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Experimental Physiology Jun 2024Osteocrin (OSTN) is an endogenous protein sharing structural similarities with the natriuretic peptides [NPs; atrial (ANP), B-type (BNP) and C-type (CNP) NP], which are...
Osteocrin (OSTN) is an endogenous protein sharing structural similarities with the natriuretic peptides [NPs; atrial (ANP), B-type (BNP) and C-type (CNP) NP], which are hormones known for their crucial role in maintaining pressure/volume homeostasis. Osteocrin competes with the NPs for binding to the receptor involved in their clearance (NPR-C). In the present study, having identified, for the first time, the major circulating form of OSTN in human and ovine plasma, we examined the integrated haemodynamic, endocrine and renal effects of vehicle-controlled incremental infusions of ovine proOSTN (83-133) and its metabolism in eight conscious normal sheep. Incremental i.v. doses of OSTN produced stepwise increases in circulating concentrations of the peptide, and its metabolic clearance rate was inversely proportional to the dose. Osteocrin increased plasma levels of ANP, BNP and CNP in a dose-dependent manner, together with concentrations of their intracellular second messenger, cGMP. Increases in plasma cGMP were associated with progressive reductions in arterial pressure and central venous pressure. Plasma cAMP, renin and aldosterone were unchanged. Despite significant increases in urinary cGMP levels, OSTN administration was not associated with natriuresis or diuresis in normal sheep. These results support OSTN as an endogenous ligand for NPR-C in regulating plasma concentrations of NPs and associated cGMP-mediated bioactivity. Collectively, our findings support a role for OSTN in maintaining cardiovascular homeostasis.
PubMed: 38890799
DOI: 10.1113/EP091826 -
Biological Research For Nursing Jun 2024Albumin plays a vital role in improving osmotic pressure and hemodynamics. A lower serum albumin level may cause pulmonary congestion and edema and contribute to...
Albumin plays a vital role in improving osmotic pressure and hemodynamics. A lower serum albumin level may cause pulmonary congestion and edema and contribute to myocardial dysfunction, diuresis resistance, and fluid retention in acute heart failure. We hypothesized that AHF patients with normal serum albumin have shorter hospital stays. Using Electronic Medical Records, patients admitted from May 2020 through May 2021 aged >18, ICD-10, and positive Framingham Heart Failure Diagnostic Criteria were included. We excluded patients without albumin records and eGFRs less than 30 mL/min/1.73 m. Prolonged hospitalization was defined as >8 days of hospitalization. During index emergency department visits, patients were symptomatic (New York Heart Association), aged median of 70 years (Interquartile range (IQR) 18), 59% ( = 103) were male, predominantly White (73%, = 128), and had a high Charleston Comorbidity index score [5, IQR (4-7)]. Nearly one-fourth (23%, = 41) of the patients had <3.5 g/dL albumin levels. The median length of hospital stay was eight days (IQR of 11). Comparing differences between lengths of hospital stays (8 vs. >8 days), there was different serum albumin (3.9 0.48 vs. 3.6 0.53, < .001) and left ventricular ejection fraction (45% (range 26-63) versus 30% (range 24-48), = .004). An increased serum albumin decreased prolonged hospitalization (odds ratio (OR), 0.28; 95% confidence interval (CI), 0.14-0.55, = <0.001). Patients in the lower albumin group had higher NT-proBNP (median: 8521 (range 2025-9134) versus 5147 (range 2966-14,795) pg/ml, = .007) and delay in administering intravenous diuretics (391 (167-964) minutes versus 271 (range 157-533) minutes, = .02). Hypoalbuminemia is strongly associated with prolonged hospitalization. Timely and effective diuretic therapy may reduce hospital stay durations, particularly with albumin supplementation.
PubMed: 38869162
DOI: 10.1177/10998004241262530 -
Pediatric Cardiology Jun 2024Pleural effusions and chylothorax are challenging morbidities post-Fontan palliation. We sought to evaluate the efficacy of our Fontan Care Pathway (FCP) in reducing the...
Pleural effusions and chylothorax are challenging morbidities post-Fontan palliation. We sought to evaluate the efficacy of our Fontan Care Pathway (FCP) in reducing the incidence of post-operative chylothorax and Time to Chest Tube Removal (TTCTR), and to determine risk factors associated with longer TTCTR. Between 2016 and 2022 our institutional approach to post-Fontan care fell into three categories: Group 1 (n = 36): no standardized approach; Group 2 (n = 30): a prophylactic chylothorax diet (fat content < 5%); Group 3 (n = 57): the FCP (a chylothorax diet, fluid restriction, supplemental O2 and aggressive diuresis). The incidence of chylothorax and TTCTR was compared between groups. Predictors of TTCTR were analyzed using linear regression modelling, adjusting for covariates. Chylothorax rate decreased in Group 3 compared to Groups 1 and 2 (9% vs. 28% and 33% respectively, p = 0.011), without alteration in TTCTR. Univariate factors associated with median TTCTR included chylothorax (+ 13.7 days, p = 0.001), additional procedures at time of Fontan (+ 2.4 days per procedure p = 0.017), Fontan revision or takedown (+ 11.7 days, p = 0.018) and minor/major complications (+ 5.1, p = 0.01 and + 15.8, p < 0.001, respectively). On multivariable analysis, chylothorax (+ 6.5 days, p = 0.005) and major complications (+ 15.8 days, p = 0.001) were associated with increased TTCTR. When chylothorax was excluded from multivariable analysis, the FCP showed a significant decrease in TTCTR (- 3.3 days, p = 0.034). A bundled therapy approach was associated with reduced laboratory confirmed chylothorax post-Fontan, whereas diet change alone was not. Additional studies in this area, with larger sample sizes are warranted.
PubMed: 38858264
DOI: 10.1007/s00246-024-03494-w -
The Journal of Physiology Jun 2024In early diabetic nephropathy (DN), recent studies have shown that albuminuria stems mostly from alterations in tubular function rather than from glomerular damage....
In early diabetic nephropathy (DN), recent studies have shown that albuminuria stems mostly from alterations in tubular function rather than from glomerular damage. Several factors in DN, including hyperfiltration, hypertrophy and reduced abundance of the albumin receptors megalin and cubilin, affect albumin endocytosis in the proximal tubule (PT). To assess their respective contribution, we developed a model of albumin handling in the rat PT that couples the transport of albumin to that of water and solutes. Our simulations suggest that, under basal conditions, ∼75% of albumin is retrieved in the S1 segment. The model predicts negligible uptake in S3, as observed experimentally. It also accurately predicts the impact of acute hyperglycaemia on urinary albumin excretion. Simulations reproduce observed increases in albumin excretion in early DN by considering the combined effects of increased glomerular filtration rate (GFR), osmotic diuresis, hypertrophy, and megalin and cubilin downregulation, without stipulating changes in glomerular permselectivity. The results indicate that in isolation, glucose-elicited osmotic diuresis and glucose transporter upregulation raise albumin excretion only slightly. Enlargement of PT diameter not only augments uptake via surface area expansion, but also reduces fluid velocity and thus shear stress-induced stimulation of endocytosis. Overall, our model predicts that downregulation of megalin and cubilin and hyperfiltration both contribute significantly to increasing albumin excretion in rats with early-stage diabetes. The results also suggest that acute sodium-glucose cotransporter 2 inhibition lowers albumin excretion only if GFR decreases sufficiently, and that angiotensin II receptor blockers mitigate urinary albumin loss in early DN in large part by upregulating albumin receptor abundance. KEY POINTS: The urinary excretion of albumin is increased in early diabetic nephropathy (DN). It is difficult to experimentally disentangle the multiple factors that affect the renal handling of albumin in DN. We developed a mathematical model of albumin transport in the rat proximal tubule (PT) to examine the impact of elevated plasma glucose, hyperfiltration, PT hypertrophy and reduced abundance of albumin receptors on albumin uptake and excretion in DN. Our model predicts that glucose-elicited osmotic diuresis per se raises albumin excretion only slightly. Conversely, increases in PT diameter and length favour reduced albumin excretion. Our results suggest that downregulation of the receptors megalin and cubilin in PT cells and hyperfiltration both contribute significantly to increasing albumin excretion in DN. The model helps to better understand the mechanisms underlying urinary loss of albumin in early-stage diabetes, and the impact of specific treatments thereupon.
PubMed: 38857419
DOI: 10.1113/JP286245 -
ESC Heart Failure Jun 2024We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring...
AIMS
We aim to identify the most accurate marker for early prediction of poor diuretic response in acute heart failure (AHF) patients with signs of congestion requiring intravenous diuretic treatment.
METHODS
In this single-centre, prospective observational study, AHF patients with signs of congestion received a standardized intravenous furosemide dose (1 mg/kg of body weight; 40 mg in bolus and remaining dose in 2 h continuous infusion). Subsequently, we assessed spot urine composition at 2 h post-administration, comparing it with total urine output at 6 h. Various potential urine markers were analysed for predicting urine output using receiver operating characteristic (ROC) curves and logistic regression models. We investigated guideline-recommended markers, including spot urine sodium (UNa) and its cut-off, and introduced the UNa/UCr (urine creatinine concentration) ratio adjusting UNa for urine dilution.
RESULTS
Out of 111 patients (85% males, 66.4 ± 13.9 years old, NTproBNP 7290 [4493-14 582] pg/ml), there were 18 (16%) with a poor diuretic response (cumulative urine output <600 ml during the first 6 h). The mean 6 h cumulative diuresis in patients with poor and good diuretic response was 406 ± 142 and 2114 ± 1164 ml, respectively, P < 0.005. After an initial evaluation of several potential biomarkers, only UNa, UCr and UNa/UCr were selected as candidates with the highest predictive value. The cut-off for UNa adjusted for urine dilution: UNa/UCr ratio <0.167 mmol/mg × 10 was determined by ROC analysis with the highest area under the curve (95% confidence interval): 0.956 (0.915-0.997), P < 0.001. When compared with the guideline-recommended cut-off (UNa <50 mmol/L as a reference, specificity-0.97; sensitivity-0.83), the odds ratio (OR) for UNa/UCreat to identify a poor diuretic response was 2.5 times greater, regardless of kidney function (OR for estimated glomerular filtration rate in the logistic regression model was 0.978 [0.945-1.013, P = 0.222]).
CONCLUSIONS
The UNa/UCr ratio in a spot urine sample 2 h after intravenous diuretic administration is a simple, highly predictive marker for the identification of AHF patients with poor diuretic response, surpassing guidelines-recommended markers like UNa.
PubMed: 38855817
DOI: 10.1002/ehf2.14883 -
Pituitary Jun 2024Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes...
PURPOSE
Copeptin efficiently predicts post-neurosurgical central diabetes insipidus (CDI) in patients with hypothalamic-pituitary lesions, but its role in characterizing changes in diuresis in individuals with acromegaly undergoing neurosurgery remains unexplored. Our study aimed to assess changes in postoperative fluid balance in acromegaly patients and correlate them with both copeptin and growth hormone (GH) levels.
METHODS
This was a secondary analysis of a prospective study involving 15 acromegaly patients undergoing endoscopic endonasal resection at our University Hospital. Fluid balance was assessed daily, and copeptin and GH levels were evaluated preoperatively (T0), and serially on the morning of the first (T2) and second (T3) postoperative day, with an additional measurement of copeptin one hour post-extubation (T1). Patients with pre-existing or post-neurosurgical CDI were excluded from the analysis.
RESULTS
Most patients (11/15) exhibited a negative fluid balance on the second postoperative day, with 4 developing polyuria. Postoperative GH levels did not differ significantly between polyuric and non-polyuric patients, but GH measured at T2 correlated significantly with negative total balance (r = -0.519, p = 0.048). Copeptin levels at T1 were significantly higher in those who developed polyuria (p = 0.013), and a copeptin value > 39.9 pmol/L at T1 showed excellent ability (Sensitivity 100%, Specificity 90.9%, p < 0.001) in predicting postoperative polyuria. Additionally, polyuric patients exhibited a higher T1 / T3 copeptin ratio (p = 0.013) and a negative fluid balance was associated with the remission of acromegaly at 12 months (p = 0.046).
CONCLUSION
The early assessment of copeptin, in addition to facilitating the rapid identification of individuals at increased risk of developing CDI, could also allow the recognition of subjects with a tendency towards non-pathological polyuria in the postoperative setting, at least in individuals affected by acromegaly.
PubMed: 38847919
DOI: 10.1007/s11102-024-01407-x