High versus low ultrafiltration rates during experimental peritoneal dialysis in rats: Acute effects on plasma volume and systemic haemodynamics

Introduction: Intradialytic hypotension is a common complication of haemodialysis, but uncommon in peritoneal dialysis (PD). This may be due to lower ultrafiltration rates in PD compared to haemodialysis, allowing for sufficient refilling of the blood plasma compartment from the interstitial volume, but the underlying mechanisms are unknown. Here we assessed plasma volume and hemodynamic alterations during experimental PD with high versus low ultrafiltration rates. Methods: Experiments were conducted in two groups of healthy Sprague-Dawley rats: one group with a high ultrafiltration rate ( N = 7) induced by 8.5% glucose and a low UF group ( N = 6; 1.5% glucose), with an initial assessment of the extracellular fluid volume, followed by 30 min PD with plasma volume measurements at baseline, 5, 10, 15 and 30 min. Mean arterial pressure, central venous pressure and heart rate were continuously monitored during the experiment. Results: No significant changes over time in plasma volume, mean arterial pressure or central venous pressure were detected during the course of the experiments, despite an ultrafiltration (UF) rate of 56 mL/h/kg in the high UF group. In the high UF group, a decrease in extracellular fluid volume of −7 mL (−10.7% (95% confidence interval: −13.8% to −7.6%)) was observed, in line with the average UF volume of 8.0 mL (standard deviation: 0.5 mL). Conclusion: Despite high UF rates, we found that plasma volumes were remarkably preserved in the present experiments, indicating effective refilling of the plasma compartment from interstitial tissues. Further studies should clarify which mechanisms preserve the plasma volume during high UF rates in PD.

Salt-Sensitivity of Volume and Blood Pressure in a Mouse with Globally Reduced ENaC γ Subunit Expression

The epithelial Na+ channel (ENaC) promotes the absorption of Na+ in the aldosterone-sensitive distal nephron, colon, and respiratory epithelia. Deletion of genes encoding ENaC's subunits results in early post-natal mortality. We present initial characterization of a mouse with dramatically suppressed expression of ENaC's γ subunit. We used this hypomorphic (γmt) allele to explore the importance of this subunit in homeostasis of electrolytes and body fluid volume. At baseline, γ subunit expression in γmt/mt mice was markedly suppressed in kidney and lung, while electrolytes resembled those of littermate controls. Aldosterone levels in γmt/mt mice exceeded those seen in littermate controls. Quantitative magnetic resonance (QMR) measurement of body composition revealed similar baseline body water, lean tissue mass, and fat tissue mass in γmt/mt mice and controls. γmt/mt mice exhibited a more rapid decline in body water and lean tissue mass in response to a low Na+ diet than controls. Replacement of drinking water with 2% saline selectively and transiently increased body water and lean tissue mass in γmt/mt mice, relative to controls. Lower blood pressures were variably observed in γmt/mt mice on a high salt diet, compared to controls. γmt/mt also exhibited reduced diurnal blood pressure variation, a "non-dipping" phenotype, on a high Na+ diet. While ENaC in renal tubules and colon work to prevent extracellular fluid volume depletion, our observations suggest that ENaC in other tissues may participate in regulating extracellular fluid volume and blood pressure.

Extracellular fluid volume: A suitable indexation variable to assess impact of bariatric surgery on glomerular filtration rate in patients with chronic kidney disease

Background Bariatric surgery (BS) might be a nephroprotective treatment in obese patients with chronic kidney disease (CKD), and the non-linear relation between body surface area (BSA) and extracellular fluid volume (ECFV) in obese people raises the question of the most relevant way to scale glomerular filtration rate (GFR) for assessing renal function changes after BS. Methods We screened 1774 BS candidates and analysed 10 consecutive participants with CKD stage 3. True GFR (mGFR), measured by the renal clearance of 51Cr-ethylenediaminetetraacetic acid (EDTA), was scaled either to BSA (mGFRBSA) or to ECFV measured by 51Cr-EDTA distribution volume (mGFRECFV) before and one year after BS. Results The 10 candidates for BS had a mean body mass index of 43.3 ± 3.6 kg/m2 and a mean GFR of 48 ± 8 mL/min/1.73 m2. Six participants had a sleeve gastrectomy and four had a Roux-en-Y gastric bypass. One year after BS, ECFV decreased (23.2 ± 6.2 to 17.9 ± 4.3 L, p = 0.001), absolute mGFR was not significantly modified (74 ± 23 versus 68 ±19 mL/min), mGFRBSA did not change significantly (53 ± 18 versus 56 ± 17 mL/min/1.73 m2) whereas mGFRECFV significantly increased (42 ± 13 versus 50 ± 14 mL/min/12.9 L, p = 0.037). The relation between mGFRECFV and mGFRBSA was different from the identity line before (p = 0.014) but not after BS (p = 0.09). Conclusion There is a difference between mGFRBSA and mGFRECFV following BS and the latter might better reflect the adequacy between renal function and corpulence.

Water and Electrolyte Homeostasis in a Mouse Model with Reduced ENaC Gamma Subunit Expression

The epithelial Na+ channel (ENaC) promotes the absorption of Na+ in the aldosterone-sensitive distal nephron, colon, and respiratory epithelia. Deletion of genes encoding ENaC’s subunits results in early post-natal mortality. We present initial characterization of a mouse with dramatically suppressed expression of the γ subunit. We use this hypomorphic (γmt) allele to explore the importance of ENaC’s γ subunit in homeostasis of electrolytes and body fluid volume. At baseline, γ subunit expression in γmt/mt mice is markedly suppressed in kidney and lung, while electrolytes resemble those of littermate controls. Challenge with a high K+ diet does not cause significant differences in blood K+, but provokes higher aldosterone in γmt/mt mice than controls. Quantitative magnetic resonance (QMR) measurement of body composition reveals similar baseline body water, lean tissue mass, and fat tissue mass in γmt/mt mice and controls. Surprisingly, euvolemia is sustained without significant changes in aldosterone or atrial natriuretic peptide. γmt/mt mice exhibit a more rapid decline in body water and lean tissue mass in response to a low Na+ diet than controls. Replacement of drinking water with 2% saline induces dramatic increases in body fat in both genotypes, and a selective transient increase in body water and lean tissue mass in γmt/mt mice. While ENaC in renal tubules and colon work to prevent extracellular fluid volume depletion, our observations suggest that ENaC in non-epithelial tissues may have a role in preventing extracellular fluid volume overload.

Abnormal increase in extracellular fluid volume as a marker of preeclampsia in women without obesity

Objective. To identify possible markers of preeclampsia in different types of arterial hypertension based on body composition analysis in pregnant women without obesity. Patients and methods. Body composition was studied in 140 non-obese women at 28-34 weeks' gestation, including 72 women with different types of arterial hypertension and 68 women with normal pregnancy, using the ABC-01 “MEDAS” moisture analyzer on the basis of State Budgetary Institution “Yaroslavl Regional Perinatal Center”. Results. There was an increase in total and extracellular fluid volume in the group with preeclampsia compared with the control group and groups with chronic and arterial hypertension in pregnancy. No differences in body composition were found in the groups with chronic arterial hypertension and arterial hypertension in pregnancy. With an increased percentage of extracellular fluid above 118% with a sensitivity of 86% and specificity of 82% preeclampsia may be diagnosed in women without obesity between 28–34 weeks' gestation. Conclusion. The data obtained enable to identify abnormal changes in body composition during pregnancy complicated by preeclampsia. An abnormal increase in the volume of extracellular fluid is a maladaptive change during pregnancy and may be regarded as a marker of the preeclampsia development. The detection of an excessive volume of total and extracellular fluid allows a high-precision diagnosis of preeclampsia, as well as the formation of high-risk groups of pregnant women. Key words: pregnancy, bioelectrical impedance analysis, extracellular fluid, total body fluid, body composition

A noninvasive method to study the evolution of extracellular fluid volume in mice using time-domain nuclear magnetic resonance

Maintaining water homeostasis is fundamental for cellular function. Many diseases and drugs affect water balance and plasma osmolality. Water homeostasis studies in small animals require the use of invasive or terminal methods that make intracellular fluid volume and extracellular fluid volume (ECF) monitoring over time stressful and time consuming. We examined the feasibility of monitoring mouse ECF by a noninvasive method using time-domain nuclear magnetic resonance (TD-NMR). This technique allows differentiation of protons in a liquid environment (free fluid) from protons in soft tissues containing a majority of either small molecules (lean) or large molecules (fat). Moreover, this apparatus enables rapid, noninvasive, and repeated measurements on the same animal. We assessed the feasibility of coupling TD-NMR analysis to a longitudinal metabolic cage study by monitoring mice daily. We determined the effect of 24-h water deprivation on mouse body parameters and detected a sequential and overlapping decrease in free fluid and lean mass during water deprivation. Finally, we studied the effect of mineralocorticoids that are known to induce a transient increase in ECF but for which no direct measurements have been performed in mice. We showed, for the first time, that mineralocorticoids induced a transient ~15% increase in free fluid in conscious mice. TD-NMR is, therefore, the first method to allow direct measurement of discrete changes in ECF in conscious small animals. This method allows analysis of kinetic changes to stimuli before investigating with terminal methods and will allow further understanding of fluid disorders.