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The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance., Competing Interests: Conflict-of-interest statement: Dominic SC Raj is supported by RO1 DK073665-01A1, 1U01DK099914-01 and IU01DK09924-01 from the National Institutes of Health. Joseph I Shapiro is supported by HL105649, HL071556 and HL109015 from the National Institutes of Health. The other authors declare no conflicts of interest.

Aim: To test whether muscle mass evaluated by creatinine excretion (EX Cr ) is maintained in patients with end-stage kidney disease (ESKD) treated by peritoneal dialysis (PD), we evaluated repeated measurements of EX Cr in a PD population., Methods: One hundred and sixty-six PD patients (94 male, 72 female) receiving the same PD dose for the duration of the study (up to approximately 2.5 years) had repeated determinations of total (in urine plus spent dialysate) 24-h EX Cr (EX Cr T) to assess the adequacy of PD by creatinine clearance. All 166 patients had two EX Cr T determinations, 84 of the 166 patients had three EX Cr T determinations and 44 of the 166 patients had four EX Cr T measurements. EX Cr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times., Results: In patients who were studied twice, with the first and second EX Cr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EX Cr T did not differ between the first and second study. In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD, EX Cr T did not differ between the first and second study, but was significantly lower in the third study compared to the first study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EX Cr T did not differ between any of the studies. The average EX Cr T value did not change significantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EX Cr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more., Conclusion: The average value of EX Cr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule. However, repeated individual EX Cr T values vary considerably in a large proportion of the patients. Further studies are needed to evaluate the clinical significance of varying EX Cr T values and the stability of EX Cr T beyond 2.5 years of PD follow-up., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.

Aim: To identify patients with end-stage renal disease treated by peritoneal dialysis (PD) who had zero body fat (BF) as determined by analysis of body composition using anthropometric formulas estimating body water (V) and to compare nutritional parameters between these patients and PD patients whose BF was above zero., Methods: Body weight (W) consists of fat-free mass (FFM) and BF. Anthropometric formulas for calculating V allow the calculation of FFM as V/0.73, where 0.73 is the water fraction of FFM at normal hydration. Wasting from loss of BF has adverse survival outcomes in PD. Advanced wasting was defined as zero BF when V/0.73 is equal to or exceeds W. This study, which analyzed 439 PD patients at their first clearance study, used the Watson formulas estimating V to identify patients with V Watson /0.73 ≥ W and compared their nutritional indices with those of PD patients with V Watson /0.73 < W., Results: The study identified at the first clearance study two male patients with V Watson /0.73 ≥ W among 439 patients on PD. Compared to 260 other male patients on PD, the two subjects with advanced wasting had exceptionally low body mass index and serum albumin concentration. The first of the two subjects also had very low values for serum creatinine concentration and total (in urine and spent peritoneal dialysate) creatinine excretion rate while the second subject had an elevated serum creatinine concentration and high creatinine excretion rate due, most probably, to non-compliance with the PD prescription., Conclusion: Advanced wasting (zero BF) in PD patients, identified by the anthropometric formulas that estimate V, while rare, is associated with indices of poor somatic and visceral nutrition., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose.

Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypovolemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium deficit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the first component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fluid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtained by the corrected sodium concentration, which represents a calculated value of the serum sodium concentration that would result from reduction of the serum glucose concentration to a normal level., Competing Interests: Conflict-of-interest statement: Helbert Rondon-Berrios is a member of the advisory board of Astute Medical Inc. The rest of the authors declare no conflict of interest.

Respiratory failure complicating the course of diabetic ketoacidosis (DKA) is a source of increased morbidity and mortality. Detection of respiratory failure in DKA requires focused clinical monitoring, careful interpretation of arterial blood gases, and investigation for conditions that can affect adversely the respiration. Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment. These conditions include deficits of potassium, magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema. Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system, pre-existing respiratory or neuromuscular disease and miscellaneous other conditions. Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA.