High-dose Diuretics Research Articles

European Consensus on use of diuretics in chronic heart failure 2019

The article presents the consensus materials of the European Society of Cardiology on the use of diuretics in chronic heart failure (CHF). Diuretics represent an important class of drugs for the treatment of heart failure from the perspective of evidence based medicine. Much attention in the consensus s paid to the algorithm of using diuretics, in particular loop diuretics, in acute decompensation of CHF. Clinical and pharmacological advantages and disadvantages of the main drugs of loop diuretics (furosemide, torasemide, bumetanide) in CHF are discussed. There was analyzed the effectiveness of low and high doses of loop diuretics, the method of administration (bolus or continuous infusion) in terms of effective diuretic therapy and prevention of tolerance to diuretics, as well as the impact on the prognosis of survival during decompensation of heart failure. It also discusses modern approaches to the diagnostic criteria for assessing the effectiveness of diuretic therapy in acute decompensation of CHF, and shows the possibility of determination the level of excretion of Na + ions in the urine as a surrogate marker of the effectiveness of diuretic therapy to optimize the dosage regimen of diuretics. An algorithm of diuretic therapy is proposed (the choice of dosages and regimens for using loop diuretics) for patients with acute decompensation of heart failure, including intravenous use of loop diuretics in an optimal increasing dose for the first 24 hours before stopping stagnation with a further transition to a maintenance dose of loop diuretic for euvolemia status and combined diuretic therapy with thiazides to obtain synergism. The recommendations for correction of electrolyte disturbances against the background of diuretic therapy is considered. Loop diuretics are recommended for CHF to prevent signs and symptoms of congestion: this is the only group of drugs with a level of recommendation as class I in patients with heart failure with a reduced or preserved ejection fraction.

A Higher Concentration of Dialysate Magnesium to Reduce the Frequency of Muscle Cramps: A Narrative Review.

Purpose of review:Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps.Sources of information:Peer-reviewed articles.Methods:We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist.Key findings:The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia.Limitations:Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.

Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial

ObjectivesThis study compared combination diuretic strategies in acute heart failure (AHF) complicated by diuretic resistance (DR). BackgroundCombination diuretic regimens to overcome loop DR are commonly used but with limited evidence. MethodsThis study was a randomized, double-blinded trial in 60 patients hospitalized with AHF and intravenous (IV) loop DR. Patients were randomized to oral metolazone, IV chlorothiazide, or tolvaptan therapy. All patients received concomitant high-dose IV infusions of furosemide. The primary outcome was 48-h weight loss. ResultsThe cohort exhibited DR prior to enrollment, producing 1,188 ± 476 ml of urine in 12 h during high-dose loop diuretic therapy (IV furosemide: 612 ± 439 mg/day). All 3 interventions significantly improved diuretic efficacy (p < 0.001). Compared to metolazone (4.6 ± 2.7 kg), neither IV chlorothiazide (5.8 ± 2.7 kg; 1.2 kg [95% confidence interval (CI)]: −2.9 to 0.6; p = 0.292) nor tolvaptan (4.1 ± 3.3 kg; 0.5 kg [95% CI: −1.5 to 2.4; p = 0.456) resulted in more weight loss at 48 h. Median (interquartile range [IQR]) cumulative urine output increased significantly and did not differ among those receiving metolazone (7.78 [IQR: 6.59 to 10.10] l) and chlorothiazide (8.77 [IQR: 7.37 to 10.86] l; p = 0.245) or tolvaptan (9.70 [IQR: 6.36 to 13.81] l; p = 0.160). Serum sodium decreased less with tolvaptan than with metolazone (+4 ± 5 vs. −1 ± 3 mEq/l; p = 0.001), but 48-h spot urine sodium was lower with tolvaptan (58 ± 25 mmol/l) than with metolazone (104 ± 16 mmol/l; p = 0.002) and with chlorothiazide (117 ± 14 mmol/l; p < 0.001). ConclusionsIn this moderately sized DR trial, weight loss was excellent with the addition of metolazone, IV chlorothiazide, or tolvaptan to loop diuretics, without a detectable between-group difference. (Comparison of Oral or Intravenous Thiazides vs. tolvaptan in Diuretic Resistant Decompensated Heart Failure [3T]; NCT02606253)

P6311Is the new PH classification useful to assess the need for heart transplantation? Looking for harder markers for hard patients

Abstract Background Pulmonary hypertension (PH) is an important prognostic marker among patients (pts) with heart failure. Recent ESC guidelines have introduced the concept of diastolic transpulmonary gradient (DPG) to differentiate combined (CpC) and isolated (IpC) post-capillary PH. However, its validation in a setting of patients evaluated for heart transplantation (HT) has been poorly explored; moreover, it doesn't incorporate right ventricular (RV) function. Purpose To analyze the prognostic role of current classification of PH and its interplay with RV function and diuretic therapy in pts with advanced heart failure referred for HT. Methods We included all pts evaluated for HT in our Center (2002–16) undergoing to a right heart cath (RHC), collecting data at first evaluation. Patients were divided into three groups: no PH (mPAP&lt;25 mmHg), IpC-PH (mean PAP &gt;25 mmHg, PVR&lt;3 WU), CpC-PH (mean PAP&gt;25 mmHg, PVR ≥3 WU and/or DPG ≥7 mmHg). Pulmonary artery pulsatility index (PAPi) was analyzed as a marker of RV function; oral furosemide&gt;125 mg/day (median value) or i.v. diuretics/dialysis were considered as high-dose diuretics (HDD). The study endpoint was the combined incidence of death or need for high urgent HT, expressed as 2-yrs survival rate. Results Among the overall cohort of 458 pts (53.1±10.9 yrs, 82,6% males, 40.3% CAD, 9.3% on IABP), 57.9% had PH: 30.8% IpC-PH, 27.1% CpC-PH. Only 8 pts (0.2%) had DPG≥7, one with PVR&lt;3. The use of HDD differed significantly according to PH classes (44.6% vs 56.3% vs 68.3%, no PH vs IpC vs CpC-PH respectively, p&lt;0.01) and was associated with a worse outcome (p&lt;0.01). The incidence of the primary endpoint in the overall cohort was 74.1±2.5%. While pts with CpC-PH had the worst prognosis, DPG≥7 did not predict the primary endpoint. At multivariate analysis, PVR ≥3 WU (HR: 16.7), PAPi &lt;3.8 (median value, HR: 4.1), HDD (HR: 5.6) were independent predictors of the primary endpoint, (p&lt;0.04 for all) as well as need for IABP (HR: 19.0, p&lt;0.01), even adjusting for clinical variables. Lower PAPi values carried an higher risk at 2 years both in IpC and CpC PH groups, thus allowing to better stratify the need for urgent HT (81.6±6.6% vs 78.6±5.7% vs 67.3±6.7% vs 49.1±7.9% respectively, p&lt;0.001) (Fig.1). Figure 1 Conclusion Our results suggest that, even if current definition of type 2 PH predicts the need of urgent HT, the incorporation of DPG ≥7 is epidemiologically irrelevant and doesn't increase accuracy, whereas combining an indirect marker of RV function (PAPi) with PVR assessment, even correcting for diuretic therapy, could help to better stratify the need of a rare resource like HT in patients with advanced heart failure and pulmonary hypertension.

A LITTLE CHANGE GOES A LONG WAY: A RARE PRESENTATION OF SARCOIDOSIS

SESSION TITLE: Tuesday Fellows Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Sarcoidosis is a granulomatous disorder, affecting multiple systems throughout the body. We present a case of sarcoidosis, presenting with nephrotic syndrome. CASE PRESENTATION: The patient is a 51-year-old female, with history of well-controlled type II diabetes and hypertension, who presented initially with bilateral lower extremity edema, first noted one week prior to admission. Her history was notable for a negative smoking and drug history, no exposures, and no relevant family history. Her physical exam was notable for 2+ to 3+ bilateral lower extremity edema, presacral edema, and 1+ upper extremity edema. Labs showed elevated serum creatinine. A 24-hour urine collection demonstrated nephrotic-range proteinuria. Chest imaging showed bilateral hilar lymphadenopathy. She was discharged on high-dose diuretics; however, edema continued to worsen and she gained 18 kg over two months. A renal biopsy was performed two months later, which demonstrated interstitial nephritis with well-formed granulomas. Electron microscopy was performed, which demonstrated podocyte effacement, consistent with minimal change disease. Endobronchial ultrasound was later performed with fine needle aspiration at lymph node stations 4R, 7, and 11R, which again demonstrated granulomatous inflammation. She was discharged home with steroids and aggressive diuresis, with resultant improvement in edema. DISCUSSION: Sarcodosis is a multi-system disease that can affect the kidneys in up to 30% of cases1. The most typical form of renal sarcoidosis is granulomatous interstitial nephritis (GIN). The majority of patients with GIN present with elevated creatinine noted at the time of diagnosis. Urinalysis in GIN is usually bland or demonstrates sterile pyuria or hematuria. Very few patients present with significant proteinuria. Minimal change disease (MCD) has only been reported in singular case reports in patients with sarcoidosis. In a retrospective study of 26 patients with biopsy-proven glomerulonephritis and sarcoidosis, only three patients had MCD, and only one was diagnosed with MCD concurrently with sarcoidosis. In adult patients, MCD is most commonly associated with drugs, particularly NSAIDs. However, in patients with mediastinal lymphadenopathy and MCD, more ominous etiologies, including Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and leukemia, should be ruled out. Steroids are the mainstay of treatment for MCD in association with sarcoidosis, but these agents may be contraindicated in the setting of malignancy. CONCLUSIONS: Minimal change disease is an exceedingly rare presenting symptom of sarcoidosis. When minimal change disease is diagnosed in the setting of mediastinal lymph adenopathy, malignancy should be ruled out by lymph node sampling. Reference #1: Bergner R, Löffler C. Renal sarcoidosis: approach to diagnosis and management. Curr Opin Pulm Med. 2018;24(5):513-520. Reference #2: Mahévas M, Lescure FX, Boffa JJ, et al. Renal sarcoidosis: clinical, laboratory, and histologic presentation and outcome in 47 patients. Medicine (Baltimore). 2009;88(2):98-106. Reference #3: Stehlé T, Joly D, Vanhille P, et al. Clinicopathological study of glomerular diseases associated with sarcoidosis: a multicenter study. Orphanet J Rare Dis. 2013;8:65. DISCLOSURES: Speaker/Speaker's Bureau relationship with boehringer ingelheim Please note: $5001 - $20000 Added 06/10/2019 by Brad Bemiss, source=Web Response, value=Travel and payment for lecture No relevant relationships by Krishnan Warrior, source=Web Response

Ambulating Patients with Femoral Intra-Aortic Balloon Pump as Bridge to Heart Transplant - A Case Series

Introduction Patients with end stage HF not responsive to GDMT are often referred for OHT. IABP are often utilized to support these patients as a bridge. Frailty has been shown to correlate with increased morbidity in such patients. Gait speed is well described in the frailty phenotype in patients with HF. We postulate that interventions to prevent or treat frailty may result in better outcomes after OHT. To that end, our center has an aggressive physical and occupational therapy program in place to assist patients with ambulation and improvement in gait speed prior to surgery. To date, no published literature describes the efficacy of ambulation in patients with femoral IABP. We review the feasibility of ambulation on femoral IABP for patients who eventually underwent OHT at our center. Methods A retrospective analysis was performed from January 2018-March 2019, which identified four patients with advanced HF who ambulated with femoral IABP prior to OHT. A KREG catalyst standing bed was utilized to advance patients (with femoral IABP) from supine immobility to in-bed tilting, standing, and finally, ambulating off the bed and into the environment with a rolling walker. The first patient was a 26 year old male with HOCM who presented in acute cardiogenic shock. He was optimized with inotropes and had a femoral IABP in place for 128 days prior to OHT. The patient progressed from standing to ambulating, and his preoperative gait speed improved from 0.23 to 1.21 m/s. He had one episode of minor bleed at the site of IABP which resolved with localized pressure. No other complications occurred. The second patient was a 58 year old male with dilated cardiomyopathy on inotropes. He had a femoral IABP for 21 days prior to OHT. He progressed from in-bed standing to ambulating, reaching a preoperative gait speed of 0.46 m/s. No complications occurred. The third patient was a 59 year old male with ICM on inotropes and high-dose diuretics. He had a femoral IABP for 43 days and improved his gait speed from 0.56 to 1.43 m/s. His IABP was displaced once, requiring a device exchange, but no other complications occurred. The fourth patient was a 38 year old male with restrictive cardiomyopathy on inotropic support. He was supported by a femoral IABP for 9 days prior to OHT and progressed from in-bed standing to ambulating, reaching a preoperative gait speed of 0.46 m/s. No complications occurred. All patients did well post-transplant. Average post-operative length of stay was 31 days. All patients walked more than 1000 feet prior to discharge. Conclusions From our small sample size of four patients ambulating with femoral IABP who eventually underwent OHT, we believe ambulation of such patients is safe and feasible. A larger sample size is needed to establish which patients are safe for ambulation with a femoral IABP and if this method can improve patient outcomes.

Subcutaneous Furosemide in the Treatment of Patients with Decompensated Heart Failure: Data from the Sub-Q Pilot Studies

Introduction IV furosemide is used in most patients hospitalized with HF. A buffered formulation of furosemide delivered via an on-body subcutaneous delivery system (scPharmacauticals) that potentially would allow for treatment to be shifted to the outpatient setting was evaluated in 2 pilot studies in patients hospitalized for HF with signs and symptoms of congestion. Hypothesis Treatment with sc furosemide is a safe and feasible approach to treatment of patients with HF and congestion. Methods Patients hospitalized for HF with and congestion regardless of EF were enrolled in 2 sequential pilot studies at 5 centers. Patients requiring high doses of iv loop diuretics (> 200 mg furosemide/day) or clinical instability were excluded. The Sub-Q inpatient pilot (IP) enrolled 20 patients and treated them for 48 hours with sc furosemide (80mg sc over 5 hours given QD or BID based on need) in place of iv loop diuretics while they remained hospitalized. The Sub-Q outpatient pilot (OP) enrolled 20 patients with transition (within 24 hours) to the OP setting where they continued sc furosemide (80mg sc over 5 hours given QD or BID based on need) for up to 7 days. Data were collected on feasibility, urine output, weights, symptoms, and safety. Results In the IP, median age was 70, median EF was 39, and median Cr was 1.4 mg/dL. Patients received a mean of 2.9 treatments over 48 hours and urine output over the 2 days of treatment was 5.3 L (figure). There were 8 device issues observed. There were 4 AEs in the IP, 3 were injection site discomfort. In the OP, median age was 61, median EF was 35, and median cr was 1.4 mg/dL. Patients received a mean of 6.9 treatments over 7 days. Signs and symptoms of congestion improved in most patients, although weight did not change significantly from baseline to day 7. There were 21 device issues in 10 unique patients (mostly difficulty the filling the delivery system). There were 18 AE's (mostly mild and related to injection site discomfort). There was 1 SAE that was unrelated to study treatment. There were 2 rehospitalizations for HF over 14 days from randomization in the OP. Conclusions Treatment of selected HF patients with sc furosemide provided the anticipated effects on decongestion in both the inpatient and outpatient settings, although there were issues with the drug delivery system that limited feasibility. Ongoing developments of the delivery system for sc furosemide may make this a safe and feasible approach for treatment of congestion in the outpatient setting in selected patients.

Acetazolamide to Increase Natriuresis in Congestive Heart Failure at High Risk for Diuretic Resistance

Introduction Signs and symptoms of congestion are the predominant reason for hospital admission with acute heart failure (AHF). Diuretics are mainstay treatment, but their optimal type and dose regimen remains unclear. Hypothesis Acetazolamide in addition to loop diuretics increases natriuresis without further neurohumoral activation, potentially improving decongestion and outcomes in AHF. Methods This prospective, 2-center study included 34 AHF patients on loop diuretics with volume overload. All patients had a serum sodium concentration 50 and/or admission serum creatinine increased with >0.3 mg/dL compared to baseline. Patients were randomized towards acetazolamide 500 mg OD plus bumetanide 1-2 mg BID versus high-dose loop diuretics (bumetanide BID with bolus dose equal to oral maintenance dose). The primary end-point was natriuresis after 24h. Results Natriuresis after 24h was similar in the combinational treatment versus loop-diuretic only arm (264±126 versus 234±133 mmol, respectively; P-value=0.515). Loop diuretic efficiency, defined as natriuresis corrected for loop diuretic dose, was higher in the group receiving acetazolamide (84±46 versus 52±42 mmol/mg bumetanide, respectively; P-value=0.048; Figure). More patients in the combinational treatment arm had an increase in serum creatinine levels >0.3 mg/dL (P-value=0.046). NT-proBNP reduction and peak neurohumoral activation within 72h were comparable among treatment arms. Median time to all-cause mortality or heart failure readmission was 273 versus 803 days in the group receiving high-dose loop diuretic monotherapy versus acetazolamide with low-dose loop diuretics, which favoured the latter group but was not statistically significant (P-value=0.098). Conclusion Addition of acetazolamide increases the natriuretic response to loop diuretics with similar neurohumoral responses compared to an increase in loop diuretic dose in AHF at high risk for diuretic resistance. ClinicalTrials.gov identifier: NCT01973335.

Natriuretic Response Is Highly Variable and Associated With 6-Month Survival: Insights From the ROSE-AHF Trial

ObjectivesThis study sought to describe sodium excretion in acute decompensated heart failure (ADHF) clearly and to evaluate the prognostic ability of urinary sodium and fluid-based metrics. BackgroundSodium retention drives volume overload, with fluid retention largely a passive, secondary phenomenon. However, parameters (urine output, body weight) used to monitor therapy in ADHF measure fluid rather than sodium balance. Thus, the accuracy of fluid-based metrics hinges on the contested assumption that urinary sodium content is consistent. MethodsPatients enrolled in the ROSE-AHF (Renal Optimization Strategies Evaluation-Acute Heart Failure) trial with 24-h sodium excretion available were studied (n = 316). Patients received protocol-driven high-dose loop diuretic therapy. ResultsSodium excretion through the first 24 h was highly variable (range 0.12 to 19.8 g; median 3.63 g, interquartile range: 1.85 to 6.02 g) and was not correlated with diuretic agent dose (r = 0.06; p = 0.27). Greater sodium excretion was associated with reduced mortality in a univariate model (hazard ratio: 0.80 per doubling of sodium excretion; 95% confidence interval: 0.66 to 0.95; p = 0.01), whereas gross urine output (p = 0.43), net fluid balance (p = 0.87), and weight change (p = 0.11) were not. Sodium excretion of less than the prescribed dietary sodium intake (2 g), even in the setting of a negative net fluid balance, portended a worse prognosis (hazard ratio: 2.02; 95% confidence interval: 1.17 to 3.46; p = 0.01). ConclusionsIn patients hospitalized with ADHF who were receiving high-dose loop diuretic agents, sodium concentration and excretion were highly variable. Sodium excretion was strongly associated with 6-month mortality, whereas traditional fluid-based metrics were not. Poor sodium excretion, even in the context of fluid loss, portends a worse prognosis.

Management of Acute Admissions of Heart Failure Patients with Kidney Disease

Acute heart failure (HF) admissions are common. They are often associated with prolonged hospitalisations and poor outcomes. One-third of chronic HF patients also suffer from chronic kidney disease (CKD). Hence, acute admissions of HF with CKD are common and are associated with longer length of stay and increased mortality. Hyperkalaemia and acute on chronic renal impairment are important challenges in the management of these cases. Cautious introduction of high-dose diuretic therapy, followed by the re-commencement of renin-angiotensin-aldosterone (RAAS) inhibitors, improves length of stay, quality of life, and prognosis. During an admission on to the medical assessment unit careful monitoring and management of the patient’s clinical condition and biochemistry is essential.

Bicalutamide-induced Eosinophilic Pneumonitis - A Serendipitous Diagnosis

Bicalutamide is a first-generation non-steroidal anti-androgen. Interstitial lung disease is a rare side effect of bicalutamide. Centres in the United States of America and Japan have previously reported bicalutamide-induced interstitial lung disease. This has not been reported in the United Kingdom.&#x0D; An 86-year-old Caucasian man with a history of advanced prostate cancer, on oral bicalutamide, presented to the emergency department with sudden onset dyspnoea and chest tightness.&#x0D; Bicalutamide-induced eosinophilic pneumonitis co-existing with community acquired pneumonia, and left ventricular systolic dysfunction were suspected, based on physical examination findings and investigation results that include blood tests, chest radiographs, echocardiogram, in addition to computed tomography pulmonary angiogram performed to rule out pulmonary embolism.&#x0D; There was a marked clinical, biochemical and radiological improvements after discontinuation of bicalutamide, initiation of a high-dose steroid, intravenous antibiotics, and diuretic. Prostate cancer retains a high incidence in the Western population. Recognising toxicities due to anti-androgen therapies is relevant to clinical practice.&#x0D;

Impact of short-acting loop diuretic doses and cardiac sympathetic nerve abnormalities on outcomes of patients with reduced left ventricular function.

Recent studies reported that high doses of short-acting loop diuretics are associated with poor outcomes in patients with heart failure (HF). Short-acting loop diuretics have been shown to activate the renin-angiotensin system (RAS) and have no favorable effects on cardiac sympathetic nervous system (SNS) activity. The goal of this study is to investigate the relationship between daily doses of furosemide and the outcomes of patients with left ventricular dysfunction (LVD) from the viewpoint of cardiac SNS abnormalities using iodine-123-labeled metaiodobenzylguanidine (123l-MIBG) myocardial scintigraphy.We enrolled 137 hospitalized patients (62.5 ± 14.2 years old, 103 men) with LVEF < 45% who underwent 123l-MIBG myocardial scintigraphy. A delayed heart-to-mediastinum ratio (delayed HMR) was assessed using 123l-MIBG scintigraphy. Cardiac events were defined as cardiac death or re-hospitalization due to the deterioration of HF. Cox proportional hazard analysis was used to identify predictors of cardiac events.Cardiac events occurred in 57 patients in a follow-up period of 33.1 ± 30 months. In a multivariate Cox proportional hazard analysis, delayed HMR and furosemide doses were identified as independent predictors of cardiac events (P = .0042, P = .033, respectively). Inverse probability of treatment weighting Cox modeling showed that the use of furosemide (≥40 mg /day) was associated with cardiac events with a hazard ratio of 1.96 (P = .003). In the Kaplan-Mayer analysis, the cardiac event-free survival rate was significantly lower in patients treated with high doses of furosemide (≥60 mg/day vs 40–60 mg/day vs <40 mg/day, the Log-rank test P < .0001). In a receiver-operating characteristic (ROC) analysis, the cut-off value for cardiac events was 40 mg/day of furosemide. The cardiac event-free rate was significantly lower in patients with delayed HMR <1.8 (median value) and receiving furosemide ≥40 mg/day than in other patients (the Log-rank test P < .0001). Significant differences in cardiac event rates according to furosemide doses among patients with delayed HMR <1.8 were observed among patients without β-blocker therapy (P = .001), but not among those with β-blocker therapy (P = .127).The present results indicate that a relationship exists between higher doses of furosemide and poor outcomes. The prognosis of HF patients with severe cardiac SNS abnormalities receiving high-dose short-acting loop diuretics is poor.

Lymphocele complications following renal transplantation

Introduction: Lymphocele formation following renal transplantation is a well-known complication. Mostly these are small and inconsequential, but large lymphocele may cause symptoms like pain, infection , renal dysfunction, surgical drainage of lymphatics Surgical damage of the lymphatics of the graft during the procurement and of the lymphatics around the iliac vessels of the recipients has been responsible with development of lymphocele. Several factors such as diabetes, obesity, blood coagulation abnormalities, anticoagulation prophylaxis, high dose of diuretics, delay in graft function and immunosuppressive drugs are known to be related to these complications. We report three cases of symptomatic lymphoceles managed at our centre during the past one year. Patients and Methods: We retrospectively reviewed patients undergoing renal transplant at our centre. Out of 18 transplant recipients 3 cases developed large symptomatic lymphoceles. These were evaluated by Computed Tomography (CT) scan/ Ultrasound (USG) and serum creatinine levels. These patients were managed by ultrasound guided aspiration and instillation of doxycyline. Results: All three patients underwent USG guided aspiration and doxycyline instillation had significant reduction in serum creatinine levels with no recurrence of lymphoceles on follow-up. Conclusions: lymphocele remains important surgical complications following renal transplantation. Prompt diagnosis and early intervention is crucial to prevent permanent renal damage..

Rationale and design of the ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) trial.

Decisive evidence on the optimal diuretic agent, dosing schedule, and administration route is lacking in acute heart failure (AHF) with congestion. The Acetazolamide in Decompensated heart failure with Volume OveRload (ADVOR) trial is designed to test the hypothesis that the carbonic anhydrase inhibitor acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption, improves decongestion when combined with loop diuretic therapy in AHF, potentially leading to better clinical outcomes. The ADVOR trial is set up as a multicentre, randomized, double-blind, placebo-controlled study, aiming to recruit 519 patients with AHF and clinically evident volume overload. All study participants receive high-dose intravenous loop diuretics as background therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg once daily vs. placebo, stratified according to including study centre and ejection fraction (< 40% vs. ≥ 40%). The primary endpoint is successful decongestion with no more than trace oedema assessed on the third morning after hospital admission, with good diuretic efficacy defined as a urine output > 3.5 L during the first 30-48 h of decongestive treatment. Secondary endpoints include all-cause mortality or heart failure readmission after 3 months, length of hospital stay for the index admission, and longitudinal changes in the EuroQol-5 dimensions questionnaire. ADVOR will investigate if acetazolamide combined with loop diuretic therapy improves decongestion in AHF with volume overload.

Protective Effects of Diuretics Against the Development of Cardiovascular Disease in Patients with Chronic Kidney Disease: A Systematic Review.

Cardiovascular disease is one of the most important risk factors for mortality and morbidity in patients with Chronic Kidney Disease (CKD). This systematic review focuses on the protective effects of diuretics against the development of cardiovascular disease in patients with CKD. Among various kinds of diuretics, spironolactone, a mineralocorticoid receptor antagonist, has been shown to have protective effects against cardiovascular disease in patients with all stages of CKD, including predialysis, hemodialysis, and peritoneal dialysis. Low-dose loop diuretics have also been shown to have cardioprotective effects in patients with CKD during the pre-dialysis and hemodialysis stages; however, high-dose loop diuretics have failed to show these cardioprotective effects. The protective effects of other classes of diuretics, including thiazide and tolvaptan, against cardiovascular diseases in patients with CKD remain unclear.

11. Rationalising diuretic use in Indian patients with decompensated liver cirrhosis: a stepping stone to set guidelines for Indian patients

Background and Aims: To determine the dose requirement of commonly used diuretics among Indian patients with decompensated liver cirrhosis presenting with ascites. Methods: This prospective study was done at Gleneagles Global Health City, Chennai. Consecutive patients with cirrhosis and ascites attending outpatient clinic for from January to March 2018 were included. Patient information included age, gender, etiology of cirrhosis, state of origin, CTP score, MELD score, drug details, complications, need for paracentesis, and response to diuretic use at a single point. The primary outcome of the study was the need for a paracentesis. Indications for paracentesis were non-response to diuretics or inability to increase the dose due to complications. Chi square test and risk ratio calculation were done. p value <0.05 was considered statistically significant. Results: A total of 73 cases with median age of 54.6 years (range 26–74 years) and predominant male sex (61,83.6%) formed the study cohort. NASH and alcohol were the most common cause for liver cirrhosis. 68.5% of cases had MELD score >15 and 57% belonged to CTP class B. Majority of the cases (54, 74%) were on a combination of drugs with furosemide and spironolactone (20/50 mg) being the commonest dose. Nineteen patients were on a single drug with spironolactone being the most commonly prescribed drug (12,63%). Side effects of diuretics were noted in 48% of cases: renal dysfunction and dyselectrolytemia being the commonest. 25 patients required paracentesis. Diuretic induced complications and poor urine output were significantly more common among those requiring paracentesis. Conclusions: Indian patients seldom require high doses of diuretics and 48% develop complications related to diuretic use even at lower doses. The occurence of diuretic induced complications and poor urine output may be used as marker of requirement of paracentesis in Indian patients. The authors have none to declare.

Osteolytic lesions (brown tumors) of primary hyperparathyroidism misdiagnosed as multifocal giant cell tumor of the distal ulna and radius: a case report

BackgroundBrown tumors represent a rare clinical manifestation reported in approximately 3% of patients with primary hyperparathyroidism and correspond to radiologically osteolytic lesions with well-defined borders in different parts of the skeleton.Case presentationWe report the case of a 53-year-old white man who presented to our hospital with osteolytic lesions of his distal ulna and radius, causing pain and swelling of 2-month duration. A subsequent biopsy revealed histological features consistent with giant cell tumor and a complete resection of his distal ulna was followed, along with curettage and cementoplasty of the distal radial metaphysis. Two weeks later, he was re-admitted with diffuse musculoskeletal soreness, anorexia, constipation, nausea, and localized abdominal pain and multiple osteolytic lesions on plain radiographs. A histopathological examination of the ulna and radius specimens showed similar findings and, given the multifocality, brown tumors related to primary or secondary hyperparathyroidism was included in the differential diagnosis. A laboratory examination showed high total serum calcium (14.5 mg/dl) and low serum phosphorus and 25-hydroxyvitamin D levels. Primary hyperparathyroidism was suspected and confirmed by the elevated parathyroid hormone levels of 1453 pg/mL. At radiological work-up, using computed tomography, ultrasonography, and parathyroid subtraction technetium-99m sestamibi scintigraphy, a 4.5 × 2.5 × 3.2 cm mass emanating from the right lobe of his thyroid gland was detected, displaying extensive uptake in the right lower parathyroid gland. After appropriate medical support including hyperhydration and high doses of diuretics and diphosphonates, his laboratory profile normalized and he underwent total thyroidectomy with removal of the parathyroid glands. Our patient is now recovering 12 months after surgery, with normal values of serum parathyroid hormone and calcium levels. The lytic bone lesions have almost disappeared and no other additional orthopedic intervention was necessary.ConclusionsThe present case report emphasizes the need of inclusion of brown tumors in the differential diagnosis of multifocal osteolytic bone lesions, in order to avoid harmful surgical interventions. Laboratory testing of serum phosphate, calcium levels, and parathyroid hormone levels should always be included in the routine survey of patients with multifocal osteolytic lesions.

Spironolactone to increase natriuresis in congestive heart failure with cardiorenal syndrome

Background: Signs and symptoms of volume overload are the most frequent reason for hospital admission in acute heart failure (AHF). Diuretics are mainstay treatment, but their optimal type and dose regimen remain unclear, especially in patients with cardiorenal syndrome.Methods: This prospective study aimed to include 80 AHF patients with volume overload and cardiorenal syndrome. Through a 2 × 2 factorial design, patients were randomised towards (1) combinational treatment with acetazolamide and low-dose loop diuretics versus high-dose loop diuretics; and (2) open-label oral spironolactone 25 mg OD given upfront versus at discharge. Here reported are the results of the spironolactone treatment arm after complete follow-up of 34/80 patients (since the study was stopped because of slow recruitment). The primary study end-point was incident hypokalaemia (<3.5 mmol/L) or hyperkalaemia (>5.5 mmol/L).Results: Serum potassium derangements were numerically less frequent in the upfront versus discharge spironolactone group, yet this result was underpowered due to incomplete study recruitment (hyperkalaemia: 6% vs. 11%; hypokalaemia: 13% vs. 28%, respectively; p-value = .270). Natriuresis after 24 h was higher in the upfront vs. discharge spironolactone group (314 ± 142 vs. 200 ± 91 mmol/L, respectively; p-value = .010). Relative change in plasma NT-proBNP level after 72 h was similar among both groups (−16 ± 29% vs. −5 ± 45%, respectively; p value = .393), with no difference in all-cause mortality (p-value = .682) or the combination of all-cause mortality and heart failure readmission (p-value = .799).Discussion: Spironolactone use upfront in AHF patients at high risk for cardiorenal syndrome is safe and increases natriuresis.

A case of functional hypoparathyoidism due to hypomagnesaemia leading to hypocalcaemic seizures

This case report describes an elderly lady who was maintained on a high dose of loop diuretics following resolution of her acute pulmonary oedema, which in turn led to wasting of calcium and magnesium at the nephron level. Her hypomagnesaemia further contributed to the hypocalcaemia by rendering ineffective the normal parathyroid negative feedback physiological response. This state of low calcium increased the neuromuscular excitability leading to myoclonic epilepsy which was resistant to benzodiazepines. Such hypocalcaemic tetany in this case would only be adequately addressed once the magnesium levels are repleted, as this would allow the parathyroid mechanism to function effectively and redress the calcium level as a result.

Author Reply

We appreciate the reviewer's supportive comments. As they stated, identifying a bidirectional causality between systemic and urologic disease states would be novel and extraordinarily impactful. Doing this in a statistically valid way would likely be in the realm of big data. Our more modest goal is focused on the ability to counsel patients on the likelihood of meaningful impact of our urologic therapies in the context of their broader systemic health. A transurethral resection of prostate may not help urinary frequency in an uncontrolled diabetic on high dose diuretics. Testosterone replacement may not help fatigue in untreated sleep apnea. Engaging the patient in their medical care to improve their urologic symptoms may be aided by the use of the anxiety, cardiovascular, testosterone deficiency, insulin (diabetes), obesity, neurologic, and sleep apnea phenotype. Similarly, we hope that the urologic community sees their time with male patients as an opportunity to improve their general health in addition to their urologic health. The urologic conditions studied in this paper affect quality of life not quantity of life in a direct manner. Quality of life impact is an impetuous for patients to seek medical care, therefore the urologist may serve as a gatekeeper for patients, particularly when they are young and their systemic conditions are modifiable.