What Does SGLT2 Inhibition Add in Managing Hyponatremia Secondary to Syndrome of Inappropriate Antidiuresis (SIAD)?

Background: Apart from treating the underlying causes, other treatment options for SIAD are of limited success. Drug repurposing of SGLT2 inhibitors for use in SIAD has been suggested. Clinical Case: A 72 years old gentleman with type 2 diabetes mellitus, hypertension, ischemic cardiomyopathy (ejection fraction 40%) and paranoid personality disorder presented with 3-day history of confusion, vomiting and reduced appetite. On examination, he was fully alert, afebrile, blood pressure 173/81 mmHg, heart rate 83 beats per minute and euvolemic. There were fine crackles in the lung bases bilaterally. Random capillary blood glucose level was 5.6 mmol/L (100 mg/dL) and there was no hypoxia. Laboratory results were suggestive of SIAD (serum sodium [Na] 115 mmol/L, serum osmolality 241 mmol/kg, urine osmolarity 458 mmol/kg, spot urine Na 56.7 mmol/L) with normal fT4 (17.6 pmol/L [1.37 ng/dL]), TSH (1.6 mIU/L) and cortisol (821 nmol/L [29.7 mcg/dL]) levels. Medications at admission were daily dosing of olanzapine 7.5 mg, sitagliptin/metformin 50/850 mg, losartan 50 mg, rosuvastatin 10 mg and aspirin 100 mg. Further investigations for causes of SIAD including magnetic resonance imaging of the brain and contrast-enhanced computed tomography of thorax, abdomen and pelvis were normal. He was treated with fluid restriction (1 liter/day) and furosemide (oral 20 mg daily for 2 doses, followed by intravenous 20 mg twice daily for 3 doses) on day 1-4, leading to negative fluid balance (total 3300 ml) with an increment in serum Na to 124 mmol/L on day 5. However, this was accompanied by a reduction in systolic blood pressure (148 to 118 mmHg) and serum potassium level (4.7 to 3.7 mmol/L), along with marked increases in urea (2.7 to 8.8 mmol/L) and creatinine levels (51 to 75 µmol/L) (eGFR from >90 to 87 mL/min/1.73m2). Hence, furosemide was stopped and empagliflozin 12.5 mg daily was initiated on day 5 with continuation of fluid restriction. Serum Na level increased by 2 mmol/L to 126 mmol/L after 12 hours and by 3 mmol/L (to 129 mmol/L) on subsequent day with negative fluid balance (950 ml per 24 hours). Urea and eGFR levels improved and losartan was reintroduced for blood pressure control. There was no euglycemic diabetic ketoacidosis episode. Patient was discharged on day 10 with a serum Na level of 131 mmol/L. Outpatient follow up 5 days after discharge showed further improvement in serum Na level to 134 mmol/L with serum osmolality 286 mmol/kg and urine osmolarity 672 mmol/kg. Clinical Lesson: SGLT2 inhibition can be considered as one of the treatment options of hyponatremia secondary to SIAD with good tolerability

Regulation of urinary calcium excretion by vasopressin

Background The antidiuretic hormone (ADH) or arginine vasopressin (AVP) regulates the body's water balance. Recently, modifications in AVP levels have been related to osteoporosis during ageing and microgravity/bed rest. Therefore the present study was devised to assess whether the absence of AVP, as in patients with central diabetes insipidus (CDI), modulates renal calcium excretion. Methods We retrospectively analysed data from 12 patients with CDI with measured 24-h urinary excretion levels of calcium. Data were available at the moment of the diagnosis when patients were drug-free and after therapy with dDAVP, an analog of AVP. Hypercalciuria was defined as 24-h urinary Ca2+ >275 mg/day in males and >250 mg/day in females and a urinary calcium (Ca):creatinine (Cr) ratio >0.20 mg/mg. Results Untreated CDI patients had a daily urinary Ca2+ excretion of 383 ± 47 mg/day and a urinary Ca:Cr ratio of 0.26 ± 0.38 mg/mg. The urine osmolarity significantly increased after the administration of dDAVP by 210% and the urinary flow decreased by 72%. Furthermore, the estimated glomerular filtration rate (eGFR) increased by 7%, which did not reach statistical significance. dDAVP treatment did not significantly modify the urinary Ca2+ concentration; however, the daily calcium excretion and the urinary Ca:Cr ratio were significantly decreased (160 ± 27 mg/day and 0.11 ± 0.02 mg/mg, respectively). Conclusions Patients with CDI show hypercalciuria even though urine is more diluted than normal controls, and dDAVP reverses this effect. These data support the intriguing relationship between AVP and osteoporosis in ageing and microgravity/bed rest.

Fluid intake in children

IntroductionWe monitored fluid intake in children. The hydration of children during morning school classes and on consumption of high-calorie drinks. Subclinical dehydration, expressed as urine osmolarity above 800 mmol / kg, may result in lack of concentration and less effective listening.Population and methodologyThe population included 3,360 children aged as follows: a) 6–35 months, b) 4–6 years, c) 7–10 years d) 11–14 years. 103 children aged 10.3 ± 1 years were included in the study regarding body hydration. The evaluation looked at the intake of food and fluids consumed by children in full-day diet over a period of 3 to 5 days and recorded by the Nutridan program. Child hydration was assessed using three urine osmolarity samples taken at bedtime, in the morning and just before lunch break. The data was evaluated statistically against the reference values for nutrient intake of DACH.Results and discussionThe median water intake in children was 101–103% of the Dietary Reference Values (DRV). In the b, c, d groups, the median was 81% - 82%, i.e 75% of DRV. 10% of 4 to 6-year-old children had water intake below 49% of DRV, 10% of 7 to 10 year-olds less than 54% of DRV and 10% of 11 to 14-year-olds less than 50% of DRV. A study regarding school children has showed that only 70% of the children drink at breakfast. 27% of the children do not consume any fluids in the morning. The mean urine osmolarity was 724 in the morning and 738 mmol / kg just before lunch. Children who had drunk less than 250 ml of water during breakfast or less than 400 ml of water during breakfast and second breakfast had a urine osmolarity of 910 and 850 mmol / kg respectively just before lunch. In school children, the proportion of sugars received from sweetened beverages accounted for 19.1% of their total calorie intake. 10% of the children in groups c) and d) had this value higher than 28.2 and 30.4% respectively. The results based on full-day diet show that sweetened drinks account for 79% of fluids consumed by children at school, whereas only for 72% at home.The results of our studies have identified the areas where it is necessary to provide education regarding nutrition of children, to raise awareness of the importance of fluid intake, particularly focusing on the systematic approach and the choice of appropriate beverages ensuring adequate fluid intake.