Phase I Study of the Administration of Low-dose Perioperative Human Atrial Natriuretic Peptide in Patients With Resectable Colorectal Cancer.

BACKGROUND/AIM: The aim of this single center, non-randomized, open-label, uncontrolled, interventional trial was to determine the feasibility of continuous administration of low-dose human atrial natriuretic peptide (hANP) perioperatively during curative operation for colorectal cancer patients without history of acute heart failure. PATIENTS AND METHODS: The study included three males and two females ranging from 27 to 70 years old. Continuous intravenous injection of hANP solution was started before surgery. The primary endpoint was safety of hANP administration, and the secondary endpoints were perioperative changes in ANP, b-type natriuretic peptide, electrocardiogram (ECG), and lung function. RESULTS: The American Society of Anaesthesiologists physical status was 1, 2, and 3 in three, one, and one patient, respectively. Grade 2 hypotension was observed in one case. No marked changes were observed between pre- and post-operation in all cases. CONCLUSION: Perioperative low-dose hANP administration is feasible and safe in patients with curative colorectal cancer.

Effect of low-dose atrial natriuretic peptide in critically ill patients with acute kidney injury: a retrospective, single-center study with propensity-score matching.

BACKGROUND: Acute kidney injury (AKI) is a major comorbidity in critically ill patients. Low-dose atrial natriuretic peptide (ANP) has been shown to effectively prevent acute kidney injury (AKI), especially in cardiovascular surgery patients. However, its treatment effects for AKI in critically ill patients are unclear. METHODS: This single-center, retrospective, observational study included patients with AKI diagnosed within 7 days after intensive care unit (ICU) admission during the period January 2010 to December 2017. We conducted a propensity-matched analysis to estimate the treatment effect of low-dose carperitide (a recombinant human ANP) on the clinical outcomes. The primary outcome was a composite of death, renal replacement therapy dependence, or no recovery from AKI (defined as an increase of the serum creatinine level to ≥200% of baseline) at hospital discharge. RESULTS: During the study period, 4479 adult patients were admitted to the ICU. We identified 1374 eligible patients with AKI diagnosed within 7 days after ICU admission. Among these patients, 346 (25.2%) were treated with low-dose carperitide, with an average dose of 0.019 µg kg- 1 min- 1. The primary outcome occurred more often in the treatment group than in the control group (29.7% versus 23.4%, respectively; p = 0.022). After propensity score matching, characteristics of 314 patients from each group were well- balanced. Significant difference of the primary outcome, as seen with the full cohort, was no longer obtained; no benefit of carperitide was detected in the matched cohort (29.0% versus 25.2%; p = 0.281). CONCLUSIONS: Low-dose ANP showed no treatment effect in general critically ill patients who developed AKI.

Predictors of responders for low-dose carperitide monotherapy in patients with acute heart failure.

Human atrial natriuretic peptide, known as carperitide, is approved for early relief of dyspnea in patients with acute heart failure (AHF). However, the diuretic effect of carperitide is sometimes insufficient for controlling volume overload. We investigated predictors for the carperitide response in patients with AHF. Forty-seven patients (age: 74 ± 10 years; left ventricular ejection fraction: 42.0% ± 15.9%) with AHF were enrolled and treated with carperitide monotherapy at a dose of 0.0125 µg/kg/min. Patients without sufficient diuresis (< 60 ml/h) or improvement of symptoms by 4 h after carperitide administration, despite increasing to twice the dose of carperitide and adding another agent, were defined as non-responders. Twenty-four (51%) patients were defined as responders and treated with low-dose carperitide monotherapy on the first day. Multiple logistic regression analysis showed that the response to carperitide monotherapy was independently predicted by serum creatinine levels and systolic blood pressure (SBP) on admission. The area under the receiver-operating characteristic curve for predicting the response to carperitide by SBP was 0.808 (95% confidence interval [0.686-0.930], sensitivity: 83.3%, specificity: 65.2%, cutoff value: 135 mmHg). Four (8.5%) patients developed asymptomatic transient hypotension. Worsening renal function occurred within 3 days of admission in three (6.4%) patients who received low-dose carperitide therapy. SBP and serum creatinine levels on admission might be useful for predicting the diuretic response to low-dose carperitide monotherapy in patients with AHF. Initial use of low-dose carperitide therapy does not have adverse effects on renal function.

A multicenter randomized controlled trial of surgery alone or surgery with atrial natriuretic peptide in lung cancer surgery: study protocol for a randomized controlled trial.

BACKGROUND: Postoperative cancer recurrence is a major problem following curative surgery. In a previous retrospective study of lung cancer surgery, we reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduced postoperative recurrence. We demonstrated that ANP inhibited the adhesion of cancer cells to vascular endothelium as a vasoprotective action. The objective of this study is to evaluate the effects of ANP on the incidence of postoperative cancer recurrence in lung cancer surgery. METHODS/DESIGN: The present study is a multicenter, randomized trial with two parallel groups of patients with lung cancer comparing surgery alone and surgery with ANP administration for 3 days during the perioperative period. A total of 500 patients will be enrolled from 10 Japanese institutions. The primary endpoint is 2-year relapse-free survival (RFS). The secondary endpoints are 2-year cancer-specific RFS, 5-year RFS, overall survival, the incidence of postoperative complications, and the completion rate of ANP treatment. DISCUSSION: The principal question addressed in this trial is whether ANP with its vasoprotective action can reduce cancer recurrence following lung cancer surgery. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000018480 . Registered on 31 July 2015.

Low-dose carperitide (α-human A-type natriuretic peptide) alleviates hemoglobin concentration decrease during prolonged oral surgery: a randomized controlled study.

PURPOSE: Surgical injury stimulates the renin-angiotensin-aldosterone system (RAAS) and causes antidiuresis, leading to postoperative oliguria. Carperitide (α-human A-type natriuretic peptide) is a cardiac peptide hormone secreted from the atrium. This peptide hormone enhances diuresis by suppressing the RAAS. In our experience, carperitide alleviates decreased hemoglobin (Hb) concentration during elective surgery. In the current study, we investigated the relationship between low-dose carperitide (0.01 µg/kg/min) and Hb concentration during oral surgery. METHODS: Patients (ASA-PS: I-II, 40-80 years old) undergoing oral maxillofacial surgery (duration of operation >8 h) were enrolled in this study. Patients were divided into two groups: the carperitide group received carperitide at 0.01 µg/kg/min and the control group received normal saline. Body fluid water [including total body water (TBW), extracellular water (ECW), and intracellular water (ICW)], urine volume, and chemical parameters such as Hb concentration, PaO2, and serum electrolytes were evaluated every 2 h. RESULTS: In the carperitide group (n = 15), Hb decreased from 12.6 ± 1.1 to 10.8 ± 1.5 g/dl, while it decreased from 12.6 ± 1.4 to 9.5 ± 1.3 g/dl in the control group (n = 15) (p < 0.05). Urine volume (2557.3 ± 983.5 mL) in the carperitide group was significantly more than it was in the control group (1108.8 ± 586.4 mL; p < 0.001). There were no significant differences in clinical characteristics, body fluid water, PaO2, and serum electrolytes between the two groups. In addition, there were no perioperative clinical respiratory and hemodynamic complications in the groups. CONCLUSION: The Hb concentration in the group administered low-dose carperitide at 0.01 µg/kg/min remained higher than that in the control group during surgery. Administration of low-dose carperitide may therefore reduce the risk of blood transfusion during surgery.

Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury: A multicenter randomized controlled trial.

PURPOSE: To evaluate the effects of atrial natriuretic peptide (ANP) on renal function and medical costs in patients with acute kidney injury (AKI) associated with cardiac surgery. MATERIALS AND METHODS: The Japanese trial for AKI in Post-cardiovascular surgery patients by ANP (JAPAN) was a prospective, multicenter, randomized, double-blind, placebo-controlled study conducted in 11 hospitals in Japan. Acute kidney injury was defined as an increase in serum creatinine of at least 0.3 mg/dL within 48 hours. The patients were randomly assigned to receive ANP (0.02 µg kg-1 min-1) or placebo. The primary end point was a change in renal function. The secondary end points were a need for renal replacement therapy, the lengths of intensive care unit and hospital stays, and medical costs incurred over the 90-day follow-up. RESULTS: Of the 77 randomized patients, 37 were in the ANP group and 40 were in the placebo group. Although ANP significantly (P = .018) increased urine output, it did not significantly improve renal function compared with placebo. There were no significant differences between the groups in the renal replacement therapy rate, the lengths of the intensive care unit and hospital stays, or medical costs. CONCLUSION: Atrial natriuretic peptide infusion did not show a renoprotective effect or cost-saving effect in the treatment of cardiac surgery-associated AKI.

Atrial natriuretic peptide protects against cisplatin-induced granulocytopenia.

PURPOSE: Granulocytopenia is the major toxicity associated with cisplatin treatment. Atrial natriuretic peptide (ANP) is a cardiac hormone used clinically for the treatment of acute heart failure in Japan. ANP exerts a wide range of protective effects on various organs, including the heart, blood vessels, lungs, and kidneys. This study's objective was to investigate the protective effects of ANP on cisplatin-induced granulocytopenia in mice. METHODS: The mice were divided into two groups: cisplatin with vehicle and cisplatin with ANP. ANP (1.5 µg/kg/min via osmotic pump, subcutaneously) or vehicle administration was started 1 day before cisplatin injection until the mice were killed. At 0, 2, 4, 8, and 14 days after cisplatin injection (16 mg/kg, intraperitoneally as a single dose), the white blood cell, red blood cell, and platelet counts were measured in the peripheral blood in both groups. The numbers of total and live cells and colony-forming unit-granulocyte-macrophage (CFU-GM) colonies in the bone marrow of the mice were also examined. In addition, at 0, 0.5, 1, and 2 days after cisplatin injection, serum granulocyte colony-stimulating factor (G-CSF) levels were measured. RESULTS: ANP significantly attenuated the white blood cell count decrease in the peripheral blood 2 and 4 days after cisplatin injection. ANP also attenuated the decrease in the number of live cells and CFU-GM colonies in bone marrow 2, 4, and 8 days after cisplatin injection. ANP significantly increased serum G-CSF levels 1 day after cisplatin injection. CONCLUSIONS: ANP has protective effects in cisplatin-induced granulocytopenia, with increased G-CSF production.

Effects of endothelin family on ANP secretion.

The endothelins (ET) peptide family consists of ET-1, ET-2, ET-3, and sarafotoxin (s6C, a snake venom) and their actions appears to be different among isoforms. The aim of this study was to compare the secretagogue effect of ET-1 on atrial natriuretic peptide (ANP) secretion with ET-3 and evaluate its physiological meaning. Isolated nonbeating atria from male Sprague-Dawley rats were used to evaluate stretch-activated ANP secretion in response to ET-1, ET-2, ET-3, and s6C. Changes in mean blood pressure (MAP) were measured during acute injection of ET-1 and ET-3 with and without natriuretic peptide receptor-A antagonist (A71915) in anesthetized rats. Changes in atrial volume induced by increased atrial pressure from o to 1, 2, 4, or 6cm H2O caused proportional increases in mechanically-stimulated extracellular fluid (ECF) translocation and stretch-activated ANP secretion. ET-1 (10nM) augmented basal and stretch-activated ANP secretion in terms of ECF translocation, which was blocked by the pretreatment with ETA receptor antagonist (BQ123, 1µM) but not by ETB receptor antagonist (BQ788, 1µM). ETA receptor antagonist itself suppressed stretch-activated ANP secretion. As compared to ET-1- induced ANP secretion (3.2-fold by 10nM), the secretagogue effects of ANP secretion by ET-2 was similar (2.8-fold by 10nM) and ET-3 and s6C were less potent (1.7-fold and 1.5-fold by 100nM, respectively). Acute injection of ET-1 or ET-3 increased mean blood pressure (MAP), which was augmented in the presence of natriuretic peptide receptor-A antagonist. Therefore, we suggest that the order of secretagogue effect of ET family on ANP secretion was ET-1≥ET-2>>ET-3>s6C and ET-1-induced ANP secretion negatively regulates the pressor effect of ET-1.

Efficacy of Carperitide in Hemodialysis Patients Undergoing Cardiac Surgery.

PURPOSE: Recently, performance of cardiac surgery in hemodialysis patients has increased, but the mortality rate is high. METHODS: We retrospectively examined the early and long-term outcomes in 128 dialysis patients who underwent cardiac surgery with or without carperitide infusion and were followed for 2 years. Sixty-three patients received carperitide infusion during surgery and 65 patients did not. RESULTS: The hospital mortality rate was 1.6% in the carperitide group and 12.3% in the non-carperitide group, being significantly lower in the carperitide group. The 2-year actuarial survival rate was 90.5% ± 3.7% in the carperitide group, and 76.9% ± 5.2% in the non-carperitide group, while the major adverse cardiovascular and cerebrovascular events (MACCE)-free rate at 2 years postoperatively was 90.5% ± 3.7% in the carperitide group and 67.7% ± 5.8% in the non-carperitide group. CONCLUSIONS: These findings suggest that carperitide improves the early postoperative outcome in dialysis patients undergoing cardiac surgery, as has already been demonstrated in non-dialysis patients. An early postoperative cardioprotective effect of carperitide and improvement of renal function in oliguric patients might have contributed to this outcome. However, this was a retrospective study, so a prospective investigation is required to demonstrate the mechanisms involved. In addition, further evaluation of the long-term results would be desirable.

Reversible Cardiomyopathy After Epirubicin Administration.

Anthracycline-containing chemotherapy can cause irreversible and progressive left ventricular dysfunction. Epirubicin, which is widely used for breast cancer chemotherapy, is an anthracycline that has less cardiac toxicity than doxorubicin. The present report describes the case of a 70-year-old woman with breast cancer who developed severe congestive heart failure and severe cardiac dysfunction at 6 weeks from epirubicin final administration. Left ventricular function gradually improved after intensive treatment for heart failure and recovered completely within 2 months. To the best of our knowledge, this is the first report to describe epirubicin-induced subacute reversible cardiotoxicity.

Cardiovascular and renal effect of CNAAC: An innovatively designed natriuretic peptide.

Natriuretic peptides (NPs) have natriuretic, diuretic and vasodilator effects. An innovative natriuretic peptide analogue called CNAAC (a new chimera peptide combining the C-terminus and ring of ANP with the N-terminus of CNP) was designed to determine whether it has any cardiovascular and renal effect. Abdominal aorta of rats were isolated and vascular ring perfusion was employed to compare the vasodilator effect and cGMP excretion effect of CNAAC with natural NPs. Urine volume and urine cGMP levels after intravenous injection of CNAAC and natural NPs were determined. Hemodynamic methods were employed to assess the effect of CNAAC and natural NPs on MAP. CNAAC relaxed abdominal aorta in a dose-dependent manner and was independent of endothelium. The vasodilating effect of CNAAC was significantly attenuated in the presence of NPR-A antibody, GC inhibitor, and KATP inhibitor and was abolished by PKG inhibitor. Abdominal aortic cGMP production increased after incubation with NPs. Urine volume, plasma cGMP, and urine cGMP increased and MAP decreased dramatically after intravenous injection of CNAAC. CNAAC has a potent vasodilating effect, probably by activating K(+) channels via NPR-A/sGC/cGMP pathway. Exogenous administration of CNAAC elicits diuretic and hypotensive effects.

Carperitide and atrial fibrillation after coronary bypass grafting: the Nihon University working group study of low-dose HANP infusion therapy during cardiac surgery trial for postoperative atrial fibrillation.

BACKGROUND: Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. METHODS AND RESULTS: A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group (P<0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid-binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of ß-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. CONCLUSIONS: -Perioperative carperitide infusion reduced the occurrence of postoperative atrial fibrillation. Accordingly, carperitide could be a useful option for preventing postoperative atrial fibrillation. CLINICAL TRIAL REGISTRATION: -URL: http://www.umin.ac.jp. Unique Identifier: UMIN000003958.

Effects of continuous infusion of low-dose human atrial natriuretic peptide (hANP) on the lungs during cardiac surgery.

OBJECTIVE: The objective of this study was to determine the effects of a continuous infusion of low-dose hANP on the lungs during cardiac surgery in patients under cardiopulmonary bypass (CPB). METHODS: We analyzed 30 consecutive cases of cardiac surgery performed at our hospital from 2007-2008. The patients were divided into a group that received hANP (hANP group) or a group that received saline and no hANP (N-hANP group). We measured various parameters before and after surgery using a PiCCO monitor. RESULT: There were no differences in the preoperative characteristics between the groups, although urine volume during the operation was significantly greater in the hANP group. After surgery, there were no significant differences between the groups in cardiac output index (CI), global enddiastolic volume index (GEDVI), intrathoracic blood volume index (ITBI), pulmonary blood volume index (PBI), extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI), total protein, and creatine. In contrast, interleukin-6 (IL-6) and renin were significantly lower, and albumin was significantly higher in the hANP group. CONCLUSION: We found that low-dose hANP during open cardiac surgery inhibited the secretion and plasma activity of IL-6 and renin. Although there were no differences in lung circulatory parameters such as the amount of fluid in the pulmonary blood vessels between the two groups, we believe that the strong diuretic effect of hANP reduced third-space fluid retention caused by CPB.

Atrial natriuretic peptide protects against cisplatin-induced acute kidney injury.

PURPOSE: Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide variety of malignancies. Acute kidney injury (AKI) is the major toxicity associated with cisplatin and sometimes necessitates a reduction in dose or discontinuation of treatment. Atrial natriuretic peptide (ANP) is secreted by the heart and exerts a wide range of renoprotective effects, including anti-inflammatory activity. The objective of this study was to investigate the protective effects of ANP on cisplatin-induced AKI in mice. METHODS: Mice were randomly divided into three groups: control, cisplatin (20 mg/kg, intraperitoneal)/vehicle treatment, and cisplatin/ANP (1.5 µg/kg/min via osmotic-pump, subcutaneous) treatment. At 72 h after cisplatin injection, serum blood urea nitrogen and creatinine, urine albumin/creatinine, and renal expression of mRNAs encoding tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and transforming growth factor (TGF)-ß were measured using real-time polymerase chain reaction. Histological changes were also evaluated. RESULTS: ANP treatment significantly attenuated cisplatin-induced increases in serum blood urea nitrogen and creatinine, urine albumin/creatinine, and renal expression of IL-1ß, IL-6, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 mRNAs. Cisplatin-induced renal dysfunction and renal tubular necrosis were thus attenuated by ANP treatment. CONCLUSIONS: Our results indicate that ANP exhibits a protective effect against cisplatin-induced AKI in mice. ANP may thus be of value in prophylactic strategies aimed at mitigating the adverse effects associated with chemotherapy agents, including cisplatin.

Subcutaneous pharmacokinetics of the cardiac hormone vessel dilator.

Vessel dilator, a hormone synthesized in the heart, eliminates 71% of human small-cell lung cancers and 67% of human breast cancers growing in mice when given subcutaneously (s.c.) via osmotic pumps. The pharmacokinetics of s.c. administered vessel dilator have not been evaluated previously. In the present study, the pharmacokinetics of vessel dilator following s.c. bolus (ScB) or 3 h s.c. infusion (ScI) were compared with those following i.v. bolus (IvB) administration in male Fischer 344 rats. The half-life (t½ ) of vessel dilator after ScI, IvB and ScB was 54, 43 and 30 min, respectively. The tmax for vessel dilator after IvB, ScB and ScI administration was 1.5, 23 and 156 min, respectively, whereas the corresponding Cmax values were 3749, 887 and 471 ng/L (normalized against the dose used for ScB and IvB). The area under the curve (AUC0-∞ ) for vessel dilator was 1166, 880 and 1652 ng h/mL (normalized) following IvB, ScB and ScI administration, respectively. The volume of distribution for vessel dilator was 2.38, 0.92 and 1.08 L following IvB, ScB and SCI administration, respectively; corresponding clearance values were 1.69, 1.50 and 0.78 L/h, respectively. Plasma concentrations of vessel dilator after each of the three methods of administration mirrored their predicted concentration-time profiles. We conclude that vessel dilator administered via ScI has a significantly greater AUC and t½ and slowed clearance compared with IvB or ScB administration (P < 0.001), suggesting that s.c. infusion is the preferred method of administration, based on pharmacokinetics, to treat cancers.

Pharmacological strategies for the prevention of acute kidney injury following cardiac surgery: an overview of systematic reviews.

CONTEXT: Post cardiac surgery acute kidney injury (AKI) is common, poorly understood and associated with a significant increase in morbidity and mortality. OBJECTIVES: An overview of systematic reviews that have evaluated pharmacological agents for the prevention of AKI post cardiac surgery. DATA SOURCES: We searched electronic databases (PubMed and the Cochrane Database of Systematic Reviews) from inception to January 2014. STUDY SELECTION: Systematic reviews of randomized controlled trials that have evaluated pharmacological agents for the prevention of AKI in adult patients undergoing cardiac surgery. DATA ANALYSIS: Numbers needed to treat (NNT) or harm (NNH) were calculated from pooled events given in each meta-analysis. Primary outcome measures were defined as (i) mortality, (ii) need for renal replacement therapy (RRT), and (iii) acute kidney injury. RESULTS: Data from 7 systematic reviews evaluating 6 different pharmacological renoprotective agents were included. Dopamine, fenoldopam and N-acetylcysteine did not demonstrate any benefit in terms of mortality, need for RRT or incidence of AKI. Atrial natriuretic peptide reduced the need for RRT (NNT = 22 (95% CI: 13 to 73) and brain natriuretic peptide reduced the incidence of AKI (NNT = 11 (95% CI: 6 to 32), although both agents did not demonstrate any effect on mortality. Loop diuretics demonstrated increased incidence of AKI (NNH = 8 (95% CI: 5 to 15). CONCLUSION: There is a paucity of effective renoprotective agents that can be used in adult cardiac surgical patients. There is an urgent need to develop novel renoprotective strategies.

Reduction in the incidence of acute kidney injury after aortic arch surgery with low-dose atrial natriuretic peptide: a randomised controlled trial.

BACKGROUND: Acute kidney injury (AKI) after surgery is associated with an increased risk of adverse events and death. Atrial natriuretic peptide (ANP) dilates the preglomerular renal arteries and inhibits the renin-angiotensin axis. A low-dose ANP infusion increases glomerular filtration rate after cardiovascular surgery, but it is not known whether it reduces the incidence of AKI or the mortality rate. OBJECTIVE: To evaluate whether an intravenous ANP infusion prevents AKI in patients undergoing aortic arch surgery requiring hypothermic circulatory arrest. DESIGN: A randomised controlled study. SETTING: Operating room and intensive care unit at Kawasaki Saiwai Hospital, Kanagawa, Japan. PATIENTS: Forty-two patients with normal preoperative renal function undergoing elective repair of an aortic arch aneurysm. INTERVENTION: Patients were assigned randomly to receive a fixed dose of ANP (0.0125 µg (-1) kg(-1)  min) or placebo. The infusion was started after induction of anaesthesia and continued for 24  h postoperatively. MAIN OUTCOME MEASURES: The primary end-point was the incidence of AKI within 48 h after surgery. RESULTS: AKI developed in 30% of patients who received ANP compared with 73% of patients who received placebo (P = 0.014). Intraoperative urine output was almost 1 l greater in patients who received ANP (1865 ±â€Š1299 versus 991 ±â€Š480  ml in the control group, P = 0.005). However, there were no differences in mean arterial pressure or number of episodes of hypotension between the groups. Length of hospital and intensive care stays were not significantly different, nor was there a difference in 30-day mortality. No patients required haemodialysis or continuous renal replacement therapy. CONCLUSION: We found that an intravenous infusion of ANP at 0.0125  µg  kg(-1)  min(-1) is an effective intervention for reducing the incidence of postoperative AKI, and appears to afford a degree of renal protection during and after cardiovascular surgery. TRIAL REGISTRATION: Kawasaki ANP trial, UMIN Clinical Trials Registry ID: UMIN000011650.

Early results of human atrial natriuretic peptide infusion in non-dialysis patients with chronic kidney disease undergoing isolated coronary artery bypass grafting: the NU-HIT trial for CKD-II.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for cardiac surgery. In the most recently reported NU-HIT trial for CKD with CKD patients underwent coronary artery bypass grafting (CABG) as subjects, carperitide was reported to be effective in terms of renal function. In the present study, a subanalysis was performed on patients registered in the NU-HIT trial for CKD from the standpoint of renin-angiotensin system, natriuresis and renal function. METHODS: 303 patients with CKD who underwent isolated CABG were divided into a group that received carperitide infusion and another group without carperitide. The renin activity, angiotensin-II, aldosterone, urine-sodium, urine- creatinine, fractional sodium excretion, renal failure index, and BNP levels. RESULTS: There were significant lower in hANP group than the placebo group, in angiotensin-II at one day postoperatively, and in aldosterone from 0 day to one month postoperatively. FENa was significantly lower in the hANP group at 3 day and one week postoperatively. CONCLUSIONS: In on pump isolated CABG patients with CKD, carperitide showed a potent natriuretic action and inhibited the renin-angiotensin system, suggesting that it prevented deterioration of postoperative renal function. Our findings raise new possibilities for the perioperative and postoperative management of patients undergoing surgery with cardiopulmonary bypass.

[Perioperative respiratory and circulatory management for chronic kidney disease].

To avoid perioperative cardiac complications and deterioration of renal function in chronic kidney disease (CKD), anesthesiologists are required to manage respiration and circulation properly. Three mechanisms are considered to worsen renal function during inappropriate mechanical ventilation; first, hypercapnia or hypoxemia, second, unstable systemic hemodynamic, and third, systemic inflammatory mediators derived from pulmonary biotrauma. Many circulatory problems are present in CKD patients, for example, hypertension, cardiac hypertrophy, cardiomyopathy, ischemic heart disease, arterial sclerotic valve disease, salt and water retention etc. Blood pressure in CKD patients should be controlled properly before surgery. Renal blood flow and renal perfusion pressure should be maintained by aggressive fluid therapy to avoid perioperative acute kidney injury (AKI) on CKD, while cardiac congestion should also be avoided. Perioerative renal protective effects of human atrial natriuretic peptide (hANP) on CKD still needs further investigation. Appropriate hemodynamic monitoring, including direct arterial pressure, left ventricular preload, intravascular volume and cardiac output could be helpful for anesthesiologists to manage CKD patients safely. In the area of CKD and anesthesia, there is lack of evidence in respiratory and circulatory strategies. Prospective studies in these aspects are required in the future.

[Planning of cardiothoracic surgery for chronic kidney disease patients].

Chronic renal failure (CRF) is related to cardiac diseases. Cardiac surgery is also related to postoperative acute kidney injury (AKI). It means heart and kidney have close relationship. We analyzed recent published data to understand how to manage CRF patients undergoing cardiovascular surgeries. We compared endovascular surgery and open procedure for aortic aneurysm, especially about contrast media-related renal damage, On or Off CABG or PCI for ischemic heart disease. We also discussed the relation between cardiopulmonary bypass and AKI and the risk factors causing AKI after CPB. Finally, we discussed prevention and treatment options of CPB related AKI, including furosemide, hANP mannitol, and statin. Published evidence in this area is still insufficient, but many studies are still carried out focusing on postoperative AKI. In the future we may be able to find the best answer for managing CRF patients undergoing cardiovascular surgeries.