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Annals of Clinical & Laboratory Science 38:88-91 (2008)
© 2008 Association of Clinical Scientists

Letter to the Editor

Associations between Body Hydration Status and Serum Markers of Apoptosis in Elderly Persons

Yong Hoon Jun1, Chung Hyun Nahm2 and Jong Weon Choi2
1 Departments of Pediatrics and 2 Laboratory Medicine, College of Medicine, Inha University, Incheon, South Korea

Address correspondence to Jong Weon Choi, M.D., Ph.D., Department of Laboratory Medicine, Inha University Hospital, 7-206, 3-ga, Shinheung-dong, Jung-gu, Incheon, 400-711, South Korea; tel 82 32 890 2503; fax 82 32 890 2529; e-mail jwchoi{at}inha.ac.kr.

Keywords: apoptosis, body hydration, geriatrics, serum sFas, serum TRAIL, total body water

To the Editor:

Healthy humans are well able to regulate their daily water balance despite exposures to stressors on hydration status. Older individuals have a higher risk of developing dehydration than younger adults. The enhanced risk is related to decreased thirst-sensation with aging and reduction of muscular mass, which is hydrated and contains 73% of body water [1]. Increasing evidence suggests that mild dehydration plays a role in the development of various morbidities. Dehydration is often linked to infection in elderly people, and is associated with chronic diseases, such as urolithiasis, venous thromboembolism, exercise asthma, and hyper-glycemia in diabetic ketoacidosis [2].

Determination of whole body bioimpedance is a non-invasive and reproducible method to monitor hydration status. Using segmental bioimpedance measurements, it is possible to obtain information about the fluid changes in each body compartment [3]. Urine concentration can be determined by measurement of urine specific gravity (USG), and the USG can serve as an index of hydration status.

The Fas molecule is an important membrane death receptor that is involved in the induction of apoptosis [4]. Triggering of Fas by its ligand results in rapid induction of apoptosis in susceptible cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is capable of inducing apoptosis in tumor cell lines and TRAIL has key roles in tumor suppression and immune cell homeostasis [5].

Few studies have examined the associations of serum soluble Fas (sFas) and TRAIL concentrations in relation to body hydration status. The present study investigated whether the ratio of extracellular fluid to total body water (ECF/TBW ratio), evaluated in conjunction with USG, is significantly related to serum sFas and TRAIL levels in elderly persons.

Materials and Methods

Adult men (n = 87; age = 55 to 67 yr) were investigated by measurements of TBW, ECF/TBW ratio, USG, and serum markers of apoptosis. Because fluid homeostasis can be influenced by various biochemical constituents, serum indices of renal function (ie, serum urea nitrogen and creatinine), serum total protein, albumin, and electrolytes (ie, sodium and potassium) were measured.

USG was tested by refractometry using a urinalysis system (Urisys 2400; Roche Diagnostics, Mannheim, FRG). The system analyzes USG in a flow cell that is filled with a urine sample during aspiration of the sample, and the results are automatically compensated for temperature because USG changes with the temperature of samples.

TBW, ECF/TBW ratio, and anthropometric parameters were assessed using an impedance-meter, the body composition analyzer (InBody 3.0, Biospace, Seoul, Korea), which provides measurements of TBW, regional water distribution, and body mass index (BMI, kg/m2) [3].

The subjects were requested to abstain from water before sample collection after an overnight fast. Serum concentrations of sFas and TRAIL were measured by enzyme immunoassays using human sAPO-1/Fas BMS245 kits (Bender MedSystems, Vienna, Austria) and Quantikine human TRAIL/TNFSF10 kits (R&D Systems, Minneapolis, MN, USA). Biochemical profiles were assayed with an automated chemical analyzer (Hitachi 7600, Hitachi, Tokyo, Japan).

Two subgroups of the subject population were selected on the basis of ECF/TBW ratio and USG: men with ECF/ TBW ratio ≥ 0.331 and USG ≤ 1.019 (n = 18) and men with ECF/TBW ratio <0.331 and USG ≥1.029 (n = 19). The provisional cutoff points applied in the selection were based on the mean level of ECF/TBW ratio and the mean value (+1 SD) of USG in the subject population. The men with ECF/ TBW ratio <0.331 and USG ≥1.029 were classified as a dehydrated group.

A non-parametric test (the Wilcoxon rank-sum test) was used to test the statistical significance of inter-group differences. Correlation coefficients were calculated by the Spearman method. All p values <0.05 were considered statistically significant.

Results and Discussion

This study shows that the change in ECF/TBW ratio and USG does not significantly influence serum concentrations of biochemical profiles but has an impact on serum sFas and TRAIL levels. In this study, there were no significant differences in serum sFas and TRAIL concentrations between the subjects with USG >1.024 and USG ≤1.024, nor between subjects with ECF/TBW ratio >0.331 and ECF/TBW ratio ≤0.331 (data not shown).

However, serum sFas and TRAIL concentrations showed significant differences when a combination index (ECF/TBW ratio and USG) was applied for categorization of the subject population (Table 1Go). Serum sFas concentrations in men with ECF/TBW ratio <0.331 and USG ≥1.029 averaged 528.6 ± 215.4 pg/ml, which significantly exceeded the values (362.3 ± 107.8 pg/ml, p <0.05) in men with ECF/TBW ratio ≥0.331 and USG <1.019. Serum TRAIL levels in men with ECF/TBW ratio <0.331 and USG ≥1.029 exceeded the values in men with ECF/TBW ratio ≥0.331 and USG ≤1.019 (76.7 ± 24.0 vs 53.1 ± 17.3 pg/ml, p <0.05).


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  		Table 1. Serum markers of apoptosis, anthropometric parameters, and biochemical profiles in relation to ECF/TBW ratio and urine specific gravity (USG) in elderly men [mean ± SD (median in parenthesis)].
 
These results suggest that serum markers of apoptosis may be more actively expressed in dehydrated subjects than in less-dehydrated individuals. It appears that the combination of USG and ECF/TBW ratio can classify more strictly the subject’s hydration status than using only the USG or the ECF/TBW ratio. These findings are consistent with the results of a previous study, which showed that water deprivation induced apoptosis in an experimental animal model [6].

Renal function, serum sodium concentration, and serum albumin levels can influence body water balance. In the present study, men with ECF/TBW ratio <0.331 and USG ≥1.029 showed a tendency toward increased serum concentrations of some biochemical parameters compared to men with ECF/TBW ratio ≥0.331 and USG ≥1.019; however, no statistically significant differences were observed between the 2 groups. These results imply that the elevated serum levels of sFas and TRAIL, which were observed in the dehydrated group, are not simply attributable to hemoconcentration.

Previous investigators have reported that increased osmolality in cell culture media elicits apoptotic changes [7]. Harada et al [8] found that a hypernatremic condition acts to promote progressive cell death. In contrast, in our study, there were no significant relationships between serum markers of apoptosis and serum sodium concentrations. These discrepancies may reflect the widely different methods of study (eg, in vivo vs in vitro systems; animal cell lines vs human serum samples).

Although there is no accepted gold standard for assessment of body hydration status, the USG, bioelectrical impedance, and urine osmolality have been widely employed to test body water balance. Concentrated urine is commonly used as an early indicator of dehydration. In the current study, USG and ECF/TBW ratio were selected as biomarkers for evaluation of hydration status. As shown in Fig. 1Go, USG was significantly correlated with serum sFas (r = 0.35, p <0.05) and TRAIL concentrations (r = 0.38, p <0.05). Based on these results, it appears that body water deficit is associated with increased serum levels of sFas and TRAIL.


Figure 1
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  		Fig. 1. Scatter plots showing the relationships of serum TRAIL (A) and sFas (B) versus USG in 87 elderly men. The equations of the correlation lines (A and B) are Y = 1285.2X – 1252.5; r = 0.38 (p <0.05) and Y = 10685X – 10493; r = 0.35 (p <0.05).

 
Considering that sFas is released from damaged cells and that TRAIL triggers cell death in susceptible tissue [9], a modest increase of serum sFas and TRAIL levels in dehydrated subjects implies that body hydration status may be related to systemic tissue damage or cell death.

In conclusion, serum sFas and TRAIL concentrations exhibited significant correlations with USG in the subjects, suggesting that body hydration status may be linked to apoptotic activity in elderly men, based on the laboratory data for sFas, TRAIL, ECF/TBW ratio, and USG.

Acknowledgement

This work was supported by a research grant from Inha University.

References

  1. Bossingham MJ, Carnell NS, Campbell WW. Water balance, hydration status, and fat-free mass hydration in younger and older adults. Am J Clin Nutr 2005;81:1342–1350.[Abstract/Free Full Text]
  2. Manz F, Wentz A. The importance of good hydration for the prevention of chronic diseases. Nutr Rev 2005;63: S2–5.[Medline]
  3. Song JH, Lee SW, Kim GA, Kim MJ. Measurement of fluid shift in CAPD patients using segmental bioelectrical impedance analysis. Perit Dial Int 1999;19:386–390.[Abstract/Free Full Text]
  4. Cascino I, Fiucci G, Papoff G, Ruberti G. Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing. J Immunol 1995;154:2706–2713.[Abstract]
  5. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A. Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 1997;277:818–821.[Abstract/Free Full Text]
  6. Hao CM, Yull F, Blackwell T, Komhoff M, Davis LS, Breyer MD. Dehydration activates an NF-kappaB-driven, COX2-dependent survival mechanism in renal medullary interstitial cells. J Clin Invest 2000;106:973–982.[Medline]
  7. Terada Y, Inoshita S, Hanada S, Shimamura H, Kuwahara M, Ogawa W, Kasuga M, Sasaki S, Marumo F. Hyperosmolality activates Akt and regulates apoptosis in renal tubular cells. Kidney Int 2001;60:553–567.[Medline]
  8. Harada T, Izaki S, Tsutsumi H, Kobayashi M, Kitamura K. Apoptosis of hair follicle cells in the second-degree burn wound under hypernatremic conditions. Burns 1998;24:464–469.[Medline]
  9. Kawahito K, Misawa Y, Fuse K. Transient rise in serum soluble Fas (APO-1/CD95) in patients undergoing cardiac surgery. Artif Organs 2000;24:628–631.[Medline]




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