Diuretic Treatment Research Articles

Potential Role of Natriuretic Response to Furosemide Stress Test During Acute Heart Failure.

Poor natriuresis has been associated with a poorer response to diuretic treatment and worse prognosis in acute heart failure. Recommendations on how and when to measure urinary sodium (UNa) are lacking. We aim to evaluate UNa quantification after a furosemide stress test (FST) capacity to predict appropriate decongestion during acute heart failure hospitalization. Patients underwent an FST on day-1 of admission, and UNa was measured 2 hours after, dividing patients into low or high UNa based on the sample median value. A semiquantitative composite congestive score (CCS; 0-9) and NT pro-BNP (N-terminal pro-B-type natriuretic peptide) quantification were assessed before the FST and at day 5 after the FST. Median UNa after FST in the 65 patients included was 113 (97-122) mmol/L. At day 5, a lower proportion of patients with a low UNa reached a 30% decrease in NT-proBNP levels (21 [66%] for low UNa versus 31 [94%] for high UNa; P=0.005) and an appropriate grade of decongestion (CCS<3) (20 [62%] for low UNa versus 32 [97%] for high UNa; P<0.001). A UNa>83 mmol/L 2 hours after FST had a 96% sensitivity to predict an NT-proBNP reduction ≥30% and 95% to predict a CCS<3 at day 5. Low UNa patients presented a lower cumulative diuresis and weight loss and presented more often with prolonged hospitalization, worsening heart failure, and readmission because of acute heart failure or death at 6 months. Low natriuresis after an FST identified patients at a higher risk of an inadequate diuretic response and an inappropriate decongestion. FST-guided diuretic treatment might help to improve decongestion, shorten hospitalizations, and to reduce adverse outcomes.

Protocolo de tratamiento del paciente con insuficiencia cardíaca aguda en urgencias

Acute decompensated heart failure is one of the most frequent reasons for consultation in the emergency department. Because it can be a life-threatening situation, it is important that effective treatment is implemented in tandem with the diagnostic process. Treatment of congestion is one of the mainstays of its treatment, as it is present in most of these patients. Adequate diuretic treatment will help to improve the symptoms and prognosis of patients with heart failure. Hypoperfusion may develop much less frequently, but worsens mortality and prognosis when present, and therefore should be diagnosed and treated promptly. Other non-pharmacological measures, primarily oxygen therapy in all its modalities, are also key in the treatment of these patients.

MO317DETERMINANTS OF LENGHT OF HOSPITAL STAY (LOS) IN NEPHROTIC SYNDROME PATIENTS

Abstract Background and Aims Generalized edema, non responsive to oral diuretics, is one of the main causes of hospital admission for nephrotic syndrome patients. Although hospital length of stay (LOS) may vary widely, in 2017 the average LOS in acute-care hospitals was lower than 8 days in OECD countries. The aim of the present study was to determine the factors commonly associated with a longer LOS in patients admitted for edema due to nephrotic syndrome in the Nephrology Unit of ICS Maugeri, Pavia, Italy Method In this retrospective study we reviewed the medical records of all patients admitted for nephrotic syndrome between 2012-2020 in the Nephrology Unit of ICS Maugeri. Inclusion criteria were the following: age between 18-85 years of age; severe edema non responsive to oral, low dose diuretics; patients with heart failure, serum creatinine &amp;gt; 3.5 g/dl or on dialysis treatment were excluded from the study. Patients were divided into two groups according to the length of stay: ≤ 7 days or ≥ 8 days. Age, gender, serum protein concentration, creatinine, and hemoglobin; serum cholesterol and tryglicerides, urinary protein excretion rate; types of glomerular disease, weight loss were recorded. Student T tests and one-way Anova were performed to evaluate the differences between the means. Results 60 patients (42 male, 18 female) with a total number of hospital accesses of 93 were enrolled in the study. Mean age was 66.8 ± 13.07 years. Average LOS was 9.02 ± 7.4 days. Protein excretion rate was 6.7 ± 3.6 g/24 hours at the admission and was not statistically changed at discharge. Mean total serum protein and creatinine concentration at the admission were 4.7 ± 0.8 g/dl and 1.8 ± 1.1 mg/dl respectively. Patients with LOS &amp;lt; 7 days were younger (64 ± 11.9 vs 69 ± 13.6 years, p &amp;lt;0.05), had a lower serum creatinine (1.55 ± 0.92 vs 2.08 ± 1.2 mg/dl, p&amp;gt;0.001) and a significantly higher total serum protein concentration (5.02 ± 0.77 vs 4.65 ± 0.76 g/dl, p&amp;lt; 0.001) and haemoglobin (12.6 ± 1.8 vs 11.4 ± 1.8 g/dl, p&amp;lt; 0.05) compared to patients with longer LOS. Proteinuria was not significantly different between the two groups (6.27 ± 3.36 vs 7.1 ± 3.9 g/24 hours, p= NS). While serum cholesterol and tryglicerides were higher in the group of patients with longer LOS, weight loss was similar in the two groups at discharge. Although the difference was not significant, the group with longer hospitalization had a greater number of patients with a diagnosis of focal segmental glomerulosclerosis (FSGS) Conclusion Our results demonstrate that age, total serum protein concentration, serum creatinine, higher lipids and probably the diagnosis of FSGS may affect the hospital length of stay of patients with nephrotic syndrome admitted for severe edema. A more aggressive diuretic treatment may be needed in elderly nephrotic syndrome patients with lower GFR and total serum protein concentration.

Effect of albumin administration on post-operation mortality, duration on ventilator, and hospital stay on patients in cardiac intensive care: An observational study

Purpose: To justify the use of albumin infusion in patients in post-surgery cardiac intensive care unit.&#x0D; Methods: All patients who were hemodynamically stable before the operation and admitted into the surgical intensive care unit following coronary artery bypass, cardiopulmonary bypass, or aortic surgery, had no excessive postoperative bleeding and not on diuretic treatment, were included in the analysis. A total of 1998 patients were divided into two cohorts, viz, the first group was placed on albumin infusion (n = 999) while the second group received normal saline infusion (n = 999). Data were obtained from DICOM files of patients and records of pharmacy. Wilcoxon test or two-tailed paired t-test followed by Tukey post-hoc tests were performed for statistical analysis at 95 % of confidence level.&#x0D; Results: Albumin and normal saline administration did not decrease the duration of mechanical ventilation, incidence of mechanical ventilation, need for blood transfusion, and length of hospital stay (p &gt; 0.05). Albumin infusion decreased the need for fresh frozen plasma transfusion from 85 to 67, reduced mortality (p = 0.0005, q = 3.959), lowered serum lactate level (p &lt; 0.0001, q = 43.853), but increased cardiac index (p &lt; 0.0001, q = 12.192) as well as financial burden (p &lt; 0.0001, q = 95.158) for the patients, compared to normal saline group.&#x0D; Conclusion: In view of the foregoing, it is recommended that the use of restriction of albumin resuscitation in surgical intensive care unit should be restricted in this subset of patients evluated in this study.

Tinnitus Frequency is Higher in Patients with Chronic Heart Failure with Reduced Ejection Fraction and is Closely Related to NT-proBNP Level.

There is not enough information about tinnitus and related parameters in patients with heart failure with reduced ejection fraction (HFrEF). In our study, we aimed to investigate the frequency of tinnitus in HFrEF patients and the clinical parameters associated with this condition. This study included 100 patients with HFrEF and whose medical treatment was arranged according to their disease stage, and 100 control patients without HFrEF with similar age, gender and cardiovascular risk factors. Routine history, physical examinations, echocardiography and laboratory examinations were performed. In addition, a detailed ear examination and tinnitus evaluation were performed in all patients. First of all, the frequency of tinnitus in patients with and without HFrEF was determined. Afterwards, all individuals included in the study were divided into two groups as individuals with and without tinnitus. It was determined that the frequency of tinnitus was higher in patients with HFrEF compared to individuals without HFrEF. (25% and 13%, p = 0.023). It was determined that hypertension and hyperlipidemia were more common in the patient group with tinnitus, the patients were older, and the frequency of use of beta blocker, diuretic or spironolactone treatment was higher (p < 0.05 for each). Serum uric acid and NT-proBNP levels were found to be higher in patients with tinnitus (p < 0.05 for each). Logistic regression analysis was performed with the parameters which were found to be significantly different in patients with tinnitus, and in this analysis, age and NT-proBNP levels were found to be independently associated with the presence of tinnitus (p < 0.001 and p = 0.005). According to this analysis, it was determined that every one year increase of age and every 20pg/mL increase of NTproBNP increased the frequency of tinnitus by 12% and 6.1%, respectively. The frequency of tinnitus increases in patients with HFrEF. Although the increased frequency of tinnitus in these patients is associated with diuretic therapy, increasing age and high NT-proBNP levels are independently associated with the presence of tinnitus in these patients. NT-proBNP may be a follow-up parameter for tinnitus in patients with HFrEF. However, our study needs to be supported by other studies and studies involving more patients.

Diuretic therapy and acute kidney injury in preterm neonates and infants.

Acute kidney injury (AKI) in preterm infants is associated with prolonged hospitalization and high mortality. Diuretic therapy has been used to enhance urine output in preterm infants with AKI. Treatment with diuretics, prescription patterns, and relationship with length of stay (LOS), mechanical ventilation (MV), and mortality in preterm infants who also had AKI have not been fully evaluated. This multicenter retrospective study used the Pediatric Hospital Information System database. We included 2121 preterm infants with AKI diagnosis from 46 hospital Neonatal Intensive Care Units (NICUs) born <37 weeks gestational age (GA). Treatment with diuretics, practice patterns across 46 NICUs in the USA, and associated outcomes including LOS, MV, and mortality were evaluated. Seventy-six percent of infants received at least one dose of diuretics (median treatment 18 days). Diuretic prescription varied significantly across hospitals and ranged from 42 to 96%. Diuretics were used more frequently in infants with younger GA and smaller birth weight. Infants with older GA who received diuretics at or before 28 days postnatally had worse survival even after adjusting for known confounders. Preterm infants with AKI diagnosis were frequently treated with diuretics. Moreover, infants with younger GA and smaller birth weight were more likely to receive diuretics. Worse survival in infants with older GA who received diuretics could be the result of more underlying severe illness in these infants and not the cause of more severe illness. Prospective studies are needed to best determine patient safety and outcomes with diuretic treatment in preterm infants with AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

The Road to Better Management in Resistant Hypertension-Diagnostic and Therapeutic Insights.

Resistant hypertension (R-HTN) implies a higher mortality and morbidity compared to non-R-HTN due to increased cardiovascular risk and associated adverse outcomes—greater risk of developing chronic kidney disease, heart failure, stroke and myocardial infarction. R-HTN is considered when failing to lower blood pressure below 140/90 mmHg despite adequate lifestyle measures and optimal treatment with at least three medications, including a diuretic, and usually a blocker of the renin-angiotensin system and a calcium channel blocker, at maximally tolerated doses. Hereby, we discuss the diagnostic and therapeutic approach to a better management of R-HTN. Excluding pseudoresistance, secondary hypertension, white-coat hypertension and medication non-adherence is an important step when diagnosing R-HTN. Most recently different phenotypes associated to R-HTN have been described, specifically refractory and controlled R-HTN and masked uncontrolled hypertension. Optimizing the three-drug regimen, including the diuretic treatment, adding a mineralocorticoid receptor antagonist as the fourth drug, a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when failing to achieve target blood pressure values are current recommendations regarding the correct management of R-HTN.

Plasma Renin Activity after Diuretic Treatment in Patients with Stable Heart Failure: With Special Reference to its Association with Electrolyte Chloride

A recent study reported an intimate association between urinary chloride (Cl) and plasma renin activity (PRA) in acute heart failure (HF) status, reflecting normal functioning of the ‘tubulo-glomerular feedback’ mechanism. Whether the ‘tubuloglomerular feedback’ mechanism functions normally in stable HF status, however, is unclear. This study examined whether the ‘tubulo-glomerular feedback’ mechanism functions normally under resolution of worsening HF after decongestive therapy. Data from 26 patients with acute HF and its recovery after decongestive therapy were analyzed. Clinical tests included measurement of peripheral blood tests, serum and spot urinary electrolytes, plasma neurohormones, and fractional urinary excretions of electrolytes. In a total of 26 patients, PRA increased after acute HF treatment (from 1.64±2.0 to 5.48±6.1 ng/ mL/h, p=0.002). Changes in the serum logPRA and urinary Cl concentration from worsening to its recovery tended to be inversely correlated (R2 =0.12, p=0.085) and logPRA and the serum Cl concentration at recovery were inversely correlated (R2 =0.23, p=0.01). When divided into 2 groups (n=13 in each) according to the median PRA, the group with greater PRA changes showed a larger decrease in the urinary Cl concentration (from 110±44 to 72.8±38, p=0.03). The group with higher PRA at recovery showed a lower serum Cl concentration than the group with lower PRA at recovery (102±6.5 vs 107±4.2 mEq/L, p=0.04). In conclusion, the association between PRA and the serum/urinary Cl concentration is blunted in stable HF under-decongestive therapy, possibly due to the physiologic status under full cardiovascular medication compared with that in acute HF status.

Osteitis Fibrosa Cystica A Rare Presentation of Primary Hyperparathyroidism

Introduction: Osteitis fibrosa cystica (OFC) is the most serious bone involvement of primary hyperparathyroidism (PHPT), it is characterized by subperiosteal resorption, lytic lesions and the appearance of brown tumors; this is why, in some cases, this condition can easily be mistaken for a malignant neoplasm. Its prevalence in developed countries is only 5%.Clinical Case: We present a 58-year-old woman, with no relevant personal history, who came to the emergency room with pain in her right shoulder after an accidental fall on the bus. The humerus radiograph shows a pathological fracture of the right humerus, with significant osteopenia. In the emergency analysis, serum Calcium 13.3 mg / d), Ionic Calcium 7.03 mg / dL, Phosphorus 2.4 mg / dL, Alkaline Phosphatase 248 U / L and normal kidney function stand out. With a diagnosis of severe hypercalcemia, treatment was started in the emergency room with serum therapy (1000 ml of 0.9% physiological saline in 4 hours) and intravenous diuretic treatment (furosemide 40mg) with a decrease in calcemia to 12.8mg / dL. Later, she was admitted to the Internal Medicine hospital ward to perform a differential diagnosis of hypercalcemia secondary to a primary tumor, Multiple Myeloma or Primary Hyperparathyroidism. The study findings are: Calcium metabolism: PTH 660 pg / ml (12 - 65), 25 Hydroxyvitamin D: 14.00. Thyroid ultrasound: Posterocaudal to right thyroid lobe, an area of ​​echogenicity slightly lower than the thyroid is identified, of dimensions not estimated by endothoracic component, which could correspond to a parathyroid adenoma. Body CT: Neck: Heterogeneous nodule dependent on the posterior region of the right thyroid nodule with endothoracic extension. Skeleton: Lytic lesions with a tumor aspect in the humerus, right scapula and bilateral seventh rib and right pubic branch. Skull: Diffuse increase in bone density of the calvaria, showing multiple punctate lytic lesions with a permeative appearance. Bone densitometry: Femur neck: - <1.5, Lumbar spine: - <3.0 With the diagnosis of PHPT causing osteitis fibrosa cystica, surgical intervention was decided. Under general anesthesia, a selective right approach was performed, finding a large parathyroid adenoma weighing 17 grams. PTH fell to 36 pg / ml after surgery. At 9 months after surgery, the patient presented calcium levels of 9 mg / dl and PTH 146 pg / ml with clear radiological improvement.Discussion: Osteitis fibrosa cystica is rare in our environment, it is often confused with other neoplasms. After parathyroidectomy, patients with PHPT have a marked and sustained recovery from OFC, although in some cases this recovery can only be achieved after several years. We consider this case of interest, since it illustrates the importance of evaluating the study of phospho-calcium metabolism and parathyroid function in all patients with bone lesions to rule out Primary Hyperparathyroidism with OFC.

Nalfurafine Combined with Standard‐of‐Care Diuretics Increases Diuresis and Limits Electrolyte Losses

Kappa opioid receptor (KOR) agonists produce a variety of beneficial effects, including a water diuresis, but their translation into the clinic has been hindered by psychotomimetic adverse effects. Nalfurafine is a novel, G protein biased KOR agonist that has been shown to produce several desired effects of KOR agonists, while avoiding central adverse effects. To more fully explore the clinical potential of this drug, this study examined the cardiovascular and renal responses to i.v. nalfurafine alone or in combination with the clinically used diuretics: furosemide, hydrochlorothiazide (HCTZ), and amiloride. Following chronic instrumentation, conscious Sprague-Dawley rats were continuously infused i.v. with isotonic saline; after stabilization, rats were administered i.v. bolus nalfurafine, diuretics, diuretics combined with nalfurafine, or vehicle, and mean arterial pressure (MAP), heart rate (HR), and urine output were recorded for 90 min. IV nalfurafine produced a marked diuresis, antinatriuresis, antikaliuresis, and decrease in MAP without eliciting a change in HR. As compared to diuretic treatment alone, co-administration of nalfurafine notably increased the total urine output to furosemide and HCTZ while reducing the amount of sodium and potassium excreted. When combined with amiloride, nalfurafine also increased the diuresis and decreased the amount of sodium excreted. In contrast to these diuretics administered alone, MAP was reduced with nalfurafine combination therapy. Together, these findings demonstrate that nalfurafine has a clinically important action to augment the diuresis to classical diuretics without causing excessive loss of electrolytes characteristic of these drugs. Combination therapy of nalfurafine with loop/thiazide diuretics may offer a new approach to treat several cardiovascular conditions such as hypertension, volume overloaded states, and electrolyte abnormalities.

Miejsce diuretyków pętlowych w leczeniu ostrej niewydolności serca

Loop diuretics are used as first-line medications in patients with heart failure as they result in symptomatic improvement related to relieving organ congestion. The recommendations regarding the use of loop diuretics are mostly based on expert opinion, without preference of specific drugs. Thus, the choice of optimal diuretic treatment strategy in acute heart failure requires knowledge about differences in the characteristics of loop diuretics available in Poland, furosemide and torasemide. Non-renal pleiotropic effects of torasemide should be also borne in mind. Clinically significant differences in the pharmacokinetics and biological effects of furosemide and torasemide have been reflected in multiple research studies and meta-analyses published in the recent several years. These studies provided consistent evidence for the good safety profile of torasemide, and its superior efficacy in regard to the improvement of exercise tolerance and reduced readmissions due to heart failure compared to furosemide. The effect of torasemide on mortality reduction in patients with heart failure, seen in some studies, requires further evaluation.

Patent ductus arteriosus in preterm newborns: A tertiary hospital experience

IntroductionPatent ductus arteriosus (PDA) in preterm infants has been associated with increased mortality and comorbidities. This study aimed to characterize the population of preterm infants diagnosed with PDA and to identify predictive factors of response to medical treatment of PDA. MethodsAn eight-year retrospective observational study was carried out, which included all preterm infants with a gestational age (GA) between 23 and 32 weeks diagnosed with PDA, admitted to the Neonatal Unit of the CHUSJ. Univariate comparative analysis was performed, and models for predicting the effectiveness of PDA treatment with ibuprofen were explored by multivariate logistic regression analysis. Results115 cases were included and 34 were excluded, with a final sample of 81 preterm infants with PDA. The univariate analysis revealed significant differences in the closure efficacy via medical treatment with ibuprofen in several variables, and a multivariate logistic regression model was obtained (discriminative capacity 72.2%, sensitivity 98.1%, specificity 57.1%), taking into account the effect of GA, type of delivery, need for diuretics treatment and platelet transfusion. ConclusionThis study enabled the population of preterm infants diagnosed with PDA to be characterized and the identification of a predictive model that can help predict the efficacy of medical treatment and thus contribute to optimizing the medical approach to the non-responders.

Prevalence of hypokalemia in older persons: results from the PolSenior national survey

Key summary pointsAimTo examine what is the prevalence of hypokalemia in the older population.FindingsThe prevalence of hypokalemia was similar in older persons and younger ones. Hypokalemia is more often found in patients with arterial hypertension treated with diuretics. Oral supplementation of potassium in these patients did not prevent hypokalemia.MessageIn older persons, diuretic treatment is the most important cause of hypokalemia. Prevention of hypokalemia with the use of oral potassium supplementation is in this population insufficient.

Worsening Heart Failure Episodes Outside a Hospital Setting in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial

ObjectivesThis study sought to evaluate the frequency and prognostic implications of urgent heart failure (HF) visits in a large global clinical trial of HF with preserved ejection fraction (HFpEF). BackgroundEpisodes of worsening HF managed without hospitalization are common and prognostically important in HF with reduced ejection fraction (EF). The significance of these ambulatory worsening HF events in HFpEF is uncertain. MethodsPARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) randomly assigned 4,796 patients with HFpEF (≥45%) to treatment with sacubitril/valsartan vs. valsartan with a primary composite endpoint of total HF hospitalizations and cardiovascular death. Urgent ambulatory HF visits requiring intravenous diuretic treatment were prospectively collected and adjudicated by a blinded committee. We examined the effect of study treatment on a prespecified expanded composite of cardiovascular death and worsening HF events (including HF hospitalizations and urgent HF visits) and the effect of each type of HF event on subsequent mortality. ResultsOf 884 first worsening HF events, 66 (7.5%) were urgent HF visits. Patients whose first episode of worsening HF event was an urgent visit had similar age, comorbidities, baseline N-terminal prohormone of B-type natriuretic peptide, and Meta-Analysis Global Group in Chronic Heart Failure risk scores to those in whom the first HF event was a hospitalization (all comparisons p > 0.05). Regardless of the treatment setting, patients with a first episode of worsening HF had higher rates of subsequent death (19.2 per 100 patient-years; 95% confidence interval [CI]: 16.9 to 21.8 for HF hospitalization and 10.1 per 100 patients-years; 95% CI: 5.4 to 18.7 for urgent HF visit) compared with those who did not experience worsening HF (death rate 4.0 per 100 patient-years; 95% CI: 3.6 to 4.4). Including total urgent HF visits in the composite study endpoint added 95 total events and would have shortened the trial duration needed for event accrual. The addition of urgent HF visits in a prespecified composite endpoint reinforced the treatment efficacy of sacubitril/valsartan compared with valsartan (rate ratio 0.86; 95% CI: 0.75 to 0.99; p = 0.040). ConclusionsLike HF hospitalizations, worsening HF events treated in the ambulatory setting are prognostically important in HFpEF. Inclusion of these events in the composite primary endpoint underscores the benefit of sacubitril/valsartan compared with valsartan in PARAGON-HF. (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)

Independent predictors for 90-day readmission of emergency department patients admitted with sepsis: a prospective cohort study

BackgroundThe primary objective of our study was to examine predictors for readmission in a prospective cohort of sepsis patients admitted to an emergency department (ED) and identified by the new Sepsis-3 criteria.MethodA single-center observational population-based cohort study among all adult (≥18 years) patients with sepsis admitted to the emergency department of Slagelse Hospital during 1.10.2017–31.03.2018. Sepsis was defined as an increase in the sequential organ failure assessment (SOFA) score of ≥2. The primary outcome was 90-day readmission. We followed patients from the date of discharge from the index admission until the end of the follow-up period or until the time of readmission to hospital, emigration or death, whichever came first. We used competing-risks regression to estimate adjusted subhazard ratios (aSHRs) with 95% confidence intervals (CI) for covariates in the regression models.ResultsA total of 2110 patients were admitted with infections, whereas 714 (33.8%) suffered sepsis. A total of 52 patients had died during admission and were excluded leaving 662 patients (44.1% female) with a median age of 74.8 (interquartile range: 66.0–84.2) years for further analysis. A total of 237 (35,8%; 95% CI 32.1–39.6) patients were readmitted within 90 days, and 54(8.2%) had died after discharge without being readmitted. We found that a history of malignant disease (aSHR 1,61; 1.16–2.23), if previously admitted with sepsis within 1 year before the index admission (aSHR; 1.41; 1.08–1.84), and treatment with diuretics (aSHR 1.51; 1.17–1.94) were independent predictors for readmission. aSHR (1.49, 1.13–1.96) for diuretic treatment was almost unchanged after exclusion of patients with heart failure, while aSHR (1.47, 0.96–2.25) for malignant disease was slightly attenuated after exclusion of patients with metastatic tumors.ConclusionsMore than one third of patients admitted with sepsis, and discharged alive, were readmitted within 90 days. A history of malignant disease, if previously admitted with sepsis, and diuretic treatment were independent predictors for 90-day readmission.

IN-HOSPITAL DIURETIC USE IS ASSOCIATED WITH WORSE OUTCOME IN PATIENTS WITH COVID-19

Objective: Background: Hypertension is associated with increased risk of severe COVID-19 and increased mortality. The knowledge about the impact of blood pressure lowering medications on outcomes is still incomplete: whilst studies about renin-angiotensin-aldosterone system inhibitors did not show association with increased mortality, less is known about the impact of other antihypertensive classes. Diuretics, in particular, are frequently used in patients with hypertension thus we aimed to investigate the association between diuretics and mortality in a cohort of COVID-19 patients hospitalized in two referral centers in the Lombardy region (Istituto Auxologico Italiano and Humanitas Research Hospital). Methods: Data of confirmed COVID-19 patients, with information available about drug treatment and outcomes, were pooled together. Socio-demographic, clinical features, and medications pre and during hospitalization were retrieved, patients were classified according to the use of diuretics before and/or during hospitalization. The effect of diuretic use before and during hospitalization on death was estimated by means of a multiple Poisson regression model with robust variance and reported as Relative Risk (RR) and 95% confidence interval (95% CI). Design and method: From the pooled sample of 637 patients, a final sample of 502 patients with complete data was analyzed (mean age 67 years, 67% males, 54% patients with hypertension). Among hypertensive patients, 64% were not treated with diuretics either pre- or during hospitalization (Reference group), 15% had diuretic treatment only during hospitalization (Group A), 9% only pre-hospitalization (Group B) and 12% both pre- and during hospitalization (Group C). After adjusting for confounders (age, sex, respiratory rate at admission, number of comorbidities, number of other drugs taken during hospitalization, orotracheal intubation), use of diuretics only during hospitalization was significantly associated with mortality (Figure 1). Conclusion: Our data show an association between diuretic use only during hospitalization and worse outcome in patients with COVID-19. Such association needs to be further investigated in order to possibly improve outcomes in patients admitted for COVID-19 Figure 1: Relative Risks and 95% confidence intervals of patients treated with diuretics only during hospitalization (Group A), only during pre-hospitalization (Group B) and during both pre- and hospitalization (Group C). The subgroup of patients not treated with diuretics neither pre- nor during hospitalization was taken as the reference group.

SEX, METABOLIC AND PHARMACOLOGICAL MODULATORS OF SODIUM HANDLING IN POPULATION WITH PREVAILING SODIUM INTAKE

Objective: Renal sodium handling is associated with sex, ethnic, central adiposity and hypertensive treatment. Design and method: In a sample of caucasian population without diuretic treatment (351 subjects) with prevailing sodium consumption (153,6 mmol/d), we studied the associations between renal sodium reabsorption in proximal (FPRNa) and distal (FDRNa) tubules assessed by endogenous lithium clearance, daily sodium intake measured by 24-h excretion of sodium (UNaV) and measures of obesity in the context of chronic treatment with ACEI or ARB. Results: In the entire population in linear regression model, we found a relation between sex and FPRNa (β = 1.06 ± 0.30, P = 0.0005), with higher sodium reabsorption in proximal tubules in men. In subjects with FPRNa below the median value, we displayed a significant reverse relation between FPRNa and ACEI/ARB treatment (β = -0.40 ± 0.18, P = 0.03) with no relation for BMI (P = 0.42). Contrary, in subjects with FPRNa above the median value, a significant positive relation between FPRNa and BMI (β = 0.10 ± 0.03, P = 0.004) was revealed, with no relation for ACEI/ARB treatment (P = 0.55). For FDRNa (P &gt; 0.10) and UNaV (P &gt; 0.06) we found no relation for ACE/ARB treatment in entire population and after divided by median. Conclusions: We found that sex, obesity and chronic treatment with ACEI/ARB influence sodium reabsorption in renal proximal tubules. This may impact both on the research and clinical practice.

DIVERSIFIED RENAL TUBULAR EPITHELIAL REMODELING AND WATER BALANCE IN GITELMAN'S SYNDROME AND THIAZIDE-TREATED HYPERTENSIVE PATIENTS

Objective: Mutations leading to loss of function of NaCl cotransporter (NCC) in the distal convoluted tubule is the basis defect of Gitelman's Syndrome (GS), which is clinically characterized by hypokaliemic metabolic alkalosis, hypomagnesemia, hypocalciuria and normal or low blood pressure with increased renin activity and high aldosterone levels. NCC is the target of thiazide diuretics (TZ) and clinical and laboratory findings of GS patients resemble those on chronic thiazide diuretics treatment. From a physiopathological perspective, this similarity in term of site of defect or site of action (NCC in distal convoluted tubule) for GS or TZ-treated patients respectively, should not alter their urine-concentrating or diluting ability. We aimed to study water balance pathways in these 2 clinical settings. Design and method: We investigated two groups of patients: 1) GS (n = 5, age range 21–43, 2 females and 3 males, mean concentration of blood potassium 2.9 mmol/L, bicarbonate 34 mmol/L and magnesium 1.2 mg/dl, normotensive) and 2) TZ hypertensive patients (n = 11, age range 26–48, 4 female and 7 males, blood pressure normalized with chronic thiazide type or like diuretics including hydrochlorothiazide, chlortalidone and indapamide maintained for at least 2 months) to evaluate their water balance pathway by determining plasma and urine osmolarity and to assess through urine aquaporin 2 (AQP2)/creatinine ratio their sensitivity to antidiuretic hormone. These measurements were repeated three times in the same patients. Results: Four out of five GS patients showed a urinary AQP2/creatinine ratio lower than TZ-treated patients (mean value of AQP2/creatinine of GS vs TZ-treated p &lt; .05), associated with lower urine osmolarity (p = 0.03). Conclusions: Our study shows that water balance in these two groups may be differently handled: A diversified renal tubular epithelial remodeling of medullary collecting duct cells related to TZ treatment could be suggested, leading to an increased prevalence of principal cells on intercalated cells, thus increasing free water reabsorption.

Femoral Vein Pulsatility: What Does It Mean?

In this report, the clinical evolution of a 72-year-old patient transferred to the surgical intensive care unit after cardiac surgery is described. The presence of a pulsatile Doppler signal of the common femoral vein was noted after surgery. On postoperative day 5, diuretics in addition to a combination of inhaled epoprostenol and milrinone were associated with normalization of femoral vein pulsatility. The observations seen in peripheral venous flow reinforce the hypothesis that pulsatility of the common femoral vein represents an associated echocardiographic sign of right ventricular dysfunction and may be used to monitor systemic venous congestion. Pulsatility in the venous system may be improved by reducing volume overload and improving right ventricular function.

Diuretic response and effects of diuretic omission in ambulatory heart failure patients on chronic low-dose loop diuretic therapy.

To study loop diuretic response and effect of loop diuretic omission in ambulatory heart failure (HF) patients on chronic low-dose loop diuretics. Urine collections were performed on two consecutive days in 40 ambulatory HF patients with 40-80 mg furosemide (day 1 with loop diuretic; day 2 without loop diuretic). Three phases were collected each day: (i) first 6h; (ii) rest of the day; and (iii) night. On the day of loop diuretic intake, the total natriuresis was 125.9 (86.9-155.0) mmol/24 h and urine output was 1650 (1380-2025) mL/24 h. There was a clear loop diuretic response with a natriuresis of 9.4 (6.7-15.9) mmol/h and a urine output of 117 (83-167) mL/h during the first 6h, followed by a significant drop in natriuresis and urine output during the rest of the day [2.6 (1.8-4.8) mmol/h and 55 (33-71) mL/h] and night [2.2 (1.6-3.5) mmol/h and 44 (34-73) mL/h]. On day 2, after loop diuretic omission, the natriuresis and urine output remained similarly low the entire day, resulting in a 50% reduction in natriuresis [55.1 (33.5-77.7) mmol/24 h; P < 0.001] and a 31% reduction in urine output [1035 (875-1425) mL/24 h; P < 0.001] compared with the day of loop diuretic intake. Patients with HF on chronic loop diuretic treatment still have a clear diuretic response phase, while loop diuretic omission leads to a significant drop in natriuresis and urine output, arguing against routine cessation of low-dose loop diuretics.