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  1. Mayne KJ, Staplin N, Keane DF, Wanner C, Brenner S, Cejka V, et al.
    J Am Soc Nephrol, 2024 Feb 01;35(2):202-215.
    PMID: 38082486 DOI: 10.1681/ASN.0000000000000271
    SIGNIFICANCE STATEMENT: SGLT2 inhibitors reduce risk of kidney progression, AKI, and cardiovascular disease, but the mechanisms of benefit are incompletely understood. Bioimpedance spectroscopy can estimate body water and fat mass. One quarter of the EMPA-KIDNEY bioimpedance substudy CKD population had clinically significant levels of bioimpedance-derived "Fluid Overload" at recruitment. Empagliflozin induced a prompt and sustained reduction in "Fluid Overload," irrespective of sex, diabetes, and baseline N-terminal pro B-type natriuretic peptide or eGFR. No significant effect on bioimpedance-derived fat mass was observed. The effects of SGLT2 inhibitors on body water may be one of the contributing mechanisms by which they mediate effects on cardiovascular risk.

    BACKGROUND: CKD is associated with fluid excess that can be estimated by bioimpedance spectroscopy. We aimed to assess effects of sodium glucose co-transporter 2 inhibition on bioimpedance-derived "Fluid Overload" and adiposity in a CKD population.

    METHODS: EMPA-KIDNEY was a double-blind placebo-controlled trial of empagliflozin 10 mg once daily in patients with CKD at risk of progression. In a substudy, bioimpedance measurements were added to the main trial procedures at randomization and at 2- and 18-month follow-up visits. The substudy's primary outcome was the study-average difference in absolute "Fluid Overload" (an estimate of excess extracellular water) analyzed using a mixed model repeated measures approach.

    RESULTS: The 660 substudy participants were broadly representative of the 6609-participant trial population. Substudy mean baseline absolute "Fluid Overload" was 0.4±1.7 L. Compared with placebo, the overall mean absolute "Fluid Overload" difference among those allocated empagliflozin was -0.24 L (95% confidence interval [CI], -0.38 to -0.11), with similar sized differences at 2 and 18 months, and in prespecified subgroups. Total body water differences comprised between-group differences in extracellular water of -0.49 L (95% CI, -0.69 to -0.30, including the -0.24 L "Fluid Overload" difference) and a -0.30 L (95% CI, -0.57 to -0.03) difference in intracellular water. There was no significant effect of empagliflozin on bioimpedance-derived adipose tissue mass (-0.28 kg [95% CI, -1.41 to 0.85]). The between-group difference in weight was -0.7 kg (95% CI, -1.3 to -0.1).

    CONCLUSIONS: In a broad range of patients with CKD, empagliflozin resulted in a sustained reduction in a bioimpedance-derived estimate of fluid overload, with no statistically significant effect on fat mass.

    TRIAL REGISTRATION: Clinicaltrials.gov: NCT03594110 ; EuDRACT: 2017-002971-24 ( https://eudract.ema.europa.eu/ ).

    Matched MeSH terms: Water-Electrolyte Imbalance*
  2. Norzila MZ, Azizi BH
    Med J Malaysia, 1994 Mar;49(1):102-4.
    PMID: 8057982
    Congenital chloride diarrhoea is a rare disorder mainly reported in Finland. A Malay child with congenital chloride diarrhoea presenting at six months of age with watery stools from birth and failure to thrive is reported.
    Matched MeSH terms: Water-Electrolyte Imbalance/congenital*; Water-Electrolyte Imbalance/drug therapy; Water-Electrolyte Imbalance/metabolism
  3. Khan YH, Sarriff A, Adnan AS, Khan AH, Mallhi TH
    PLoS One, 2016;11(7):e0159335.
    PMID: 27442587 DOI: 10.1371/journal.pone.0159335
    BACKGROUND: Despite promising role of diuretics to manage fluid overload among chronic kidney disease (CKD) patients, their use is associated with adverse renal outcomes. Current study aimed to determine the extent of renal deterioration with diuretic therapy.

    METHODS: A total 312 non-dialysis dependent CKD (NDD-CKD) patients were prospectively followed-up for one year. Fluid overload was assessed via bioimpedance spectroscopy. Estimated GFR (eGFR) was calculated from serum creatinine values by using Chronic Kidney Disease- Epidemiology Collaboration (CKD-EPI) equation.

    RESULTS: Out of 312 patients, 64 (20.5%) were hypovolemic while euvolemia and hypervolemia were observed in 113 (36.1%) and 135 (43.4%) patients. Overall 144 patients were using diuretics among which 98 (72.6%) were hypervolemic, 35 (30.9%) euvolemic and 11 (17.2%) were hypovolemic. The mean decline in estimated GFR of entire cohort was -2.5 ± 1.4 ml/min/1.73m2 at the end of follow up. The use of diuretics was significantly associated with decline in eGFR. A total of 36 (11.5%) patients initiated renal replacement therapy (RRT) and need of RRT was more profound among diuretic users.

    CONCLUSIONS: The use of diuretics was associated with adverse renal outcomes indicated by decline in eGFR and increasing risk of RRT initiation in our cohort of NDD-CKD patients. Therefore, it is cautiously suggested to carefully prescribe diuretics by keeping in view benefit versus harm for each patient.

    Matched MeSH terms: Water-Electrolyte Imbalance/complications*; Water-Electrolyte Imbalance/drug therapy*; Water-Electrolyte Imbalance/physiopathology
  4. Chong PF, Paraidathathu T
    Asia Pac J Clin Nutr, 2013;22(4):548-56.
    PMID: 24231015 DOI: 10.6133/apjcn.2013.22.4.15
    The effectiveness of the Nutrition Support Team (NST) at Hospital Sungai Buloh, a large public hospital in Kuala Lumpur, Malaysia, in optimising parenteral nutrition (PN) has not been evaluated. To evaluate the effects of this NST in optimising patient outcomes, treatment outcomes, and adherence to biochemical monitoring guidelines, two groups of patients, those given PN before (n = 106) NST intervention and those given PN after (n=106) NST intervention, were retrospectively compared. Intervention by the NST significantly reduced metabolic abnormalities, reducing sodium abnormalities from 67% to 44% (p<0.01); potassium abnormalities from 42% to 15% (p<0.01); magnesium abnormalities from 13% to 3% (p<0.05) and phosphate abnormalities from 21% to 9% (p=0.01). Intervention by the NST also significantly reduced the incidence of hypertriglyceridemia from 68% to 45% (p=0.002) and significantly improved adherence to biochemical monitoring guidelines from 46% to 72% (p<0.01). However, the length of hospital stay, patient mortality, and duration of PN were similar in both groups. This study failed to demonstrate that the establishment of a NST gave better outcomes in terms of the common measures of effectiveness. In conclusion, although management by an NST significantly reduced metabolic abnormalities and improved adherence to biochemical monitoring guidelines, the NST did not improve patient mortality rates and length of hospital stay.
    Matched MeSH terms: Water-Electrolyte Imbalance/etiology; Water-Electrolyte Imbalance/epidemiology*
  5. Sim Mervyn Ian, Nor Zuraida Zainal, Aili Hanim
    MyJurnal
    Osmotic demyelination syndrome (ODS) may occur as a consequence of a
    rapid change in serum osmolality. We report a case of a 32-year-old woman
    who presented to the hospital with symptoms suggestive of severe
    hyperemesis gravidarum. Blood investigation results showed that patient had
    severe hyponatraemia (serum sodium 109 mmol/L) and hypokalaemia
    (serum potassium 1.7 mmol/L). Active and vigorous corrections to these
    electrolyte imbalances had led to an overly increased of serum sodium levels
    within a short duration of time. Four days after the rapid correction, patient
    started exhibiting neuropsychiatric manifestations. Radiological findings
    were consistent with the diagnosis of ODS. The neuropsychiatric symptoms
    experienced by patient gradually worsened with time. Subsequently,
    intravenous methylprednisolone was administered to patient. Patient showed
    marked response to the steroid given. At the time of discharge, twenty-seven
    days later, patient had recovered from most of the neuropsychiatric sequelae;
    but still required assistance during ambulation. In conclusion, correction of
    electrolyte imbalances should be done in a more judicious manner. Prudent
    corrections of electrolyte alterations could have possibly prevented the onset
    of ODS and its’ devastating neuropsychiatric sequelae in this patient.
    Matched MeSH terms: Water-Electrolyte Imbalance
  6. Lu HT, Loo HC, Ng KS, Wong YO, Nordin R
    Malays Fam Physician, 2019;14(2):39-43.
    PMID: 31827736
    Diuretics have a long and distinguished history in the treatment of hypertension and heart failure. Clinical practice guidelines recommend that diuretics should be considered to be as suitable as other antihypertensive agents for the initiation and maintenance of antihypertensive treatment. However, diuretics may potentially cause electrolyte disturbances and metabolic side effects. Diuretic-induced hyponatremia is probably more prevalent than generally acknowledged. We present an unusual case of indapamide-induced hyponatremia and hypokalemia complicated by cardiac arrhythmia. The adverse drug reaction was reversible and non-life-threatening, but this case serves as a reminder that careful evaluation and constant monitoring are necessary when prescribing diuretics.
    Matched MeSH terms: Water-Electrolyte Imbalance
  7. Khan YH, Sarriff A, Adnan AS, Khan AH, Mallhi TH
    Clin Exp Nephrol, 2017 Jun;21(3):488-496.
    PMID: 27402286 DOI: 10.1007/s10157-016-1303-7
    INTRODUCTION: The relationship between hypertension and fluid overload in pre-dialysis CKD patients need to be elucidated. Current study aimed to find relationship between fluid overload and hypertension along with prescribed diuretic therapy using bioimpedance spectroscopy (BIS).

    METHODOLOGY: A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by BIS.

    RESULTS: A total of 312 CKD patients with mean eGFR 24.5 ± 11.2 ml/min/1.73 m2were enrolled. Based on OH value ≥7 %, 135 (43.3 %) patients were hypervolemic while euvolemia was observed in 177 (56.7 %) patients. Patients were categorized in different regions of hydration reference plot (HRP) generated by BIS i.e., 5.1 % in region-N (normal BP and fluid status), 20.5 % in region I (hypertensive with severe fluid overload), 29.5 % in region I-II (hypertensive with mild fluid overload), 22 % in region II (hypertensive with normohydration), 10.2 % in region III (underhydration with normal/low BP) and 12.5 % in region IV (normal BP with severe fluid overload). A total of 144 (46 %) patients received diuretics on basis of physician assessment of BP and edema. Maximum diuretics 100 (69.4 %) were prescribed in patients belonging to regions I and I-II of HRP. Interestingly, a similar number of diuretic prescriptions were observed in region II (13 %) and region IV (12 %). Surprisingly, 7 (4.9 %) of patients in region III who were neither hypervolemic nor hypertensive were also prescribed with diuretics.

    CONCLUSION: BIS can aid clinicians to categorize CKD patients on basis of their fluid status and provide individualized pharmacotherapy to manage hypertensive CKD patients.

    Matched MeSH terms: Water-Electrolyte Imbalance/diagnosis; Water-Electrolyte Imbalance/drug therapy*; Water-Electrolyte Imbalance/epidemiology; Water-Electrolyte Imbalance/physiopathology
  8. Vilhena-Franco T, Mecawi AS, Elias LL, Antunes-Rodrigues J
    J Endocrinol, 2016 Nov;231(2):167-180.
    PMID: 27613338
    Water deprivation (WD) induces changes in plasma volume and osmolality, which in turn activate several responses, including thirst, the activation of the renin-angiotensin system (RAS) and vasopressin (AVP) and oxytocin (OT) secretion. These systems seem to be influenced by oestradiol, as evidenced by the expression of its receptor in brain areas that control fluid balance. Thus, we investigated the effects of oestradiol treatment on behavioural and neuroendocrine changes of ovariectomized rats in response to WD. We observed that in response to WD, oestradiol treatment attenuated water intake, plasma osmolality and haematocrit but did not change urinary volume or osmolality. Moreover, oestradiol potentiated WD-induced AVP secretion, but did not alter the plasma OT or angiotensin II (Ang II) concentrations. Immunohistochemical data showed that oestradiol potentiated vasopressinergic neuronal activation in the lateral magnocellular PVN (PaLM) and supraoptic (SON) nuclei but did not induce further changes in Fos expression in the median preoptic nucleus (MnPO) or subfornical organ (SFO) or in oxytocinergic neuronal activation in the SON and PVN of WD rats. Regarding mRNA expression, oestradiol increased OT mRNA expression in the SON and PVN under basal conditions and after WD, but did not induce additional changes in the mRNA expression for AVP in the SON or PVN. It also did not affect the mRNA expression of RAS components in the PVN. In conclusion, our results show that oestradiol acts mainly on the vasopressinergic system in response to WD, potentiating vasopressinergic neuronal activation and AVP secretion without altering AVP mRNA expression.
    Matched MeSH terms: Water-Electrolyte Imbalance/blood; Water-Electrolyte Imbalance/etiology; Water-Electrolyte Imbalance/physiopathology; Water-Electrolyte Imbalance/prevention & control*
  9. Freiria-Oliveira AH, Blanch GT, Pedrino GR, Cravo SL, Murphy D, Menani JV, et al.
    Am J Physiol Regul Integr Comp Physiol, 2015 Nov 01;309(9):R1082-91.
    PMID: 26333788 DOI: 10.1152/ajpregu.00432.2014
    Noradrenergic A2 neurons of the nucleus of the solitary tract (NTS) have been suggested to contribute to body fluid homeostasis and cardiovascular regulation. In the present study, we investigated the effects of lesions of A2 neurons of the commissural NTS (cNTS) on the c-Fos expression in neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, arterial pressure, water intake, and urinary excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) received an injection of anti-dopamine-β-hydroxylase-saporin (12.6 ng/60 nl; cNTS/A2-lesion, n = 28) or immunoglobulin G (IgG)-saporin (12.6 ng/60 nl; sham, n = 24) into the cNTS. The cNTS/A2 lesions increased the number of neurons expressing c-Fos in the magnocellular PVN in rats treated with hypertonic NaCl (90 ± 13, vs. sham: 47 ± 20; n = 4), without changing the number of neurons expressing c-Fos in the parvocellular PVN or in the SON. Contrary to sham rats, intragastric 2 M NaCl also increased arterial pressure in cNTS/A2-lesioned rats (16 ± 3, vs. sham: 2 ± 2 mmHg 60 min after the intragastric load; n = 9), an effect blocked by the pretreatment with the vasopressin antagonist Manning compound (0 ± 3 mmHg; n = 10). In addition, cNTS/A2 lesions enhanced hyperosmolality-induced water intake (10.5 ± 1.4, vs. sham: 7.7 ± 0.8 ml/60 min; n = 8-10), without changing renal responses to hyperosmolality. The results suggest that inhibitory mechanisms dependent on cNTS/A2 neurons reduce water intake and vasopressin-dependent pressor response to an acute increase in plasma osmolality.
    Matched MeSH terms: Water-Electrolyte Imbalance
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