Background and Aims Veverimer, an investigational, novel, orally-administered, non-absorbed polym... more Background and Aims Veverimer, an investigational, novel, orally-administered, non-absorbed polymer that binds gastrointestinal hydrochloric acid and results in an increase in serum bicarbonate, is being developed as a treatment for metabolic acidosis in patients with chronic kidney disease (CKD). Metabolic acidosis is a complication of CKD that has deleterious effects on kidney function, bone (demineralization), and muscle (protein catabolism).1 Albuminuria and metabolic acidosis are independently associated with CKD progression and treatment of each may reduce the risk of kidney failure.2,3 We sought to assess (post-hoc) if albuminuria impacts the ability of veverimer to increase serum bicarbonate level and improve physical functioning. Method TRCA-301E is a multicenter, Phase 3, randomized, blinded, placebo-controlled trial in 196 patients with CKD (eGFR 20 - 40 ml/min/1.73 m2) and metabolic acidosis (serum bicarbonate 12 - 20 mEq/L) who were treated for up to 1 year with veverim...
Background and Aims Lupus nephritis (LN) is a leading cause of morbidity and mortality in systemi... more Background and Aims Lupus nephritis (LN) is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. T cells are believed to play a central role in the pathogenesis of both SLE and LN. CD6 is a co-stimulatory receptor, predominantly expressed on T cells, that binds to activated leukocyte cell adhesion molecule (ALCAM), a ligand expressed on antigen presenting cells and various epithelial and endothelial tissues. The CD6-ALCAM pathway plays an integral role in modulating T cell activation, proliferation, differentiation and trafficking, and is central to immune mediated inflammation. Itolizumab (EQ001) is a humanized IgG1 monoclonal antibody that binds CD6, blocks the interaction between CD6 and ALCAM, and inhibits both the activation and trafficking of T cells. Inhibiting the CD6-ALCAM pathway with itolizumab potentially represents a promising therapeutic approach for the treatment of LN. The aim of this study is to assess the safety and tolerabilit...
Clinical journal of the American Society of Nephrology : CJASN, Jan 4, 2017
Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, ... more Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, muscle, and bone. We tested the efficacy and safety of TRC101, a novel, sodium-free, nonabsorbed hydrochloric acid binder, to increase serum bicarbonate in patients with CKD and metabolic acidosis. One hundred thirty-five patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter, in-unit study (designated the TRCA-101 Study). Patients had a mean baseline eGFR of 35 ml/min per 1.73 m(2), a mean baseline serum bicarbonate of 17.7 mEq/L, and comorbidities, including hypertension (93%), diabetes (70%), and heart failure (21%). Patients ate a controlled diet and were treated for 14 days with placebo or one of four TRC101 dosing regimens (1.5, 3, or 4.5 g twice daily or 6 g once daily). After treatment, patients were discharged and followed for 7-14 days. All TRC101 treatment groups had a mean within-group increase in serum bicarbonate of ≥1.3 mEq/L (P<0.001) ...
Key Points Andexanet reversed apixaban anticoagulation in healthy volunteers within minutes after... more Key Points Andexanet reversed apixaban anticoagulation in healthy volunteers within minutes after administration and for the duration of infusion. Andexanet was generally well tolerated, with no evidence of prothrombotic activity in preclinical models and in healthy subjects.
Direct FXa inhibitors have demonstrated convincing anticoagulant efficacy. However, risk of major... more Direct FXa inhibitors have demonstrated convincing anticoagulant efficacy. However, risk of major bleeding is a concern and no specific antidotes are available for reversal. Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors. We report data from the ANNEXA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;! Phase 3 registration studies in older healthy subjects anticoagulated with apixaban (apix) or rivaroxaban (riva). ANNEXA A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;R were 2 phase 3, randomized, double-blind, placebo-controlled studies of AnXa in healthy subjects age 50 to 75 administered either apixaban or rivaroxaban. Andexanet dose selection was based on phase 2 data and PK/PD modeling, which will be presented. In ANNEXA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;!-A, subjects were treated with apix 5 mg twice daily for 4 days to achieve steady-state concentrations. AnXa (Part 1: 400 mg bolus; Part 2: 400 mg bolus plus 4 mg/min × 2-hour infusion) or placebo was administered on day 4, 3 hours after the last apix dose. In ANNEXA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;!-R, subjects were treated with riva 20 mg every day for 4 days to achieve steady-state concentrations. AnXa (part 1: 800 mg bolus; part 2: 800 mg bolus plus 8 mg/min × 2-hour infusion) or placebo was administered on day 4, 4 hours after the last riva dose. Safety data were collected through day 43. ANNEXA-A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;R enrolled 63 and 82 subjects, respectively. The primary efficacy end point, percent change from baseline in anti-FXa activity to nadir (part 1: between 2 and 5 minutes postbolus; part 2: between 10 minutes before and 5 minutes after the end of the continuous infusion) was met for each part with high statistical significance (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001 vs placebo). Additional efficacy end points, including reduction in plasma free inhibitor concentration and restoration of thrombin generation, were also met. There were no serious adverse events, thrombotic events, or antibodies to FX or FXa. The andexanet PK/PD model accurately predicted the riva and apix anti-FXa activity observed in this study. ANNEXA-A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;R achieved all primary and secondary end points with high statistical significance. AnXa treatment resulted in rapid and sustained reversal of both apix- and riva-induced anticoagulation. A phase 3b/4 confirmatory study (ANNEXA-4) in patients with acute major bleeds is ongoing.
Journal of Nuclear Cardiology Official Publication of the American Society of Nuclear Cardiology, 2008
Patients with reactive airways are at risk for adenosine-induced bronchoconstriction, mediated vi... more Patients with reactive airways are at risk for adenosine-induced bronchoconstriction, mediated via A(2B) and/or A(3) adenosine receptors. To examine the effects of regadenoson, a selective adenosine A(2A) receptor agonist, on airway resistance, we conducted a randomized, double-blind, placebo-controlled crossover trial in asthmatic patients with a positive adenosine monophosphate challenge test. The mean ratio of the forced expiratory volume in 1 second (FEV(1)) at each tested time point relative to the baseline FEV(1) was significantly higher after treatment with regadenoson compared with placebo from 10 to 60 minutes after treatment. One patient had a substantial but asymptomatic FEV(1) reduction (-36.2%) after regadenoson that reversed spontaneously. The most common adverse events with regadenoson were tachycardia (66%), dizziness (53%), headache (45%), and dyspnea (34%). The mean heart rate significantly increased with regadenoson (maximum of +10.4 beats/min) versus placebo. In this pilot safety study of 48 patients with mild or moderate asthma who had bronchial reactivity to adenosine monophosphate, regadenoson was safe and well tolerated.
Renal transplantation using infant donors is associated with significantly less graft survival (G... more Renal transplantation using infant donors is associated with significantly less graft survival (GS) and increased morbidity, especially from very young and small donors. We report our results using specific strategies to determine which age and size donor require en bloc renal transplant reconstruction and associated immunologic protocols for optimization of subsequent GS. Forty cadaveric pediatric en bloc renal transplants were performed. Mean donor age was 23.6+/-18.4 months with subgroups: 2-12 months, n=14; 13-24 months, n=19; and 25-60 months, n=7. Mean donor weight was 14.4+/-4.5 kg. All kidneys were placed in primary, nonsensitized (peak PRA = 7.9+/-5.6%) adult (41.6+/-16 years) recipients. Low weight was preferred (62.4+/-12.8 kg). Mean cold ischemia time was 26.9+/-8.6 hr. Immunosuppression consisted of quadruple immunosuppression (QI) with OKT3 induction. All patients had ureteral stents placed intraoperatively. Mean follow-up was 16.9 months. Actuarial GS at 12, 24, and 33 months were 100% (n=13), 85% (n=20), and 71% (n=7), respectively. Total GS was 35/40=88%. All grafts functioned immediately and there were no technical losses. Biopsy proven rejections occurred in 12 (30%) patients, developing at 16-167 days postoperatively (mean = 50.3 days). Mean serum creatinine at one week and 1, 6, 12, and 18 months were 2.1+/-2.0, 1.5+/-0.8, 1.3+/-0.5, 1.1+/-0.4, and 0.9+/-0.4 mg/dl, respectively. Functional isotopic renography, as well as sonographic monitoring reflected rapid initial and continued growth in these kidneys. Mean BP at 12 and 24 months postoperatively were 145/83+/-18/13 and 122/76+/-20/10 mmHg, respectively, with no significant proteinuria noted. Excellent results with minimal complications utilizing very small and young infant donors can be achieved with QI immunosuppression, and selection of low immune reactive and noncomplicated adult recipients. Additionally, maximal renal dosing by minimizing recipient weight may prevent future hyperfiltration damage.
Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal isch... more Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, fenoldopam rapidly decreases blood pressure, increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of fenoldopam that increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. Randomized, double-blind, placebo-controlled, cross-over study. Clinical research unit. Fourteen normal male volunteers. Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of fenoldopam (0.03, 0.1, and 0.3 Lg/kg/min) on both a high-sodium and a low-sodium diet. Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 + 148 vs. 576 + 85 mUmin at 0.03 iLg/kg/min; 777 + 172 vs. 579 + 80 mUmin at 0.1 tig/kg/min; and 784 + 170 vs. 592 + 165 mUmin at 0.3 ilg/kg/min (p &lt; .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 ILg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 Lgl/kg/ min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group: 62.5 + 6.4 vs. 63.6 + 2.6 mm Hg, respectively, at 0.3 tg/kg/min (p &lt; .05). None of the effects of fenoldopam were altered by volume status. Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive.
Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathoph... more Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathophysiologically linked. A recent study in patients with severe CHF demonstrated that renal plasma flow was inversely correlated with pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction. This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessing cardiac function and volume status in patients with CKD and examines the safety and efficacy of BNP therapy in patients with renal insufficiency and decompensated heart failure.
Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathoph... more Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathophysiologically linked. A recent study in patients with severe CHF demonstrated that renal plasma flow was inversely correlated with pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction. This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessing cardiac function and volume status in patients with CKD and examines the safety and efficacy of BNP therapy in patients with renal insufficiency and decompensated heart failure.
Background and Aims Veverimer, an investigational, novel, orally-administered, non-absorbed polym... more Background and Aims Veverimer, an investigational, novel, orally-administered, non-absorbed polymer that binds gastrointestinal hydrochloric acid and results in an increase in serum bicarbonate, is being developed as a treatment for metabolic acidosis in patients with chronic kidney disease (CKD). Metabolic acidosis is a complication of CKD that has deleterious effects on kidney function, bone (demineralization), and muscle (protein catabolism).1 Albuminuria and metabolic acidosis are independently associated with CKD progression and treatment of each may reduce the risk of kidney failure.2,3 We sought to assess (post-hoc) if albuminuria impacts the ability of veverimer to increase serum bicarbonate level and improve physical functioning. Method TRCA-301E is a multicenter, Phase 3, randomized, blinded, placebo-controlled trial in 196 patients with CKD (eGFR 20 - 40 ml/min/1.73 m2) and metabolic acidosis (serum bicarbonate 12 - 20 mEq/L) who were treated for up to 1 year with veverim...
Background and Aims Lupus nephritis (LN) is a leading cause of morbidity and mortality in systemi... more Background and Aims Lupus nephritis (LN) is a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. T cells are believed to play a central role in the pathogenesis of both SLE and LN. CD6 is a co-stimulatory receptor, predominantly expressed on T cells, that binds to activated leukocyte cell adhesion molecule (ALCAM), a ligand expressed on antigen presenting cells and various epithelial and endothelial tissues. The CD6-ALCAM pathway plays an integral role in modulating T cell activation, proliferation, differentiation and trafficking, and is central to immune mediated inflammation. Itolizumab (EQ001) is a humanized IgG1 monoclonal antibody that binds CD6, blocks the interaction between CD6 and ALCAM, and inhibits both the activation and trafficking of T cells. Inhibiting the CD6-ALCAM pathway with itolizumab potentially represents a promising therapeutic approach for the treatment of LN. The aim of this study is to assess the safety and tolerabilit...
Clinical journal of the American Society of Nephrology : CJASN, Jan 4, 2017
Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, ... more Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, muscle, and bone. We tested the efficacy and safety of TRC101, a novel, sodium-free, nonabsorbed hydrochloric acid binder, to increase serum bicarbonate in patients with CKD and metabolic acidosis. One hundred thirty-five patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter, in-unit study (designated the TRCA-101 Study). Patients had a mean baseline eGFR of 35 ml/min per 1.73 m(2), a mean baseline serum bicarbonate of 17.7 mEq/L, and comorbidities, including hypertension (93%), diabetes (70%), and heart failure (21%). Patients ate a controlled diet and were treated for 14 days with placebo or one of four TRC101 dosing regimens (1.5, 3, or 4.5 g twice daily or 6 g once daily). After treatment, patients were discharged and followed for 7-14 days. All TRC101 treatment groups had a mean within-group increase in serum bicarbonate of ≥1.3 mEq/L (P<0.001) ...
Key Points Andexanet reversed apixaban anticoagulation in healthy volunteers within minutes after... more Key Points Andexanet reversed apixaban anticoagulation in healthy volunteers within minutes after administration and for the duration of infusion. Andexanet was generally well tolerated, with no evidence of prothrombotic activity in preclinical models and in healthy subjects.
Direct FXa inhibitors have demonstrated convincing anticoagulant efficacy. However, risk of major... more Direct FXa inhibitors have demonstrated convincing anticoagulant efficacy. However, risk of major bleeding is a concern and no specific antidotes are available for reversal. Andexanet alfa (AnXa), a recombinant modified FXa, is an investigational specific antidote for FXa inhibitors. We report data from the ANNEXA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;! Phase 3 registration studies in older healthy subjects anticoagulated with apixaban (apix) or rivaroxaban (riva). ANNEXA A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;R were 2 phase 3, randomized, double-blind, placebo-controlled studies of AnXa in healthy subjects age 50 to 75 administered either apixaban or rivaroxaban. Andexanet dose selection was based on phase 2 data and PK/PD modeling, which will be presented. In ANNEXA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;!-A, subjects were treated with apix 5 mg twice daily for 4 days to achieve steady-state concentrations. AnXa (Part 1: 400 mg bolus; Part 2: 400 mg bolus plus 4 mg/min × 2-hour infusion) or placebo was administered on day 4, 3 hours after the last apix dose. In ANNEXA&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;!-R, subjects were treated with riva 20 mg every day for 4 days to achieve steady-state concentrations. AnXa (part 1: 800 mg bolus; part 2: 800 mg bolus plus 8 mg/min × 2-hour infusion) or placebo was administered on day 4, 4 hours after the last riva dose. Safety data were collected through day 43. ANNEXA-A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;R enrolled 63 and 82 subjects, respectively. The primary efficacy end point, percent change from baseline in anti-FXa activity to nadir (part 1: between 2 and 5 minutes postbolus; part 2: between 10 minutes before and 5 minutes after the end of the continuous infusion) was met for each part with high statistical significance (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001 vs placebo). Additional efficacy end points, including reduction in plasma free inhibitor concentration and restoration of thrombin generation, were also met. There were no serious adverse events, thrombotic events, or antibodies to FX or FXa. The andexanet PK/PD model accurately predicted the riva and apix anti-FXa activity observed in this study. ANNEXA-A&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;R achieved all primary and secondary end points with high statistical significance. AnXa treatment resulted in rapid and sustained reversal of both apix- and riva-induced anticoagulation. A phase 3b/4 confirmatory study (ANNEXA-4) in patients with acute major bleeds is ongoing.
Journal of Nuclear Cardiology Official Publication of the American Society of Nuclear Cardiology, 2008
Patients with reactive airways are at risk for adenosine-induced bronchoconstriction, mediated vi... more Patients with reactive airways are at risk for adenosine-induced bronchoconstriction, mediated via A(2B) and/or A(3) adenosine receptors. To examine the effects of regadenoson, a selective adenosine A(2A) receptor agonist, on airway resistance, we conducted a randomized, double-blind, placebo-controlled crossover trial in asthmatic patients with a positive adenosine monophosphate challenge test. The mean ratio of the forced expiratory volume in 1 second (FEV(1)) at each tested time point relative to the baseline FEV(1) was significantly higher after treatment with regadenoson compared with placebo from 10 to 60 minutes after treatment. One patient had a substantial but asymptomatic FEV(1) reduction (-36.2%) after regadenoson that reversed spontaneously. The most common adverse events with regadenoson were tachycardia (66%), dizziness (53%), headache (45%), and dyspnea (34%). The mean heart rate significantly increased with regadenoson (maximum of +10.4 beats/min) versus placebo. In this pilot safety study of 48 patients with mild or moderate asthma who had bronchial reactivity to adenosine monophosphate, regadenoson was safe and well tolerated.
Renal transplantation using infant donors is associated with significantly less graft survival (G... more Renal transplantation using infant donors is associated with significantly less graft survival (GS) and increased morbidity, especially from very young and small donors. We report our results using specific strategies to determine which age and size donor require en bloc renal transplant reconstruction and associated immunologic protocols for optimization of subsequent GS. Forty cadaveric pediatric en bloc renal transplants were performed. Mean donor age was 23.6+/-18.4 months with subgroups: 2-12 months, n=14; 13-24 months, n=19; and 25-60 months, n=7. Mean donor weight was 14.4+/-4.5 kg. All kidneys were placed in primary, nonsensitized (peak PRA = 7.9+/-5.6%) adult (41.6+/-16 years) recipients. Low weight was preferred (62.4+/-12.8 kg). Mean cold ischemia time was 26.9+/-8.6 hr. Immunosuppression consisted of quadruple immunosuppression (QI) with OKT3 induction. All patients had ureteral stents placed intraoperatively. Mean follow-up was 16.9 months. Actuarial GS at 12, 24, and 33 months were 100% (n=13), 85% (n=20), and 71% (n=7), respectively. Total GS was 35/40=88%. All grafts functioned immediately and there were no technical losses. Biopsy proven rejections occurred in 12 (30%) patients, developing at 16-167 days postoperatively (mean = 50.3 days). Mean serum creatinine at one week and 1, 6, 12, and 18 months were 2.1+/-2.0, 1.5+/-0.8, 1.3+/-0.5, 1.1+/-0.4, and 0.9+/-0.4 mg/dl, respectively. Functional isotopic renography, as well as sonographic monitoring reflected rapid initial and continued growth in these kidneys. Mean BP at 12 and 24 months postoperatively were 145/83+/-18/13 and 122/76+/-20/10 mmHg, respectively, with no significant proteinuria noted. Excellent results with minimal complications utilizing very small and young infant donors can be achieved with QI immunosuppression, and selection of low immune reactive and noncomplicated adult recipients. Additionally, maximal renal dosing by minimizing recipient weight may prevent future hyperfiltration damage.
Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal isch... more Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, fenoldopam rapidly decreases blood pressure, increases renal blood flow, and maintains or improves the glomerular filtration rate. We sought to determine a dose of fenoldopam that increases renal blood flow without inducing hypotension in normotensive patients and to explore the role of volume status (sodium replete vs. deplete) in these effects. Randomized, double-blind, placebo-controlled, cross-over study. Clinical research unit. Fourteen normal male volunteers. Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of fenoldopam (0.03, 0.1, and 0.3 Lg/kg/min) on both a high-sodium and a low-sodium diet. Fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 + 148 vs. 576 + 85 mUmin at 0.03 iLg/kg/min; 777 + 172 vs. 579 + 80 mUmin at 0.1 tig/kg/min; and 784 + 170 vs. 592 + 165 mUmin at 0.3 ilg/kg/min (p &lt; .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 ILg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 Lgl/kg/ min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group: 62.5 + 6.4 vs. 63.6 + 2.6 mm Hg, respectively, at 0.3 tg/kg/min (p &lt; .05). None of the effects of fenoldopam were altered by volume status. Fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive.
Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathoph... more Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathophysiologically linked. A recent study in patients with severe CHF demonstrated that renal plasma flow was inversely correlated with pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction. This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessing cardiac function and volume status in patients with CKD and examines the safety and efficacy of BNP therapy in patients with renal insufficiency and decompensated heart failure.
Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathoph... more Chronic kidney disease (CKD) and congestive heart failure (CHF) are epidemiologically and pathophysiologically linked. A recent study in patients with severe CHF demonstrated that renal plasma flow was inversely correlated with pulmonary capillary wedge pressure, right atrial pressure, pulmonary pressure, and right ventricular ejection fraction. This article reviews the utility of B-type natriuretic peptide (BNP) levels in assessing cardiac function and volume status in patients with CKD and examines the safety and efficacy of BNP therapy in patients with renal insufficiency and decompensated heart failure.
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