Comparison of preventive effects of combined furosemide and mannitol versus single diuretics, furosemide or mannitol, on cisplatin-induced nephrotoxicity.

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m2, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m2) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.

Mannitol versus furosemide in patients with thoracic malignancies who received cisplatin-based chemotherapy using short hydration: A randomized phase II trial.

BACKGROUND: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. METHODS: This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. RESULTS: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). CONCLUSIONS: Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.

Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF.

BACKGROUND: The TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) found no significant difference in all-cause mortality or hospitalization among patients randomized to a strategy of torsemide versus furosemide following a heart failure (HF) hospitalization. However, outcomes and responses to some therapies differ by left ventricular ejection fraction (LVEF). Thus, we sought to explore the effect of torsemide versus furosemide by baseline LVEF and to assess outcomes across LVEF groups. METHODS: We compared baseline patient characteristics and randomized treatment effects for various end points in TRANSFORM-HF stratified by LVEF: HF with reduced LVEF, ≤40% versus HF with mildly reduced LVEF, 41% to 49% versus HF with preserved LVEF, ≥50%. We also evaluated associations between LVEF and clinical outcomes. Study end points were all-cause mortality or hospitalization at 30 days and 12 months, total hospitalizations at 12 months, and change from baseline in Kansas City Cardiomyopathy Questionnaire clinical summary score. RESULTS: Overall, 2635 patients (median 64 years, 36% female, 34% Black) had LVEF data. Compared with HF with reduced LVEF, patients with HF with mildly reduced LVEF and HF with preserved LVEF had a higher prevalence of comorbidities. After adjusting for covariates, there was no significant difference in risk of clinical outcomes across the LVEF groups (adjusted hazard ratio for 12-month all-cause mortality, 0.91 [95% CI, 0.59-1.39] for HF with mildly reduced LVEF versus HF with reduced LVEF and 0.91 [95% CI, 0.70-1.17] for HF with preserved LVEF versus HF with reduced LVEF; P=0.73). In addition, there was no significant difference between torsemide and furosemide (1) for mortality and hospitalization outcomes, irrespective of LVEF group and (2) in changes in Kansas City Cardiomyopathy Questionnaire clinical summary score in any LVEF subgroup. CONCLUSIONS: Despite baseline demographic and clinical differences between LVEF cohorts in TRANSFORM-HF, there were no significant differences in the clinical end points with torsemide versus furosemide across the LVEF spectrum. There was a substantial risk for all-cause mortality and subsequent hospitalization independent of baseline LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813.

Could admission level of uric acid predict total diuretic dose in acute heart failure?

BACKGROUND: Recent studies have shown that increases in serum UA levels are associated with adverse clinical outcomes in patients with chronic heart failure (CHF); the aim of this study was to determine the relationship between serum uric acid and total diuretic dose received during hospitalization in hospitalized patients with acute exacerbation of heart failure. The main purpose of this study is to determine the role of uric acid as a biomarker that can be a substitute for pro-BNP in clinical evaluation and the need for diuretics in hospitalized patients with acute heart failure. METHODS: After approving the plan in the Research Council of the Heart Department and obtaining an ethical code from the Regional Committee on Research Ethics (Human Subjects Studies), the researcher referred to the archives of our center, the case of 100 patients diagnosed with acute heart failure. Cardiac patients were selected, and the information required for the study was collected using a pre-prepared data collection form, and the information was entered into SPSS software after categorization and appropriate analysis and statistical tests were performed on it. Were performed and in all statistical tests the statistical significance level was considered 0.05: RESULTS: 100 patients with acute heart failure were included in this study with a mean age of 63.43 ± 14.78 years. 66% of them were men. The mean dose of furosemide in these patients was 680.92 ± 377.47 mg and the mean serum uric acid level in these patients was 8.55 ± 2.50 mg / dL. In the study of the relationship between the variables, there was a significant relationship between the dose of furosemide received with the serum level of serum uric acid (P = 0.017, r = 0.248 and P = 0.009, r = -0.267, respectively). There is also a significant relationship between serum uric acid level and patient mortality (P = 0.013, r = 0.247). However this relationship lost its significance after multivariate analysis. CONCLUSION: There is a significant relationship between serum uric acid level and diuretic use. However, in-hospital mortality is not related to uric acid levels at admission.

Diuretic Use in Post-Kidney Transplant Patients: A Retrospective Chart Review.

BACKGROUND: The occurrence of delayed graft function (DGF) significantly enhances the possibility of both acute and chronic rejection of the transplanted organ, thereby reducing patient quality of life and survival rates. To prevent and manage oliguria in renal transplant patients, loop diuretics are presently commonly used. In our study, we assessed the possible impact of furosemide on the incidence of DGF among kidney transplant recipients. METHODS: A review of medical records was conducted to examine demographic characteristics and kidney transplant outcomes in an adult (older than 18 years old) population. The primary objective was to determine the incidence of delayed graft function (DGF), whereas the secondary objective was to compare the creatinine levels and estimated glomerular filtration rate (eGFR) at day 30 and day 90 post-transplantation in patients who were administered furosemide vs those who were not. RESULTS: This study included 330 patients who underwent kidney transplantation. Furosemide was administered to 169 (51.3%), whereas 161(48.7%) patients did not receive continued dose of diuretic postoperatively. The rate of DGF was significantly higher in patients who received furosemide than in those who did not (furosemide 44% vs 4%; P < .001). The eGFR was lower in the furosemide group compared to the no furosemide group at day 30 (56 ± 24 vs 71 ± 24 mL/min/1.73 m2, P < .001) and day 90 (66 ± 27 vs 78 ± 25 mL/min/1.73 m2, P < .001). CONCLUSIONS: Our results show that there is no benefit in treating an oliguric AKI with furosemide. Administration of furosemide, especially in high doses, may increase the risk of toxicity, delay dialysis, and increase the length of stay.

Association between methotrexate-induced Stevens-Johnson syndrome/toxic epidermal necrolysis and furosemide: a real-world disproportionality analysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and life-threatening skin adverse reactions that are usually induced by drugs. This study aimed to assess the association between methotrexate and SJS/TEN when combined with furosemide. RESEARCH DESIGN AND METHODS: Data on suspicious, interactions (PS, SS, I) from the FDA Adverse Event Reporting System database for 2016-2021 were analyzed using the reporting odds ratio (ROR), information component (IC), proportional reporting ratio (PRR) and the Medications and Health Care Products Regulatory Agency (MHRA). RESULTS: We identified 28 case reports of TEN associated with the combination of furosemide and methotrexate and 10 reports of SJS associated with furosemide and methotrexate. The association of methotrexate with SJS/TEN was more significant in the entire data set when combined with furosemide than when methotrexate was not combined with furosemide. The association of methotrexate with SJS/TEN remained significant when furosemide was combined with methotrexate in a tumor-based disease context. After sensitivity analysis of the entire dataset as well as all antineoplastic drug datasets, consistent results were observed for TEN. CONCLUSIONS: Our study confirmed a significant association between methotrexate and SJS/TEN when combined with furosemide, with an increased risk of SJS/TEN.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Use of loop diuretics in patients with chronic heart failure: an observational overview.

INTRODUCTION: This study aimed to evaluate the use and dose of loop diuretics (LDs) across the entire ejection fraction (EF) spectrum in a large, 'real-world' cohort of chronic heart failure (HF) patients. METHODS: A total of 10 366 patients with chronic HF from 34 Dutch outpatient HF clinics were analysed regarding diuretic use and diuretic dose. Data regarding daily diuretic dose were stratified by furosemide dose equivalent (FDE)>80 mg or ≤80 mg. Multivariable logistic regression models were used to assess the association between diuretic dose and clinical features. RESULTS: In this cohort, 8512 (82.1%) patients used diuretics, of which 8179 (96.1%) used LDs. LD use was highest among HF with reduced EF (HFrEF) patients (81.1%) followed by HF with mild-reduced EF (76.1%) and HF with preserved ejection fraction EF (73.8%, p<0.001). Among all LDs users, the median FDE was 40 mg (IQR: 40-80). The results of the multivariable analysis showed that New York Heart Association classes III and IV and diabetes mellitus were one of the strongest determinants of an FDE >80 mg, across all HF categories. Renal impairment was associated with a higher FDE across the entire EF spectrum. CONCLUSION: In this large registry of real-world HF patients, LD use was highest among HFrEF patients. Advanced symptoms, diabetes mellitus and worse renal function were significantly associated with a higher diuretic dose regardless of left ventricular ejection fraction.

Hospitalized patients received furosemide undergoing acute kidney injury: the risk and prediction tool.

PURPOSE: Furosemide, a frequently prescribed diuretic for managing congestive heart failure and edema, remains a topic of debate regarding its potential risk of inducing acute kidney injury (AKI) in patients. Consequently, this study aims to examine the occurrence of hospital-acquired AKI (HA-AKI) in hospitalized patients who are administered furosemide and to investigate potential risk factors associated with this outcome. METHODS: This study encompassed a cohort of 22374 hospitalized patients who either received furosemide treatment or not from June 1, 2012, to December 31, 2017. Propensity score matching was employed to establish comparability between the two groups regarding covariates. Subsequently, a nomogram was constructed to predict the probability of AKI occurrence among patients who underwent furosemide treatment. RESULTS: The regression analysis identified the single-day total dose of furosemide as the most significant factor for AKI, followed by ICU administration, estimated glomerular filtration rate, antibiotic, statin, NSAIDs, ß-blockers, proton pump inhibitor, chronic kidney disease, and 7 other indicators. Subgroup analysis revealed a synergistic effect of furosemide with surgical operation, previous treatment with ß-blockers, ACEI/ARB and antibiotics, leading to an increased risk of AKI when used in combination. Subsequently, a visually represented prognostic nomogram was developed to predict AKI occurrence in furosemide users. The predictive accuracy of the nomogram was assessed through calibration analyses, demonstrating an excellent agreement between the nomogram predictions and the actual likelihood of AKI, with a probability of 77.40%. CONCLUSIONS: Careful consideration of factors such as dosage, concurrent medication use, and renal function of the patient is necessary for clinical practice when using furosemide. Our practical prognostic model for HA-AKI associated with furosemide use can be utilized to assist clinicians in making informed decisions about patient care and treatment.

Dermatologic adverse effect of subcutaneous furosemide administration in a cat.

Background: Furosemide is a mainstay of treatment in congestive heart failure (CHF) and is widely prescribed to dogs and cats by several formulations, including the subcutaneous one. In canine and human medicine, dermatologic adverse effects of subcutaneous furosemide (SF) have been documented; conversely, no prior case has been published describing skin reactions to this therapeutic protocol in cats. In this report, we describe, for the first time in feline medicine, a suspected dermatologic adverse effect after SF in a cat. Case Description: A 2-year-old domestic shorthair cat was presented for CHF associated with lung edema and pleural effusion. Echocardiography revealed asymmetric left ventricular myocardial thickening and severe left atrial dilation. The cat was hospitalized and initially treated with oxygen, intravenous furosemide, and clopidogrel. After discharge, the route of administration of furosemide was switched from intravenous to oral. Within the following 2 weeks, the cat experienced two relapses of lung edema despite the progressive increase of the furosemide dose, the addition of spironolactone and adherence to the therapeutic protocol by the owners. The dose of furosemide was further increased and its route of administration at home was switched from oral to parental. As the owner was not able to administrate intramuscular injections, SF was prescribed. This allowed the prevention of further episodes of lung edema. However, although the cat had never presented skin problems before, multiple well-defined circular, crusted ulcerative cutaneous lesions associated with alopecia developed at the sites of furosemide injections 2 weeks later. After ruling out several differential diagnoses for these lesions, a rare side effect of furosemide, not yet described in cats but already known in canine and human medicine, was strongly suspected as the possible cause. Therefore, the ongoing injectable formulation of furosemide was interrupted and substituted with an alternative brand, maintaining the same dose and route of administration. Thanks to this change, the dermal ulcerations disappeared within 1 month. Subsequently, the cat experienced neither further skin problems nor a recurrence of lung edema. Conclusion: Although SF is sometimes prescribed in small animal practice, it should be noticed that this may lead to dermatologic adverse reactions in the cat.

Evaluation of diuretic efficiency of intravenous furosemide in patients with advanced heart failure in a heart failure clinic.

INTRODUCTION: Diuretic efficiency (DE) is an independent predictor of all-cause mortality in acute heart failure (HF) at long-term follow-up. The performance of DE in advanced HF and the outpatient scenario is unclear. METHODS: Survival function analysis on a retrospective cohort of patients with advanced HF followed at the outpatient clinic of Hospital Universitario San Ignacio (Bogotá, Colombia) between 2017 and 2021. DE was calculated as the average of total diuresis in milliliters divided by the dose of IV furosemide in milligrams for each 6-h session, considering all the sessions in which the patient received levosimendan and IV furosemide. We stratified DE in high or low using the median value of the cohort as the cutoff value. The primary outcome was a composite of all-cause mortality and HF hospitalizations during a 12-month follow-up. Kaplan-Meier curves and log-rank test were used to compare patients with high and low DE. RESULTS: In all, 41 patients (66.5 ± 13.2 years old, 75.6% men) were included in the study, with a median DE of 24.5 mL/mg. In total, 20 patients were categorized as low and 21 as high DE. The composite outcome occurred more often in the high DE group (13 versus 5, log-rank test p = 0.0385); the all-cause mortality rate was 29.2% and was more frequent in the high DE group (11 versus 1, log-rank test p = 0.0026). CONCLUSION: In patients with advanced HF on intermittent inotropic therapy, a high DE efficiency is associated with a higher risk of mortality or HF hospitalization in a 12-month follow-up period.

Tolvaptan's Association with Low Risk of Acute Kidney Injury in Patients with Advanced Chronic Kidney Disease and Acute Decompensated Heart Failure.

INTRODUCTION: Furosemide, a loop diuretic, is often empirically used to treat acute decompensated heart failure (ADHF) initially. Conversely, decongestion using tolvaptan, an aquaretic, is thought to maintain renal function compared to furosemide. However, it has not been investigated in patients with advanced chronic kidney disease (CKD) at high risk of developing acute kidney injury (AKI). This study aimed to investigate AKI incidence using tolvaptan add-on treatment, compared to increased furosemide treatment for patients with ADHF complicated by advanced CKD. METHODS: We retrospectively studied patients with advanced CKD (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m2) who developed ADHF under outpatient furosemide treatment. The exposure was set to tolvaptan add-on treatment, and the control was set to increased furosemide treatment. RESULTS: Of the 163 patients enrolled, 79 were in the tolvaptan group and 84 in the furosemide group. The mean age was 71.6 years, the percentage of males was 63.8%, the mean eGFR was 15.7 mL/min/1.73 m2, and patients with CKD stage G5 were 61.9%. AKI incidence was 17.7% in the tolvaptan group and 42.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.13-0.86], p = 0.023 in multivariate logistic regression analysis). Persistent AKI incidence was 11.8% in the tolvaptan group and 32.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.10-1.06], p = 0.066 in the multinomial logit analysis). CONCLUSION: This study suggests that tolvaptan may be better than furosemide in patients with ADHF experiencing complicated advanced CKD.

Acute kidney injury biomarker olfactomedin 4 predicts furosemide responsiveness.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality in critically ill patients. Olfactomedin 4 (OLFM4), a secreted glycoprotein expressed in neutrophils and stressed epithelial cells, is upregulated in loop of Henle (LOH) cells following AKI. We hypothesized that urine OLFM4 (uOLFM4) will increase in patients with AKI and may predict furosemide responsiveness. METHODS: Urine from critically ill children was collected prospectively and tested for uOLFM4 concentrations with a Luminex immunoassay. Severe AKI was defined by KDIGO (stage 2/3) serum creatinine criteria. Furosemide responsiveness was defined as > 3 mL/kg/h of urine output in the 4 h after a 1 mg/kg IV furosemide dose administered as part of standard of care. RESULTS: Fifty-seven patients contributed 178 urine samples. Irrespective of sepsis status or AKI cause, uOLFM4 concentrations were higher in patients with AKI (221 ng/mL [IQR 93-425] vs. 36 ng/mL [IQR 15-115], p = 0.007). uOLFM4 concentrations were higher in patients unresponsive to furosemide (230 ng/mL [IQR 102-534] vs. 42 ng/mL [IQR 21-161], p = 0.04). Area under the receiver operating curve for association with furosemide responsiveness was 0.75 (95% CI, 0.60-0.90). CONCLUSIONS: AKI is associated with increased uOLFM4. Higher uOLFM4 is associated with a lack of response to furosemide. Further testing is warranted to determine whether uOLFM4 could identify patients most likely to benefit from earlier escalation from diuretics to kidney replacement therapy to maintain fluid balance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Refinement of systemic guinea pig deafening in hearing research: Sensorineural hearing loss induced by co-administration of kanamycin and furosemide via the leg veins.

Auditory disabilities have a large impact on the human population worldwide. Research into understanding and treating hearing disabilities has increased significantly in recent years. One of the most relevant animal species in this context is the guinea pig, which has to be deafened to study several of the hearing pathologies and develop novel therapies. Applying kanamycin subcutaneously and furosemide intravenously is a long-established method in hearing research, leading to permanent hearing loss without surgical intervention at the ear. The intravenous application of furosemide requires invasive surgery in the cervical area of the animals to expose the jugular vein, since a relatively large volume (1 ml per 500 g body weight) must be injected over a period of about 2.5 min. We have established a gentler alternative by applying the furosemide by puncture of the leg veins. For this, custom-made cannula-needle devices were built to allow the vein puncture and subsequent slow injection of the furosemide. This approach was tested in 11 guinea pigs through the foreleg via the cephalic antebrachial vein and through the hind leg via the saphenous vein. Frequency-specific hearing thresholds were measured before and after the procedure to verify normal hearing and successful deafening, respectively. The novel approach of systemic deafening was successfully implemented in 10 out of 11 animals. The Vena saphena was best suited to the application. Since the animals' condition, post leg vein application, was better in comparison to animals deafened by exposure of the Vena jugularis, the postulated refinement that reduced animal stress was deemed successful.

N-Acetyl-L-cysteine Affects Ototoxicity Evoked by Amikacin and Furosemide Either Alone or in Combination in a Mouse Model of Hearing Threshold Decrease.

Drug-induced ototoxicity resulting from therapy with aminoglycoside antibiotics and loop diuretics is one of the main well-known causes of hearing loss in patients. Unfortunately, no specific protection and prevention from hearing loss are recommended for these patients. This study aimed at evaluating the ototoxic effects produced by mixtures of amikacin (AMI, an aminoglycoside antibiotic) and furosemide (FUR, a loop diuretic) in the mouse model as the hearing threshold decreased by 20% and 50% using auditory brainstem responses (ABRs). Ototoxicity was produced by the combinations of a constant dose of AMI (500 mg/kg; i.p.) on FUR-induced hearing threshold decreases, and a fixed dose of FUR (30 mg/kg; i.p.) on AMI-induced hearing threshold decreases, which were determined in two sets of experiments. Additionally, the effects of N-acetyl-L-cysteine (NAC; 500 mg/kg; i.p.) on the hearing threshold decrease of 20% and 50% were determined by means of an isobolographic transformation of interactions to detect the otoprotective action of NAC in mice. The results indicate that the influence of a constant dose of AMI on FUR-induced hearing threshold decreases was more ototoxic in experimental mice than a fixed dose of FUR on AMI-induced ototoxicity. Moreover, NAC reversed the AMI-induced, but not FUR-induced, hearing threshold decreases in this mouse model of hearing loss. NAC could be considered an otoprotectant in the prevention of hearing loss in patients receiving AMI alone and in combination with FUR.

Diuretic and renal effects of angiotensin receptor-neprilysin inhibitor in patients hospitalized for acute heart failure.

In patients hospitalized for acute decompensation of heart failure (HF), the impact of angiotensin receptor-neprilysin inhibitor (ARNI) on diuresis and renal function has not been fully investigated. Patients with HF and reduced ejection fraction who were hospitalized for acute decompensation and newly initiated ARNI after hemodynamic stabilization were enrolled. Changes in urine volume (UV), body weight, estimated glomerular filtration rate (eGFR), and urine N-acetyl-beta-d-glucosaminidase (uNAG) levels before and after ARNI initiation were investigated. Changes in the diuretic response [DR, calculated as urine volume/(intravenous furosemide volume/40 mg)], N-terminal pro-brain natriuretic peptide (NT-proBNP), hematocrit, and plasma volume (PV) were also evaluated. A total of 60 patients were enrolled. ARNI was initiated at a median of 6 [5, 7] days after hospitalization. After initiation of ARNI, body weight, NT-proBNP, and PV decreased. UV and DR increased only on the day of ARNI initiation (delta UV 400 ± 957 ml and delta DR 1100 ± 3107 ml/40 mg furosemide) and then decreased to baseline levels. In the multivariable linear regression analysis, younger age, higher BMI, and higher NT-proBNP levels were significantly associated with greater UV after ARNI initiation. eGFR and uNAG did not significantly change after the initiation of ARNI [delta eGFR -1.7 ± 12.0 mL/min/1.73 m2 and delta uNAG 2.0 (-5.6, 6.9) IU/L]. In patients hospitalized for HF, the initiation of ARNI was associated with a small and transient increase in UV and DR, and was not associated with worsening of renal function or tubular injury.

Furosemide-induced haemolytic anaemia in an extreme elderly patient.

Furosemide, a loop diuretic, is commonly used to treat fluid overload symptoms and heart failure. Drug-induced immune haemolytic anaemia is an unusual drug-adverse event. Furosemide-induced haemolysis is even rarer. This case report presents a 91-year-old male who developed acute haemolytic anaemia 3 days after initiating furosemide to treat myocardial infarction complicated with acute decompensated heart failure. He had increased lactate dehydrogenase and unconjugated bilirubin with undetectable haptoglobin, which indicated the destruction of red blood cells. Other causes for haemolytic anaemia, including hereditary, microangiopathic haemolytic anaemia, and paroxysmal nocturnal haemoglobinuria, were also excluded. He improved with drug cessation and a short course of glucocorticoids. This report aims to raise awareness of this rare complication caused by commonly prescribed drugs. Despite a negative result of a direct antiglobulin test, physicians must remain suspicious of drug-induced immune haemolytic anaemia in unclear cases of haemolysis.