The Diagnosis Algorithm of Chronic Hypokalemia in Bartter Syndrome and Gitelman Syndrome: A Case Report

Introduction: Hypokalemia is common disorder characterized by low plasma potassium levels (<3.5 mEq / L). Hypokalemia can be caused by genetic disorders. Bartter syndrome and Gitelman syndrome are rare genetic disorders that cause damage to the tubular kidneys. The cause of hypokalemia must be determined by analyzing the diagnosis algorithm of hypokalemia. Case Illustration: A 27-year-old woman was brought to the emergency room with complaints of weakness in both legs since 1 day ago. Obtained a history of chronic hypokalemia since 5 years ago. No history of thyroid disease, and never taking diuretic drugs. The patient is calm. Vital signs: BP: 110/60, regular pulse 88x/minute, temperature: 36.7°C, respiratory rate 14x/minute, oxygen saturation 99% in room air. ECG showed Normal sinus rhythm with normal T wave. Laboratory findings showed severe hypokalemia with plasma potassium 1.7 mEq/L, increased urine potassium (71.1 mmol/24 hours), increased urine sodium 306 mmol/24 hours, and increased urine chloride (342 mmol/24 hours), plasma magnesium levels were normal (1.91 mg/dL). KCl infusion was given to correct electrolyte imbalance condition. Discussion: : Several examinations must be performed to confirm the cause of hypokalemia condition. The diagnosis of this patient was suspected to lead to Bartter syndrome and Gitelman syndrome, because there was an increase in urinary potassium excretion, normotensive conditions, no suspicion of metabolic acidosis, and no symptoms of nausea and vomiting and no history of diuretic drugs usage. Keywords: Hypokalemia, Bartter syndrome, Gitelman syndrome

Severe tricuspid regurgitation worsens prognosis outcome after edge-to-edge mitral valve repair

Introduction MitraClip has been well established for treatment of severe mitral regurgitation (MR). MR and tricuspid regurgitation (TR) often occur simultaneously and symptoms of biventricular heart failure can overlap. While it has been shown that TR grade regression can be achieved through repair of MR1, presence of moderate to severe TR can increase all-cause mortality after MitraClip2. There is currently no consensus on the management of combined MR and TR. We evaluated the impact of TR on echocardiographic and functional outcome after MitraClip. Methods 370 patients underwent MitraClip for moderate to severe MR at our center from 2010 to 2018. Patients were dichotomized into low grade TR (grade &lt;I - I (trace - mild)) and high grade TR (grade III - V (severe - torrential)). Moderate TR (grade II) was excluded. After MitraClip for MR, patients were followed up for 12 months and their echocardiographic and functional outcome was evaluated. Use of diuretic drugs throughout 12 month follow-up was registered. Results Low grade TR (&lt;I - I) occurred in 225 patients (67.0%), high grade TR (III - V) was present in 111 patients (33.0%). 34 patients (9.2%) with moderate TR (II) were excluded. Patients with high grade TR had an increased morbidity (higher age, worse renal function, higher prevalence of atrial fibrillation, higher levels of natriuretic peptides, increased left atrial and right heart diameters, higher TR gradient). These patients also received significantly higher doses of torasemid (33.5±36.7 mg vs. 21.6±20.9 mg, p=0.003) and furosemid (163.4±155.5 mg vs. 75.8±72.3 mg, p=0.01). Average grade of MR at baseline was similar in both groups (2.9±0.46 vs. 2.8±0.5, p=0.66). Procedural success of MR repair was achieved similarly in both groups (96.4% vs. 96.9%, p=0.82) and residual MR grade immediately after device implantation was comparable (p=0.61). However, recurrent MR in the high grade TR group increased during follow up, while MR further decreased in the low grade TR group (3 months: 1.24±0.7 vs. 1.16±0.7, p=0.5; 12 months: 1.46±0.93 vs. 1.12±0.61, p=0.04). Accordingly, use of diuretic drugs after 12 months rose in the high grade TR group while it did not change or even decreased in the low grade TR group (torasemid: 40.2±48.4 mg vs. 24.1±30.0 mg, p=0.04; furosemid: 197.5±251.0 mg vs. 67.1±81.8 mg, p=0.22). Kaplan-Meier-Analysis showed significantly higher mortality (24.9 vs. 14.1%, p=0.01), higher risk for heart failure induced rehospitalisation (25,4 vs. 12,5%, p=0.005) and for major adverse cardiac and cerebrovascular events (MACCE: 42.3 vs. 29.1%, p=0.008) in the high grade TR group after 12 months. Conclusion MitraClip patients for MR with concomitant high grade TR (≥ III) had an increased morbidity at baseline compared to low grade TR patients. By MitraClip comparable reduction of MR was achieved. However, during 12 month follow-up in the high grade TR group recurrent MR occurred more often while use of diuretics increased. FUNDunding Acknowledgement Type of funding sources: None.

Simultaneous determination of five diuretic drugs using quantitative analysis of multiple components by a single marker

Background Loop diuretics are commonly used in clinical practice to manage high fluid loads and to control fluid balance. In this paper, a novel quantitative analysis method for multiple components with a single marker (QAMS) was developed for the simultaneous determination of 5 diuretic drugs furosemide, torasemide, azosemide, etacrynic acid, and bumetanide, by HPLC. Qualitative analysis was performed using relative retention time and ultraviolet (UV) spectral similarity as the double indicator. The QAMS method was conducted with etacrynic acid as an internal reference substance. The quantities of the other four diuretics were calculated by using the relative correction factors for etacrynic acid. The quantities of the 5 diuretic drugs were also determined by the external standard method (ESM). Chromatographic separation was achieved on a Shimadzu HC-C18 column (150 mm × 4.6 mm, 5 µm) using 50 mM potassium dihydrogen phosphate (pH adjusted to 4.0 with phosphoric acid) with acetonitrile (64:36, v/v) as the mobile phase at a flow rate of 1.0 mL/min and a column temperature of 30 ℃. Results Under these conditions, the 5 diuretic drugs were well separated, showing linear relationships within certain ranges. The quantitative results showed that there was no significant difference between the QAMS and ESM methods. Conclusions Overall, the HPLC-QAMS analytical scheme established in this study is a simple, efficient, economical, and accurate method for the quantitative evaluation of 5 diuretic drugs.

Simultaneous determination of some illegal antihypertensive and diuretic drugs in traditional herbal preparations by HPLC-DAD

A simple, stable, and specific high-performance liquid chromatography coupled with a&nbsp;DAD detector (HPLC-DAD) method has been developed and validated for the simultaneous&nbsp;determination of amlodipine, felodipine, furosemide, nifedipine, and spironolactone in&nbsp;traditional herbal products. The analytes were extracted in acetonitrile: water (50 : 50, v/v) with&nbsp;help of the ultrasonic. The separation of analytes was performed in an Apollo C18 column (250&nbsp;&times; 4.6 mm; 5 &mu;m) and a mobile phase consisting of mixture acetonitrile: 0.1% phosphoric acid in&nbsp;gradient elution. The analyzed drugs were detected at 238 nm. The method was validated according&nbsp;to the AOAC International guidelines concerning specificity, linearity, precision (repeatability,&nbsp;intermediate precision), accuracy, limit of detection (LOD), and limit of quantification (LOQ).&nbsp;The method can detect the studied drugs at the concentration of 0.66 to 1.25 &mu;g/g for dry&nbsp;samples and 0.10 to 0.24 &mu;g/mL for liquid samples. The method was successfully applied in the&nbsp;analysis of 17 samples in the local market. No samples were found positive for the substances to&nbsp;be analyzed.

Simultaneous determination of 5 diuretic drugs using an HPLC method by quantitative analysis of multiple components by a single marker

Background: Loop diuretics are commonly used in clinical practice to manage high fluid loads and to control fluid balance. In this paper, a novel quantitative analysis method for multiple components with a single marker (QAMS) was developed for the simultaneous determination of 5 diuretic drugs furosemide, torasemide, azosemide, etacrynic acid, and bumetanide, by HPLC. Qualitative analysis was performed using relative retention time and ultraviolet (UV) spectral similarity as the double indicator. The QAMS method was conducted with etacrynic acid as an internal reference substance. The quantities of the other four diuretics were calculated by using the relative correction factors for etacrynic acid. The quantities of the 5 diuretic drugs were also determined by the external standard method (ESM). Chromatographic separation was achieved on a Shimadzu HC-C18 column (150 mm× 4.6 mm, 5µm) using 50 mM potassium dihydrogen phosphate (pH adjusted to 4.0 with phosphoric acid) with acetonitrile (64:36, v/v) as the mobile phase at a flow rate of 1.0 mL/min and a column temperature of 30 ℃. Results: Under these conditions, the 5 diuretic drugs were well separated, showing linear relationships within certain ranges. The quantitative results showed that there was no significant difference between the QAMS and ESM methods. Conclusions: Overall, the HPLC-QAMS analytical scheme established in this study is a simple, efficient, economical, and accurate method for the quantitative evaluation of 5 diuretic drugs.

Renin-angiotensin-aldosterone system blockers could contribute to the gender-related disparities in STEMI outcomes

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Romanian Ministry of Education and Research, CNCS - UEFISCDI BACKGROUND Women with ST-segment elevation myocardial infarction (STEMI) have been shown to present higher in-hospital mortality compared to their male counterparts. However, most of these data were obtained in the pre-percutaneous coronary intervention (PCI) or even in the pre-thrombolytic era. PURPOSE We aimed to investigate the contribution of female gender to the occurrence of in-hospital complications in STEMI patients treated by primary PCI. METHODS Data regarding in-hospital outcomes (i.e., mortality, inotropic and diuretic drugs usage, occurrence of cardiogenic shock, cardiac arrest) were evaluated in 848 consecutive patients treated by primary PCI for STEMI. Occurrence of new-onset kidney dysfunction and length of hospital stay were also analysed. The relationship between gender and the occurrence of STEMI-related complications was evaluated. RESULTS Out of the 848 patients included in the study, 254 (29.9%) were women. Compared to their male counterparts, female STEMI patients were older (65.7 ± 11.3 vs. 60.1 ± 11.8 years; p&lt; 0.0001), had more often pre-existing heart failure, hypertension, diabetes mellitus, and chronic kidney disease (all p&lt; 0.05), longer symptom onset-to-cardiac catheterization laboratory time intervals (7.9 ± 6.7 vs. 6.4 ± 5.0 h; p&lt; 0.001), and higher Killip class on admission (p = 0.02). Cardiogenic shock, inotropic and diuretic drugs usage, kidney dysfunction, and cardiac arrest occurred more often in female than in male patients (all p&lt; 0.01). The length of hospital stay (p&lt; 0.01) and in-hospital death (RR 1.89 [95%CI 1.43-2.50], p&lt; 0.001) were also higher in female compared to male patients, whereas renin-angiotensin-aldosterone system (RAAS) blockers were used more rarely in female patients (p = 0.01). When corrected for potential confounders, female gender remained an independent predictor of in-hospital mortality (p = 0.01). However, when in-hospital RAAS blockers usage was included in the model, female gender was no longer associated with increased in-hospital mortality (p = 0.15). CONCLUSIONS Female patients with STEMI continue to display significantly higher in-hospital mortality rates compared to their male peers including in the primary PCI era. The difference in in-hospital mortality between female and male patients with STEMI could be at least partially due to the significantly lower usage of RAAS blockers in women. Increasing in-hospital RAAS blockers usage in female patients with STEMI may improve survival in this high-risk population.

Simultaneous determination of 5 diuretic drugs using a HPLC method by quantitative analysis of multi-components by single-marker

Background: Loop diuretics is commonly used in clinical practices to manage the high fluid load and to control fluid balance. In this paper, a quantitative analysis of multiple components with a single marker (QAMS) method was firstly developed for simultaneous determination of 5 diuretic drugs including furosemide, torasemide, azosemide, etacrynic acid, and bumetanide by HPLC. The qualitative analysis was performed using relative capacity factor and ultraviolet (UV) spectral similarity as the double indicator. The QAMS method was conducted with etacrynic acid as an internal reference substance. The other four diuretics were calculated by using the relative correction factors for etacrynic acid. The contents of the 5 diuretic drugs were also determined by the external standard method (ESM). The chromatographic separation was achieved on an Shimadzu HC-C18 column (150mm× 4.6mm, 5µm) using 50 mM of potassium dihydrogen phosphate (pH adjusted to 4.0 with phosphoric acid) with acetonitrile (64:36, v/v) as mobile phase at the flow rate of 1.0 ml/min and a column temperature of 30℃. Results: Under these conditions, the 5 diuretic drugs are well separated, showing linear relationships within certain ranges. The quantitative results showed that there was no significant difference between the QAMS and ESM method. Conclusions: Overall, the HPLC-QAMS analytical scheme established in this study should be a simple, efficient, economical, and accurate method for quantitative evaluation of 5 diuretic drugs.

Lactic acidosis associated with metformin in diabetic patients with chronic kidney disease: a multicentre case-control study using electronic health records

Background: Several studies have assessed the risk of lactic acidosis with metformin use. However, data of this association in patients with renal impairment are still scarce and controversial. Our aim was therefore to assess the association between metformin and lactic acidosis in Spanish type 2 diabetic patients with chronic kidney disease.Methods: A case-control study (ALIMAR-C2) was performed using the electronic health records from hospitals linked to their corresponding primary healthcare regions. The cases were adult (≥18 years) diabetic patients with chronic kidney disease, admitted to seven Spanish hospitals from 2010 to 2016. Ten controls (≥18 years, diabetic patients with chronic kidney disease) per case were selected from the population within the same primary healthcare region of the hospital cases. The patients’ hospital health records were linked to their corresponding primary healthcare information. Analyses included multivariable logistic regression and adjustment for potential confounders. Results: Our study included 126 cases and 1,260 matched controls. The current use of metformin and administration at high doses (>2g) were associated with lactic acidosis (adjusted OR: 1.92, 95% CI: 1.21-3.03; OR: 3.13, 95% CI: 1.63-6.01, respectively). The estimated case fatality rate was 46.8% (95% CI: 38.3-55.5%). An increased risk of lactic acidosis was observed In patients with mild to moderate renal impairment (OR: 3.41, 95% CI: 1.48-7.85). As an unexpected finding, diuretic drugs use was also associated with lactic acidosis (OR: 2.73, 95% CI: 1.67 - 4.46).Conclusions: Metformin was associated with an increased risk of lactic acidosis in patients with type 2 diabetes mellitus and chronic kidney disease. New data is needed to confirm the association between diuretic drugs and lactic acidosis in this group of patients.

Lactic acidosis associated with metformin in diabetic patients with chronic kidney disease: a multicentre case-control study using electronic health records

Background Several studies have assessed the risk of lactic acidosis with metformin use. However, data of this association in patients with renal impairment are still scarce and controversial. Our aim was therefore to assess the association between metformin and lactic acidosis in Spanish type 2 diabetic patients with chronic kidney disease. Methods A case-control study (ALIMAR-C2) was performed using the electronic health records from hospitals linked to their corresponding primary healthcare regions. The cases were adult (≥ 18 years) diabetic patients with chronic kidney disease, admitted to seven Spanish hospitals from 2010 to 2016. Ten controls (≥ 18 years, diabetic patients with chronic kidney disease) per case were selected from the population within the same primary healthcare region of the hospital cases. The patients’ hospital health records were linked to their corresponding primary healthcare information. Analyses included multivariable logistic regression and adjustment for potential confounders. Results Our study included 126 cases and 1,260 matched controls. The current use of metformin and administration at high doses (> 2 g) were associated with lactic acidosis (adjusted OR: 1.92, 95% CI: 1.21–3.03; OR: 3.13, 95% CI: 1.63–6.01, respectively). The estimated case fatality rate was 46.8% (95% CI: 38.3–55.5%). An increased risk of lactic acidosis was observed in patients with mild to moderate renal impairment (OR: 3.41, 95% CI: 1.48–7.85). As an unexpected finding, diuretic drugs use was also associated with lactic acidosis (OR: 2.73, 95% CI: 1.67–4.46). Conclusions Metformin was associated with an increased risk of lactic acidosis in patients with type 2 diabetes mellitus and chronic kidney disease. New data is needed to confirm the association between diuretic drugs and lactic acidosis in this group of patients.