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1.
Kardiologiia ; 64(4): 38-44, 2024 Apr 30.
Article Ru, En | MEDLINE | ID: mdl-38742514

AIM: To evaluate a potential role of different patterns of intrarenal blood flow using Doppler ultrasound as a part of determining the severity of venous congestion, predicting impairment of renal function and an unfavorable prognosis in patients with acute decompensated chronic heart failure (ADCHF). MATERIAL AND METHODS: This prospective observational single-site study included 75 patients admitted in the intensive care unit for ADCHF. Upon admission all patients underwent bedside renal venous Doppler ultrasound to determine the blood flow pattern (continuous, biphasic, monophasic). In one hour after the initiation of intravenous diuretic therapy, sodium concentration was measured in a urine sample. The primary endpoint was the development of acute kidney injury (AKI). The secondary endpoints were the development of diuretic resistance (a need to increase the furosemide daily dose by more than 2 times compared with the baseline), decreased natriuretic response (defined as urine sodium concentration less than 50-70 mmol/l), and in-hospital death. RESULTS: According to the data of Doppler ultrasound, normal renal blood flow was observed in 40 (53%) patients, biphasic in 21 (28%) patients, and monophasic in 14 (19%) patients. The monophasic pattern of intrarenal blood flow was associated with the highest incidence of AKI: among 14 patients in this group, AKI developed in 100% of cases (OR 3.8, 95% CI: 2.5-5.8, p<0.01), while among patients with normal and moderate impairment of renal blood flow, there was no significant increase in the risk of developing AKI. The odds of in-hospital death were increased 25.77 times in patients with monophasic renal blood flow (95% CI: 5.35-123.99, p<0.001). Patients with a monophasic intrarenal blood flow pattern were also more likely to develop diuretic resistance compared to patients with other blood flow patterns (p<0.001) and had a decreased sodium concentration to less than 50 mmol/l (p<0.001) in a spot urine test obtained one hour after the initiation of furosemide administration. CONCLUSION: Patients with monophasic intrarenal blood flow are at a higher risk of developing AKI, diuretic resistance with decreased natriuretic response, and in-hospital death.


Acute Kidney Injury , Heart Failure , Hemodynamics , Humans , Female , Male , Heart Failure/physiopathology , Aged , Prognosis , Prospective Studies , Acute Kidney Injury/physiopathology , Acute Kidney Injury/etiology , Middle Aged , Renal Circulation/physiology , Ultrasonography, Doppler/methods , Diuretics/administration & dosage , Kidney/physiopathology
2.
Physiol Rep ; 12(9): e16033, 2024 May.
Article En | MEDLINE | ID: mdl-38740564

The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs.


Furosemide , Heart Failure , Kidney , Natriuretic Peptide, Brain , Sodium , Stroke Volume , Humans , Heart Failure/physiopathology , Heart Failure/metabolism , Male , Female , Aged , Pilot Projects , Furosemide/pharmacology , Furosemide/administration & dosage , Sodium/metabolism , Sodium/urine , Natriuretic Peptide, Brain/blood , Natriuretic Peptide, Brain/metabolism , Kidney/metabolism , Kidney/physiopathology , Kidney/drug effects , Middle Aged , Natriuresis/drug effects , Diuretics/pharmacology , Diuretics/administration & dosage , Cyclic GMP/metabolism , Cyclic GMP/urine , Aged, 80 and over
3.
Sci Rep ; 14(1): 10511, 2024 05 07.
Article En | MEDLINE | ID: mdl-38714773

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.


Cisplatin , Diuretics , Furosemide , Mannitol , Furosemide/adverse effects , Furosemide/administration & dosage , Cisplatin/adverse effects , Humans , Mannitol/therapeutic use , Mannitol/administration & dosage , Male , Female , Diuretics/administration & dosage , Diuretics/adverse effects , Diuretics/therapeutic use , Middle Aged , Retrospective Studies , Aged , Risk Factors , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Drug Therapy, Combination , Antineoplastic Agents/adverse effects , Adult
5.
Rev Clin Esp (Barc) ; 224(5): 259-266, 2024 May.
Article En | MEDLINE | ID: mdl-38588945

BACKGROUND: some studies suggest that hypochloremia is a risk factor in the prognosis of heart failure (HF) in patients with recent decompensation. MATERIALS AND METHODS: retrospective cohort study of patients discharged due to HF decompensation who began follow-up in a specialized clinic. Two groups are defined: patients with hypochloremia (chloride < 98 mmol/L) and normochloremic patients (chloride > 98 mmol/L) in the initial assessment within the first month after discharge. The rate of intravenous diuretic rescue, emergency department visits, readmission for HF and cardiovascular (CV) death are compared using a Cox proportional hazards model. RESULTS: 165 patients were included (59% women, mean age 85 years), with 60 (36%) having hypochloremia. Both groups were comparable in terms of baseline characteristics, except for female sex, presence of peripheral artery disease, moderate-to-severe liver disease (more prevalent in the hypochloremia group), PROFUND index, and baseline furosemide dose (higher in patients with hypochloremia). The incidence of the primary event was higher in subjects with hypochloremia than in normochloremic subjects (HR: 1.59, 95% CI 0.97-2.62), mainly due to the need for intravenous diuretic rescue (HR: 1.86, 95% CI 1.07-3.24). CONCLUSIONS: hypochloremia following admission for HF decompensation is associated with a greater need for intravenous diuretic rescue therapy and probably worse overall prognosis across the spectrum of the disease, regardless of left ventricular ejection fraction (LVEF).


Heart Failure , Humans , Female , Retrospective Studies , Heart Failure/blood , Male , Aged, 80 and over , Prognosis , Aged , Chlorides/blood , Diuretics/administration & dosage , Risk Factors
7.
J Am Pharm Assoc (2003) ; 64(3): 102063, 2024.
Article En | MEDLINE | ID: mdl-38432480

BACKGROUND: Literature on pregabalin use in patients with heart failure is largely limited to patient case reports and cohort studies. OBJECTIVE: This study aimed to evaluate the effect of pregabalin initiation on diuretic requirements in patients with heart failure. METHODS: A retrospective analysis of patients with heart failure who were started on pregabalin between January 1, 2014, and September 1, 2021, at the Veterans Affairs North Texas Health Care System was used. The primary objective was to determine the median change in loop diuretic dose, in furosemide dose equivalents, 6 months after pregabalin initiation. RESULTS: Of 58 patients analyzed, there was no statistically significant difference in the primary outcome (P = 0.162). The secondary outcomes were found to be nonstatistically significant, and there was no correlation between pregabalin dose and outcomes. CONCLUSION: This represents the largest analysis of diuretic dose requirements in patients with heart failure after initiation of pregabalin. Although there was no difference in the median change of diuretic dose prescribed, pregabalin should still be used with caution.


Heart Failure , Pregabalin , Humans , Heart Failure/drug therapy , Heart Failure/physiopathology , Pregabalin/administration & dosage , Pregabalin/therapeutic use , Retrospective Studies , Male , Female , Aged , Middle Aged , Furosemide/administration & dosage , Furosemide/therapeutic use , Texas , Aged, 80 and over , Chronic Disease/drug therapy , Diuretics/administration & dosage , Diuretics/therapeutic use , Dose-Response Relationship, Drug , Sodium Potassium Chloride Symporter Inhibitors/administration & dosage , Sodium Potassium Chloride Symporter Inhibitors/therapeutic use
8.
Am J Obstet Gynecol MFM ; 6(4): 101348, 2024 Apr.
Article En | MEDLINE | ID: mdl-38485054

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control. OBJECTIVE: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure. STUDY DESIGN: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure. RESULTS: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention. CONCLUSION: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected.


Antihypertensive Agents , Diuretics , Furosemide , Humans , Furosemide/administration & dosage , Female , Pregnancy , Double-Blind Method , Adult , Diuretics/administration & dosage , Antihypertensive Agents/administration & dosage , Blood Pressure/drug effects , Blood Pressure/physiology , Hypertension, Pregnancy-Induced/drug therapy , Hypertension, Pregnancy-Induced/physiopathology , Hypertension, Pregnancy-Induced/diagnosis , Drug Therapy, Combination/methods , Treatment Outcome
12.
Circ J ; 88(5): 680-691, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38143082

BACKGROUND: This retrospective observational study investigated the incidence of worsening renal function (WRF) in patients hospitalized for heart failure (HF) and treated with intravenous diuretics in Japan.Methods and Results: Associations between WRF at any point and HF treatments, and the effects of WRF on outcomes were evaluated (Diagnosis Procedure Combination database). Of 1,788 patients analyzed (mean [±SD] age 80.5±10.2 years; 54.4% male), 641 (35.9%) had WRF during a course of hospitalization for worsening HF: 208 (32.4%) presented with WRF before admission (BA-WRF; estimated glomerular filtration rate decreased by ≥25% from baseline at least once between 30 days prior to admission and admission); 44 (6.9%) had WRF that persisted before and after admission (P-WRF); and 389 (60.7%) had WRF develop after admission (AA-WRF). Delayed initial diuretic administration, higher maximum doses of intravenous diuretics during hospitalization, and diuretic readministration during hospitalization were associated with a significantly higher incidence of AA-WRF. Patients with WRF at any time point were at higher risk of death during hospitalization compared with patients without WRF, with adjusted hazard ratios of 3.56 (95% confidence interval [CI] 2.23-5.69) for BA-WRF, 3.23 (95% CI 2.21-4.71) for AA-WRF, and 13.16 (95% CI 8.19-21.15) for P-WRF (all P<0.0001). CONCLUSIONS: Forty percent of WRF occurred before admission for acute HF; there was no difference in mortality between patients with BA-WRF and AA-WRF.


Diuretics , Heart Failure , Hospitalization , Aged , Aged, 80 and over , Female , Humans , Male , Administration, Intravenous , Diuretics/administration & dosage , Diuretics/adverse effects , Glomerular Filtration Rate , Heart Failure/drug therapy , Heart Failure/physiopathology , Heart Failure/mortality , Japan/epidemiology , Retrospective Studies , Time Factors
13.
Med. clín (Ed. impr.) ; 161(4): 154-157, ago. 2023. ilus, tab
Article Es | IBECS | ID: ibc-224118

Introducción y objetivo En la insuficiencia cardíaca la congestión es el síntoma más frecuente y es habitual la resistencia diurética. El objetivo del estudio es analizar si la ultrafiltración (UF) ambulatoria de corta duración por vía periférica es útil y segura en estos pacientes. Material y métodos Se analizaron los 5 primeros pacientes ultrafiltrados por resistencia diurética en una unidad de gestión rápida de un hospital de referencia durante 12h. Resultados Estos pacientes estaban en tratamiento con al menos 3 diuréticos por vía oral; la UF permitió reducir y/o retirar algunos. El volumen extraído durante el procedimiento fue de 1520±271ml. Hubo cambios significativos en la diuresis (pre-UF: 1360±164; post-UF: 1670±254ml; p=0,035); peso (pre-UF: 69,6±14; post-UF: 66,2±15kg; p=0,0001) y creatinina (pre-UF: 2,1±0,3; post-UF: 1,8±0,4mg; p=0,023). Conclusiones En pacientes en régimen ambulatorio con insuficiencia cardíaca y resistencia a los diuréticos, la UF de corta duración por vía periférica resultó efectiva y segura (AU)


Introduction and objective In heart failure congestion is the most common symptom and diuretic resistance is frequent. This study aims to analyse whether short-term peripheral outpatient ultrafiltration (UF) is useful and safe in these patients. Material and methods The first 5 patients ultrafiltrated for diuretic resistance in a fast-track unit of a referral hospital for 12hours were analysed. Results These patients were on treatment with at least 3 oral diuretics; UF made it possible to reduce and/or withdraw some of them. The volume extracted during the procedure was 1520±271ml. There were significant changes in diuresis (PreUF: 1360±164, PostUF: 1670±254ml; P=.035), weight (PreUF: 69.6±14, PostUF: 66.2±15kg; P=.0001) and creatinine (PreUF: 2.1±0.3, PostUF: 1.8±0.4mg; P= 0.023). Conclusions In outpatients with heart failure and diuretic resistance, short-course peripheral UF was effective and safe (AU)


Humans , Male , Female , Aged, 80 and over , Ultrafiltration/methods , Diuretics/administration & dosage , Heart Failure/therapy , Treatment Outcome , Retrospective Studies
14.
N Engl J Med ; 388(9): 781-791, 2023 03 02.
Article En | MEDLINE | ID: mdl-36856614

BACKGROUND: Nephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited. Furthermore, dose-response data are also limited. METHODS: In this double-blind trial, we randomly assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. The main objective was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of preexisting stones that had been observed on the baseline image. Safety was also assessed. RESULTS: In all, 416 patients underwent randomization and were followed for a median of 2.9 years. A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). There was no relation between the hydrochlorothiazide dose and the occurrence of a primary end-point event (P = 0.66). Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo. CONCLUSIONS: Among patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily. (Funded by the Swiss National Science Foundation and Inselspital; NOSTONE ClinicalTrials.gov number, NCT03057431.).


Diuretics , Hydrochlorothiazide , Kidney Calculi , Humans , Hydrochlorothiazide/administration & dosage , Hydrochlorothiazide/adverse effects , Hydrochlorothiazide/therapeutic use , Kidney/diagnostic imaging , Kidney Calculi/diagnostic imaging , Kidney Calculi/prevention & control , Sodium Chloride Symporter Inhibitors/administration & dosage , Sodium Chloride Symporter Inhibitors/adverse effects , Sodium Chloride Symporter Inhibitors/therapeutic use , Recurrence , Double-Blind Method , Dose-Response Relationship, Drug , Diuretics/administration & dosage , Diuretics/adverse effects , Diuretics/therapeutic use
15.
Actas dermo-sifiliogr. (Ed. impr.) ; 113(5): 498-504, Mayo 2022. ilus, tab
Article Es | IBECS | ID: ibc-206495

La hidroclorotiazida (HCTZ) y otros diuréticos tiazídicos son fármacos que se han empleado desde hace décadas para el tratamiento de la hipertensión arterial, la insuficiencia cardíaca o la enfermedad renal crónica. Las tiazidas se han asociado con reacciones de fotosensibilidad, siendo heterogéneas en cuanto a manifestación clínica y tiempo de recuperación, y en las cuales, el fototest, el fotoparche y la biopsia cutánea nos pueden ser útiles en el diagnóstico. En relación con estos fármacos, en los últimos años se ha evidenciado también un mayor riesgo dosis-dependiente de desarrollar determinados tipos de cáncer cutáneo en pacientes tratados de forma crónica con HCTZ. En esta revisión se comentan, asimismo, otros efectos adversos menos habituales o reconocidos de los diuréticos tiazídicos reportados de forma aislada en la literatura (AU)


Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports (AU)


Humans , Hydrochlorothiazide/administration & dosage , Hydrochlorothiazide/adverse effects , Diuretics/administration & dosage , Diuretics/adverse effects , Skin Neoplasms/chemically induced
16.
Actas dermo-sifiliogr. (Ed. impr.) ; 113(5): t498-t504, Mayo 2022.
Article En | IBECS | ID: ibc-206496

Hydrochlorothiazide and other thiazide diuretics have been used for decades to treat high blood pressure, heart failure, and chronic kidney disease. Thiazides have been linked to photosensitivity with heterogeneous clinical manifestations and recovery times. Diagnosis can be aided by phototesting, photopatch testing, and skin biopsy. Long-term use of hydrochlorothiazide has been linked to an increased dose-dependent risk of certain types of skin cancer in recent years. In this review, we also look at other less common or lesser-known adverse effects of thiazide diuretics that have been described in isolated reports (AU)


La hidroclorotiazida (HCTZ) y otros diuréticos tiazídicos son fármacos que se han empleado desde hace décadas para el tratamiento de la hipertensión arterial, la insuficiencia cardíaca o la enfermedad renal crónica. Las tiazidas se han asociado con reacciones de fotosensibilidad, siendo heterogéneas en cuanto a manifestación clínica y tiempo de recuperación, y en las cuales, el fototest, el fotoparche y la biopsia cutánea nos pueden ser útiles en el diagnóstico. En relación con estos fármacos, en los últimos años se ha evidenciado también un mayor riesgo dosis-dependiente de desarrollar determinados tipos de cáncer cutáneo en pacientes tratados de forma crónica con HCTZ. En esta revisión se comentan, asimismo, otros efectos adversos menos habituales o reconocidos de los diuréticos tiazídicos reportados de forma aislada en la literatura (AU)


Humans , Hydrochlorothiazide/administration & dosage , Hydrochlorothiazide/adverse effects , Diuretics/administration & dosage , Diuretics/adverse effects , Skin Neoplasms/chemically induced
17.
Sci Rep ; 12(1): 2127, 2022 02 08.
Article En | MEDLINE | ID: mdl-35136147

Although intravenous diuretics is a cornerstone of acute heart failure treatment (AHF), its optimal initial dose is unclear. This is a post-hoc analysis of the REALITY-AHF, a prospective multicentre observational registry of AHF. The initial intravenous diuretic dose used in each patient was categorised into below, standard, or above the recommended dose groups according to guideline-recommended initial intravenous diuretic dose. The recommended dose was individualised based on the oral diuretic dose taken at admission. We compared the study endpoints, including 60-day mortality, diuretics response within six hours, and length of hospital stay (HS). Of 1093 patients, 429, 558, and 106 were assigned to the Below, Standard, and Above groups, respectively. The diuretics response and HS were significantly greater in the Below group than in the Standard group after adjusting for covariates. Kaplan-Meier analysis indicated a significantly higher incidence of 60-day mortality in the Above group than the Standard group. This difference was retained after adjusting for other prognostic factors. Treatment with a lower than guideline-recommended intravenous diuretic dose was associated with longer HS, whereas above the guideline-recommended dose was associated with a higher 60-day mortality rate. Our results reconfirm that the guideline-recommended initial intravenous diuretic dose is feasible for AHF.


Diuretics/administration & dosage , Furosemide/administration & dosage , Heart Failure/drug therapy , Registries , Administration, Intravenous , Aged , Aged, 80 and over , Female , Heart Failure/mortality , Humans , Japan/epidemiology , Male , Retrospective Studies
18.
PLoS One ; 17(2): e0263682, 2022.
Article En | MEDLINE | ID: mdl-35139129

Acute kidney injury (AKI) associated with "Triple Whammy" drug therapy consisting of renin-angiotensin system inhibitors, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported. There have been no reports investigating "Triple Whammy" drug therapy and the time to AKI onset using adverse drug events report databases. The aim of this study was to determine the relationship between the time to AKI onset and treatment with "Triple Whammy" drug therapy. We analyzed AKI cases registered in the Japanese Adverse Drug Event Report database. The data were analyzed using the Kaplan-Meier approach, generalized Wilcoxon tests, and Weibull distribution. AKI was reported in 18,415 cases, of which 7,466 cases used Triple Whammy drugs. All combinations of Triple Whammy drugs were associated with significantly higher odds ratios for reporting AKI. In Weibull analysis, AKI onset was early for most combination patterns of Triple Whammy drugs. The Kaplan-Meier approach showed that the treatment duration to AKI onset was much shorter in cases using NSAIDs; median onsets, 8 days for triple combination, 7 days for NSAIDs added to renin-angiotensin system inhibitors, 9 days for NSAIDs added to diuretics, 6 days for diuretics added to NSAIDs, and 9 days for NSAIDs alone. AKI associated with Triple Whammy drugs is likely to occur in the early stages of treatment, especially with concomitant NSAIDs. Patients should be monitored for the occurrence of AKI within the first 2 weeks.


Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antihypertensive Agents/adverse effects , Diuretics/adverse effects , Adverse Drug Reaction Reporting Systems/organization & administration , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Aged , Aged, 80 and over , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/adverse effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Antihypertensive Agents/administration & dosage , Databases, Factual/statistics & numerical data , Diuretics/administration & dosage , Drug Therapy, Combination/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Incidence , Japan/epidemiology , Male , Middle Aged , Time Factors
19.
BMC Nephrol ; 23(1): 3, 2022 01 03.
Article En | MEDLINE | ID: mdl-34979962

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.


Cardio-Renal Syndrome/drug therapy , Cardio-Renal Syndrome/physiopathology , Diuretics/administration & dosage , Adult , Chlorthalidone/administration & dosage , Chlorthalidone/adverse effects , Diuretics/adverse effects , Double-Blind Method , Drug Administration Schedule , Female , Furosemide/administration & dosage , Furosemide/adverse effects , Humans , Infusions, Intravenous , Male , Middle Aged , Pilot Projects , Prospective Studies , Spironolactone/administration & dosage , Spironolactone/adverse effects , Treatment Outcome
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