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European Journal of Heart Failure Feb 2022Insufficient diuretic response frequently occurs in patients admitted for acute heart failure (HF) and is associated with worse clinical outcomes. Recent studies have... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Insufficient diuretic response frequently occurs in patients admitted for acute heart failure (HF) and is associated with worse clinical outcomes. Recent studies have shown that measuring natriuresis early after hospital admission could reliably identify patients with a poor diuretic response during hospitalization who might require enhanced diuretic treatment. This study will test the hypothesis that natriuresis-guided therapy in patients with acute HF improves natriuresis and clinical outcomes.
METHODS
The Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) is a pragmatic, single-centre, randomized, controlled, open-label study, aiming to recruit 310 acute HF patients requiring treatment with intravenous loop diuretics. Patients will be randomized to natriuresis-guided therapy or standard of care. Natriuresis will be determined at set time points after initiation of intravenous loop diuretics, and treatment will be adjusted based on the urinary sodium levels in the natriuresis-guided group using a pre-specified stepwise approach of increasing doses of loop diuretics and the initiation of combination diuretic therapy. The co-primary endpoint is 24-h urinary sodium excretion after start of loop diuretic therapy and a combined endpoint of all-cause mortality or first HF rehospitalization at 6 months. Secondary endpoints include 48- and 72-h sodium excretion, length of hospital stay, and percentage change in N-terminal pro brain natriuretic peptide at 48 and 72 h.
CONCLUSION
The PUSH-AHF study will investigate whether natriuresis-guided therapy, using a pre-specified stepwise diuretic treatment approach, improves natriuresis and clinical outcomes in patients with acute HF.
Topics: Algorithms; Diuretics; Heart Failure; Humans; Natriuresis; Sodium; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 34791756
DOI: 10.1002/ejhf.2385 -
Journal of the American College of... Feb 2021Most acute decompensated heart failure admissions are driven by congestion. However, residual congestion is common and often driven by the lack of reliable tools to...
BACKGROUND
Most acute decompensated heart failure admissions are driven by congestion. However, residual congestion is common and often driven by the lack of reliable tools to titrate diuretic therapy. The authors previously developed a natriuretic response prediction equation (NRPE), which predicts sodium output using a spot urine sample collected 2 h after loop diuretic administration.
OBJECTIVES
The purpose of this study was to validate the NRPE and describe proof-of-concept that the NRPE can be used to guide diuretic therapy.
METHODS
Two cohorts were assembled: 1) the Diagnosing and Targeting Mechanisms of Diuretic Resistance (MDR) cohort was used to validate the NRPE to predict 6-h sodium output after a loop diuretic, which was defined as poor (<50 mmol), suboptimal (<100 mmol), or excellent (>150 mmol); and 2) the Yale Diuretic Pathway (YDP) cohort, which used the NRPE to guide loop diuretic titration via a nurse-driven automated protocol.
RESULTS
Evaluating 638 loop diuretic administrations, the NRPE showed excellent discrimination with areas under the curve ≥0.90 to predict poor, suboptimal, and excellent natriuretic response, and outperformed clinically obtained net fluid loss (p < 0.05 for all cutpoints). In the YDP cohort (n = 161) using the NRPE to direct therapy mean daily urine output (1.8 ± 0.9 l vs. 3.0 ± 0.8 l), net fluid output (-1.1 ± 0.9 l vs. -2.1 ± 0.9 l), and weight loss (-0.3 ± 0.3 kg vs. -2.5 ± 0.3 kg) improved substantially following initiation of the YDP (p < 0.001 for all pre-post comparisons).
CONCLUSIONS
Natriuretic response can be rapidly and accurately predicted by the NRPE, and this information can be used to guide diuretic therapy during acute decompensated heart failure. Additional study of diuresis guided by the NRPE is warranted.
Topics: Aged; Biomarkers; Cohort Studies; Drug Monitoring; Female; Heart Failure; Humans; Male; Middle Aged; Models, Biological; Natriuresis; Proof of Concept Study; Sodium; Sodium Potassium Chloride Symporter Inhibitors; Urinalysis
PubMed: 33573739
DOI: 10.1016/j.jacc.2020.12.022 -
Indian Journal of Nephrology 2023Acute kidney injury represents one of the most severe complications of rhabdomyolysis.
INTRODUCTION
Acute kidney injury represents one of the most severe complications of rhabdomyolysis.
METHODS
We performed a prospective observational study to analyze the etiology, clinical manifestations, laboratory profile, and outcome in patients with biopsy-proven pigment-induced nephropathy between January 2017 and September 2019. History, clinical examination findings, laboratory investigations, and outcomes were recorded.
RESULTS
A total of 26 patients were included. Mean age was 34.81 ± 11.89 years. Mean peak serum creatinine was 6.79 ± 4.07 mg/dL. Median values of Creatine phosphokinase (CPK) and Lactate dehydrogenase (LDH) were 12500 U/L (3187, 17167.50) and 447 U/L (354.50, 908.75), respectively. Of the patients presenting with rhabdomyolysis, 12 patients (46%) had traumatic causes and 14 patients (54%) had nontraumatic causes. Nontraumatic etiology of rhabdomyolysis included seizures (1), wasp sting (1), paraphenylenediamine ingestion (2), rat killer ingestion (2), leptospirosis (2), dehydration (3), acute limb ischemia (1), Gloriosa superba ingestion (1), and prolonged immobilization (1). On renal biopsy, 16 patients had myoglobin cast nephropathy and one had immunoglobulin A deposits in addition to pigment nephropathy. Twenty (76.9%) were initiated on hemodialysis, and two patients (7.6%) were treated with peritoneal dialysis and four patients (15.5%) were treated with forced alkaline diuresis. A total of four patients died (15.4%) due to sepsis/disseminated intravascular coagulation and respiratory failure. At the mean follow-up of 6 months, two patients (7.7%) progressed to chronic kidney disease (CKD).
CONCLUSIONS
Rhabdomyolysis-associated acute kidney injury is an important cause of renal failure requiring renal replacement therapy. In our study, it was more common in males. Traumatic and nontraumatic causes played an equal causative role. Most of the patients recovered from AKI. Forced alkaline diuresis was found useful in nontraumatic rhabdomyolysis AKI.
PubMed: 37234438
DOI: 10.4103/ijn.ijn_247_21 -
Nature Medicine Oct 2023Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute... (Randomized Controlled Trial)
Randomized Controlled Trial
Measurement of natriuresis has been suggested as a reliable, easily obtainable biomarker for assessment of the response to diuretic treatment in patients with acute heart failure (AHF). Here, to assess whether natriuresis-guided diuretic therapy in patients with AHF improves natriuresis and clinical outcomes, we conducted the pragmatic, open-label Pragmatic Urinary Sodium-based algoritHm in Acute Heart Failure trial, in which 310 patients (45% female) with AHF requiring treatment with intravenous loop diuretics were randomly assigned to natriuresis-guided therapy or standard of care (SOC). In the natriuresis-guided arm, natriuresis was determined at set timepoints, prompting treatment intensification if spot urinary sodium levels were <70 mmol l. The dual primary endpoints were 24 h urinary sodium excretion and a combined endpoint of time to all-cause mortality or adjudicated heart failure rehospitalization at 180 days. The first primary endpoint was met, as natriuresis in the natriuresis-guided and SOC arms was 409 ± 178 mmol arm versus 345 ± 202 mmol, respectively (P = 0.0061). However, there were no significant differences between the two arms for the combined endpoint of time to all-cause mortality or first heart failure rehospitalization, which occurred in 46 (31%) and 50 (31%) of patients in the natriuresis-guided and SOC arms, respectively (hazard ratio 0.92 [95% confidence interval 0.62-1.38], P = 0.6980). These findings suggest that natriuresis-guided therapy could be a first step towards personalized treatment of AHF. ClinicalTrials.gov registration: NCT04606927 .
Topics: Female; Humans; Male; Acute Disease; Diuretics; Heart Failure; Natriuresis; Sodium; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 37640861
DOI: 10.1038/s41591-023-02532-z -
European Journal of Heart Failure Nov 2019To investigate the effects of acetazolamide on natriuresis, decongestion, kidney function and neurohumoral activation in acute heart failure (AHF). (Comparative Study)
Comparative Study Randomized Controlled Trial
AIMS
To investigate the effects of acetazolamide on natriuresis, decongestion, kidney function and neurohumoral activation in acute heart failure (AHF).
METHODS AND RESULTS
This prospective, two-centre study included 34 AHF patients on loop diuretics with volume overload. All had a serum sodium concentration < 135 mmol/L and/or serum urea/creatinine ratio > 50 and/or an admission serum creatinine increase of > 0.3 mg/dL compared to baseline. Patients were randomised towards acetazolamide 250-500 mg daily plus bumetanide 1-2 mg bid vs. high-dose loop diuretics (bumetanide bid with daily dose twice the oral maintenance dose). The primary endpoint was natriuresis after 24 h. Natriuresis after 24 h was similar in the combinational treatment vs. loop diuretic only arm (264 ± 126 vs. 234 ± 133 mmol; P = 0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84 ± 46 vs. 52 ± 42 mmol/mg bumetanide; P = 0.048). More patients in the combinational treatment arm had an increase in serum creatinine levels > 0.3 mg/dL (P = 0.046). N-terminal pro-B-type natriuretic peptide reduction and peak neurohumoral activation within 72 h were comparable among treatment arms. There was a non-significant trend towards lower all-cause mortality or heart failure readmissions in the group receiving acetazolamide with low-dose loop diuretics vs. high-dose loop diuretic monotherapy (P = 0.098).
CONCLUSION
Addition of acetazolamide increases the natriuretic response to loop diuretics compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01973335.
Topics: Acetazolamide; Adult; Aged; Bumetanide; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Female; Heart Failure; Humans; Kidney Function Tests; Male; Middle Aged; Natriuresis; Prospective Studies; Risk Factors; Sodium Potassium Chloride Symporter Inhibitors; Survival Analysis
PubMed: 31074184
DOI: 10.1002/ejhf.1478 -
Vnitrni Lekarstvi 2023Nephrotic syndrome (NS) is characterized by high proteinuria (over 3,5g/24 hrs), hypalbuminaemia, general edemas and hypercoagulation. Beside of primary...
Nephrotic syndrome (NS) is characterized by high proteinuria (over 3,5g/24 hrs), hypalbuminaemia, general edemas and hypercoagulation. Beside of primary glomerulonephritides this is found in secundary glomerulopaties eg. diabetes, systemic inflammatory diseases, oncology, damage by drugs and poisoning, by alergy, serious infections and in children from hereditary reasons. The most frequent reason for NS in adults patiens is diabetes and diabetes with nephropathy represents almost 40% of dialysed patiens. From this point of view, there is great interest focusing on gliflozins (SGLT2 inhibitors) with positive nephroprotecive effect. It leads do increasing of glycosuria with concomitant natriuresis and osmotic diuresis. The effect is proportional to glomerulal filtration, but the effect on natriuresis stay in all stages of renal insufficiency.
Topics: Child; Adult; Humans; Nephrotic Syndrome; Multimorbidity; Proteinuria
PubMed: 37468310
DOI: 10.36290/vnl.2023.028 -
Revue Medicale Suisse Feb 2024
Topics: Humans; Natriuresis; Heart Failure
PubMed: 38323775
DOI: 10.53738/REVMED.2024.20.860.327