Prehemodialysis hyponatremia and extracellular water: Is it simply too much water?

Abstract

Observational hemodialysis (HD) studies report an association between hyponatremia and increased mortality. As volume overload is also associated with mortality, we wished to determine whether hyponatremia is linked to increased extracellular water (ECW). We measured ECW, total body water (TBW) and body composition predialysis with multifrequency bioimpedance, arm strength with pinch gauge and hand grip strength (PS, HGS), standard biochemistry profiles, comorbidity and clinical frailty scores (CFS). We reviewed 324 patients, 195 (60.2%) male, mean age 62.3 ± 15.6 years. Thirty‐eight (11.7%) patients were hyponatremic (sodium ≤135 mmol/L), ECW/height2 was not different, but ECW/TBW (0.409 ± 0.016 vs. 0.402 ± 0.016, p < 0.01), C reactive protein (CRP) (9(4–6) vs. 5(2–12) g/L, p < 0.05), CFS (5(4–6) vs. 4(3–6), p < 0.05) were higher in hyponatremic patients, whereas appendicular lean mass index (8.6 ± 1.7 vs. 9.4 ± 1.8 kg/m2, p < 0.01), serum albumin (36.3 ± 5.5 vs. 38.8 ± 5.0 g/L, p < 0.01) and PS (3.7(2.7–4.7) vs. 4.7 (3.2–6.5) kg, p < 0.05)) were lower. Both serum sodium, and serum sodium after adjustment for glucose were associated with serum creatinine (β 4.26, (95% confidence limits [CL] 1.9–6.7), β 3.98 (CL 1.6–6.4), both p = 0.001, respectively) and negatively with CRP (β −0.76, [CL] ‐1.5 to −0.5), β −0.72 (CL −1.44 to −0.12), p = 0.036, p = 0.046, respectively) in a multivariable model. Hyponatremic HD patients did not simply have an increased ECW, as the increased ECW/TBW and ECW/ICW ratios were more likely secondary to loss of muscle mass and strength, associated with increased CRP and reduced albumin, suggesting that hyponatremia is associated with inflammation, loss of muscle mass and increasing frailty.

Application of the Clinical Frailty Score and body composition and upper arm strength in haemodialysis patients

“…For the whole cohort there was a negative association between lean mass and appendicular mass indexed for height and percentage body fat ( r = 0.2, P < 0.001). Previous observational studies have noted an increased prevalence of sarcopenic obesity in HD patients, particularly for female patients, due to the combination of reduced muscle mass and increased fat mass [ 34 ]. This study supports these earlier reports, as more female patients were classed as being frail.…”

Body Composition and COPD: A New Perspective

“…Finally, impedance ratio significantly increased and phase angle decreased in patients with severe sarcopenia and in cachectic patients. Roohi Chhabra et al 102 2021 Prospective cohort study British Age, gender, Dialysis months, No BP meds, Clinical Frailty score, Davies grade, weight, BMI, TBW, ECW, ICW, FFM, FM%, ECW/TBW More patients in the lower predialysis serum sodium cohort had diabetes, greater frailty scores, higher CRP, and higher ratios of both ECW/ICW and ECW/TBW, with lower serum creatnine, LMI and right arm lean mass, and muscle strength. ECW/TBW (0.409 ± 0.016 vs 0.402 ± 0.016, p < 0.01), C reactive protein (CRP) (9 (4–6) vs 5 (2–12) g/L, p < 0.05), CFS (5 (4–6) vs 4 (3–6), p <0.05) were higher.…”

Fluid Overload and Tissue Sodium Accumulation as Main Drivers of Protein Energy Malnutrition in Dialysis Patients

“…Hyponatremia is difficult to explain in an anuric dialysis patient in which dialysis is the main source of exchange (sodium and water) with external milieu [ 61 ]. Several hypotheses have been advocated: Firstly, the release of mediators (vasopressin, angiotensin 2) [ 85 ] or factors (tonicity, thirst) that affect sodium-free water intake or retention; secondly, vascular leakage and sick-cell syndrome linked to inflammation that facilitate water intercompartmental imbalance [ 86 , 87 ]; thirdly, reorientation of liver protein synthesis to acute phase proteins, reducing albumin circulating levels. A new and interesting hypothesis may be formulated according to the findings in rodent models of tissue sodium content on muscle metabolism.…”