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Background: Effective diuretic regimens using loop diuretics in patients with acute decompensated heart failure are often limited by the development of worsening kidney function. Sodium-glucose cotransporter-2 inhibitors induce glucosuria and sodium excretion with nephroprotective effects in patients with stable heart failure but their role in acute decompensated heart failure is unclear. Methods: In this single-center, prospective, double-blind, placebo-controlled, randomized study, we randomly assigned patients with acute decompensated heart failure to empagliflozin 25 mg daily or placebo in addition to standard decongestive treatments that included loop diuretics. The primary end point was cumulative urine output over 5 days. Secondary end points included diuretic efficiency, dynamics in markers of kidney function and injury, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Results: Sixty patients were randomized within 12 hours of hospitalization for acute decompensated heart failure. Addition of empagliflozin daily to standard medical treatment of acute decompensated heart failure resulted in a 25% increase in cumulative urine output over 5 days (median 10.8 versus 8.7 L mL in placebo, group difference estimation 2.2 L [95% CI, 8.4 to 3.6]; P =0.003). Empagliflozin increased diuretic efficiency compared with placebo (14.1 mL urine per milligram furosemide equivalent [95% CI, 0.6–27.7]; P =0.041) without affecting markers of renal function (estimated glomerular filtration rate, 51±19 versus 54±17 mL/min per 1.73 m²; P =0.599) or injury (total urinary protein, 492±845 versus 503±847 mg/g creatinine; P =0.975; and urinary α1-microglobulin, 55.4±38.6 versus 31.3±33.6 mg/g creatinine; P =0.066) with more pronounced decrease in NT-proBNP in the empagliflozin group compared with placebo (−1861 versus −727.2 pg/mL after 5 days; quotient in slope, 0.89 [95% CI, 0.83–0.95]; P Conclusions: Early addition of empagliflozin to standard diuretic therapy increases urine output without affecting renal function in patients with acute decompensated heart failure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04049045.

Background: Determination of adequacy of decongestion remains a significant challenge in the management of acute heart failure (AHF). Methods: This is a prospective single center cohort study of patients (>18 years old) admitted for AHF on intravenous diuretics, with BNP >100 pg/mL or echocardiographic findings of reduced ejection fraction or diastolic dysfunction, and at least 1 clinical sign of volume overload. Patients with eGFR ≤45 mL/min or on dialysis, and with exposure to contrast dye or nephrotoxins were excluded. Serum and spot urine osmolality were obtained in the early morning simultaneously daily for 5 days or until discharge. Receiver operating characteristic curves were used to analyze the optimal cutoffs for the osmolality values in the prediction of heart failure (HF) readmissions Results: Of the total 100 patients, 62% were male and 59% were Black American. The mean age was 64.41 ± 12.53 and 34% had preserved ejection fraction. Patients with 30-day readmission had higher serum osmolality (mOsm/kg) on admission (305 [299–310] vs. 298 [294–303]; p = 0.044) and had higher drop in serum osmolality between admission and discharge (−7.5 [−9.0, −1.25] vs. −1.0 [−4.0, 4.0]; p = 0.044). Serum osmolality on admission of >299 mOsm/kg (sensitivity: 83%, specificity: 61%) and drop in serum osmolality between admission and discharge of >2 mOsm/kg (sensitivity: 83%, specificity: 65%) was associated with 30-day HF readmissions. No patients discharged with urine osmolality more than 500 mOsm/kg had 30-day readmissions, but this was not statistically significant, p = 0.334. Conclusion: Measurement of serum osmolality and urine osmolality may have some utility in AHF, but interpretation should consider baseline values and dynamic changes to account for individual differences in sodium and water handling.

AIMS: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively. METHODS AND RESULTS: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use=40mg of furosemide or equivalent for >1month, and a BNP>250ng/L or an N-terminal pro-B-type natriuretic peptide>1000pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2h and urine output after 6h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization. CONCLUSIONS: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.

Aims Fluid congestion is a leading cause of hospital admission, readmission, and mortality in heart failure (HF). We performed a systematic review and meta‐analysis to determine the effectiveness of an advanced fluid management programme (AFMP). The AFMP was defined as an intervention providing tailored diuretic therapy guided by intravascular volume assessment, in hospitalized patients or after discharge. The AFMP group was compared with patients who received standard care treatment. The aim of this systematic review and meta‐analysis was to determine the effectiveness of an AFMP in improving patient outcomes. Methods and results A systematic review of randomized controlled trials, case–control studies, and crossover studies using the terms ‘heart failure’, ‘fluid management’, and ‘readmission’ was conducted in PubMed, CINAHL, and Scopus up until November 2020. Studies reporting the association of an AFMP on readmission and/or mortality were included in our meta‐analyses. Risk of bias was assessed in non‐randomized studies using the Newcastle–Ottawa Scale. From 232 retrieved studies, 12 were included in the data synthesis. The 6040 patients in the included studies had a mean age of 72 ± 4 years and mean left ventricular ejection fraction of 39 ± 8%, there were slightly more men (n = 3022) than women, and the follow‐up period was a mean of 4.8 ± 3.1 months. Readmission data were available in 5362 patients; of these, 1629 were readmitted. Mortality data were available in 5787 patients; of these, 584 died. HF patients who had an AFMP in hospital and/or after discharge had lower odds of all‐cause readmission (odds ratio—OR 0.64 [95% confidence interval—CI 0.44, 0.92], P = 0.02) with moderate heterogeneity (I 2 = 46.5) and lower odds of all‐cause mortality (OR 0.82 [95% CI 0.69, 0.98], P = 0.03) with low heterogeneity (I 2 = 0). The use of an AFMP was equally effective in reducing readmission and mortality regardless of age and follow‐up duration. Effective pre‐discharge diuresis was associated with significantly lower readmission odds (OR 0.43 [95% CI 0.26, 0.71], P = 0.001) compared with a fluid management plan as part of post‐discharge follow‐up. Conclusions An effective AFMP is associated with improving readmission and mortality in HF. Our results encourage attainment of optimal volume status at discharge and prescription of optimal diuretic dose. Ongoing support to maintain euvolaemia and effective collaboration between healthcare teams, along with effective patient education and engagement, may help to reduce adverse outcomes in HF patients.

BACKGROUND Acute kidney injury (AKI) is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In the present secondary analysis of a blinded randomized controlled trial, we evaluated the effects of a colloid-based versus a conventional crystalloid-based prime on tubular injury and postoperative renal function in patients undergoing cardiac surgery with CPB. METHODS Eighty-four adult patients undergoing cardiac surgery with CPB were randomized to receive either a crystalloid- or colloid- (dextran 40) based CPB priming solution. The crystalloid solution was based on Ringer-Acetate plus mannitol. The tubular injury biomarker, N-acetyl-b-D-glucosaminidase (NAG), serum creatinine and diuresis were measured before, during and after CPB. The incidence of AKI was assessed according to the KDIGO criteria. RESULTS The urinary-NAG/urinary-creatinine ratio rose in both groups during and after CPB, with a more pronounced increase in the crystalloid group (p = .038). One hour after CPB, the urinary-NAG/urinary-creatinine ratio was 88% higher in the crystalloid group (4.7 ± 6.3 vs. 2.5 ± 2.7, p = .045). Patients that received the dextran 40-based priming solution had a significantly lower intraoperative diuresis (p

Background: The effect of mannitol usage during kidney donation and kidney transplantation is still unclear. Therefore, we performed a systematic review and meta-analysis to research the difference in graft function between kidney grafts treated with and without mannitol. Methods: A literature search was performed in 5 databases and included 8 eligible studies out of 3570 references, which were included up to July 12, 2021. Relevant outcomes for analysis were graft survival, rejection, acute renal failure, delayed graft function, renal failure, creatinine clearance, diuresis, and serum creatinine. Results: Eight studies were identified, 1 study examining the effect of mannitol during kidney donation and 7 studies during kidney transplantation, of which 6 eligible for meta-analysis. A total of 1143 patients were included in these studies. The following outcome measures demonstrated significant differences in favor of mannitol usage compared with a control group: acute renal failure (risk ratio [RR], 0.45; 95% confidence interval [CI], 0.26–0.79; P < .01]) and delayed graft function (RR, 0.25; 95% CI, 0.08–0.77; P = 0.02 and RR, 0.69; 95% CI, 0.51–0.94; P = 0.94). Differences in other outcome parameters were not significant. Conclusions: This systematic review and meta-analysis suggested that the use of mannitol during kidney transplantation leads to lower incidence of acute renal failure and delayed graft function. For all other outcomes, no significant difference was found. Further research should be conducted on the use of mannitol during donor nephrectomy because of the limited availability of studies. Finally, for interpretation of the outcomes, the quality of the evidence should be taken into consideration and we emphasize the need for more up-to-date research.

We have recently reported that hypobaric hypoxia (HH) reduces plasma volume (PV) in men by decreasing total circulating plasma protein (TCPP). Here, we investigated whether this applies to women and whether an inflammatory response and/or endothelial glycocalyx shedding could facilitate the TCCP reduction. We further investigated whether acute HH induces a short-lived diuretic response that was overlooked in our recent study, where only 24-h urine volumes were evaluated. In a strictly controlled crossover protocol, 12 women underwent two 4-day sojourns in a hypobaric chamber: one in normoxia (NX) and one in HH equivalent to 3,500-m altitude. PV, urine output, TCPP, and markers for inflammation and glycocalyx shedding were repeatedly measured. Total body water (TBW) was determined pre- and postsojourns by deuterium dilution. PV was reduced after 12 h of HH and thereafter remained 230-330 mL lower than in NX (P < 0.0001). Urine flow was 45% higher in HH than in NX throughout the first 6 h (P = 0.01) but lower during the second half of the first day (P < 0.001). Twenty-four-hour urine volumes (P ≥ 0.37) and TBW (P ≥ 0.14) were not different between the sojourns. TCPP was lower in HH than in NX at the same time points as PV (P < 0.001), but inflammatory or glycocalyx shedding markers were not consistently increased. As in men, and despite initially increased diuresis, HH-induced PV contraction in women is driven by a loss of TCPP and ensuing fluid redistribution, rather than by fluid loss. The mechanism underlying the TCPP reduction remains unclear but does not seem to involve inflammation or glycocalyx shedding.NEW & NOTEWORTHY This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

Background In typical cases of Bartter syndrome (BS), assessing response to diuretics (furosemide and thiazide), hereinafter referred to as diuretic loading test, may be used to diagnose the type by detecting which part of the kidney tubule is not functioning correctly. However, the diuretic loading test may not always agree with the results of genetic analyses. Case presentation A 5-year-old boy was admitted due to lower extremity weakness and abnormal gait. He had a recurrent episode of muscle weakness and laboratory results showed severe hypokalemia. The direct genomic sequencing of the case revealed a new mutation in the SLC12A1 gene, which is associated with type I Bartter syndrome. Because there was the difference between the phenotype and genotype, we conducted a diuretic loading test to confirm the diagnosis. However, the results showed a clear increase in urine excretion of Na and Cl. These results were not consistent with typical type I BS, but consistent with the patient’s phenotype. Conclusion The diuretic loading test has limited utility for diagnosis especially in atypical cases. On the other hand, this test, which allows assessment of channel function, is useful for better understanding of the genotype-phenotype correlation.

In animal and human neonates, expansion of the extracellular fluid volume is associated with "wet" lung and poor respiratory outcomes. To define fluid status changes during the transition from fetal to neonatal life in infants of diabetic mothers (IDM), we conducted a single-centre (Policlinico Abano Terme, Abano Terme, Italy) study of 66 IDM and a 1:2 matched control group from January 1 to September 30, 2020. Fluid status changes were assessed by computing Δ Hct from umbilical cord blood at birth and capillary heel Hct at 48 h, accounting for body weight decrease. IDM presented with significantly lower cord blood Hct levels in comparison to controls (47.33 ± 4.52 vs 50.03 ± 3.51%, p < 0.001), mainly if delivered by elective cesarean Sect. (45.01 ± 3.77 vs 48.43 ± 3.50%, p = 0.001). Hct levels at 48 h were comparable (55.18 ± 5.42 vs 54.62 ± 7.41%, p = 0.703), concurrently with similar body weight decrease (- 217.21 ± 113.34 vs - 217.51 ± 67.28 g, p = 0.614). This supports significantly higher ∆ Hct in IDM (5.13 ± 5.24 vs 7.29 ± 6.48, p < 0.01) and extra circulating fluid loss of 2-3%.Conclusion: Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung. What is Known: • In neonates, evidence suggests that expansion of the extracellular fluid volume prior to the postnatal diuresis is associated with poor respiratory outcomes. What is New: • Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung.

Aims Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) had distinct haemodynamic characteristics in the setting of acute heart failure. The aim of our study is to evaluate the differential response to aggressive diuresis in HFrEF and HFpEF. Methods and results Patients in the Diuretic Optimization Strategies Evaluation trial with left ventricular ejection fraction measurement were included (n = 300) and classified into HFrEF [left ventricular ejection fraction (LVEF)

Background Delayed graft function (DGF) is a frequent complication after kidney transplantation affecting long-term outcome. Patients and methods A total of 525 consecutive recipients (age 54.2 ± 13.4 years, 33% female) of kidneys from deceased donors transplanted between 2005 and 2012 were retrospectively examined. DGF was defined as the need of dialysis within the first week after transplantation. Results DGF developed in 21.1% (n = 111). Factors associated with DGF (P ≤ .035, respectively) were recipient body mass index, C-reactive protein of the recipient, residual diuresis, cold ischemia time, donor age, and diuresis in the first hour after transplantation. Median duration of DGF was 16 (2-66) days. Patients after DGF had a significantly lower GFR compared with recipients without DGF either after 3 (32.9 ± 16.5 vs 46.3 ± 18.4 mL/min/1.73 m2) or after 12 months (38.9 ± 19.3 vs 48.6 ± 20.4 mL/min/1.73 m2, P Conclusion DGF affects 1 out of 5 kidney transplants from deceased donors. Minimizing modifiable risk factors, in particular immunologic risk, may ameliorate the incidence and outcome of DGF. The outcome of DGF depends mainly on the diagnosis of any rejection and worsens upon detection of transplant glomerulitis and pronounced interstitial fibrosis and tubular atrophy (IFTA).

Objective Treatment of symptomatic hyponatremia is not well established. The European guidelines recommend bolus-wise administration of 150 mL of 3% hypertonic saline. This recommendation is, however, based on low level of evidence. Design Observational study. Methods Sixty-two consecutive hyponatremic patients admitted to the emergency department or intensive care unit of the University Hospital Wuerzburg were divided in subgroups according to treatment (150 mL bolus of 3% hypertonic saline or conventional treatment) and symptom severity. Treatment target was defined as an increase in serum sodium by 5–10 mEq/L within first 24 h and maximum 8 mEq/L during subsequent 24 h. Results Thirty-three out of sixty-two patients (53%) were presented with moderate symptoms and 29/62 (47%) with severe symptoms. Thirty-six were treated with hypertonic saline and 26 conventionally. In the hypertonic saline group, serum sodium increased from 116 ± 7 to 123 ± 6 (24 h) and 127 ± 6 mEq/L (48 h) and from 121 ± 6 to 126 ± 5 and 129 ± 4 mEq/L in the conventional group, respectively. Overcorrection at 24 h occurred more frequent in patients with severe symptoms than with moderate symptoms (38% vs 6%, P < 0.05). Diuresis correlated positively with the degree of sodium overcorrection at 24 h (r = 0.6, P < 0.01). Conventional therapies exposed patients to higher degrees of sodium fluctuations and an increased risk for insufficient sodium correction at 24 h compared to hypertonic saline (RR: 2.8, 95% CI: 1.4–5.5). Conclusion Sodium increase was more constant with hypertonic saline, but overcorrection rate was high, especially in severely symptomatic patients. Reducing bolus-volume and reevaluation before repeating bolus infusion might prevent overcorrection. Symptoms caused by hypovolemia can be misinterpreted as severely symptomatic hyponatremia and diuresis should be monitored.

Aims There is paucity of clinical data comparing continuous infusion (CI) with bolus injection (BI) of intravenous loop diuretics in patients with acute decompensated heart failure (ADHF) and chronic renal dysfunction. This study aimed to compare the efficacy and safety of CI versus BI intravenous furosemide administration in patients with ADHF and moderate chronic renal insufficiency. Methods and results Acute decompensated heart failure and moderate chronic renal insufficiency [with estimated glomerular filtration rate (eGFR) 15.0–44.9 mL/min/1.73 m2] were randomized to start intravenous furosemide by BI or by a 6 h CI. End points included freedom from congestion at 72 h, the degree of dyspnoea assessed using the 0–10 Borg's category ratio scale, net daily urine output, weight loss during the study, length of hospital stay, total urinary sodium excretion, and development of acute kidney injury or electrolyte disturbance. After 72 h of treatment, the rate of the primary endpoint of freedom from congestion in the CI group was significantly higher than that in the BI group (69.05% vs. 43.59%, P = 0.02). The modified Borg scale indicated patients in the CI group had lower dyspnoea score than those in the BI group at 48 h (4.29 ± 1.23 vs. 5.97 ± 1.56; P = 0.02) and 72 h (1.15 ± 0.35 vs. 2.66 ± 0.83; P = 0.003). There were other significant differences favouring the CI group with regard to net urine output at 72 h (5145.98 ± 621.37 mL vs. 3755.95 ± 456.93 mL; P = 0.007), the mean body weight loss (4.72 ± 1.01 kg vs. 3.53 ± 0.73 kg; P = 0.02) and the total urinary sodium excretion (385.05 ± 38.15 vs. 320.33 ± 37.67; P = 0.02). The length of hospitalization in the CI group was significantly shorter than that in the BI group (10.36 ± 4.20 days vs. 15.68 ± 6.15 days; P = 0.02). No significant differences were observed between groups in the frequency of acute kidney injury, tinnitus, electrolyte disturbance or mortality. Conclusions Continuous intravenous infusion of furosemide resulted in significantly greater diuresis than bolus administration of an equal dose in patients with moderate chronic renal insufficiency and ADHF, while no differences emerged in terms of side effects or mortality.

We previously demonstrated that exogenous ketosis reduces urine production during exercise, however, the underlying physiological mechanism remained unclear. Here, we, for the first time demonstrate that exogenous ketosis suppresses the exercise-induced release of atrial natriuretic peptide (ANP). However, given the limited effects of ANP on renal haemodynamics during exercise, the underlying physiological mechanism remains unknown. But downregulation of ANP might explain a new physiological mechanism by which exogenous ketosis lowers blood-free fatty acid levels.

Data are lacking regarding the use of diuretics in facilitating closure of the open abdomen (OA). For patients with an OA after 2 laparotomies, we hypothesized that diuretic use was associated with a higher rate of primary fascial closure than no diuretic use. A retrospective review of patients with trauma laparotomies over 7 years was performed. Primary fascial closure (PFC) was defined as apposition of fascial edges without interposition mesh. Of 321 patients, 30 (9%) remained with an OA after 2 laparotomies. Prior to the third laparotomy, median cumulative fluid balance was +12.6 L. Thirteen (43%) received diuretics. Primary fascial closure rates were similar for diuretic use vs no diuretic (38% vs 59%, P = .46). Primary fascial closure was not associated with age ( P = .2), gender ( P = 0.7), cumulative fluid balance ( P = .3), or units of packed cells ( P = .4). Diuretic use in trauma patients with an OA after 2 laparotomies was not associated with successful PFC.

Repository corticotropin injection (RCI; Acthar Gel) is indicated to induce a diuresis or a remission of proteinuria in nephrotic syndrome (NS) without uremia of the idiopathic type or that due to lupus erythematosus. This study compares patient characteristics and measurable healthcare resource utilization (HCRU) between NS patients who received a prescription for RCI and then were either approved or denied treatment by their insurers.A retrospective analysis of adults with NS from January 2015 to December 2018 was conducted using a de-identified open-source claims database. Patients were included in the study if they had ≥1diagnosis associated with NS, were age 18+, and had medical claims activity at some point in the year preceding ("baseline") and year following ("follow up") their first approved or denied RCI prescription. Baseline characteristics were reported with p-values indicating the significance of characteristics between cohorts. To assess outcomes, approved and denied patients were matched (1:1) using propensity-matching to account for underlying differences.Overall, 1,232 patients met inclusion criteria for the study. At baseline, approved patients were older than denied patients (mean age 53.9 vs. 48.4) and had higher rates of comorbidities. A greater proportion of approved patients required inpatient admissions (34.1 vs. 28.0%) and "high" doses of corticosteroids (CS) (26.2 vs. 20.7%) at baseline. Matched outcomes showed directionally more denied patients with inpatient admissions compared to approved (64 vs. 52) and a greater utilization of deep vein thrombosis ultrasound (12.2 vs. 6.6%) and dialysis (10.5 vs. 6.1%). Matched, denied patients had directionally greater CS use during follow-up both in the number of patients receiving CS (104 vs. 95) and the average annualized daily dose (4.1 vs. 3.4 mg).Patients denied access to RCI treatment had directionally higher HCRU compared to matched, approved counterparts. Thus, the results of this study may aid providers and payers in evaluating scenarios where RCI may be beneficial and improve quality of care for NS patients.

Introduction and hypothesis Nocturia, defined as the act of waking to pass urine during sleeping, is a common problem in older women and is associated with significant morbidity and impairments in health-related quality of life. The aim of this review was to synthesize the current evidence regarding the incidence, impact, pathophysiology, and specific diagnostic approach of nocturia in the postmenopausal population. Methods We searched PubMed and Web of Science databases to identify relevant studies published through June 2020. Reference lists of the reviews obtained were screened for other articles deemed pertinent by the authors. Results Genitourinary symptoms attributed to the menopause have been reported to occur in nearly 90% of postmenopausal women, and nocturia is one of the most common. The relative deficiency in endogenous estrogen production after the menopause is thought to exacerbate all major pathophysiological mechanisms that may underlie nocturia, including reduced bladder capacity, nocturnal polyuria, global polyuria, and sleep disorders. Diminished estrogen may induce anatomical and physiological bladder changes, contributing to a reduction in functional bladder capacity. Excess nocturnal urine production can also be provoked by estrogen depletion, either via free water-predominant diuresis by an impaired secretion of antidiuretic hormone, or a salt-predominant diuresis owing to diminished activation of the renin-angiotensin-aldosterone axis. Additionally, a relationship between the transition to menopause and impaired sleep has been described, mediated by increased incidence in vasomotor symptoms and obstructive sleep apnea signs during the menopause. Conclusion Further research is necessary to better characterize and manage nocturia in postmenopausal women.

Parathyroidectomy (PTX) is routinely performed in hypercalciuric renal stone patients with primary hyperparathyroidism (PHPT). However, some data indicate a persistent stone activity following PTX, raising the issue of the link between PHPT and stone disease. We performed an observational study on 30 renal stone patients diagnosed with PHPT. Patients were selected among 1448 hypercalciuric patients referred in our department for a diagnostic evaluation. Patients with no parathyroid surgery or any biological follow-up were excluded. Clinical and biological data (including 24-h urine collection and a calcium load test) were collected before and within 12 months following surgery. Stone recurrence was evaluated by direct phone contact (median 43 months). Comparison of biological data before and after surgery showed a significant decrease of ionized calcium and serum parathyroid hormone after PTX. All stones contained calcium-dependent species such as carbapatite, brushite or dihydrate calcium oxalate. Urine saturation indexes and calciuria significantly decreased after surgery (from 9.9 to 5.9 mmol/d, p

Clinical parameters with correlation to diuretic effects after initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors are unclear. We aimed to identify the factors associated with the diuretic effect observed following the initiation of SGLT2 inhibitors in patients with diabetes having an acute heart failure (HF). Fifty-six patients included were hospitalized for acute HF with diabetes and started on SGLT2 inhibitors. Changes in urine volume (ΔUV) and blood/urine laboratory parameters before and during the first 4 days of therapy were evaluated. Data were prospectively obtained under clinically stable conditions after initial HF treatment. UV increased following the initiation of SGLT2 inhibitors [UV at baseline (BL): 1383 ± 479 mL/day; ΔUV over 4 days: + 189 ± 358 mL/day]. Multivariate analysis revealed no association between BL-hemoglobin A1c or BL-estimated glomerular filtration rate and ΔUV. Conversely, higher BL-fasting plasma glucose (FPG) and higher BL-urine N-acetyl-β-D-glucosaminidase (NAG) were associated with a higher ΔUV. ΔUV was inversely associated with ΔFPG and ΔNAG, and positively associated with Δurinary sodium excretion. Elevated FPG and NAG both improved over 4 days of treatment. In conclusion, the diuretic effect of SGLT2 inhibitors was glycemia-dependent, and was associated with a reduction in elevated renal-tubular markers in hospitalized HF complicated with diabetes.

Background: Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. Summary: Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.

Objective: The aim of the study was to describe the surgical technique of totally robotic kidney transplantation with transvaginal insertion and to assess its safety and feasibility. Methods: It is a prospective analysis of the first 5 cases of robotic kidney transplantation with transvaginal insertion. Robotic-assisted kidney transplantation was performed after transvaginal insertion of a living donor kidney graft. Donor’s and recipient’s characteristics, intraoperative variables, postoperative complications, and surgical outcomes were assessed. Results: The median operative time was 220 min. Mean rewarming ischemia time of 53 min, with immediate diuresis. No intraoperative complications were observed. Mean hospitalization period was 9 days, with mean Cr of 1.5 mg/dL at discharge. Conclusions: Robotic kidney transplantation with transvaginal insertion is feasible and safe. A greater number of procedures are required to confirm the results of this new technique.

Heart failure (HF) continues to be a serious public health challenge despite significant advancements in therapeutics and is often complicated by multiple other comorbidities. Of particular concern is type 2 diabetes mellitus (T2DM) which not only amplifies the risk, but also limits the treatment options available to patients. The sodium-glucose linked cotransporter subtype 2 (SGLT2)-inhibitor class, which was initially developed as a treatment for T2DM, has shown great promise in reducing cardiovascular risk, particularly around HF outcomes – regardless of diabetes status.There are ongoing efforts to elucidate the true mechanism of action of this novel drug class. Its primary mechanism of inducing glycosuria and diuresis from receptor blockade in the renal nephron seems unlikely to be responsible for the rapid and striking benefits seen in clinical trials. Early mechanistic work around conventional therapeutic targets seem to be inconclusive. There are some emerging theories around its effect on myocardial energetics and calcium balance as well as on renal physiology. In this review, we discuss some of the cutting-edge hypotheses and concepts currently being explored around this drug class in an attempt better understand the molecular mechanics of this novel agent.

OBJECTIVES Our goal was to investigate the efficacy of balanced forced diuresis in reducing the rate of acute kidney injury (AKI) in cardiac surgical patients requiring cardiopulmonary bypass (CPB), using the RenalGuard® (RG) system. METHODS Patients at risk of developing AKI (history of diabetes and/or anaemia; estimated glomerular filtration rate 20–60 ml/min/1.73 m2; anticipated CPB time >120 min; log EuroSCORE > 5) were randomized to the RG system group (n = 110) or managed according to current practice (control = 110). The primary end point was the development of AKI within the first 3 postoperative days as defined by the RIFLE (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) criteria. RESULTS There were no significant differences in preoperative and intraoperative characteristics between the 2 groups. Postoperative AKI rates were significantly lower in the RG system group compared to the control group [10% (11/110) vs 20.9% (23/110); P = 0.025]. This effect persisted even after controlling for a number of potential confounders (odds ratio 2.82, 95% confidence interval 1.20–6.60; P = 0.017) when assessed by binary logistic regression analysis. The mean volumes of urine produced during surgery and within the first 24 h postoperatively were significantly higher in the RG system group (P, Acute kidney injury (AKI) after cardiac surgery is well documented [1].

Mannitol and furosemide have been used as diuretics intraoperatively to facilitate early renal allograft function and reduce delayed graft function. As the evidence of any efficacy of these agents is limited, we sought to characterize the use of diuretics among transplant surgeons.An anonymous online survey was sent to all Canadian transplant programs where kidney transplants are routinely performed. Questions were related to the use and indications for mannitol and furosemide. Responses were collected and analyzed as counts and percentages of respondents. We used χ2 analysis to assess the relationship between demographic factors and survey responses.Thirty-five surgeons completed the survey (response rate 50%). Seventy per cent of respondents reported performing 26 or more transplants per year, 88% had formal transplant fellowship training and 67% indicated that they currently train fellows. Only 24% and 12% reported believing that delayed graft function is reduced by mannitol and furosemide use, respectively. However, 73% routinely gave mannitol to patients and 53% routinely gave furosemide. The most common justification given for mannitol use was to induce diuresis (54%); 37% of respondents reported using mannitol because of training dogma. Likewise, 57% used furosemide for diuresis, with 23% reporting that their use of this agent was based on dogma. No relationship emerged between fellowship training, case volume or training program status and the use of any agent. Interestingly, 71% of respondents indicated that a randomized controlled trial evaluating the utility of intraoperative diuretics is needed and that they were interested in participating in such a trial.Use of intraoperative diuretics and the rationale for their use vary among surgeons. A substantial proportion of surgeons use these medications on the basis of dogma alone. A randomized controlled trial is needed to clarify the role of intraoperative diuretics in kidney transplant surgery.On a utilisé le mannitol et le furosémide comme diurétiques peropératoires pour stimuler le fonctionnement précoce de l’allogreffe rénale et réduire le retard de fonctionnement du greffon. Comme les données probantes quant à l’efficacité de ces agents sont limitées, nous avons voulu caractériser l’utilisation des diurétiques chez les chirurgiens qui effectuent ces transplantations.Un sondage anonyme en ligne a été envoyé à tous les programmes de greffe canadiens où des greffes rénales sont couramment effectuées. Les questions avaient trait à l’utilisation et aux indications du mannitol et du furosémide. Les réponses ont été recueillies et analysées sous forme de nombres et de pourcentages des répondants. Le test du χ2 a été utilisé pour évaluer le lien entre les facteurs démographiques et les réponses au sondage.Trente-cinq chirurgiens ont répondu au sondage (taux de réponse 50 %). Soixante-dix pour cent des répondants ont indiqué effectuer annuellement 26 greffes ou plus, 88 % avaient suivi une spécialisation formelle pour l’exécution des greffes et 67 % ont dit être en cours de spécialisation. Seulement 24 % et 12 % respectivement ont dit croire que le mannitol et le furosémide permettent de réduire le retard de fonctionnement du greffon. Toutefois, 73 % et 53 % respectivement administraient de routine du mannitol et du furosémide aux patients. La justification la plus fréquente de l’utilisation du mannitol était d’induire la diurèse (54 %); 37 % des répondants ont dit utiliser le mannitol parce que c’est ce qu’on leur a enseigné durant leur formation. De même, 57 % utilisaient le furosémide pour la diurèse, dont 23 % disaient que c’est ce qu’on leur avait enseigné durant leur formation. Aucun lien n’est ressorti entre la spécialisation, le volume de cas ou le statut à l’égard du programme de formation et l’utilisation d’un agent quelconque. Fait à noter, 71 % des répondants ont indiqué qu’un essai randomisé et contrôlé sur l’utilité des diurétiques peropératoires serait nécessaire et qu’ils y participeraient volontiers.L’utilisation de diurétiques peropératoires et la justification de leur utilisation varient d’un chirurgien à l’autre. En majeure partie, les chirurgiens utilisent ces médicaments sur la base des notions théoriques seulement. Un essai randomisé et contrôlé s’impose pour clarifier le rôle des diurétiques peropératoires dans la greffe rénale.

Background In human patients, cumulative urine volume (uVol) and urine sodium (uNa) can be predicted using spot urine samples and these quantitative measures help detect low diuretic responsiveness (LDR). Hypothesis/objectives Formulas using spot urine samples predict cumulative uVol and uNa output after oral administration of furosemide to dogs. Animals Eight healthy dogs, 6 dogs with congestive heart failure (CHF). Methods Prospective interventional study. Spot urine samples at 180 and 270 minutes after furosemide (3 mg/kg PO) were used to predict cumulative uVol and uNa output over 7 hours. Differentiation of dogs fulfilling predefined criteria for LDR was examined using receiver operating characteristic (ROC) curves. Results Predicted uNa output at 180 minutes (r s = 0.763, [95% confidence interval [CI], 0.375‐0.923], P = .002) and 270 minutes (r = 0.816, [95% CI, 0.503‐0.940], P

Background: Congestion predominates in exacerbations of heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), but evidence suggests that excess volume may be distributed differently in these 2 subgroups. Methods and Results: In this retrospective study, diuretic efficiency (DE, or net urine output per 40-mg of intravenous furosemide equivalent) during the first 72 hours was compared between patients hospitalized with HFrEF (n = 121) versus HFpEF (n = 120). Multivariate analysis was used to compare the 2 groups based on expected baseline differences (e.g., demographics, heart failure etiology, concomitant therapy). During the first 72 hours, mean daily diuretic doses were higher in patients with HFpEF versus HFrEF (172.0 vs. 159.9 mg, respectively, P = 0.026) but urine output was not significantly different (2603.3 mL vs. 2667.5 mL, respectively, adjusted P = 0.100). Similarly, mean cumulative DE did not differ (−673.5 vs. −637.8 mL/40-mg in the HFrEF and HFpEF groups, respectively, adjusted P = 0.884). An exploratory analysis of propensity-matched cohorts yielded similar findings. Correlations between the components of DE varied considerably and only became weak to moderately correlated toward the end of the observation period. Conclusions: Although cumulative DE did not differ between patients with HFrEF and HFpEF, variable correlations in the components of DE suggest there may be differences in diuretic response that warrant future analysis.

Lower severe edema is a common condition faced by advanced cancer patients with an impact on comfort, quality of life, and care planning. Diuresis and mechanical interventions are the mainstream options for the treatment of edema, but, although effective, may not be indicated for frail, bed-bound, and dependent patients cared for in the community setting. We present a case report of a young female with severe edema to her right lower limb, which accepted controlled subcutaneous fluid drainage at her home. Subcutaneous fluid drainage at home was effective, safe, and feasible and improved the patient’s comfort and well-being.

Background: Combined use of furosemide with albumin is an approved therapy to overcome diuretic resistance in treatment of ascites in decompensated chronic liver disease. Bolus dosing of diuretics has its own limitations due to pre-existing hypotension, post diuretic sodium retention and braking phenomenon. Slow albumin and furosemide Infusion has been shown to mobilize large ascites with improved diuresis and hemodynamic stability in decompensated chronic liver disease. This study was undertaken to compare efficacy and safety of infusion therapy vs bolus therapy in term the management of refractory ascites.Methods: Decompensated chronic liver disease patients with refractory ascites were randomly assigned into two groups of 15 each - Bolus therapy (intravenous albumin and furosemide as boluses) and Infusion therapy (furosemide infusion at 2mg/hour and albumin at 2g/hour for three days). Diuresis, natriuresis, change in abdominal girth and body weight, and hemodynamic stability (change in SBP) were compared between the two groups.Results: Infusion therapy, as compared to bolus therapy, showed a significantly better diuresis (mean urinary output increment 483ml vs 243ml, p

Objective: To identify the risk factors for the development of acute kidney injury and for short and long-term mortality of patients with acute kidney injury after admission to the Pediatric Intensive Care Unit. Materials and methods: Retrospective analysis of patients admitted to the Pediatric Intensive Care Unit from January 2004 to December 2008. Acute kidney injury was defined by the KDIGO criterion. Risk factors for acute kidney injury, in-hospital, and long-term mortality were obtained through multivariate logistic regression analysis. Long-term mortality (up to 2011) was obtained by searching the institution's database and by telephone contact with patients' family members. Results: A total of 434 patients were evaluated and the incidence of acute kidney injury was 64%. Most acute kidney injury episodes (78%) occurred within the first 24hours after admission to the Pediatric Intensive Care Unit. The risk factors for the development of acute kidney injury were: low volume of diuresis, younger age, mechanical ventilation, vasoactive drugs, diuretics, and amphotericin. Lower weight, positive fluid balance, acute kidney injury, dopamine use and mechanical ventilation were independent risk factors for in-hospital mortality. Long-term mortality was 17.8%. Systolic blood pressure, PRISM score, low volume of diuresis, and mechanical ventilation were independent risk factors associated with long-term mortality after admission to the Pediatric Intensive Care Unit. Conclusion: Acute kidney injury was a frequent, early event, and was associated with in-hospital mortality and long-term mortality after admission to the Pediatric Intensive Care Unit. Resumo Objetivo: Identificar os fatores de risco para o desenvolvimento de lesão renal aguda, mortalidade a curto e em longo prazo de pacientes com lesão renal aguda após internação em Unidade de Terapia Intensiva Pediátrica. Materiais e métodos: Análise retrospectiva de pacientes internados em unidade de terapia intensiva pediátrica de janeiro de 2004 a dezembro de 2008. Lesão renal aguda foi definida pelo critério KDIGO. Fatores de risco para lesão renal aguda, mortalidade hospitalar e em longo prazo foram obtidos através de análise multivariada por regressão logística. Mortalidade em longo prazo (até 2011) foi obtida através de busca no banco de dados da instituição e contato telefônico com parentes dos pacientes. Resultados: Foram avaliados 434 pacientes e a incidência de lesão renal aguda foi de 64%. A maioria dos episódios de lesão renal aguda (78%) ocorreu nas primeiras 24 horas após internação na Unidade de Terapia Intensiva Pediátrica. Os fatores de risco para o desenvolvimento de lesão renal aguda encontrados foram: baixo volume de diurese, menoridade, uso de ventilação mecânica, droga vasoativa, diurético e anfotericina. Menor peso, balanço hídrico positivo, lesão renal aguda, uso de dopamina e ventilação mecânica foram fatores de risco independentes para mortalidade hospitalar. A mortalidade em longo prazo foi de 17,8%. Pressão arterial sistólica, escore PRISM, baixo volume de diurese e ventilação mecânica foram fatores de risco independentes associados à mortalidade em longo prazo após internação na Unidade de Terapia Intensiva Pediátrica. Conclusão: Lesão renal aguda foi um evento frequente, precoce e esteve associada à mortalidade hospitalar e em longo prazo após internação na Unidade de Terapia Intensiva Pediátrica.

Aims Hyponatremia is associated with poorer outcomes and diuretic response in patients hospitalized for heart failure. This study compared a tolvaptan‐based vs. furosemide‐based diuretic regimen on short‐term clinical responses in hyponatremic acute heart failure. Methods and results Prospective, randomized, open‐label, parallel‐group, single‐centre study comparing oral tolvaptan vs. continuous infusion furosemide. Thirty‐three subjects requiring hospitalization for acute congestive heart failure, and a serum sodium

Background Infusion with 0.9% saline is a mainstay in the treatment of severe hyperglycemia, but the kinetics of the saline volume in this setting has not been studied. Methods An intravenous infusion of 1 L of 0.9% saline over 30 minutes was given on 31 occasions to 17 patients with hyperglycemia due to poorly controlled diabetes (mean age 51 years). A two-volume kinetic model was fitted to serial data on the hemodilution and urinary excretion, using mixed-effects modeling software. Results Plasma glucose was 36 ± 9 mmol/L on arrival to the hospital. The central volume of distribution (the plasma) was only 2.38 L (mean; 95% confidence interval 1.73-3.04) on the day of admission. Uptake into a remote compartment, believed to be the cells, amounted to 300 mL of the first liter of saline, although only small amounts of insulin were given. Plasma glucose, plasma bicarbonate, urine glucose, and plasma creatinine served as covariates in the kinetic model and mathematically affected the urinary excretion. For example, elimination of the infused fluid tripled from an increase in plasma glucose from 5 to 35 mmol/L and doubled from a reduction in plasma bicarbonate from 24 to 5 mmol/L. Conclusions The excretion of 0.9% saline was increased depending on the degree of hyperglycemia. The kinetics was characterized by glucose-accelerated diuresis, and an intracellular uptake that occurred at two thirds the urine flow rate. These data could help to determine appropriate volumes and rates of infusion of crystalloids in hyperglycemia.

Background Dopaminergic symptoms may be extremely pronounced in some migraine patients during the attack, representing a major source of disability. Objectives We aimed to carefully characterize the clinical picture of migraine patients with dopaminergic symptoms in a large patients’ population as a putative migraine endophenotype, allowing more precise disease management, treatment and outcome prediction. Methods We screened 1148 consecutive tertiary care episodic and chronic migraine patients with face-to-face interviews collecting thorough data on lifestyle, socio-demographic factors, and clinical migraine features. Results We identified 374 patients with migraine with dopaminergic symptoms (32.6%). The most frequent dopaminergic symptom was yawning followed by somnolence, nausea, vomiting, fatigue, mood changes and diuresis. Migraine patients with dopaminergic symptoms had longer attack duration (OR: 1.82; 95% CI: 1.41–2.36, p Conclusions Migraine patients with dopaminergic symptoms are characterized by a full-blown, more disabling migraine. Dopaminergic system modulation should be carefully considered in individuals with migraine with dopaminergic symptoms for both acute and preventative treatments in future ad hoc designed studies.

Objective The primary objective of the study was to evaluate the correlation between semi-quantitative F-18 FDG PET parameters and renal cell carcinoma (RCC) grade and its role in predicting the histopathological grade in RCC. The secondary objective was to evaluate the role of forced diuresis in improving the diagnostic accuracy of F-18 FDG for RCC. Methods Thirty-three patients with radiologically proven RCC were included in the study. All patients underwent PET/CT on a dedicated PET/CT scanner (Biograph mCT; Siemens Medical Solutions, Erlangen, Germany) 45-60 min post-injection F-18-FDG. Patients were then injected 1 mg/kg body weight furosemide (upto 40 mg) and regional PET/CT images of abdomen were acquired after 2 h. For both baseline and post-diuretic F-18-FDG PET/CT scans, maximum standardized uptake value for tumor (SUVmax), mean SUV for tumor, metabolic tumor volume (MTV), tumor-to-liver (T/L) and tumor-to-kidney ratio (T/K) were calculated. Histopathology findings were considered as the reference standard. To assess the incremental value of diuresis in scan interpretation, visual analysis of scans was done. Results Of 33 patients, histopathology grading was available for comparison with metabolic tumor markers in all except four. Of 29 patients (mean age = 51.89 ± 13.54 years), 20 patients had clear cell (cc) type while rest had non-cc RCC. Difference between the mean values among the categories was insignificant for all parameters except T/K. Fuhrman grading was obtained in 25 patients (17 low and eight high). SUVmax, MTV and T/L were found to be significantly different between low and high grade patients. Significantly strong positive correlation was observed between Furhman grades and tumor metabolism (r ≥ 0.5). No significant difference was observed between baseline and post-diuretic scan in any of the patients. Conclusion Semi-quantitative F-18 FDG PET parameters (SUVmax, MTV and T/L) were found to be significantly correlated with Fuhrman grade in patients with RCC and are important markers for differentiation between low- and high-grade tumors. Furthermore, forced diuresis had no incremental value in characterization of primary RCC lesions.

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a new class of drugs for patients with type 2 diabetes (T2DM) which inhibit urinary glucose reabsorption in the proximal tubule of the nephron and result in glucosuria, natriuresis and diuresis. In large, randomized clinical trials, SGLT-2i have been shown to reduce major cardiovascular (CV) events and heart failure (HF) hospitalizations in patients with T2DM who have atherosclerotic CV disease or CV risk factors. In these trials, SGLT-2i is have their greatest and most consistent effect on reducing the risk of HF hospitalization. The reduction in HF hospitalization was also observed in subgroups of patients with a HF diagnosis at baseline, which raised the possibility of a clinical benefit of SGLT-2i in HF patients, regardless of the presence or absence of T2DM. In very recently published DAPA-HF trial, a SGLT-2i, dapagliflozin treatment on top of standard HF therapy has been shown to have clear clinical benefits in terms of reducing HF hospitalization, CV mortality, all-cause mortality and improving quality of life in HF patients. This compelling evidence suggests that SGLT-2i have a potential to be an effective treatment option in HF, regardless of diabetes. This article provides a comprehensive overview focused on the role of SGLT-2i in the treatment of HF.

Tolvaptan is an effective therapy for heart failure patients with symptomatic congestion and hyponatremia. The efficacy of its use in patients with continuous-flow left ventricular assist devices (LVADs) is unknown. The aim of this study was to assess the clinical efficacy and safety of tolvaptan in LVAD patients. We retrospectively reviewed medical records of patients who underwent LVAD implantation between January 2014 and August 2018. Among 217 consecutive LVAD patients, tolvaptan was used in 20 patients. Mean age was 46 ± 14 years old and 14 patients were males. The duration of tolvaptan therapy was 4 (interquartile range 1–8) days. Urine volume significantly increased from 2,623 ± 1,109 ml/day before tolvaptan to 4,308 ± 1,432 ml/day during tolvaptan therapy (p < 0.001). Serum sodium increased from 127 ± 3 to 133 ± 3 mEq/L at the end of tolvaptan therapy (p < 0.001). No patients developed hypernatremia (serum sodium >150 mEq/L). The 90-day overall survival following tolvaptan therapy was 89% in both the tolvaptan group and a propensity score-matched non-tolvaptan group (p = 0.918). Survival free of heart failure readmissions was also comparable between the groups (p = 0.751). In conclusion, short-term use of tolvaptan following LVAD implantation is a safe and effective therapy to augment diuresis and improve hyponatremia.

Two recent studies challenged traditional paradigms of mammalian sodium physiology, suggesting that sodium reduction might cause weight gain by altering metabolism. This new theory has important implications for population-wide dietary recommendations. However, these observations have not been confirmed. In the DASH (Dietary Approaches to Stop Hypertension)-Sodium trial, 412 adults with systolic blood pressure of 120 to 159 mm Hg and diastolic blood pressure of 80 to 95 mm Hg not taking antihypertensive medications were randomly assigned to the DASH diet or a control diet (parallel design). On their assigned diet, participants randomly consumed each of the 3 sodium levels for 4 weeks (crossover design). Participants were provided all meals but could drink noncaloric beverages (eg, water) freely. Throughout the trial, energy intake was adjusted to maintain weight constant. The 3 sodium levels (at 2100 kcal/day) were: low (1150 mg of Na/day), medium (2300 mg of Na/day), and high (3450 mg of Na/day). Energy intake, weight, self-reported thirst, and 24-hour urine volume were assessed after each period. Participants were 57% women and 57% black; mean age was 48 years [SD, 10]). Among those assigned the control, mean weight increased slightly with higher sodium but not among those assigned DASH. Energy intake did not vary across sodium levels in either diet ( P -trends ≥0.36). Higher sodium resulted in more thirst ( P -trends P -trend=0.007). Reducing sodium did not increase energy requirements to maintain stable weights but did decrease thirst and urine volume (control diet only), findings consistent with the traditional understanding of mammalian sodium physiology. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000608.

Purpose: In urolithiasis patients, preoperative non-contrast computed tomography (NCCT) commonly fails to provide sufficient distention of the renal collecting system to allow reliable preoperative...

8-Aminoguanine and 8-aminoguanosine (via metabolism to 8-aminoguanine) are endogenous 8-aminopurines that induce diuresis, natriuresis, and glucosuria by inhibiting purine nucleoside phosphorylase (PNPase); moreover, both 8-aminopurines cause antikaliuresis by other mechanisms. Because 8-aminoinosine and 8-aminohypoxanthine are structurally similar to 8-aminoguanosine and 8-aminoguanine, respectively, we sought to define their renal excretory effects. First, we compared the ability of 8-aminoguanine, 8-aminohypoxanthine, and 8-aminoinosine to inhibit recombinant PNPase. These compounds inhibited PNPase with a potency order of 8-aminoguanine8-aminohypoxanthine = 8-aminoinosine. Additional studies showed that 8-aminoinosine is a competitive substrate that is metabolized to a competitive PNPase inhibitor, namely 8-aminohypoxanthine. Administration of each 8-aminopurine (33.5 µmol/kg) reduced the guanine-to-guanosine and hypoxanthine-to-inosine ratios in urine, a finding confirming their ability to inhibit PNPase in vivo. All three 8-aminopurines induced diuresis, natriuresis, and glucosuria; however, the glucosuric effects of 8-aminohypoxanthine and 8-aminoinosine were less pronounced than those of 8-aminoguanine. Neither 8-aminohypoxanthine nor 8-aminoinosine altered potassium excretion, whereas 8-aminoguanine caused antikaliuresis. In vivo administration of 8-aminoinosine increased 8-aminohypoxanthine excretion, indicating that 8-aminohypoxanthine mediates, in part, the effects of 8-aminoinosine. Finally, 8-aminohypoxanthine was metabolized to 8-aminoxanthine by xanthine oxidase. Using ultraperformance liquid chromatography-tandem mass spectrometry, we identified 8-aminoinosine as an endogenous 8-aminopurine. In conclusion, 8-aminopurines have useful pharmacological profiles. To induce diuresis, natriuresis, glucosuria, and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be preferred. If only diuresis and natriuresis, without marked glucosuria or antikaliuresis, is desired, 8-aminohypoxanthine or 8-aminoinosine might be useful. Finally, here we report the in vivo existence of another pharmacologically active 8-aminopurine, namely 8-aminoinosine. SIGNIFICANCE STATEMENT: Here, we report that a family of 8-aminopurines affects renal excretory function: effects that may be useful for treating multiple diseases including hypertension, heart failure, and chronic kidney disease. For diuresis and natriuresis accompanied by glucosuria and antikaliuresis, 8-aminoguanine (or its prodrug 8-aminoguanosine) would be useful; if only diuresis and natriuresis is called for, 8-aminohypoxanthine or 8-aminoinosine would be useful. Previously, we identified 8-aminoguanine and 8-aminoguanosine as endogenous 8-aminopurines; here, we extend the family of endogenous 8-aminopurines to include 8-aminoinosine.

Background To investigate the efficacy of Qingre Lishi Decoction(QLRD), in the treatment of acute gouty arthritis, and its influence on the expression levels of inflammatory factor nucleotide-binding oligomerization domain-like receptor(NALP 3) in patients. Methods A total of 78 patients with acute gouty arthritis admitted to our hospital were randomly divided into the control group and the observation group, with 39 cases in each group. The control group was given basic treatment and colchicine tablets, and the observation group was given “heat-clearing and diuresis-promoting” prescription for intervention treatment. The main symptom score, treatment effective rate and laboratory indexes of the two groups were compared 7 days after treatment. Results After treatment, the scores of joint redness, hot pain, joint flexion and extension disorder, oliguria and constipation were improved in both groups, and the improvement degree in observation group was higher than that in control group (P Conclusion The “heat-clearing and diuresis-promoting” prescription for intervention treatment can effectively improve the clinical symptoms of patients with acute gouty arthritis and reduce the level of inflammatory factor NALP3, maintaining remarkable effect.

Type-one cardiorenal syndrome (CRS) is defined by acute decompensated heart failure leading to secondary acute kidney injury. No study evaluates the reliability of transthoracic echocardiography as a help tool for diagnosis and optimization of CRS. Therefore, the aim of this study was to assess echocardiographic parameters in patients with CRS in the Intensive Care Unit.We conducted an observational, prospective, single-center study in the ICU department of a general hospital. Patients admitted in the ICU and presenting with type 1 CRS were included. Transthoracic echocardiography was performed at baseline and at day end after treatment by the same trained operator for the same patients. We report various echocardiographic indices at these two timepoints.Twenty-seven patients were included. At baseline 96.3% of patients had signs of congestion (IVC dilation2 cm), 76% had an altered S-wave (11.5 cm/s), 72.73% had an altered TAPSE (17 mm), 85.19% had an elevated RV/LV diameter ratio (0.6). Between baseline and D end, IVC size and, the number of patients with an elevated RV/LV diameter ratio significantly decreased. Weight decreased, whereas natriuresis significantly increased, and the amount of vasopressors support decreased. Diuresis, and S-wave velocity showed non-significant changes.Main echocardiographic findings at baseline in patients with type 1 CRS consist of a right ventricular dysfunction associated an IVC dilation. We report that weight, RV/LV diameter ratio, and IVC diameter might constitute good follow-up parameters to monitor treatment response.

The objective of this study is to assess the safety and efficacy of forced diuresis as an antiretropulsion strategy during the pneumatic disintegration of solitary lower ureteric stones with semi-rigid ureteroscopy (URS). A prospective randomized double-blind study was carried out from March 2019 to June 2021 for patients presented with unilateral solitary radiopaque lower ureteric stones ≤ 20 mm. Patients were randomized for URS into two groups, according to the use of forced diuresis using furosemide 1 mg/kg (GII) or not (GI). Perioperative parameters were compared between both groups, including retropulsion rate, stone-free rate (SFR), and need for auxiliary procedures and complications. A total of 148 patients were included; 72 (48.6%) in GI and 76 in the GII (51.4%), with respective stone size of 11.8 ± 2.6 vs.12.1 ± 2.4 mm. Both groups were comparable in demographic and baseline data, with a mean age of 47 ± 16 and 50 ± 14 years for GI and GII, respectively. GII had a significantly shorter disintegration time (10.5 ± 1.3 vs. 4.2 ± 2.1 min, p p p = 0.04), lower retropulsion rate (1.3% vs. 11%, p = 0.02), higher SFR (96.1% vs. 86.1%, p = 0.04), and lower auxiliary procedures (3.9% vs. 13.8%, p = 0.03). Intraoperative and 6-h postoperative changes in heart rate and mean systolic blood pressure were comparable between both groups. Ephedrine injection (6–18 mg) was needed in significantly more GII patients (39.5% vs. 20.8%, p ≤ 0.01). It seems that forced diuresis during pneumatic lithotripsy of the lower ureteric stones is a safe and effective antiretropulsion technique. This would expand the alternative options to the antiretropulsion strategy, especially in centers where the laser and flexible ureteroscopes are not available.

Background In people and dogs, torasemide has higher bioavailability, longer half-life, and longer duration of action than equivalent doses of furosemide but data regarding pharmacological properties of torasemide in cats are limited. Objective To assess pharmacokinetic and pharmacodynamic parameters of torasemide in healthy cats, and to investigate the effects of a single administration of torasemide on indicators of diuresis, plasma creatinine concentration, blood pressure, electrolyte concentrations and markers of the renin-angiotensin-aldosterone system (RAAS). Animals Six clinically healthy adult European shorthair cats. Methods Randomized 4-period crossover design with 3 groups and 4 treatments. Pharmacokinetic parameters were obtained using a noncompartmental analysis, and the clinically effective dose was assessed using a Hill model. Results Mean absolute bioavailability was estimated at 88.1%. Mean total body clearance was 3.64 mL/h/kg and mean terminal half-life was 12.9 hours. Urine output significantly increased after torasemide administration (P < .001). The urine sodium : potassium ratio (uNa : uK) paralleled and was statistically correlated to urine output (P < .001). Administration of a single torasemide dose led to a significant dose-dependent increase in urine aldosterone : creatinine ratio (uAldo : C; P < .001) and a transient decrease in plasma potassium concentration (P < .001) but did not affect blood pressure or plasma creatinine concentration. Conclusions and Clinical Importance A single torasemide dose leads to a significant increase in diuresis and renin-angiotensin-aldosterone system (RAAS) activation in healthy cats, with high absolute bioavailability, and without clinically relevant adverse effects. Pharmacokinetic parameters indicate that once daily dosing of 0.27 mg/kg may be appropriate in a clinical setting.

Aim The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). Methods In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. Results From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). Conclusion In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

Feeding a ventral hernia repair (VHR) patient before the return of bowel function (ROBF) can lead to distention and emesis. Many patients spontaneously diurese after surgery. We hypothesized that this auto-diuresis would signal ROBF.A total of 395 patients who underwent open, laparoscopic, or mixed VHR were evaluated for correlation between fluid status and ROBF or discharge. ROBF within 24 hours and discharge within 24 hours or 48 hours were used as outcome measures.Patients remained an average 3.59 days after surgery in the hospital and the average ROBF was on day 2.99. The first shift of ≥700 mL of urine predicted ROBF ( P =0.03) and discharge ( P =0.04) within 24 hours. The first shift output of ≥500 mL predicted discharge within 48 hours ( P =0.02).Auto-diuresis after surgery is correlated to ROBF and discharge. Accurate fluid measurement can predict bowel function and allow early diet and discharge.