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Pharmacological interventions for the prevention of renal injury in surgical patients: a systematic literature review and meta-analysis.
Pathak, S, Olivieri, G, Mohamed, W, Abbasciano, R, Roman, M, Tomassini, S, Lai, F, Wozniak, M, Murphy, GJ
British journal of anaesthesia. 2021;(1):131-138
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Abstract
BACKGROUND The aim of this systematic review was to summarise the results of randomised controlled trials (RCTs) that have evaluated pharmacological interventions for renoprotection in people undergoing surgery. METHODS Searches were conducted to update a previous review using the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to August 23, 2019. RCTs evaluating the use of pharmacological interventions for renal protection in the perioperative period were included. The co-primary outcome measures were 30-day mortality and acute kidney injury (AKI). Pooled effect estimates were expressed as risk ratios (RRs) (95% confidence intervals). RESULTS We included 228 trials enrolling 56 047 patients. Twenty-three trials were considered to be at low risk of bias across all domains. Atrial natriuretic peptides (14 trials; n=2207) reduced 30-day mortality (RR: 0.63 [0.41, 0.97]) and AKI events (RR: 0.43 [0.33, 0.56]) without heterogeneity. These effects were consistent across cardiac surgery and vascular surgery subgroups, and in sensitivity analyses restricted to studies at low risk of bias. Inodilators (13 trials; n=2941) reduced mortality (RR: 0.71 [0.53, 0.94]) and AKI events (RR: 0.65 [0.50, 0.85]) in the primary analysis and in cardiac surgery cohorts. Vasopressors (4 trials; n=1047) reduced AKI (RR: 0.56 [0.36, 0.86]). Nitric oxide donors, alpha-2-agonists, and calcium channel blockers reduced AKI in primary analyses, but not after exclusion of studies at risk of bias. Overall, assessment of the certainty of the effect estimates was low. CONCLUSIONS There are multiple effective pharmacological renoprotective interventions for people undergoing surgery.
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First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension.
Chen, HH, Wan, SH, Iyer, SR, Cannone, V, Sangaralingham, SJ, Nuetel, J, Burnett, JC
Hypertension (Dallas, Tex. : 1979). 2021;(6):1859-1867
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Abstract
[Figure: see text].
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Intensive Lifestyle Intervention Increases Plasma Midregional Proatrial Natriuretic Peptide Concentrations in Overweight Children.
Thomsen, CF, Goharian, TS, Larsen, KT, Goetze, JP, Andersen, LB, Jeppesen, JL
Journal of the American Heart Association. 2021;(13):e020676
Abstract
Background Overweight adults have low circulating concentrations of ANP (atrial natriuretic peptide) and proANP fragments. We tested the hypothesis that an intensive lifestyle intervention with an intended weight loss would increase plasma concentrations of a proANP fragment in overweight children. Methods and Results We measured MR-proANP (midregional proANP) concentrations in plasma from overweight children who participated in the OOIS (Odense Overweight Intervention Study). OOIS randomized 115 overweight children (11-13 years, 55% girls) to an intensive day-camp intervention arm with increased physical activity and healthy diet or to a less intensive standard intervention arm for 6 weeks. We used linear mixed-effects modeling for repeated measures to estimate the difference in the mean change with 95% CIs in fasting plasma MR-proANP concentrations between the 2 arms, and we used partial least squares regression analysis to identify candidate mediators. Differences in weight, fitness, and metabolic factors were also analyzed. At baseline, fasting plasma MR-proANP concentrations were (median [interquartile range]) 35.0 pmol/L (26.8-42.0) in the day-camp intervention arm and 37.2 pmol/L (31.7-44.7) in standard intervention arm participants, respectively. After 6 weeks intervention, children in the day-camp intervention arm had increased their MR-proANP (5.4 pmol/L [0.8-10.0], P=0.022) and their fitness (2.33 mL O2/min per kg [0.52-4.14], P=0.012) and they had deceased their body mass index (-2.12 kg/m2 [-2.59 to -1.65], P<0.001) as compared with children in standard intervention arm. In the partial least squares analysis, decreases in fasting insulin and in estimated insulin resistance were associated with the observed increase in MR-proANP concentrations. Conclusions An intensive lifestyle intervention increases plasma MR-proANP among overweight children. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01574352.
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The plasma levels of atrial natriuretic peptide and brain natriuretic peptide in type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor.
Feng, X, Gu, Q, Gao, G, Yuan, L, Li, Q, Zhang, Y
Annales d'endocrinologie. 2020;(5):476-481
Abstract
PURPOSE The aim of this study was to determine the levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) after treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitor or dipeptidyl peptidase-4 (DPP4) inhibitor in patients with type-2 diabetes inadequately controlled by insulin, and to determine whether variation in ANP levels can explain favorable cardiovascular outcome. METHODS We enrolled 56 patients, aged 18-80years, with type-2 diabetes inadequately controlled by insulin: i.e., HbA1c level 7.5-10.5% despite at least 8weeks' injectable insulin at a stable mean dose of 20-150IU daily, with or without no more than two oral antidiabetic agents. FINDINGS The 56 patients were randomized between 3 treatment groups: SGLT2 inhibitor (n=18), DPP4 inhibitor (n=19) and placebo (n=19). Patients who received SGLT2 inhibitor or DPP4 inhibitor treatment all showed significantly lower HbA1c levels, fasting blood glucose (FBG) levels and systolic blood pressure at 24weeks than controls. SGLT2 inhibitor treatment decreased ANP levels, BNP levels, systolic blood pressure and weight compared with placebo. Compared to those receiving DPP4 inhibitor, patients receiving SGLT2 inhibitor showed lower HbA1c levels (7.01 vs. 7.58%; P=0.03), ANP levels (28.41 vs. 43.03 pg/mL; P=0.00) and weight (66.14 vs. 71.76 kg; P=0.04) at 24weeks after adjusting for baseline values. The SGLT2 inhibitor group showed higher sodium concentrations than the placebo and DPP4 inhibitor groups (145.89 vs. 143.89 and 144.79 mmol/L, respectively; P=0.00 and P=0.04) at 24 weeks. ANP and BNP levels did not significantly correlate with HbA1c and blood glucose levels. IMPLICATIONS These results indicated that SGLT2 inhibitors may be superior to DPP4 inhibitors in reducing risk of cardiovascular disease in diabetic patients. The major study limitation was the small number of patients per group, which should be enlarged in further research.
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The central blood volume as measured by thoracic electrical impedance and plasma proANP is not compromised by donation of 900 mL of blood in men.
Gybel-Brask, M, Nordsborg, NB, Goetze, JP, Johansson, PI, Secher, NH, Bejder, J
Transfusion medicine (Oxford, England). 2020;(6):450-455
Abstract
OBJECTIVES To evaluate whether the donation of 900 mL of blood reduces the central blood volume (CBV) assessed by thoracic electrical impedance (TI) and plasma pro-atrial natriuretic peptide (proANP). BACKGROUND Donation of 450 mL of blood carries a 1% risk of a vasovagal reaction. Withdrawal of 900 mL of blood decreases cardiac output; however, the effect on CBV remains unknown. METHODS/MATERIALS A randomised, single-blinded, placebo-controlled, crossover design was used, where 21 healthy semi-recumbent men donated 2 × 450 mL blood or were sham-phlebotomised. Changes in CBV were estimated by proANP and TI at 1.5 (TI1.5 ) and 100 (TI100 ) kHz, reflecting extracellular volume and (regional) total body water, respectively, and the index value (IDX; 1/T1.5 -1/TI100 ) was used to estimate changes in intracellular (red cell) volume. Systolic, diastolic and mean arterial blood pressure; heart rate; stroke volume; cardiac output; and systemic vascular resistance were monitored. After completion of the study, 1000 mL of isotonic saline was infused. RESULTS Changes (mean% ± SD) in TI1.5 , TI100 and IDX were similar after 450 mL (-0.2 ± 1.6%, 0.0 ± 1.1%, -0.4 ± 10.1%) and 900 mL (0.1 ± 1.6%, 0.2 ± 1.5% and -2.0 ± 15.8%) of blood donation compared to after a sham donation of 450 mL (-0.9 ± 1.2%, -0.5 ± 1.5% and -0.1 ± 6.1%) and 900 mL (-1.2 ± 1.5%, -0.6 ± 1.3% and 0.5 ± 9.9%). In addition, changes in plasma proANP were similar after 450 and 900 mL of blood donation (-0.8 ± 6.7% and -7.6 ± 7.9%) as after sham donations (1.3 ± 7.3% and -4.5 ± 5.6%). Monitoring haemodynamic variables revealed that stroke volume decreased after the donation of 900 mL of blood (-12 ± 12 mL) compared to sham donations. CONCLUSION During a 900-mL blood loss in semi-recumbent men, CBV measured by TI and plasma proANP is not affected.
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Chronic heart failure as a state of reduced effectiveness of the natriuretic peptide system: implications for therapy.
Díez, J
European journal of heart failure. 2017;(2):167-176
Abstract
Natriuretic peptides (NPs) promote diuresis, natriuresis and vasodilation in early chronic heart failure (CHF), countering renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) overstimulation. Despite dramatic increases in circulating NP concentrations as CHF progresses, their effects become blunted. Increases in diuresis, natriuresis, and vasodilation after administration of exogenous atrial (ANP) or brain (BNP) natriuretic peptides are attenuated in patients with advanced CHF compared with controls. Several major factors may account for the reduced effectiveness of the natriuretic peptide system (NPS) in CHF. First, there is reduced availability of active forms of NPs, namely BNP. Second, target organ responsiveness becomes diminished. Third, the counter-regulatory hormones of the RAAS and SNS, and endothelin-1 become over-activated. Therefore, pharmacological approaches to enhance the functional effectiveness of the NPS in CHF have been explored in recent years. In terms of clinical outcomes, studies of synthetic BNP, or of neprilysin inhibitors alone or associated with an angiotensin converting enzyme inhibitor, have been controversial for several reasons. Recently, however, encouraging results have been obtained with the angiotensin receptor neprilysin inhibitor sacubitril/valsartan. The available data show that treatment with sacubitril/valsartan is associated with increased levels of NPs and their intracellular mediator cyclic guanosine monophosphate, suggesting improved functional effectiveness of the NPS, in addition to beneficial effects on mortality and morbidity outcomes. Therefore, combined targeting of the NPS and RAAS with sacubitril/valsartan emerges as the current optimal approach for redressing the neurohormonal imbalance in CHF.
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Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial.
Skov, J, Pedersen, M, Holst, JJ, Madsen, B, Goetze, JP, Rittig, S, Jonassen, T, Frøkiaer, J, Dejgaard, A, Christiansen, JS
Diabetes, obesity & metabolism. 2016;(6):581-9
Abstract
AIMS: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes. METHODS The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included (51) Cr-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation. RESULTS Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2) ] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines. CONCLUSIONS Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.
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Analysis of the gene polymorphism of aldosterone synthase (CYP11B2) and atrial natriuretic peptide (ANP) in women with preeclampsia.
Bogacz, A, Bartkowiak-Wieczorek, J, Procyk, D, Seremak-Mrozikiewicz, A, Majchrzycki, M, Dziekan, K, Bienert, A, Czerny, B
European journal of obstetrics, gynecology, and reproductive biology. 2016;:11-5
Abstract
OBJECTIVE Preeclampsia (PE) is a major cause of mortality of mothers, fetuses and newborns around the world. The etiology of preeclampsia has not yet been clarified, but many studies indicate a multifactorial basis of PE. Aldosterone synthase (CYP11B2) is responsible for synthesis of aldosterone responsible for regulating blood pressure. Similarly, natriuretic peptide (ANP) regulates blood pressure through a variety of mechanisms affecting the sodium concentration and the amount of extracellular fluid. Currently, attention is paid to the role of the polymorphisms in the expression level of these genes. The aim of the study was to determine the frequencies of genotypes and alleles for polymorphisms of -344C>T CYP11B2 gene and 2238T>C ANP gene in women with preeclampsia and healthy pregnant women from the Caucasian population. STUDY DESIGN The study included a group of 165 pregnant women (59 women with preeclampsia and 109 healthy pregnant women). DNA was extracted from peripheral blood. Determination of the polymorphism of -344C>T CYP11B2 gene and 2238T>C ANP gene was performed by PCR-RFLP method. RESULTS The results showed that the frequencies of the TC and CC genotypes of 2238T>C polymorphism in ANP gene were significantly higher in patients with PE compared to control group. For -344C>T polymorphism of CYP11B2 gene, the frequency of TT genotype was significantly higher in patients with hypertension than in controls (32.2% vs. 23.58%). CONCLUSIONS Our findings showed that gene polymorphism of CYP11B2 (-344C>T) and ANP (2238T>C) may be associated with developing PE during pregnancy.
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ANP system activity predicts variability of fat mass reduction and insulin sensitivity during weight loss.
Brachs, M, Wiegand, S, Leupelt, V, Ernert, A, Kintscher, U, Jumpertz von Schwarzenberg, R, Decker, AM, Bobbert, T, Hübner, N, Chen, W, et al
Metabolism: clinical and experimental. 2016;(6):935-43
Abstract
INTRODUCTION In weight loss trials, a considerable inter-individual variability in reduction of fat mass and changes of insulin resistance is observed, even under standardized study conditions. The underlying mechanisms are not well understood. Given the metabolic properties of the atrial natriuretic peptide (ANP) system, we hypothesized that ANP signaling might be involved in this phenomenon by changes of ANP secretion or receptor balance. Therefore, we investigated the impact of systemic, adipose and myocellular ANP system on metabolic and anthropometric improvements during weight loss. METHODS We comprehensively investigated 143 subjects (31 male, 112 female) before and after a 3 month-standardized weight loss program. The time course of BMI, fat mass, insulin sensitivity, circulating mid-regional proANP (MR-proANP) levels as well as adipose and myocellular natriuretic receptor A (NPR-A) and C (NPR-C) mRNA expression were investigated. RESULTS BMI decreased by -12.6±3.7%. This was accompanied by a remarkable decrease of adipose NPR-C expression (1005.0±488.4 vs. 556.7±465.6; p<0.001) as well as a tendency towards increased adipose NPR-A expression (4644.7±946.8 vs. 4877.6±869.8; p=0.051). Weight loss induced changes in NPR-C (ΔNPR-C) was linked to relative reduction of total fat mass (ΔFM) (r=0.281; p<0.05), reduction of BMI (r=0.277; p<0.01), and increase of free fatty acids (ΔFFA) (r=-0.258; p<0.05). Basal NPR-C expression and weight loss induced ΔNPR-C independently explained 22.7% of ΔFM. In addition, ΔMR-proANP was independently associated with improvement of insulin sensitivity (standardized ß=0.246, p<0.01). DISCUSSION ANP receptor expression predicted the degree of weight loss induced fat mass reduction. Our comprehensive human data support that peripheral ANP signalling is involved in control of adipose tissue plasticity and function during weight loss. (Funded by the Deutsche Forschungsgemeinschaft (KFO281/2), the Berlin Institute of Health (BIH) and the German Centre for Cardiovascular Research (DZHK/BMBF); ClinicalTrials.gov number: NCT00850629).
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Atrial natriuretic factor: is it responsible for hyponatremia and natriuresis in neurosurgery?
Gasparotto, AP, Falcão, AL, Kosour, C, Araújo, S, Cintra, EA, Oliveira, RA, Martins, LC, Dragosavac, D
Revista Brasileira de terapia intensiva. 2016;(2):154-60
Abstract
OBJECTIVE To evaluate the presence of hyponatremia and natriuresis and their association with atrial natriuretic factor in neurosurgery patients. METHODS The study included 30 patients who had been submitted to intracranial tumor resection and cerebral aneurism clipping. Both plasma and urinary sodium and plasma atrial natriuretic factor were measured during the preoperative and postoperative time periods. RESULTS Hyponatremia was present in 63.33% of the patients, particularly on the first postoperative day. Natriuresis was present in 93.33% of the patients, particularly on the second postoperative day. Plasma atrial natriuretic factor was increased in 92.60% of the patients in at least one of the postoperative days; however, there was no statistically significant association between the atrial natriuretic factor and plasma sodium and between the atrial natriuretic factor and urinary sodium. CONCLUSION Hyponatremia and natriuresis were present in most patients after neurosurgery; however, the atrial natriuretic factor cannot be considered to be directly responsible for these alterations in neurosurgery patients. Other natriuretic factors are likely to be involved.