Dextrose solution for priming and rinsing the extracorporeal circuit in hemodialysis patients: A prospective pilot study

Introduction: Excess sodium intake and consequent volume overload are major clinical problems in hemodialysis (HD) contributing to adverse outcomes. Saline used for priming and rinsing of the extracorporeal circuit is a potentially underappreciated source of intradialytic sodium gain. We aimed to examine the feasibility and clinical effects of replacing saline as the priming and rinsing fluid by a 5% dextrose solution. Materials and methods: We enrolled non-diabetic and anuric stable HD patients. First, the extracorporeal circuit was primed and rinsed with approximately 200–250 mL of isotonic saline during 4 weeks (Phase 1), subsequently a similar volume of a 5% dextrose solution replaced the saline for another 4 weeks (Phase 2), followed by another 4 weeks of saline (Phase 3). We collected data on interdialytic weight gain (IDWG), pre- and post-dialysis blood pressure, intradialytic symptoms, and thirst. Results: Seventeen chronic HD patients (11 males, age 54.1 ± 18.7 years) completed the study. The average priming and rinsing volumes were 236.7 ± 77.5 and 245.0 ± 91.8 mL respectively. The mean IDWG did not significantly change (2.52 ± 0.88 kg in Phase 1; 2.28 ± 0.70 kg in Phase 2; and 2.51 ± 1.2 kg in Phase 3). No differences in blood pressures, intradialytic symptoms or thirst were observed. Conclusions: Replacing saline by 5% dextrose for priming and rinsing is feasible in stable HD patients and may reduce intradialytic sodium loading. A non-significant trend toward a lower IDWG was observed when 5% dextrose was used. Prospective studies with a larger sample size and longer follow-up are needed to gain further insight into the possible effects of using alternate priming and rinsing solutions lowering intradialytic sodium loading. Trial registration: Identifier NCT01168947 (ClinicalTrials.gov).

Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Chronic Fatigue Syndrome or Myalgic Encephaloymelitis (ME/CFS) is a frequent debilitating disease with an enigmatic etiology. The finding of autoantibodies against ß2-adrenergic receptors (ß2AdR) prompted us to hypothesize that ß2AdR dysfunction is of critical importance in the pathophysiology of ME/CFS. Our hypothesis published previously considers ME/CFS as a disease caused by a dysfunctional autonomic nervous system (ANS) system: sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles, which in the latter is opposed by the metabolically stimulated release of endogenous vasodilators (functional sympatholysis). An enigmatic bioenergetic disturbance in skeletal muscle strongly contributes to this release. Excessive generation of these vasodilators with algesic properties and spillover into the systemic circulation could explain hypovolemia, suppression of renin (paradoxon) and the enigmatic symptoms. In this hypothesis paper the mechanisms underlying the energetic disturbance in muscles will be explained and merged with the first hypothesis. The key information is that ß2AdR also stimulates the Na+/K+-ATPase in skeletal muscles. Appropriate muscular perfusion as well as function of the Na+/K+-ATPase determine muscle fatigability. We presume that dysfunction of the ß2AdR also leads to an insufficient stimulation of the Na+/K+-ATPase causing sodium overload which reverses the transport direction of the sodium-calcium exchanger (NCX) to import calcium instead of exporting it as is also known from the ischemia–reperfusion paradigm. The ensuing calcium overload affects the mitochondria, cytoplasmatic metabolism and the endothelium which further worsens the energetic situation (vicious circle) to explain postexertional malaise, exercise intolerance and chronification. Reduced Na+/K+-ATPase activity is not the only cause for cellular sodium loading. In poor energetic situations increased proton production raises intracellular sodium via sodium-proton-exchanger subtype-1 (NHE1), the most important proton-extruder in skeletal muscle. Finally, sodium overload is due to diminished sodium outward transport and enhanced cellular sodium loading. As soon as this disturbance would have occurred in a severe manner the threshold for re-induction would be strongly lowered, mainly due to an upregulated NHE1, so that it could repeat at low levels of exercise, even by activities of everyday life, re-inducing mitochondrial, metabolic and vascular dysfunction to perpetuate the disease.

Distinct osmoregulatory responses to sodium loading in patients with altered glycosaminoglycan structure: a randomized cross-over trial

Background By binding to negatively charged polysaccharides called glycosaminoglycans, sodium can be stored in the body—particularly in the skin—without concurrent water retention. Concordantly, individuals with changed glycosaminoglycan structure (e.g. type 1 diabetes (DM1) and hereditary multiple exostosis (HME) patients) may have altered sodium and water homeostasis. Methods We investigated responses to acute (30-min infusion) and chronic (1-week diet) sodium loading in 8 DM1 patients and 7 HME patients in comparison to 12 healthy controls. Blood samples, urine samples, and skin biopsies were taken to investigate glycosaminoglycan sulfation patterns and both systemic and cellular osmoregulatory responses. Results Hypertonic sodium infusion increased plasma sodium in all groups, but more in DM1 patients than in controls. High sodium diet increased expression of nuclear factor of activated t-cells 5 (NFAT5)—a transcription factor responsive to changes in osmolarity—and moderately sulfated heparan sulfate in skin of healthy controls. In HME patients, skin dermatan sulfate, rather than heparan sulfate, increased in response to high sodium diet, while in DM1 patients, no changes were observed. Conclusion DM1 and HME patients show distinct osmoregulatory responses to sodium loading when comparing to controls with indications for reduced sodium storage capacity in DM1 patients, suggesting that intact glycosaminoglycan biosynthesis is important in sodium and water homeostasis. Trial registration These trials were registered with the Netherlands trial register with registration numbers: NTR4095 (https://www.trialregister.nl/trial/3933 at 2013-07-29) and NTR4788 (https://www.trialregister.nl/trial/4645 at 2014-09-12).

Reassessment of Urinary Aldosterone Measurement After Saline Infusion in Primary Aldosteronism

Context Urinary aldosterone levels (Uald) are widely measured in the oral sodium-loading test to confirm primary aldosteronism (PA), but reliable studies on their diagnostic value are limited. This may be due to the difficulty in collecting urine with reliable accuracy, keeping oral sodium intake constant between patients. Therefore, we focused on 24-hour Uald after intravenous saline infusion in a hospitalized setting, which provides a reliable sodium load in consistent amounts. Objective Comparing plasma aldosterone concentrations (PAC) and Uald after saline infusion in the sitting position, to evaluate the accuracy in determining PA subtypes and the correlation of both measurements. Design and Setting This was a retrospective cross-sectional study in a single referral center. Patients Of 53 patients without renal dysfunction who were diagnosed with PA and underwent adrenal venous sampling, 16 and 37 were diagnosed with unilateral and bilateral PA, respectively. Main Outcome Measures Uald collected for 24 hours and PAC after saline infusion. Results The area under the receiver operating characteristic curve for diagnosing unilateral PA was not significantly different between Uald and PAC after saline infusion (0.921 and 0.958, respectively; P = 0.370). The predicted optimal cutoff value of Uald was 16.5 μg/day (sensitivity, 87.5%; specificity, 100%), and that of PAC after saline infusion was 19.3 ng/dL (sensitivity, 87.5%; specificity, 97.3%). In studied patients with PA, Uald was positively correlated with PAC after saline infusion (r = 0.617; P < 0.001). Conclusions We reassessed Uald in PA patients under sufficient sodium loading and demonstrated the correlation between Uald and PAC after saline infusion.

SAT-550 Changes in Albuminuria Precede Dietary Sodium-Dependent Changes in BP During Aging - a Longitudinal Study

Background: Hypertension (HT) is a well-established independent risk factor for adverse cardiovascular and renal (CVR) outcomes and a high salt (HS) diet is the main cause for high blood pressure (BP). Despite extensive research focusing on HT, surprisingly there are no longitudinal studies assessing the long-term effects of HS. Aims: This study aimed (1) to evaluate the timing of onset for changes in CVR health during long-term sodium loading and (2) to assess whether salt restriction can prevent these effects. Methods: C57BL/6 mice were randomized to HS, moderate (NS) or low (LS) salt diet and followed longitudinally for 50 weeks (wks). BP, urinary albumin/creatinine ratio (AC), plasma aldosterone (PA) and renin activity (PRA) were assessed monthly. At the end of the study, renal artery resistance and left ventricular (LV) parameters were measured by ultrasound and echocardiogram. Renal AT1 expression (Western Blot) and activity (IHQ) were quantified. Results: At the beginning of the study, there were no differences in BP and AC between the three dietary groups. Relative to wk 1, BP (mmHg) in the HS group was higher in wk 21 (131±1.7 vs. 115±3.0, p= 0.05). Sodium restriction delayed this increase: SBP was higher in wk 41 in the NS group compared to the wk 1 (128±3.4 vs. 115±6.4, p= 0.05) but did not reach significance in the LS group until the end of the study. Similarly, relative to wk 1, AC (µg/mg) only in the HS group reached significantly higher levels in wk 17 (44±4.2, p<0.05). Again, sodium restriction delayed the occurrence of renal damage. AC reached significance in wks 25 and 41 for NS and LS (35±1.1 and 42±2.6 respectively, p<0.05 vs. baseline). Interestingly, the changes in AC always preceded the changes in BP, irrespective of diet. PA and PRA were appropriately activated by dietary salt restriction and suppressed by aging. The aging-induced suppression appeared stronger for PA than for PRA in the HS group only. Long-term sodium loading (HS) induced increased renal resistance, which was prevented in the LS but not in the NS group. Relative to HS, the LV mass index and cardiac output were lower in the NS and LS groups (p<0.05). LV volume indices and ejection fraction did not differ between groups. Renal AT1 protein expression and activation status (IHQ) were decreased in the sodium restricted group. Conclusions: Our study showed that long-term exposure to HS induced a progressive increase in BP and AC in mice. Importantly, these changes were delayed by long-term reduction in sodium intake. Interestingly, changes in AC preceded those in BP, irrespective of diet. Cardiac parameters suggest a sodium-induced eccentric cardiac hypertrophy in the older age, which was prevented by sodium restriction. One possible mechanism behind these effects is the overactivation of the AT1 receptor pathway.