713T, -214A, -153A). In clinical studies, Hap I is linked to human hypertension. This study examines haplotype-dependent and age-associated transcriptional regulation of the hAT1R gene. In this regard, we have engineered transgenic (TG) mice with either haplotype of the hAT1R gene using a 166-kb bacterial artificial chromosome. ChIP assay shows increased RNA-Pol II binding (~1.6 fold higher) to the chromatin extracts from renal tissues of adult (4-6 months) male Hap I-TG mice with increased hAT1R expression (~6 fold higher). This was accompanied by higher baseline blood pressure in Hap I-TG mice (Hap I- 129±3 vs. Hap II- 116±4, p<0.05). Next, we examined the effects of age on this haplotype-dependent regulation of the hAT1R. Aged (>18 months), male mice were used for this part of the study. hAT1R expression increases with age in both haplotypes; however, this increase is significantly higher in Hap I-TG mice (3.17±0.5 to 5.5±0.75 fold) as opposed to mice with Hap II (1.1±0.2 to 1.8±0.1 fold). Age-associated change (Δ) in inflammatory and redox markers was significantly (p<0.05) greater in TG mice with Hap I including, IL1 (4.6±0.8 vs. 2.1±0.49 fold), IL6 (4.0±0.69 vs. 2.1±0.2 fold) and NOX1 (8.3±0.4 vs. 2.5±0.6 fold). This is accompanied by age-associated reduction in levels of antioxidant defenses (SOD1: 0.97±0.0 vs. 1.4±0.1 fold; HO1: 0.77±0.1 vs. 1.3±0.2 fold) and pro-survival genes including, NAMPTS (2.1 folds lower in Hap I vs. Hap II) and SIRT1 (1.8 fold lower in Hap I vs. Hap II). Thus, haplotype-dependent transcriptional regulation of the hAT 1 R gene causes increased hAT1R expression and blood pressure, in Hap I TG mice. Importantly, aging exacerbates this differential gene-expression regulation, further increasing hAT1R and promoting a prooxidant/inflammatory milieu in mice with Hap I.

scholarly journals Oral drugs for hypertensive urgencies: systematic review and meta-analysis

2009 ◽  
Vol 127 (6) ◽  
pp. 366-372 ◽  
Author(s):  
Luciana Mendes Souza ◽  
Rachel Riera ◽  
Humberto Saconato ◽  
Adriana Demathé ◽  
Álvaro Nagib Atallah
Keyword(s):  
Blood Pressure ◽  
Angiotensin Converting Enzyme ◽  
Enzyme Inhibitors ◽  
Target Organ Damage ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Organ Damage ◽  
Channel Blockers ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Hypertensive Urgencies

CONTEXT AND OBJECTIVE: Hypertensive urgencies are defined as severe elevations in blood pressure without evidence of acute or progressive target-organ damage. The need for treatment is considered urgent but allows for slow control using oral or sublingual drugs. If the increase in blood pressure is not associated with risk to life or acute target-organ damage, blood pressure control must be implemented slowly over 24 hours. For hypertensive urgencies, it is not known which class of antihypertensive drug provides the best results and there is controversy regarding when to use antihypertensive drugs and which ones to use in these situations. The aim of this review was to assess the effectiveness and safety of oral drugs for hypertensive urgencies. METHODS: This systematic review of the literature was developed at the Brazilian Cochrane Center, and in the Discipline of Emergency Medicine and Evidence-Based Medicine at the Universidade Federal de São Paulo - Escola Paulista de Medicina (Unifesp-EPM), in accordance with the methodology of the Cochrane Collaboration. RESULTS: Sixteen randomized clinical trials including 769 participants were selected. They showed that angiotensin-converting enzyme inhibitors had a superior effect in treating hypertensive urgencies, evaluated among 223 participants. The commonest adverse event for calcium channel blockers were headache (35/206), flushing (17/172) and palpitations (14/189). For angiotensin-converting enzyme inhibitors, the principal side effect was bad taste (25/38). CONCLUSIONS: There is important evidence in favor of the use of angiotensin-converting enzyme inhibitors for treating hypertensive urgencies, compared with calcium channel blockers, considering the better effectiveness and the lower frequency of adverse effects (like headache and flushing).

scholarly journals Effect of Renal Impairment on the Pharmacokinetics and Safety of Rivipansel in Subjects with Renal Impairment and in Healthy Subjects

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1083-1083
Author(s):  
Brinda Tammara ◽  
Kelly Ryan ◽  
Anna Plotka ◽  
Frank E. Shafer ◽  
Hua Wei ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Healthy Subjects ◽  
Severe Renal Impairment ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Mild Renal Impairment ◽  
Plasma And Urine Samples

Abstract Background: Rivipansel is a pan-selectin inhibitor in phase 3 development for treatment of sickle cell disease vaso-occlusive crises. Previous studies have shown almost complete elimination of unchanged drug in urine following an intravenous (IV) infusion. The objective of this study was to evaluate the effect of varying degrees of renal impairment on the pharmacokinetics (PK), safety, and tolerability of rivipansel. Methods: A single 840-mg dose of open-label rivipansel was administered IV over 20 minutes to 7 subjects with mild, 7 with moderate, and 7 with severe renal impairment, and to 7 healthy subjects with normal renal function. Classification of renal impairment groups was based on the Cockroft-Gault estimated glomerular filtration rate (CGeGFR): 60-89 mL/min (mild), 30-59 mL/min (moderate), and <30 mL/min (severe). Normal renal function was CGeGFR ≥90 mL/min. Plasma and urine samples were collected for 96 hours postdose and analyzed by validated LC-MS/MS methods. Pharmacokinetic parameters were estimated using noncompartmental modeling. ANOVA was used to assess the effect of renal impairment on PK parameters. Results: All 28 subjects completed the study. A summary of PK parameters is presented in Table 1. Overall rivipansel exposure was greater in subjects with mild, moderate, and severe renal impairment, with values 1.4×, 2.3×, and 5.5× that of subjects with normal renal function, respectively. Renal clearance decreased with decreasing renal function. Total clearance was lower by 31%, 56%, and 82% in the mild, moderate, and severe renal impairment groups, respectively, compared with the normal renal function group. Five treatment-emergent adverse events (TEAEs) were reported in 3 subjects in the mild renal impairment group, and 3 TEAEs were reported in 2 subjects in the severe renal impairment group. None of the TEAEs reported was considered to be treatment-related. Conclusions: Greater rivipansel exposure and decreased clearance were observed in subjects with renal impairment compared with subjects with normal renal function. A single 840-mg IV dose of rivipansel was well tolerated in all groups. Disclosures Tammara: Pfizer Inc.: Employment. Ryan:Pfizer Inc.: Employment. Plotka:Pfizer Inc.: Employment. Shafer:Pfizer Inc.: Employment. Wei:Pfizer Inc.: Employment. Readett:Pfizer Inc.: Employment. Fang:Pfizer Inc.: Employment. Korth-Bradley:Pfizer Inc.: Employment.

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