Diuretic Group Research Articles

A new hydration strategy can reduce contrast-induced acute kidney injury after PCI in patients with chronic heart failure and chronic kidney disease: a two-center randomized controlled trial

Abstract Backgrounds Adequate hydration is crucial for preventing contrast-induced acute kidney injury (CI-AKI), particularly in patients with chronic kidney disease (CKD). The current guidelines recommend half-volume hydration for patients with chronic heart failure (CHF) to prevent pulmonary edema. Thus, it is challenging to administer hydration therapy in patients with CHF and CKD. This study was aimed to compare different hydration strategies in this subset of patients. Methods This two-center, open-label, randomized clinical trial enrolled 303 CHF (patients with elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion) patients with CKD (estimated glomerular filtration rate [eGFR] of 15-60 mL/min/1.73m2) undergoing selective coronary angiography (CAG) from two tertiary hospitals from October 2020 to December 2023. Patients were randomized into three groups: half-volume hydration group (HH group, 0.5 mL/Kg/h hydration), standard hydration group (SH group, 1 mL/Kg/h hydration), and standard hydration with diuretic group (SH+D group, 1 mL/Kg/h hydration + immediate postoperative intravenous injection of furosemide 20 mg). All patients received hydration from 6 to 12 hours before to 24 hours after the procedure. The primary endpoint was CI-AKI, defined as a serum creatinine (SCr) increase of more than 0.3 mg/dL or 1.5-1.9 times greater than the baseline 48-72 hours after CAG. Safety endpoints included pulmonary edema during hydration, perioperative mortality, and the need for dialysis. Results A total of 101 patients were included in each group. Baseline characteristics (mean age, proportion of males, left ventricular ejection fraction and eGFR) were similar among groups. SCr, cystatin C levels, and SCr level changes between 48 and 72 hours after procedure did not significantly differ among groups (P > 0.05). The incidence of CI-AKI was highest in the HH group (22.8%), lowest in the SH+D group (11.9%), and intermediate in the SH group (17.8%) (P = 0.041). Regarding safety endpoints, there were 2 patients in the HH group, 3 patients in the SH group and 1 patient in the SH+D group experienced heart failure or pulmonary edema during hydration, with no statistically significant differences among the groups (P = 0.874). Perioperative mortality occurred in 1 patient in the HH group and 2 patients in the SH+D group, with no statistically significant differences (P = 0.776). No patient required renal replacement therapy. Conclusions In CHF patients with CKD, the half-volume hydration regimen recommended by guidelines was associated with a higher incidence of CI-AKI compared to standard hydration. However, standard hydration combine with diuretic fails to reduce the risk of heart failure during hydration or perioperative mortality, even if this novel strategy does not increase the risk of CI-AKI compared to standard hydration therapy.

Tolvaptan and the role of kidney aquaporin-2 abundance in managing volume overload in patients with CKD

ABSTRACT Objective This retrospective study evaluated tolvaptan's efficacy, safety, and predictive indicators in managing volume overload in chronic kidney disease (CKD) patients. Methods CKD patients with volume overload, treated with loop diuretics alone or with tolvaptan at Zhongda Hospital, Southeast University, from 1 March 2022 to 31 December 2023, were included. Patients were divided into loop diuretic (Group C) and loop diuretic combined with tolvaptan (Group T) cohorts. Primary outcomes included volume control, changes in weight, urine output, and laboratory parameters within 1 week post-medication. Adverse events such as hypernatremia and hyperkalemia, etc., were recorded. We further conducted immunohistochemical staining of renal biopsy tissues to investigate the roles of aquaporin-2 (AQP2) in the collecting duct and plasma albumin in predicting the efficacy of tolvaptan. Results Of 174 CKD patients with volume overload, 108 (67.07%) were male. Group C and Group T each comprised 87 patients. At baseline, no significant differences in urine output and weight were noted. By day 3, Group T exhibited a greater increase in urine output (P < .001) and weight reduction (P < .001). At day 7, Group T maintained more significant diuretic effects (P < .001). More Group C patients required ultrafiltration therapy (P = .040). Adverse event rates did not significantly differ. Notably, AQP2 expression in the collecting duct may predict tolvaptan responsiveness, while plasma albumin did not affect efficacy. Conclusion Tolvaptan showed efficacy and safety in managing volume overload in CKD patients. The expression of AQP2 in the collecting duct could predict tolvaptan's efficacy. This study protocol was approved by the Ethics Committee of Zhongda Hospital Affiliated to Southeast University (Approval No. 2023ZDSYLL180-P01, Clinical Trial Registration No. ChiCTR2300075274, Trial Registration Link: https://www.chictr.org.cn/guide.html).

Thiazide diuretics versus loop diuretics in stage 3-5 CKD: impact on cardiorenal outcomes

ABSTRACT Objectives The association between diuretic use and cardiorenal outcomes remains limited in patients with stage 3–5 chronic kidney disease (CKD) and hypertension. To address this gap, we aim to investigate the long-term clinical impact of diuretic use with its pharmacological classification in Taiwanese patients with stage 3–5 CKD and hypertension who were concurrently received angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). Methods Using data from the National Health Insurance Research Database (January 2008 to December 2019), we focused on individuals with stage 3–5 CKD receiving ACEIs/ARBs between 2010 and 2018. We categorized the cohort into non-diuretic, loop diuretic (furosemide), thiazide diuretic, and combination diuretic groups. We used a Cox proportional hazards regression model with propensity score matching to analyze the influence of diuretics on all-cause mortality, cardiovascular (CV) death, and cardiorenal adverse outcomes. Results The study included 59,719 patients, with 17,585 in the non-diuretic group and 42,134 in the diuretic group. Diuretics including furosemide use was significantly associated the risks of hospitalization for decompensated congestive heart failure (CHF), acute renal failure (ARF), end-stage renal disease (ESRD) requiring dialysis, CV mortality, and all-cause mortality (p-value <0.001). Thiazide diuretics showed no such adverse outcomes associations. The group receiving both thiazide and furosemide was more associated with all-cause mortality than the nondiuretic, thiazide, and furosemide monotherapy groups (all p-value <0.001). Conclusion Among stage 3–5 CKD patients on ACEIs/ARBs, loop diuretics exposure was associated with increased mortality and hospitalization for cardiorenal events, while thiazide diuretics exposure in isolation had no such associations. In the present data, we cannot evaluate the relationship between furosemide-associated adverse outcomes and worse renal function. These findings highlight the need for randomized controlled trials to assess the safety of loop diuretics in this population, urging caution in their prescription without a clear clinical indication.

Women have a higher risk of hospital admission associated with hyponatremia than men while using diuretics.

Hyponatremia is a common electrolyte disturbance and known adverse drug reaction of diuretics. Women tend to be more susceptible for diuretic associated hyponatremia. The aim of this study was to find more evidence whether women have a higher risk of diuretic associated hyponatremia than men measured at hospital admission for specific diuretic groups and whether there is a sex difference in risk of severity of hyponatremia. All patients using a diuretic and admitted for any reason to Tergooi MC and Haga Teaching hospital in the Netherlands between the 1st of January 2017 and the 31st of December 2021, with recorded sodium levels at admission were included in this study. Cases were defined as patients with a sodium level <135mmol/L, while control patients had a sodium level ≥135mmol/L at admission. Logistic regression analysis was used to calculate odds ratios (OR) with 95% CIs for women versus men and adjusted for potential confounding covariables (age, body mass index, potassium serum level, systolic and diastolic blood pressure, estimated glomerular filtration rate, number of diuretics, comedications and comorbidities). Stratified analyses were conducted for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists), and adjusted for dose. Furthermore, stratified analyses were performed by severity of hyponatremia (severe: <125mmol/L), mild: 125-134mmol/L). A total of 2,506 patients (50.0% women) were included, of which 516 had hyponatremia at admission (20.6%, 56.2% women). Women had a statistically significantly higher risk for hyponatremia at admission than men (OR 1.37; 95% CI 1.12-1.66) and after adjustment for potential risk factors (ORadj 1.55; 95% CI 1.22-1.98). Stratified analyses showed increased odds ratios for thiazides (ORadj 1.35; 95% CI 1.00-1.83) and loop diuretics (ORadj 1.62; 95% CI 1.19-2.19) among women. Use of aldosterone antagonists was also increased but not statistically significant (ORadj 1.15; 95% CI 0.73-1.81). Women had a statistically higher risk to develop mild and severe hyponatremia than men (ORadj 1.36; 95% CI 1.10-1.68 and ORadj 1.96; 95%CI 1.04-3.68, respectively). Women have a higher risk of a hospital admission associated with hyponatremia while using diuretics than men. Further research is necessary to provide sex-specific recommendations.

THE SIMULTANEOUS SPECTRAL DETERMINATION OF CANDESARTAN CILEXETIL AND HYDROCHLOROTHIAZIDE IN TABLETS USING THE TRIVARIATE CLASSICAL LEAST SQUARES METHOD

Objective: Candesartan cilexetil (CDS) is a member of the sartan group of drugs and is widely used to lower blood pressure. Hydrochlorothiazide (HCT) is the most commonly used diuretic group of drugs and is prescribed together with candesartan cilexetil in cases where blood pressure cannot be reduced. Pharmaceutical preparations containing these two active compounds in combination are preferred today to provide a more effective pharmacological effect. Therefore, it is of great importance to determine the quantities of these combined pharmaceutical preparations with new analytical methods that are fast, easy, and sensitive in quality control and routine analysis. In this study, a new trivariate classical least squares calibration method (TCLS) was developed for the simultaneous quantification of candesartan cilexetil (CDS) and hydrochlorothiazide (HCT) in binary mixtures and commercial tablets without using a preliminary separation step. Material and Method: CDS and HCT compounds were kindly donated by National Pharm Ind., Turkey. HPLC-grade methanol (J.T. Baker, Netherlands) was used as a solvent for the spectrophotometric analysis. In the application of the TCLS method, the determination and quantification of CDS and HCT were carried out using UV spectrophotometric measurements with 1 cm quartz cells in the 200-310 nm spectral region (slit range 2 nm). The newly developed TCLS method was tested using a validation set consisting of eight synthetic mixture solutions within the working ranges of 4.0-20.0 μg/ml for CDS and HCT. Simultaneous quantification analyses of CDS and HCT were performed on ATACAND PLUS® Tablet supplied by Astra Zeneca İlaç Ltd Şti. Result and Discussion: The method is based on the application of TCLS to the absorbance measurements at three different wavelength points (223.5, 240.0, and 268.5 nm). The absorptivity values (µg-1mlcm-1) of pure CDS and pure HCT were 6.67x10-2, 2.76x10-2, 2.33x10-2, and 11.41x10-2, 0.46x10-2, 6.42x10-2 at the selected wavelengths, respectively. Recovery values and relative standard deviation values were calculated as 97.2% and 1.61% for CDS and 99.7% and 3.67% for HCT, respectively. This method was successfully applied to the spectrophotometric quantitative analysis of tablets containing CDS and HCT, and then, a good agreement was reported.

Sodium-Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction.

We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.

Novel Leptin-Cardiac TRH pathway responsible for the cardiac alterations in the Hyperleptinemic obesity.

The association between hypertension andobesity-induced cardiac damage is usually accepted.However, no studies have been focused on cardiac alterations in obesity, independently of blood pressure increase. It iswell known that Cardiac TRH induces Left Ventricular Hypertrophy (LVH) and fibrosis, and its inhibition prevents the development ofhypertrophy. Also, it has been described that the adiponectin leptin induces TRH expression. Thus, we hypothesized that in obesity, the increase in TRH induced by hyperleptinemia is responsible for LVH, until now mostly attributed to pressure load. We studied obese Agouti mice suffering from hypertension with hyperleptinemia and found a significant LVH development with increased TRH gene expression. Consequently, we found higher fibrotic (collagens and TGF-β) and hypertrophic markers (BNP and β-MHC) expressionvs lean black controls. As pressure could explain these results, we treated obese mice with diuretic (hydrochlorothiazide 20mg/kg/day) since weaning. Diuretic treatment was successful as the diuretic group was normotensive in contrast to control obese mice. Nevertheless, both groups showed LVH development, higher cardiac precursor TRH gene and peptide expressions and elevated fibrotic and hypertrophic markers expression,pointing out that obesity-induced LVH is not due to hypertension. In addition, we performed Cardiac TRH inhibition by specific siRNA injection compared to control siRNA treatment and evaluated cardiac damage. As expected, expressions and protein increase in hypertrophic and fibrotic markers observed in the AG mouse with the native cTRH system were not seen in the AG mouse with the cTRH silencing. Indeed, the AG + TRH-siRNA group showed hypertrophicmarkers expression and fibrosis measurements similar to the lean BL mice. On the whole, these results point out that the novel Leptin-Cardiac TRH pathway is responsible for the cardiac alterations present in hyperleptinemic obesity, independent of blood pressure, and cTRH long-term silencing since early stages totally preventLVH development and cardiac fibrosis.

Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study

BackgroundLoop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics...

Real-world evidence of the effects of sodium-glucose co-transporter 2 inhibitors on the dosing of diuretics in patients with heart failure: a retrospective cohort study.

Background: Heart failure (HF) was estimated to impact approximately 64 million individuals worldwide in 2017 and is predicted to rise in the coming years. Therefore, the aim of our study was to evaluate the effects of sodium-glucose transport protein 2 (SGLT2) inhibitors on the dosing of diuretics among individuals diagnosed with HF. Methods: A retrospective cohort study was conducted at Security Forces Hospital in Riyadh, Saudi Arabia, between January 2018 and August 2022. The study included adult patients who were diagnosed with heart failure and received dapagliflozin and/or diuretic. A descriptive analysis was conducted to identify significant differences between both groups by using the chi-square test for categorical variables and the Student's t-test for continuous variables. A logistic regression model was also run to identify the odds of each event. Statistical significance was indicated by p values less than .05. Results: Overall reduction in diuretics was reported in 68 patients in the SGLT2 inhibitors plus diuretic therapy group, while in the diuretic therapy group 25 patients reported overall reduction in diuretics (OR = 4.81, 95% [2.74-8.45]). The reduction of the loop dose level was reported by 58 patients in the SGLT2 inhibitors plus diuretic group and by 25 patients in the diuretic group (OR = 3.48, 95% [1.98-6.11]). The discontinuation of thiazide was reported by 16 patients in the SGLT2 inhibitors plus diuretic therapy group, but by only two patients in the diuretic group (OR = 9.04, 95% [2.03-40.19]). After 6 months, ejection fraction was increased by 2.74 in the SGLT2 inhibitors plus diuretic group (p = .0019) and decreased by 2.56 in the diuretic group (p = .0485), both of which were statistically significant. The mean dose changes were decreased by 14.52 in the SGLT2 inhibitors plus diuretic group (p < .0001), which was statistically significant. Conclusion: Treatment with SGLT2 inhibitors plus diuretic significantly reduced the patients' diuretic requirements. Therefore, our finding supports the theoretical concept of minimizing the level of diuretic upon the initiation of SGLT2 inhibitors.

Risk of CKD among patients with DM taking diuretics or SGLT2i: a retrospective cohort study in Taiwan

BackgroundThis study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i.MethodsWe selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities.ResultsThe diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68–3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32–0.63; aHR, 0.26, 95% CI, 0.17–0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36–0.94) than the both SGLT2i and diuretics group.ConclusionThis study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.

Association between chronic diuretics and postnatal growth in preterm infants with bronchopulmonary dysplasia

BackgroundChronic diuretics such as thiazides and spironolactone are frequently used off-label in preterm infants with evolving or established bronchopulmonary dysplasia (BPD). Infants who are high risk for BPD are already predisposed to poor postnatal growth and the effect of chronic diuretics on postnatal growth is not well studied. ObjectiveExploratory study to determine the association between chronic diuretic exposure and short-term postnatal growth in preterm infants born at less than ≤ 29 weeks gestational age (GA). MethodsSingle-center retrospective cohort study in a level IV neonatal intensive care unit over a 2-year period (2021–22). Eligible infants exposed to chronic diuretics > 5 days for BPD (diuretic group) were compared to infants who were not (non-diuretic group). ResultsIn total, 53 infants (19 diuretic, and 35 non-diuretic group) were identified. The GA (25.3 vs 27.0 weeks) and birth weight (780 vs. 995 gs) were significantly lower in diuretic vs. non-diuretic group (p = 0.01). Diuretic group had higher intubation rate at birth, more days on non-invasive ventilation, higher incidence of moderate/severe BPD, and longer hospital stay (all p < 0.05). The GA adjusted z-scores for weight, length, and head circumference at birth, at 36-week corrected GA, and at discharge were similar in both groups. Also, the z-score change from birth at 36-week corrected GA, and at discharge were similar in both groups. There was no significant short-term change in weight z-score in the 2 weeks following chronic diuretic exposure. ConclusionsChronic diuretic exposure has no significant association with short-term postnatal growth in preterm infants.

Comparative estimation of the effects of antihypertensive medications on schizophrenia occurrence: a multinational observational cohort study

BackgroundThe association between antihypertensive medication and schizophrenia has received increasing attention; however, evidence of the impact of antihypertensive medication on subsequent schizophrenia based on large-scale observational studies is limited. We aimed to compare the schizophrenia risk in large claims-based US and Korea cohort of patients with hypertension using angiotensin-converting enzyme (ACE) inhibitors versus those using angiotensin receptor blockers (ARBs) or thiazide diuretics.MethodsAdults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia.Results5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99–1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78–1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71–1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05–1.43]).ConclusionsThe risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years.

Comparison of Urinary Biomarkers in Diagnosis of Ureteropelvic Junction Obstruction and Differentiation from Nonobstructive Dilatation.

Differentiation of nonobstructive dilatation (NOD) from ureteropelvic junction obstruction (UPJO) is a challenge in children with antenatally detected hydronephrosis. The aim of this study is to compare the utility of urinary biomarkers: carbohydrate antigen (CA 19-9), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule (KIM) in diagnosing UPJO. A prospective study was conducted after obtaining ethical clearance between 2021 and 2022. Group 1 - control group (n = 30): children with normal antenatal ultrasound with no urinary symptoms. Group 2 - study group (n = 48): children with unilateral hydronephrosis: Group 2a - NOD (n = 24): children stable on ultrasound and diuretic renogram and Group 2b - UPJO (n = 24): children who worsened to Grade 4 hydronephrosis on ultrasound/worsening of differential renal function (10% drop) on renogram who underwent pyeloplasty. Urinary biomarkers NGAL, KIM-1, and CA 19-9 were measured using the enzyme-linked immune absorbent assay method. The urine CA 19-9 level was 128.05 ± 4.08 U/mL in the UPJO group, and this was significantly higher (P = 0.001) than NOD, 70.29 ± 4.41, and controls, 1.91 ± 1.57. The urine NGAL level was 21.41 ± 4.44 pg/mL in UPJO, and this was significantly higher than controls, 2.669 ± 0.513, but not NOD, 24.55 ± 2.67. The urine KIM level was 817 ± 15.84 pg/mL in the UPJO group, and this was significantly higher than controls, 285 ± 8.10, but not NOD, 768.23 ± 15.12. Receiver operating characteristic analysis of CA 19-9 revealed a urine biomarker cutoff of 95 U/mL for diagnosing UPJO (sensitivity 95%; specificity 96%; and area under the curve 0.99). CA 19-9 is a superior marker compared to NGAL and KIM in differentiating UPJO from NOD. Further studies with larger numbers are warranted.

Сложности и ограничения в медикаментозной терапии пациента с рецидивирующим нефролитиазом и сопутствующими хроническими заболеваниями сердечно-сосудистой системы

Nowadays, under conditions of an aging population, the comorbidity problem is of utmost importance in all branches of clinical medicine. The greatest difficulties are caused by the case when drug therapy of one nosology contradict with drugs prescribed for the treatment of another. In modern cardiology, extensive groups of diuretics and antihypertensives are widely used for therapy. At the same time, doctors do not always take into account the negative impact of cardiotropic therapy on the kidney stone disease process, as well as the general principles of metaphylaxis of nephrolithiasis on the cardiovascular system state. The paper presents data that allows to recommend the prescription of thiazides and combined antihypertensives, which have such in their composition, if the form of nephrolithiasis is idiopathic (stiff restriction). Besides, in conditions of urate nephrolithiasis, it is desirable to replace acetylsalicylic acid with clopidogrel, losartan with another sartan or an angiotensin-converting enzyme inhibitor. It is worth prescribing citrate mixtures with caution in metaphylaxis and nephrolithiasis litholysis, if there is no complete confidence in compensated cardiovascular diseases. KEYWORDS: recurrent nephrolithiasis, thiazides, potassium-sparing diuretics, gliflozines, losartan, acetylsalicylic acid, furosemide, acetazolamide, natural diuretics, urine pH. FOR CITATION: Yarovoy S.K., Royuk R.V. Difficulties and limitations in drug therapy of a patient with recurrent nephrolithiasis and concomitant chronic cardiovascular diseases. Russian Medical Inquiry. 2024;8(4):235–239 (in Russ.). DOI: 10.32364/2587-6821-2024-8-4-8.

Ciddi Nörolojik Bulgularla Birlikte Giden Lityum Zehirlenmesi Olgusu

Lithium is used for the treatment of bipolar disorder and some other psychiatric disorders. Due to the narrow therapeutic range, intoxications are common. In this case, chronic lithium intoxication with severe neurological symptoms was discussed in light of the literature. A 72-year-old female patient. The patient had been receiving psychiatric treatment for 7 years with the diagnosis of unipolar depression. In the 6th month of lithium use, she was brought by her relatives with complaints of drowsiness, tremor, muscle twitching, and difficulty walking. On examination, consciousness was confused, there was no cooperation orientation and there was general rigidity, tremor, fasciculations, and ataxic gait. Vital signs; blood pressure 147/92 mmHg, heart rate 69 bpm, SpO2: 94%. The laboratory tests: lithium 2.98 mEq/L, potassium 5.8 mmol/l, sodium 129 mmol/l, creatinine 1.66 mg/dl, urea 166 mg/dl. The patient was transferred to the internal medicine clinic with the diagnosis of lithium intoxication. Lithium treatment was discontinued. On the 7th day, her neurological symptoms improved with supportive treatment, and biochemical parameters returned to normal. A lithium concentration of more than 3.5 mEq/L was defined as severe poisoning. Neurological findings are prominent in severe poisonings. Especially, geriatric population is at greater risk. In our case; age, use of three different groups of diuretics as antihypertensive treatment, and urinary tract infection were defined as factors that predispose to poisoning. In this case, it's emphasized that although the lithium blood level isn't very high, severe neurological symptoms can be seen clinically in the presence of risk factors.

Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker

The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood. To determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up. This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at least 1 other coronary heart disease risk factor for up to 23 years, from February 23, 1994, to December 31, 2017. Trial participants were linked with administrative databases for posttrial mortality (N = 32 804) and morbidity outcomes (n = 22 754). Statistical analysis was performed from January 2022 to October 2023. Participants were randomly assigned to receive a thiazide-type diuretic (n = 15 002), a CCB (n = 8898), or an ACE inhibitor (n = 8904) for planned in-trial follow-up of approximately 4 to 8 years and posttrial passive follow-up for up to 23 years. The primary end point was mortality due to cardiovascular disease (CVD). Secondary outcomes included all-cause mortality, combined fatal and nonfatal (morbidity) CVD, and both mortality and morbidity for coronary heart disease, stroke, heart failure, end-stage renal disease, and cancer. A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]). In this secondary analysis of a randomized clinical trial in an adult population with hypertension and coronary heart disease risk factors, CVD mortality was similar between all 3 groups. ACE inhibitors increased the risk of stroke outcomes by 11% compared with diuretics, and this effect persisted well beyond the trial period. ClinicalTrials.gov Identifier: NCT00000542.

Extracorporeal membrane oxygenation and acute kidney injury: a single-center retrospective cohort

To assess the relationship between acute kidney injury (AKI) with outcomes among patients requiring extracorporeal membrane oxygenation (ECMO). This is a single-center, retrospective cohort study of adult patients admitted to intensive care units (ICU) at a tertiary referral hospital requiring ECMO from July 1, 2015, to August 30, 2019. We assessed the temporal relationship of AKI and renal replacement therapy with ECMO type (VV vs. VA). The primary outcome was in-hospital mortality rates. We used Kruskal–Wallis or chi-square tests for pairwise comparisons, cause-specific Cox proportional hazards models were utilized for the association between AKI prevalence and in-hospital mortality, and a time-dependent Cox model was used to describe the association between AKI incidence and mortality. After the screening, 190 patients met eligibility criteria [133 (70%) AKI, 81 (43%) required RRT]. The median age was 61 years, and 61% were males. Among AKI patients, 48 (36%) and 85 (64%) patients developed AKI before and after ECMO, respectively. The SOFA Day 1, baseline creatinine, respiratory rate (RR), use of vasopressin, vancomycin, proton pump inhibitor, antibiotics, duration of mechanical ventilation and ECMO, and ICU length of stay were higher in AKI patients compared with those without AKI (P < 0.01). While ICU and in-hospital mortality rates were 46% and 50%, respectively, there were no differences based on the AKI status. The type and characteristics of ECMO support were not associated with AKI risk. Among AKI patients, 77 (58%) were oliguric, and 46 (60%) of them received diuretics. Urine output in the diuretic group was only higher on the first day than in those who did not receive diuretics (P = 0.03). Among ECMO patients, AKI was not associated with increased mortality but was associated with prolonged duration of mechanical ventilation and ICU length of stay.

The effect of perioperative diuretic administration on acute kidney injury in patients with acute myocardial infarction after percutaneous coronary intervention: a real-world retrospective study.

The relationship between diuretic use and contrast-induced acute kidney injury (CI-AKI) after contrast exposure remains unclear. In this study, we conducted a retrospective analysis using propensity score matching (PSM) to investigate the effect of perioperative diuretic administration on contrast-induced acute kidney injury (CI-AKI) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). A total of 1894 patients with AMI who underwent PCI were retrospectively analyzed using PSM and multivariate models. Depending on whether diuretics were used, the patients were divided into two groups: the perioperative diuretic group (497 patients, 26.2%) and the non-diuretic group (1397 patients, 73.8%). And the relationship between perioperative diuretic administration and CI-AKI was evaluated by multiple regression models. Furthermore, Kaplan Meier survival curve ratio was used to evaluate and compare overall postoperative survival between the two groups. Most patients who received diuretics were older (67 vs. 60years, respectively, p < 0.001) and women (22.5% vs. 15.2%, p < 0.001) and had combined hypertension (62.8% vs. 47%, p < 0.001), atrial fibrillation (5.4% vs. 1.8%, p < 0.001), stroke (9.3% vs. 4.9%, p < 0.001), and diabetes mellitus (33.4% vs. 23.6%, p < 0.001) compared to those who did not. After the baseline characteristics were balanced using the PSM model, no significant difference was observed in the incidence of postoperative CI-AKI (22.7% vs. 19.5%, p = 0.356) and major cardiovascular adverse events (21.5% vs. 18.7%, p = 0.398). Multiple regression analysis showed no association between perioperative diuretic administration and postoperative CI-AKI occurrence (odds ratio: 1.14, 95% confidence interval: 0.86-1.51, p = 0.371). Further subgroup analysis and sensitivity analysis confirmed the above findings. We found no significant association between perioperative diuretic administration and postoperative CI-AKI in patients with AMI who underwent PCI.

#4949 COMBINED ORAL DIURETICS: A BETTER ALTERNATIVE FOR NEPHROTIC EDEMA THAN INTRAVENOUS FUROSEMIDE?

Abstract Background and Aims Edema is a serious complication of nephrotic syndrome and is the main reason why patients usually address to a doctor. There is no guideline on managing nephrotic edema. Besides non pharmacological interventions such as sodium and water restrictions, most doctors would choose high doses of intravenous furosemide as the first option, but still many patients fail to properly decrease their volume overload, as they become diuretic resistant. Amiloride, an ENaC mediated diuretic, is an optimistic management option, especially when used with other diuretics. The aim of the present study was to assess the non inferiority of the combined oral diuretics furosemide and the fixed combination of hydrochlorothiazide/amiloride diuretics with intravenous furosemide in diuretic resistant nephrotic edema. Method We conducted a prospective randomized trial in 22 patients with diuretic resistant nephrotic edema. Based on a computer-generated randomization we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day). Clinical and laboratory measurements were performed daily, for five days (body weight, urinary output, blood pressure and hydration status by bioimpedance twice, creatinine, urea, albumin, hematocrit, Na, K, Ca, Mg, bicarbonate, pH). The primary outcome was weight and hydration status change from baseline to day 5. Secondary outcomes were safety outcomes (low blood pressure, severe dyselectrolytemia, acute kidney injury or aggravated hypervolemia). Results The patients were equally distributed between the two groups. Mean age was 47,77±15,97 (54,5% females and 45,5% males). Half of the patients had membranous nephropathy (45,5%), followed by minimal change disease (22,7%) and lupus nephritis (9,1%). 86,4% of patients had their first episode of nephrotic edema. The mean weight decrease was of significantly larger magnitude in the combined oral diuretics group compared with the intravenous furosemide group (-7,97±2,83 [SD] vs -4,5±2,6 [SD] kg; p = 0,018). Although the increase in 24-hour urine sodium excretion was higher in combined oral diuretics as compared to intravenous furosemide group, this increment was not statistically significant different (26,79±33,48 [SD] vs 16,04±42,81 mmol/24 h [SD]; p = 0,5). Mean values for changes in systolic and diastolic BP, 24-hour urine volume, hydration status measured by bioimpedance were not significantly different between the two groups. A total of 5 patients could not be followed through, 4 in the intravenous furosemide (two patients experienced low blood, one patient had no response to iv furosemide and one patient suffered from insomnia due to iv pump) and one patient in the oral combination of diuretics group had severe hyperkalemia (&amp;gt;6,5 mmol/l). Conclusion Combined oral diuretics with furosemide, amiloride and hydrochlorothiazide is more effective and safer than intravenous furosemide for the treatment of refractory nephrotic edema. These results make amiloride a promising diuretic and further trials with larger sample sizes and longer follow-up are needed in this regard.

Safety and Efficacy of Empagliflozin and Diuretic Use in Patients with Heart Failure and Preserved Ejection Fraction

The diuretic effect of sodium-glucose cotransporter 2 inhibitors may result in interaction with background diuretic therapy in patients with heart failure and preserved ejection fraction (HFpEF). To assess the safety and efficacy of empagliflozin in combination with background diuretic therapy and the association of empagliflozin with the need for conventional diuretics. This was a post hoc analysis of the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved). EMPEROR-Preserved was a phase 3, randomized, placebo-controlled, double-blind clinical trial conducted from March 2017 to April 2021. Patients with class II to IV heart failure and left ventricular ejection fraction greater than 40% were included. Of 5988 patients enrolled, 5815 (97.1%) had baseline data on diuretic use and were included in this analysis, which was conducted from November 2021 to August 2022. Participants in EMPEROR-Preserved were randomized to empagliflozin or placebo. In this analysis, participants were divided into 4 subgroups: no diuretics and furosemide-equivalent diuretic dose of less than 40 mg, 40 mg, and greater than 40 mg at baseline. The main outcomes of interest were first hospitalization for heart failure (HHF) or cardiovascular death (CV death) and its components. Association of empagliflozin vs placebo with outcomes by baseline diuretic status (no diuretic vs any dose) and dose (no diuretic, <40 mg, 40 mg, and > 40mg) was assessed. Association of empagliflozin use with changes in diuretic therapy was also studied. Among 5815 patients (mean [SD] age, 71.9 [9.4] years; 2594 [44.6%] female) with known baseline diuretic use, 1179 (20.3%) were not taking diuretics, 1725 (29.7%) were taking less than 40 mg, 1772 (30.5%) were taking 40 mg, and 1139 (19.6%) were taking greater than 40 mg. In the placebo arm, patients with higher diuretic doses had worse outcomes. Empagliflozin decreased the risk of HHF or CV death, regardless of background diuretic status (hazard ratio [HR], 0.81; 95% CI, 0.70-0.93] for the diuretic group vs HR, 0.72; 95% CI, 0.48-1.06 for the nondiuretic group; P for interaction = .58). Similarly, diuretic status was not associated with changes in improvements in first HHF, total HHF, rate of decline in estimated glomerular filtration rate, and Kansas City Cardiomyopathy Questionnaire 23 clinical summary score with empagliflozin. Findings were consistent when patients were categorized by diuretic dose. Empagliflozin was associated with a decreased likelihood of diuretic dose escalation (HR, 0.74; 95% CI, 0.65-0.84) and an increased likelihood of de-escalation (HR, 1.15; 95% CI, 1.02-1.30). Empagliflozin was associated with an increased risk of volume depletion in patients taking diuretics (HR, 1.34; 95% CI, 1.13-1.59). In this study, treatment with empagliflozin was similar regardless of diuretic use or dose. Empagliflozin use was associated with decreased conventional diuretic dosing. ClinicalTrials.gov Identifier: NCT03057951.