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NDT Advance Access originally published online on September 21, 2007
Nephrology Dialysis Transplantation 2008 23(2):687-692; doi:10.1093/ndt/gfm618
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


Seasonal variations in serum sodium levels and other biochemical parameters among peritoneal dialysis patients

Szu-Yuan Li1, Jinn-Yang Chen2, Chiao-Lin Chuang3 and Tzen-Wen Chen4

1Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital, 2Division of Nephrology 3Division of General Medicine, Department of Internal Medicine, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University and 4Division of Nephrology, Department of Internal Medicine, Taipei Medical University and Hospital, Taipei, Taiwan

Correspondence to: Tzen-Wen Chen, MD, PhD, Division of Nephrology, Department of Medicine, Taipei Medical University and Hospital, No. 252, Wu Hsing St., Sinyi District, Taipei 110, Taiwan. Email: twchen{at}tmu.edu.tw



   Abstract
Top
 Abstract
Introduction
 Materials and methods
 Results
 Discussion
 References
 
Background. Although modest seasonal variations in blood biochemical composition have been reported in end-stage renal disease patients treated with haemodialysis, there have been no adequate explanations. The current study aimed to explore whether these phenomena are present in peritoneal dialysis patients and to discuss these variations.

Methods. This was a retrospective study with an enrollment of 44 anuric PD patients. Serum biochemical parameters, peritoneal function, dialysis adequacy, peritoneal ultrafiltration volume and body weight were analysed in relation to climate variables for a study period of 2 years.

Results. PD patients exhibited cyclic variations in blood biochemical concentrations. Monthly mean outdoor temperature was inversely correlated with serum concentrations of sodium (r = –0.712, P < 0.001), potassium (r = –0.697, P < 0.001), bicarbonate (r = –0.642, P < 0.001), BUN (r = –0.654, P < 0.001), albumin (r = –0.496, P = 0.012), peritoneal ultrafiltration volume (r = –0.723, P = 0.001) and body weight (r = –0.623, P < 0.001). Serum chloride and creatinine concentrations were not correlated with temperature or other climate variables.

Conclusions. PD patients showed seasonal variations in serum electrolyte concentration and peritoneal ultrafiltration volume. Monthly outdoor mean temperature was inversely correlated with serum electrolytes and ultrafiltration volume. A likely explanation is loss of these electrolytes through perspiration. Neglect of this annual cycle in PD patients may lead to biases in interpretation of clinical study and individual laboratory data.

Keywords: electrolyte; end-stage renal disease; peritoneal dialysis; perspiration; seasonal variation; ultrafiltration



   Introduction
Top
 Abstract
 Introduction
Materials and methods
 Results
 Discussion
 References
 
In the general population, seasonal variations have been demonstrated in calcium metabolism [1,2], affective disorder rate [3], cardiovascular disease risk [4,5] as well as numerous infectious [6,7] and rheumatologic diseases [8,9]. In end-stage renal disease (ESRD) patients, blood pressure varies seasonally, with higher values in the winter and lower values in the summer, and this is independent of treatment with haemodialysis (HD) [10–12], peritoneal dialysis (PD) [13] or renal transplantation [14]. In addition to blood pressure, seasonal variation may also affect blood biochemical composition in HD patients. Even though the magnitudes were modest, serum sodium, potassium, bicarbonate, BUN, albumin and ultrafiltration volume were reported to be higher in the winter and inversely correlated with outdoor temperatures in HD patients [11]. Although the authors suggested that seasonal protein intake may explain variations in BUN, they did not comment on the changes in electrolytes. In an additional study conducted in the Mediterranean region, higher total cholesterol, LDL cholesterol, albumin and glucose level were observed in warmer months among HD patients, and the authors speculated that these increases resulted from neurohormonal influences [15]. However, the primary mechanism responsible for these phenomena has not been well established. In order to identify the influence of climate on PD patients, we measured and analysed serum biochemical parameters during changes in climate variables.



   Materials and methods
Top
 Abstract
 Introduction
 Materials and methods
Results
 Discussion
 References
 
Subjects
Forty-four anuric PD patients (M/F = 15/29) from Taipei Veteran General Hospital were enrolled and studied between October 2004 and October 2006. Their demographic data are listed in Table 1.The mean age was 52.4 years and the mean dialysis duration at first recording was 62.8 months. All patients received lactate-based PD fluid and the PD prescription varied according to individual need. The sodium, lactate and chloride levels of the PD fluid were 132, 40 and 96 mmol/l, respectively. The target dry weight for each patient was determined by his or her primary nephrologist. Body weight and serum biochemical data were recorded on monthly fixed days. Peritoneal membrane function was evaluated with a standard peritoneal equilibration test at six-month intervals. Both nKT/V and nWCC were calculated using 24-hr effluent at 4-month intervals. For analysis, data of peritoneal function and dialysis adequacy were divided into cold months and hot months based on calendar months. The PD dialysate consumption was obtained from delivery records from dialysate suppliers. In Taiwan, every PD patient keeps his or her record of daily ultrafiltration volume. The monthly mean of daily-recorded peritoneal ultrafiltration volume was used in this study.


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  		Table 1. Characteristics of PD patients at study onset

 
Assays
Blood samples were centrifuged and sera were measured immediately with a Hitachi 7600 chemical auto-analyzer (Hitachi, Co., Ltd, Tokyo, Japan). Albumin level was obtained by the BCG method. Serum sodium, potassium and chloride concentrations were analysed by ion selective electrodes. Bicarbonate concentration was measured by the PEPC method. BUN was measured by standard urease assays and creatinine level was measured by Jaffe reaction. Body weight was measured using an electrical scale with minimal units of 0.1 kg. The subjects were weighed with light clothes in a temperature-controlled room.

Climatic data
As a subtropical island (22–25.5°N) within the Western Pacific Island chain, Taiwan experiences an annual variation in climate. This variation is basically established by the alternation of two monsoon components: the summer southwest monsoon and the winter northeast monsoon. Taipei (25°N), which is located in the north of Taiwan with a typical subtropical monsoon climate, has an abundant temperature variation and high relative humidity. Climate data were obtained from the Taiwan Central Weather Bureau (http://www.cwb.gov.tw). Monthly precipitation, monthly means of daily averages of temperature, and relative humidity measurements were used in the study.

Statistical analysis
All data grouped according to calendar months were expressed as means ± SD. Data that were not normally distributed were analysed using non-parametric methods. D/D0, D/P ratio, nKT/V and nWCC were analysed with paired t-tests. Multivariate analysis was used to identify the effect of climate parameters on clinical and laboratory data. Statistical analysis was performed using SPSS 14.0 for windows web version provided by Taipei Veteran General Hospital. All probabilities were two-tailed. A P-value less than 0.05 was considered as statistically significant.



   Results
Top
 Abstract
 Introduction
 Materials and methods
 Results
Discussion
 References
 
Climatic data
During the 2-year study period, monthly mean outdoor temperatures ranged from 16°C in winter to 30°C in summer. Relative humidity ranged from 70 to 85%. Monthly precipitation ranged from 20 to 666 mm, with the most humid days occurring during the typhoon season and rainy months.

Variations in biochemical data and ultrafiltration volumes
There was a cyclic variation in serum sodium, potassium, bicarbonate, BUN concentration and ultrafiltration volume during the 2-year study period (Figure 1). The mean (±SD) peak values of sodium (140.70 ± 4.5 mmol/l), potassium (4.05 ± 0.78 mmol/l), bicarbonate (29.72 ± 2.64 mmol/l), BUN (62.65 ± 16.75 mg/dl), albumin (4.05 ± 0.46 g/dl), peritoneal ultrafiltration volume (1089 ± 165 ml/day) and body weight (56.05 ±10.26 kg) all occurred in the winter. The nadir values of sodium (133.74 ± 4.9 mmol/l), potassium (3.65 ±0.55 mmol/l), bicarbonate (24.61 ± 3.20 mmol/l), BUN (47.3 ± 14.19 mg/dl), albumin (3.76 ± 0.38 g/dl), peritoneal ultrafiltration volume (886 ± 190 ml/day) and body weight (53.25 ± 10.76 kg) occurred in the summer.


Figure 1
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  		Fig. 1. Longitudinal data of serum sodium (A), bicarbonate (B), potassium (C), BUN (D), UF volume (E) and body weight (F). Biochemical data and UF volume are expressed as means ± SD. Monthly mean outdoor temperature is expressed in open squares. The biochemical parameters have a yearly cyclic pattern, with lower values in the summer and higher values in the winter.

 
Of the three climate variables that were studied, only monthly mean outdoor temperature was significantly correlated with the serum biochemical parameters (P < 0.05) in multivariate analysis. It was inversely correlated with serum sodium (r = –0.712, P < 0.001), potassium (r = –0.697, P < 0.001), bicarbonate (r = –0.642, P < 0.001), BUN (r = –0.654, P < 0.001), albumin (r = –0.496, P = 0.012), peritoneal ultrafiltration volume(r = –0.723, P < 0.001) and body weight (r = –0.623, P < 0.001). Chloride (P = 0.062) and creatinine (P = 0.65) were not correlated with temperature or the other climate variables. In the linear regression model, the serum sodium concentration prediction equation was Na (mmol/l) = –0.31 xtemperature (°C) + 145.18. These findings are summarized in Table 2 and Figure 2.


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  		Table 2. Variations in clinical/biochemical data and correlations with monthly mean temperature

 

Figure 2
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  		Fig. 2. Each dot represents the monthly mean value of 44 patients. The graphs show inverse correlations between temperature and serum concentrations of sodium (A), bicarbonate (B), potassium (C), BUN (D), UF volume (E) and body weight (F), respectively.

 
Peritoneal function and dialysis adequacy
We defined hot months as April to September and cold months October to March. There were no differences in D/D0 (0.391 ± 0.057 vs 0.386 ± 0.074, P = 0.242), D/P ratio (0.654 ± 0.089 vs 0.654 ± 0.102, P = 0.686), nWCC (60.85 ± 11.43 vs 59.59 ± 10.71, P = 0.379) or nKT/V (2.17 ± 0.29 vs 2.20 ± 0.31 l/week/1.73m2, P = 0.851) between hot and cold months.



   Discussion
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
References
 
In contrast to healthy individuals, ESRD patients are unable to maintain homeostasis. There have been several previous studies that examined the effects of climate on uremia patients [11,12,15–21]. Most of these focused on seasonal blood pressure variations. Outdoor temperature, relative humidity, rainfall and light span were all reported to affect blood pressure in HD patients [16]. However, only temperature has been correlated with serum biochemical parameters [11]. In the current study, only temperature and not the other climate variables affected biochemical parameters in multivariate analysis. Neither annual differences in humidity nor rainfall had an effect on biochemical variables.

Theoretically, the variation in body weight can be attributed to the change in lean body mass or fluid weight. Furthermore, we speculate that the seasonal variation in biochemical parameters was due simply to the dilution effect. However, the simultaneous changes in sodium and body weight, both in the same direction, contradict this hypothesis. An alternate explanation is that higher protein and energy intakes in winter result in greater weight and sodium concentration. This would explain the variation in BUN but not the changes in electrolytes. The most reasonable hypothesis is that the loss of homeostatic capability, which functions in normal kidneys, cannot be totally replaced by current renal replacement therapies. For example, people in summer have greater perspiration than water intake, and subjects with normal kidneys are able to maintain fluid and electrolyte homeostasis whereas ESRD patients are not. PD patients tend to have less peritoneal ultrafiltration volume in summer (Figure 1), which is similar to the findings observed in HD patients [11,12,16,20]. Our PD dialysate consumption records also confirmed greater requirements for high glucose PD solutions in winter (Figure 3). Because sodium removal during PD is strongly related to the ultrafiltration volume [22–24], PD patients should have less peritoneal sodium extraction in hot months. However, we observed that the serum sodium nadir occurred in summer. Because patients lost more sodium from sweating and received identical electrolyte concentration in PD fluid, this may result in greater net sodium loss and explain the decrease in summer. In the current study, differences in sweat volume from summer to winter were around 200 ml/day (the mean difference in daily peritoneal ultrafiltration volume from summer to winter). By factoring in sweat sodium concentration (43 mmol/l) in renal failure patients [25], we calculate that 258 mmol more sodium is lost monthly in the summer [0.2(l) x 43(mmol/l) x 30(day)], which would create an 8 mmol/l decrease in serum sodium concentration in these patients.[258(mmol)/(54(kg) x 0.6)]. This prediction is close to our observation of a 7 mmol/l decrease in average sodium concentration. In contrast to the small difference in sweat sodium concentration between uremic and healthy subjects [25], potassium [25] and urea [26] concentrations in sweat fluid are much higher in uremic patients, which accounts for the higher magnitudes in seasonal variations in our study (5, 10 and 28% for sodium, potassium and urea, respectively). Although albumin and BUN levels may be also affected by seasonal protein intakes and catabolism differences, cyclic serum electrolyte variations still support the hypotheses that the skin acts as an excretory organ in uremia [27] and that perspiration contributes, at least in part, to the seasonal electrolyte variations. In contrast to HD, PD is characterized by continuous treatment with less abrupt serum composition changes and less haemodynamic changes. Because of these features associated with PD, we are confident about the present correlations and feel that PD use may explain differences between the present and previous reports using HD. Nevertheless, even though our patients did not have three times a week correction by diffusion during HD, the magnitude of these serum biochemical seasonal variations in our study are much greater than in previous reports using HD (0.6, 1.5 and 4.0% for sodium, potassium and BUN, respectively) [11]. These variations are about seven times greater in PD than in HD for all studied serum parameters. In the linear regression model, serum sodium concentration fell by ~0.31 mmol/l for each centigrade increase in monthly mean temperature. This effect may be trivial in countries having relatively constant temperatures, but should not be ignored in areas with abundant temperature variations.


Figure 3
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  		Fig. 3. The uptake of different glucose concentrations in PD fluid has a seasonal cyclic pattern (A). The ratio of 1.5% PD dialysate consumption is higher in the summer, indicating that PD patients require higher PD dialysate glucose in the winter (B).

 
Ancient medicine was aware of environmental temperature effects on blood purification via the skin. In early Rome and later in the Middle Ages, hot baths and sweating therapies had been used for treating uremia (Greek for urine poisoning, or literally, ‘urine in the blood’) [27]. The present study, which included in 44 patients over a period of 2 years, demonstrated the influence of climate on biochemical data in ESRD patients treated with PD. This is the first detailed report showing seasonal variation effects on biochemical parameters, body weight and peritoneal ultrafiltration volume in PD patients. There were several limitations in the current study. In this retrospective observational study, we did not have bioimpedance data to demonstrate body water change; however, a previous study by Cheng et al. [13] failed to show seasonal variations in extracellular water in PD patients. The calculation of sweat volume is another limitation. Actual sweat volume and electrolyte concentration measurements were lacking. Sweat volume was calculated based on the concept of dynamic balance. Despite these limitations, we believe that our study has some useful features. As a novel finding, we found that PD patients tend to have a relative hyponatremia in summer. In terms of fluid and blood pressure control, low sodium-containing PD solutions have been widely discussed [28,29], and our findings have the potential to affect clinical decisions with regard to peritoneal dialysate composition.

In conclusion, PD patients exhibit seasonal variations in serum sodium levels and other biochemical parameters. This knowledge may have future effects on clinical decisions with regard to peritoneal dialysate composition and medication dosage. In addition, ignorance of this annular cycle in PD patients could potentially lead to biases in the interpretation of clinical studies and individual laboratory data. Although the causes of these variations are not yet clear, elimination of toxins and electrolytes through perspiration is an attractive explanation. The ancient idea that substitution of renal function by the detoxification ability of skin may still play a role in PD in current practice.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 References
 

  1. Rapuri PB, Kinyamu HK, Gallagher JC, et al. Seasonal changes in calciotropic hormones, bone markers, and bone mineral density in elderly women. J Clin Endocrinol Metab (2002) 87:2024–2032.[Abstract/Free Full Text]
  2. Viljakainen HT, Palssa A, Karkkainen M, et al. A seasonal variation of calcitropic hormones, bone turnover and bone mineral density in early and mid-puberty girls – a cross-sectional study. Br J Nutr (2006) 96:124–130.[CrossRef][Web of Science][Medline]
  3. Lam RW, Levitan RD. Pathophysiology of seasonal affective disorder: a review. J Psychiatry Neurosci (2000) 25:469–480.[Web of Science][Medline]
  4. Shahar DR, Froom P, Harari G, et al. Changes in dietary intake account for seasonal changes in cardiovascular disease risk factors. Eur J Clin Nutr (1999) 53:395–400.[CrossRef][Web of Science][Medline]
  5. Boulay F, Berthier F, Sisteron O, et al. Seasonal variation in chronic heart failure hospitalizations and mortality in France. Circulation (1999) 100:280–286.[Abstract/Free Full Text]
  6. Altizer S, Dobson A, Hosseini P, et al. Seasonality and the dynamics of infectious diseases. Ecol Lett (2006) 9:467–484.[CrossRef][Web of Science][Medline]
  7. Dowell SF. Seasonal variation in host susceptibility and cycles of certain infectious diseases. Emerg Infect Dis (2001) 7:369–374.[Web of Science][Medline]
  8. Hawley DJ, Wolfe F, Lue FA, et al. Seasonal symptom severity in patients with rheumatic diseases: a study of 1,424 patients. J Rheumatol (2001) 28:1900–1909.[Abstract/Free Full Text]
  9. Gallerani M, Govoni M, Mucinelli M, et al. Seasonal variation in the onset of acute microcrystalline arthritis. Rheumatology (Oxford) (1999) 38:1003–1006.[CrossRef][Medline]
  10. Argiles A, Mourad G, Mion C. Seasonal changes in blood pressure in patients with end-stage renal disease treated with hemodialysis. N Engl J Med (1998) 339:1364–1370.[Abstract/Free Full Text]
  11. Cheung AK, Yan G, Greene T, et al. Seasonal variations in clinical and laboratory variables among chronic hemodialysis patients. J Am Soc Nephrol (2002) 13:2345–2352.[Abstract/Free Full Text]
  12. Sposito M, Nieto FJ, Ventura JE. Seasonal variations of blood pressure and overhydration in patients on chronic hemodialysis. Am J Kidney Dis (2000) 35:812–818.[Web of Science][Medline]
  13. Cheng LT, Jiang HY, Tang LJ, et al. Seasonal variation in blood pressure of patients on continuous ambulatory peritoneal dialysis. Blood Purif (2006) 24:499–507.[CrossRef][Web of Science][Medline]
  14. Prasad GV, Nash MM, Zaltzman JS. Seasonal variation in outpatient blood pressure in stable renal transplant recipients. Transplant (2001) 72:1792–1794.[Web of Science][Medline]
  15. Kovacic V, Kovacic V. Seasonal variations of clinical and biochemical parameters in chronic haemodialysis. Ann Acad Med Singapore (2004) 33:763–768.[Web of Science][Medline]
  16. Argiles A, Lorho R, Servel MF, et al. Seasonal modifications in blood pressure are mainly related to interdialytic body weight gain in dialysis patients. Kidney Int (2004) 65:1795–1801.[CrossRef][Web of Science][Medline]
  17. Szeto CC, Chow KM, Wong TY, et al. Influence of climate on the incidence of peritoneal dialysis-related peritonitis. Perit Dial Int (2003) 23:580–586.[Abstract/Free Full Text]
  18. Kim MJ, Song JH, Park YJ, et al. The influence of seasonal factors on the incidence of peritonitis in continuous ambulatory peritoneal dialysis in the temperate zone. Adv Perit Dial (2000) 16:243–247.[Medline]
  19. Fine A. Lack of seasonal variation in blood pressure in patients on hemodialysis in a North American center. Am J Kidney Dis (2000) 36:562–565.[Web of Science][Medline]
  20. Tozawa M, Iseki K, Iseki C, et al. Seasonal blood pressure and body weight variation in patients on chronic hemodialysis. Am J Nephrol (1999) 19:660–667.[CrossRef][Web of Science][Medline]
  21. Argiles A, Lorho R, Servel MF, et al. Blood pressure is correlated with vitamin d(3) serum levels in dialysis patients. Blood Purif (2002) 20:370–375.[CrossRef][Web of Science][Medline]
  22. Wang T, Waniewski J, Heimburger O, et al. A quantitative analysis of sodium transport and removal during peritoneal dialysis. Kidney Int (1997) 52:1609–1616.[Web of Science][Medline]
  23. Uribarri J, Prabhakar S, Kahn T. Hyponatremia in peritoneal dialysis patients. Clin Nephrol (2004) 61:54–58.[Web of Science][Medline]
  24. Rodriguez-Carmona A, Fontan MP. Sodium removal in patients undergoing CAPD and automated peritoneal dialysis. Perit Dial Int (2002) 22:705–713.[Abstract/Free Full Text]
  25. Yosipovitch G, Reis J, Tur E, et al. Sweat electrolytes in patients with advanced renal failure. J Lab Clin Med (1994) 124:808–812.[Web of Science][Medline]
  26. al-Tamer YY, Hadi EA, al B II. Sweat urea, uric acid and creatinine concentrations in uraemic patients. Urol Res (1997) 25:337–340.[CrossRef][Web of Science][Medline]
  27. Diamandopoulos AA, Goudas PC. Substitution of renal function through skin catharsis: evidence from the classical period to the middle ages. Kidney Int (2001) 59:1580–1589.[CrossRef][Web of Science][Medline]
  28. Khandelwal M, Oreopoulos DG. Is there a need for low sodium dialysis solution for peritoneal dialysis patients? Adv Perit Dial (2004) 20:156–162.[Medline]
  29. Van Biesen W, Vanholder R, Veys N, et al. Improving salt balance in peritoneal dialysis patients. Perit Dial Int (2005) 25(Suppl 3):S73–S75.[Abstract/Free Full Text]
Received for publication: 23. 2.07
Accepted in revised form: 14. 8.07


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