- Email: [email protected]
Clinical determinants of interdialytic weight gain
Clinical Determinants of Interdialytic Weight Gain Angelo Testa, MD,* and Annick Plou, MD* Objective: We recently found a close relationship between high interdialytic weight gain (IDWG) and nutritional parameters, confirming the potential role of IDWG as a marker of calorie and protein intake in hemodialysis patients. In this population, the control of volume status to achieve the “appropriate dry weight” suggests a correlation between blood pressure (BP) and IDWG. The aim of our study was to investigate the clinical determinants of IDWG, particularly regarding sodium balance and nutritional intake, in a cohort of clinically stable hemodialysis patients. Patients and Methods: During a 1-year period, we collected clinical and biological data from 32 of 75 patients who underwent dialysis at our Center. To investigate the dietary protein intake, calorie intake, and sodium intake, a dietician assessed a 3-day dietary record. Urea kinetic parameters and interdialytic sodium load were calculated for all patients. Results: There were 19 men and 13 women with a mean age of 71.3 ⫾ 13.7 years, 10 of 32 patients were hypertensive, and 14% were diabetics. The mean IDWG calculated during the 3-day interval was 4.5 ⫾ 1.5%. Simple and multiple regression analysis showed a significant and positive correlation between IDWG and protein catabolic rate (PCR) (P ⬍ .0001). In contrast, we did not find any relationship between sodium load, sodium intake, and IDWG, nor between BP and IDWG. In 15 of 32 patients with steadily high IDWG, PCR and calorie intake were significantly higher than in patients with low IDWG (1.3 ⫾ 0.3 v 0.9 ⫾ 0.3 g/kg/d, P ⬍ .0001, respectively; 28 ⫾ 7.5 v 21.6 ⫾ 6.4 cal/kg/d, P ⬍ .02, respectively). No changes were found in sodium load and sodium intake. Conclusions: We confirm that, in hemodialysis patients, a stable IDWG may be a useful clinical marker of adequate calorie and protein intake. IDWG does not seem directly related to BP, even in hypertensive patients, suggesting that additional factors play a role in the control of BP in this population. © 2001 by the National Kidney Foundation, Inc.
I
NTERDIALYTIC weight gain (IDWG) is usually considered as a measurement of compliance with medical management of hemodialysis (HD) patients because it may be affected, at least in part, by patient behavior.1,2 However, in this population, IDWG may be accounted for by intake of beverages or solid food with high nutritional value that indirectly indicates a good nutritional status rather than a lack of patient self-discipline. We and others recently found a close relationship between IDWG and nutritional parameters, confirming the potential role of IDWG as a marker of caloric and protein in-
*Expansion Centre d’He´modialyse de l’Ouest Hoˆpital St Jacques, Nantes, France. Presented at the 10th International Congress on Nutrition and Metabolism in Renal Disease, Lyon, France, July 6-8, 2000. Address reprint requests to Angelo Testa, MD, Espansion Centre d’He´modialyse de l’Ouest, 85 Rue St Jacques, 44202 Nantes, France. E-mail: [email protected] © 2001 by the National Kidney Foundation, Inc. 1051-2276/01/1103-0006$35.00/0 doi:10.1053/jren.2001.24362
Journal of Renal Nutrition, Vol 11, No 3 ( July), 2001: pp 155-160
take.3,4 A very low interdialytic fluid gain and protein catabolic rate (PCR) found in HD patients suggest that this population could be at risk for malnutrition. Control of volume status by vigorous ultrafiltration to achieve the appropriate dry weight can normalize blood pressure and suggests a relationship between IDWG, extracellular volume, exchangeable sodium, and blood pressure (BP). In contrast, higher IDWG did not result in higher interdialytic BP; recently, several studies were unable to find a direct correlation between short-term interdialytic weight changes and BP.5,6 This confirms that IDWG is a poor surrogate for changes in intravascular volume and, probably, sodium balance should be a far more important determinant of changes in extracellular volume. The aim of our study was to investigate the clinical determinants of IDWG, particularly regarding sodium balance and nutritional intake, in a cohort of clinically stable HD patients.
155
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Patients and Methods From January to December 1997, we collected clinical and biological data from 32 of 75 patients who underwent dialysis at our Center. To avoid selection bias, patients hospitalized and/or presenting acute illness during the study were excluded from the analysis. The residual diuresis was negligible for all (⬍300 mL) and the majority of patients were anuric. The cause of end-stage renal disease was chronic glomerulonephritis in 4 patients, diabetic nephropathy in 5 patients, chronic interstitial nephritis in 8 patients, acute interstitial nephritis in 2 patients, polycystic kidney disease in 3 patients, arterial renal thrombosis in 2 patients, others and unknown in 8 patients. The dialysis nurse measured blood pressure with a semiautomated sphygmomanometer on the arm without arteriovenous fistula, with the patient supine before starting the session and at the end of the session after removing the needle. All patients underwent dialysis 3 times weekly for a total of 12 to 15 hours per week. HD treatments were performed using bicarbonate as buffer dialysate (Na⫹ 138 mEq/L and HCO3⫺ 34 mEq/L, respectively) and biocompatible membranes (polysulfone, polyacrylonitrile). Blood flow ranged from 300 to 350 mL/min and dialysate was 500 mL/ min. Fistula recirculation, evaluated by Transonic, (Transonic Systems, Ithaca, NY) was ⬍5%.7 Medical staff, who regularly reviewed the BP records, clinically assessed the individual patient’s dry weight on the basis of hydration status. To investigate dietary protein intake (DPI), calorie intake (CI), and sodium intake, a dietician assessed a 3-day dietary record at least 2 times during the study. During the first 3-day interval of each month, IDWG was calculated (predialysis weight ⫺ preceding postdialysis weight) and expressed as a percent of current dry weight. Urea kinetic parameters were calculated using appropriate formulas.8,9 We also arbitrarily defined 2 groups of patients with “regularly high” or “normal” IDWG on the basis of dialysis sessions with an IDWG ⬎5% during the time of the study. The interdialytic sodium load (SL) was calculated using the following formula: predialysis sodium ⫻ (postdialysis total body water [TBW] ⫹ weight gain) ⫺ (postdialysis sodium ⫻ postdialysis TBW) ⫼ postdialysis TBW.10 Where TBW represents total body water estimation using the equation of
Watson et al.11 Mean arterial pressure (MAP) was defined as follows: diastolic BP ⫹ 1⁄3 ⫻ (systolic BP ⫺ diastolic BP). Albumin, transferrin, and C reactive protein (CRP) serum levels were determined by immunoturbidometric method, according to the manufacturer instructions (Cobe Integra Roche, Neuilly s/Seine, France); normal values were 35 to 43 g/L, 2 to 3.6 g/L, and less than 5 mg/L, respectively. To test the relationship between continuous variables, simple and multiple regression analyses were performed. The Student t test was used to compare means between the groups. All statistical tests were 2-tailed. Statview software (Abacus Concepts, Berkeley, CA) was used for all statistical analysis.
Results There were 19 men and 13 women in the study, 14% of patients were diabetics and 33% were hypertensive (defined as a patient taking at least one medication). The mean age was 71.3 ⫾ 13.7 years (range, 25 to 88) and the length of dialysis time was 54.1 ⫾ 45 months (range, 3 to 226). The mean IDWG was 4.5% ⫾ 1.5%. Systolic and diastolic BP before and after dialysis were, respectively, 150.9 ⫾ 25, 75.6 ⫾ 13.4, 131.9 ⫾ 24.8, and 68 ⫾ 13.5 mm Hg. Hypertensive patients presented a significant increase of MAP before and after dialysis than normotensive (111.7 ⫾ 13.9 v 94.9 ⫾ 13.9; 102.8 ⫾ 15.9 v 88 ⫾ 13.3 mm Hg; P ⬍ .0001). In contrast, no difference among IDWG, SL, and dietary sodium intake could be found. There was no significant association between IDWG and patient gender (P ⫽ NS by analysis of variance), or between the presence of diabetes and changes in IDWG (P ⫽ NS by analysis of variance). As reported in Table 1, we were unable to describe any correlation between IDWG, MAP,
Table 1. Correlation Coefficient Among MAP, IDWG, SL, and Dietary Sodium Intake in 32 Hemodialysis Patients
IDWG IDWG IDWG IDWG
v v v v
MAP before HD MAP after HD SL dietary sodium intake
r
P
.12 .08 .09 .12
NS NS NS NS
157
INTERDIALYTIC WEIGHT GAIN Table 2. Kinetic and Nutritional Parameters of the 32 Patients
Dry weight (kg) Body mass index PCR (g/kg/d) DPI (g/kg/d) CI (cal/kg/d) Albumin (g/L) Transferrin (g/L) CRP (mg/mL) Serum potassium (mEq/L) Serum phosphate (mmol/L) Urea reduction ratio (%) Kt/V
Mean ⫾ SD
Range
64.6 ⫾ 12.5 24.5 ⫾ 3.1 1.18 ⫾ 0.4 1.1 ⫾ 0.3 25.2 ⫾ 7.7 37.3 ⫾ 3.0 2.08 ⫾ 0.4 11.4 ⫾ 19.2
34.7-94.7 17.2-31.1 0.29-2.6 0.6-2 13.2-47.9 29.5-43.3 0.96-3.3 0.1-113
5.2 ⫾ 0.7
3.3-8.1
1.74 ⫾ 0.7 71.5 ⫾ 6.5 1.55 ⫾ 0.2
0.48-12.3 48-86.7 0.80-2.4
SL, and/or sodium intake. Only in hypertensive patients did SL show significant positive correlation with IDWG (SL v IDWG r ⫽ 0.20; P ⬍ .03). Urea kinetic and nutritional parameters are shown in Table 2. Dialysis dose achieved recommended goals for Kt/V and other markers of adequacy. Albumin levels, transferrin serum levels, PCR, and DPI were normal; only CI was less than current recommendations. Simple and multiple regression analyses showed a significant and positive correlation between IDWG and PCR (Fig 1). IDWG showed no significant relationship with other nutritional parameters (albumin v IDWG r ⫽ .17; P ⫽ NS, transferrin v IDWG r ⫽ .05; P ⫽ NS, DPI v IDWG r ⫽ .06; P ⫽ NS, and CI v IDWG r ⫽ .007; P ⫽ NS). Interestingly, CRP negatively correlated with both IDWG and nPCR (CRP v IDWG, r ⫽ .29; P ⬍ .02 and
Table 3. Urea Kinetic and Nutritional Parameters in 15 Patients With a Regularly High IDWG High IDWG Normal IDWG No. of patients Dry weight (kg) Body mass index PCR (g/kg/d) DPI (g/kg/d) CI (cal/kg/d) Albumin (g/L) Transferrin (g/L) CRP (mg/mL) Serum potassium (mEq/L) Serum phosphate (mmol/L) Urea reduction ratio (%) Kt/V
P
15 64.1 ⫾ 13.6 24.2 ⫾ 2.8 1.3 ⫾ 0.3 1.2 ⫾ 0.3 28.0 ⫾ 7.5 37.1 ⫾ 3.0 2.1 ⫾ 0.4 10.1 ⫾ 15.7
17 65.1 ⫾ 11.1 24.8 ⫾ 3.2 0.9 ⫾ 0.3 1.0 ⫾ 0.2 21.6 ⫾ 6.4 37.4 ⫾ 3.1 2.0 ⫾ 3.5 13 ⫾ 22.9
— NS NS .0001 NS .02 NS NS NS
5.0 ⫾ 0.7
5.3 ⫾ 0.6
.0001
1.8 ⫾ 0.9
1.5 ⫾ 0.4
.001
72.2 ⫾ 7.1 1.6 ⫾ 0.3
70.6 ⫾ 5.7 1.4 ⫾ 0.2
.03 .0001
Note. Values are expressed as mean ⫾ SD
CRP v PCR, r ⫽ .33; P ⬍ .007). Similarly, age negatively correlated both IDWG and PCR (age v PCR, r ⫽ .27 and age v IDWG, r ⫽ .29; P ⬍ .0001). There was no significant association between IDWG and serum potassium and between IDWG and phosphate concentration (IDWG v serum potassium and IDWG v serum phosphate, respectively, r ⫽ .09 and r ⫽ .05; P ⫽ NS). Table 3 shows the results of the urea kinetic and nutritional parameters in 15 of 32 patients with a regularly high IDWG. In this group, IDWG, PCR, and CI were significantly increased in comparison with other patients (normal IDWG). We also found in these patients a significant increase in systolic BP before HD and diastolic BP before and after HD (159.3 ⫾ 25.1 v 146.3 ⫾ 24.1; P ⬍ .002, 79.0 ⫾ 13.7 v 71.8 ⫾ 12.0; P ⬍ .0001, and 69.9 ⫾ 13.9 v 65.7 ⫾ 12.7 mm Hg; P ⬍ .005, respectively). In contrast, the systolic BP after dialysis was unchanged (132.6 ⫾ 25.8 v 132.1 ⫾ 24.9 mm Hg; P ⫽ NS). There were no changes in sodium intake and SL.
Discussion
Figure 1. Correlation between IDWG and PCR in 32 patients (IDWG v PCR r ⫽ .85; P ⬍ .0001).
In dialysis patients, the pathogenesis of hypertension, a well-known risk factor for cardiovascular complications, is multifactorial.12 It seems that a major role is played by fluid retention because the majority of HD patients become normotensive after dialysis treatment is initiated
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and the excess volume is removed. This practice assumes a direct relationship between IDWG and increased BP.13 Indeed, IDWG has been charged in HD patients with a negative clinical connotation with regard to cardiovascular mortality and morbidity.14 However, it has recently been suggested that this relationship may not be so clear cut in either normotensive or hypertensive patients5,6 and that IDWG did not modify the association of mortality risk with the level of predialysis BP.15 As previously shown, we reported no correlation between IDWG and predialytic and postdialytic BP, confirming that there is no major influence of interdialytic fluid load on BP control in elderly, well-nourished HD patients studied over a long period (1 year). Other factors, such as an activated renin angiotensin system, increased vasopressin, endothelin, cathecolamine, and perhaps decreased nitric oxide activity, seem to influence the BP levels in HD patients and could explain why a different percentage of HD patients remain hypertensive despite vigorous ultrafiltration.16-19 The differences in predialytic systolic and diastolic BP in the group of patients with regularly high IDWG could be explained by the presence of different pressor systems in hypertensive patients, confirming that in dialysis patients, hypertension has a complex and intriguing pathophysiology.12 The role of salt ingestion as a determinant of weight gain in dialysis patients remains contradictory. IDWG can be considered the result of the accumulation of water, which if distributed across total body water, would be expected to have a minimal effect on circulating volume. In our study, we chose to determine the sodium balance by indirect measurements; mass balance studies would have provided more powerful significance, but they are difficult to assess clinically.19 Despite this limitation, the lack of relationship between sodium intake, SL, and IDWG suggests that weight gain is a poor surrogate for changes in intravascular volume. The sodium balance could be a far more important determinant of changes in extracellular volume and compliance with salt restriction associated with a moderate reduction of sodium dialysate and may, therefore, be a more important influence on BP than fluid restriction in hypertensive HD patients without altering dry body weight.20 Indeed, our data, obtained in patients who underwent dialysis regularly with
moderately low sodium dialysate (138 mEq/L) and with dietary salt restriction (ⱕ5 g/day), suggest a contrast with the classical relationship of high IDWG, high sodium intake, and high circulating volume. As has been recently shown, we confirm a close relationship between IDWG and PCR.3 In patients with a regularly high IDWG (⬎5%), levels of PCR, DPI, and CI were found to be higher than in controls. Our results suggest that in HD patients who are at risk of malnutrition, the stability of IDWG may be a useful clinical index, in association with other factors, to prevent inadequate nutritional intake. The excessive pressure exerted by medical staff on HD patients to limit IDWG and to avoid fluid overload may result in inadequate caloric and protein intake, confirming that a large IDWG may be accounted for by the consumption of beverages or solid food with nutritional value, and indirectly reflects a good nutritional status rather than a lack of compliance. Our study shows a negative correlation among age, IDWG, and PCR. This result suggests that a low interdialytic fluid gain found in elderly patients should be viewed with concern. If low IDWG persists in this population, the nutritional status should be the object of special monitoring. CRP is a well-known nonspecific marker of inflammatory response in multiple patient populations. CRP is reported to be elevated in patients with end-stage renal disease. This has been linked to multiple factors, including effects of the HD procedure and the biocompatibility of the dialysis membrane, as well as multiple hospitalizations due to infections and/or other factors.21 It has been suggested that proinflammatory cytokines (TNF-␣ and interleukins) induce an acute-phase response in the liver, resulting in an increase in the degradation of albumin. In malnourished HD patients, high concentrations of acute-phase reactant proteins, such as CRP, are correlated with low serum albumin.22 It is of interest that, in our well-nourished patients, this relationship is still present (data not shown) and that CRP seems to influence other nutritional parameters such as PCR and IDWG. These results suggest a synergism among different mechanisms contributing to the generation of malnutrition in HD patients.23 Compliance with medical treatment of HD patients is associated with improved outcomes
159
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and survival.24 Clearly, compliance is a multifactorial phenomenon that involves several types of behavior, such as dietary and medical regimens, and treatment schedules. IDWG and other biologic and clinical parameters have usually been used to estimate and quantify HD patients’ behavior.25 We found that both mean serum potassium and phosphate concentrations did not correlate with IDWG. In patients with regularly high IDWG, the mean concentration of these 2 ions varies differently than in controls. This confirms that, as we previously suggested, there is a need to discriminate between noncompliant patients and those patients in whom high IDWG simply reflects good food intake.3 It is our opinion that IDWG, as serum ion concentrations, may be affected by multiple variables that reduce their usefulness as an objective measurement to estimate the compliance in HD population. To our knowledge, this is the first time that IDWG, sodium balance, and nutritional intake were simultaneously investigated in a clinically stable HD population over a long period of time. Despite the fact that this observational study was ruled out because it did not have a control group, we were able to confirm that in HD patients there is a strong association between IDWG and nPCR. The hypothesis that IDWG can be used as useful clinical marker, in association with other factors, to detect an adequate calorie and protein intake was confirmed. In addition to previous studies, we also show that salt balance, investigated by SL and sodium intake, does not seem to influence IDWG in both normotensive and hypertensive HD patients, and that there is a lack of direct relationship between IDWG and predialysis and postdialysis BP, even in hypertensive patients. On one hand, this suggests that the relationship between salt balance and IDWG is difficult to assess in HD patients and, on the other hand, it emphasizes the role of additional factors in the control of BP in this population.
Acknowledgment The authors thank the head nurse and the staff of the Expansion des Centres d’Hemodialyse de l’Ouest (ECHO, Monfort) for their help in performing this study. The authors also appreciate the help of Dr Nguyen Vo for careful reading of the manuscript.
References 1. Oldenburg B, Macdonald GJ, Perkins RJ: Factors influencing excessive thirst and fluid intake in dialysis patients. Dial Transplant 17:21-24, 1988 2. Morduchowicz G, Sulkes J, Gabbay U, et al: Compliance in hemodialysis patients: A multivariate regression analysis. Nephron 64:365-368, 1993 3. Testa A, Beaud JM: The other side of the coin: Interdialytic weight gain as an index of good nutrition. Am J Kidney Dis 31:830-834, 1998 4. Sherman RA, Cody RP, Rogers ME, et al: Interdialytic weight gain and nutritional parameters in chronic hemodialysis patients. Am J Kidney Dis 25:579-583, 1995 5. Luik AJ, van Kuijk WHM, Spek J, et al: Effects of hypervolemia on interdialytic hemodinamics and blood pressure control in hemodialysis patients. Am J Kidney Dis 30:466-474, 1997 6. Savage T, Fabbian F, Giles M, et al: Interdialytic weight gain and 48-h blood pressure in hemodialysis patients. Nephrol Dial Transplant 12:2308-2311, 1997 7. Depner TA, Krivitski NM, MacGibbon D: Hemodialysis access recirculation measured by ultrasound dilution. ASAIO J 41:749-753, 1995 8. Daugirdas JT: Second generation logarithmic estimates of single-pool variable volume Kt/V: An analysis of error. J Am Soc Nephrol 4:1205-1213, 1993 9. Garred LJ, Tang W, Barichello DL, et al: Equations for the calculation of the protein catabolic rate from predialysis and postdialysis urea concentrations and residual clearance in stable hemodialysis patients. Blood Purif 15:157-168, 1997 10. Coomer RW, Schulman G, Breyer JA, et al: Ambulatory blood pressure monitoring in dialysis patients and estimation of mean interdialytic blood pressure. Am J Kidney Dis 29:678-84, 1997 11. Watson PE, Watson ID, Batt RD: Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr 33:27-39, 1980 12. Luik AJ, Kooman JP, Leunissen KML: Hypertension in hemodialysis patients: Is it only hypervolemia? Nephrol Dial Transplant 12:1557-1560, 1997 13. Lins RL, Elseviers M, Rogiers P, et al: Importance of volume factors in dialysis related hypertension. Clin Nephrol 48:29-33, 1997 14. Kramer P, Broyer M, Brunner FP, et al: Combined report on regular dialysis and transplantation in Europe, XIV, 1983. Proc Eur Dial Transplant Assoc-Eur Renal Assoc 21:2-65, 1985 15. Port FK, Hulbert-Shearon TE, Wolfe RA, et al: Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients. Am J Kidney Dis 33:507517, 1999 16. Schultze G, Piefke S, Molzahn M: Blood pressure in terminal renal failure: Fluid space and the renin-angiotensin system. Nephron 25:15-24, 1980 17. Schohn D, Weidmann P, Jahn H, et al: Norepinephrinerelated mechanism in hypertensive accompanying renal failure. Kidney Int 28:814-822, 1985 18. Brunet P, Lorec AM, Leonetti F, et al: Plasma endothelin in hemodialysis patients treated with recombinant human erytropoietin. Nephrol Dial Transplant 9:650-654, 1994 19. Vallance P, Leone A, Calver A, et al: Accumulation of an
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endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572-575, 1992 20. Krautzig S, Janssen U, Koch KM, et al: Dietary salt restriction and reduction of dialysate sodium to control hypertension in maintenance haemodialysis patients. Nephrol Dial Transplant 13:552-553, 1998 21. McIntryre C, Harper I, Macdougall IC, et al: Serum C-reactive protein as a marker for infection and inflammation in regular dialysis patients. Clin Nephrol 48:371-374, 1997 22. Qureshi AR, Alvestrand A, Danielsson A, et al: Factors
influencing malnutrition in hemodialysis patients: A cross-sectional study. Kidney Int 53:773-782, 1998 23. Bergstro¨m J, Lindholm B: Malnutrition, cardiac disease, and mortality: An integrate point of view. Am J Kidney Dis 32:834-841, 1998 24. Kimmel PL, Peterson RA, Weihs KL, et al: Psycosocial factors, behavioral compliance and survival in urban hemodialysis patients. Kidney Int 54:245-254, 1998 25. O’Brien ME: Compliance and long-term maintenance dialysis. Am J Kidney Dis 15:209-214, 1990
I
NTERDIALYTIC weight gain (IDWG) is usually considered as a measurement of compliance with medical management of hemodialysis (HD) patients because it may be affected, at least in part, by patient behavior.1,2 However, in this population, IDWG may be accounted for by intake of beverages or solid food with high nutritional value that indirectly indicates a good nutritional status rather than a lack of patient self-discipline. We and others recently found a close relationship between IDWG and nutritional parameters, confirming the potential role of IDWG as a marker of caloric and protein in-
*Expansion Centre d’He´modialyse de l’Ouest Hoˆpital St Jacques, Nantes, France. Presented at the 10th International Congress on Nutrition and Metabolism in Renal Disease, Lyon, France, July 6-8, 2000. Address reprint requests to Angelo Testa, MD, Espansion Centre d’He´modialyse de l’Ouest, 85 Rue St Jacques, 44202 Nantes, France. E-mail: [email protected] © 2001 by the National Kidney Foundation, Inc. 1051-2276/01/1103-0006$35.00/0 doi:10.1053/jren.2001.24362
Journal of Renal Nutrition, Vol 11, No 3 ( July), 2001: pp 155-160
take.3,4 A very low interdialytic fluid gain and protein catabolic rate (PCR) found in HD patients suggest that this population could be at risk for malnutrition. Control of volume status by vigorous ultrafiltration to achieve the appropriate dry weight can normalize blood pressure and suggests a relationship between IDWG, extracellular volume, exchangeable sodium, and blood pressure (BP). In contrast, higher IDWG did not result in higher interdialytic BP; recently, several studies were unable to find a direct correlation between short-term interdialytic weight changes and BP.5,6 This confirms that IDWG is a poor surrogate for changes in intravascular volume and, probably, sodium balance should be a far more important determinant of changes in extracellular volume. The aim of our study was to investigate the clinical determinants of IDWG, particularly regarding sodium balance and nutritional intake, in a cohort of clinically stable HD patients.
155
156
TESTA AND PLOU
Patients and Methods From January to December 1997, we collected clinical and biological data from 32 of 75 patients who underwent dialysis at our Center. To avoid selection bias, patients hospitalized and/or presenting acute illness during the study were excluded from the analysis. The residual diuresis was negligible for all (⬍300 mL) and the majority of patients were anuric. The cause of end-stage renal disease was chronic glomerulonephritis in 4 patients, diabetic nephropathy in 5 patients, chronic interstitial nephritis in 8 patients, acute interstitial nephritis in 2 patients, polycystic kidney disease in 3 patients, arterial renal thrombosis in 2 patients, others and unknown in 8 patients. The dialysis nurse measured blood pressure with a semiautomated sphygmomanometer on the arm without arteriovenous fistula, with the patient supine before starting the session and at the end of the session after removing the needle. All patients underwent dialysis 3 times weekly for a total of 12 to 15 hours per week. HD treatments were performed using bicarbonate as buffer dialysate (Na⫹ 138 mEq/L and HCO3⫺ 34 mEq/L, respectively) and biocompatible membranes (polysulfone, polyacrylonitrile). Blood flow ranged from 300 to 350 mL/min and dialysate was 500 mL/ min. Fistula recirculation, evaluated by Transonic, (Transonic Systems, Ithaca, NY) was ⬍5%.7 Medical staff, who regularly reviewed the BP records, clinically assessed the individual patient’s dry weight on the basis of hydration status. To investigate dietary protein intake (DPI), calorie intake (CI), and sodium intake, a dietician assessed a 3-day dietary record at least 2 times during the study. During the first 3-day interval of each month, IDWG was calculated (predialysis weight ⫺ preceding postdialysis weight) and expressed as a percent of current dry weight. Urea kinetic parameters were calculated using appropriate formulas.8,9 We also arbitrarily defined 2 groups of patients with “regularly high” or “normal” IDWG on the basis of dialysis sessions with an IDWG ⬎5% during the time of the study. The interdialytic sodium load (SL) was calculated using the following formula: predialysis sodium ⫻ (postdialysis total body water [TBW] ⫹ weight gain) ⫺ (postdialysis sodium ⫻ postdialysis TBW) ⫼ postdialysis TBW.10 Where TBW represents total body water estimation using the equation of
Watson et al.11 Mean arterial pressure (MAP) was defined as follows: diastolic BP ⫹ 1⁄3 ⫻ (systolic BP ⫺ diastolic BP). Albumin, transferrin, and C reactive protein (CRP) serum levels were determined by immunoturbidometric method, according to the manufacturer instructions (Cobe Integra Roche, Neuilly s/Seine, France); normal values were 35 to 43 g/L, 2 to 3.6 g/L, and less than 5 mg/L, respectively. To test the relationship between continuous variables, simple and multiple regression analyses were performed. The Student t test was used to compare means between the groups. All statistical tests were 2-tailed. Statview software (Abacus Concepts, Berkeley, CA) was used for all statistical analysis.
Results There were 19 men and 13 women in the study, 14% of patients were diabetics and 33% were hypertensive (defined as a patient taking at least one medication). The mean age was 71.3 ⫾ 13.7 years (range, 25 to 88) and the length of dialysis time was 54.1 ⫾ 45 months (range, 3 to 226). The mean IDWG was 4.5% ⫾ 1.5%. Systolic and diastolic BP before and after dialysis were, respectively, 150.9 ⫾ 25, 75.6 ⫾ 13.4, 131.9 ⫾ 24.8, and 68 ⫾ 13.5 mm Hg. Hypertensive patients presented a significant increase of MAP before and after dialysis than normotensive (111.7 ⫾ 13.9 v 94.9 ⫾ 13.9; 102.8 ⫾ 15.9 v 88 ⫾ 13.3 mm Hg; P ⬍ .0001). In contrast, no difference among IDWG, SL, and dietary sodium intake could be found. There was no significant association between IDWG and patient gender (P ⫽ NS by analysis of variance), or between the presence of diabetes and changes in IDWG (P ⫽ NS by analysis of variance). As reported in Table 1, we were unable to describe any correlation between IDWG, MAP,
Table 1. Correlation Coefficient Among MAP, IDWG, SL, and Dietary Sodium Intake in 32 Hemodialysis Patients
IDWG IDWG IDWG IDWG
v v v v
MAP before HD MAP after HD SL dietary sodium intake
r
P
.12 .08 .09 .12
NS NS NS NS
157
INTERDIALYTIC WEIGHT GAIN Table 2. Kinetic and Nutritional Parameters of the 32 Patients
Dry weight (kg) Body mass index PCR (g/kg/d) DPI (g/kg/d) CI (cal/kg/d) Albumin (g/L) Transferrin (g/L) CRP (mg/mL) Serum potassium (mEq/L) Serum phosphate (mmol/L) Urea reduction ratio (%) Kt/V
Mean ⫾ SD
Range
64.6 ⫾ 12.5 24.5 ⫾ 3.1 1.18 ⫾ 0.4 1.1 ⫾ 0.3 25.2 ⫾ 7.7 37.3 ⫾ 3.0 2.08 ⫾ 0.4 11.4 ⫾ 19.2
34.7-94.7 17.2-31.1 0.29-2.6 0.6-2 13.2-47.9 29.5-43.3 0.96-3.3 0.1-113
5.2 ⫾ 0.7
3.3-8.1
1.74 ⫾ 0.7 71.5 ⫾ 6.5 1.55 ⫾ 0.2
0.48-12.3 48-86.7 0.80-2.4
SL, and/or sodium intake. Only in hypertensive patients did SL show significant positive correlation with IDWG (SL v IDWG r ⫽ 0.20; P ⬍ .03). Urea kinetic and nutritional parameters are shown in Table 2. Dialysis dose achieved recommended goals for Kt/V and other markers of adequacy. Albumin levels, transferrin serum levels, PCR, and DPI were normal; only CI was less than current recommendations. Simple and multiple regression analyses showed a significant and positive correlation between IDWG and PCR (Fig 1). IDWG showed no significant relationship with other nutritional parameters (albumin v IDWG r ⫽ .17; P ⫽ NS, transferrin v IDWG r ⫽ .05; P ⫽ NS, DPI v IDWG r ⫽ .06; P ⫽ NS, and CI v IDWG r ⫽ .007; P ⫽ NS). Interestingly, CRP negatively correlated with both IDWG and nPCR (CRP v IDWG, r ⫽ .29; P ⬍ .02 and
Table 3. Urea Kinetic and Nutritional Parameters in 15 Patients With a Regularly High IDWG High IDWG Normal IDWG No. of patients Dry weight (kg) Body mass index PCR (g/kg/d) DPI (g/kg/d) CI (cal/kg/d) Albumin (g/L) Transferrin (g/L) CRP (mg/mL) Serum potassium (mEq/L) Serum phosphate (mmol/L) Urea reduction ratio (%) Kt/V
P
15 64.1 ⫾ 13.6 24.2 ⫾ 2.8 1.3 ⫾ 0.3 1.2 ⫾ 0.3 28.0 ⫾ 7.5 37.1 ⫾ 3.0 2.1 ⫾ 0.4 10.1 ⫾ 15.7
17 65.1 ⫾ 11.1 24.8 ⫾ 3.2 0.9 ⫾ 0.3 1.0 ⫾ 0.2 21.6 ⫾ 6.4 37.4 ⫾ 3.1 2.0 ⫾ 3.5 13 ⫾ 22.9
— NS NS .0001 NS .02 NS NS NS
5.0 ⫾ 0.7
5.3 ⫾ 0.6
.0001
1.8 ⫾ 0.9
1.5 ⫾ 0.4
.001
72.2 ⫾ 7.1 1.6 ⫾ 0.3
70.6 ⫾ 5.7 1.4 ⫾ 0.2
.03 .0001
Note. Values are expressed as mean ⫾ SD
CRP v PCR, r ⫽ .33; P ⬍ .007). Similarly, age negatively correlated both IDWG and PCR (age v PCR, r ⫽ .27 and age v IDWG, r ⫽ .29; P ⬍ .0001). There was no significant association between IDWG and serum potassium and between IDWG and phosphate concentration (IDWG v serum potassium and IDWG v serum phosphate, respectively, r ⫽ .09 and r ⫽ .05; P ⫽ NS). Table 3 shows the results of the urea kinetic and nutritional parameters in 15 of 32 patients with a regularly high IDWG. In this group, IDWG, PCR, and CI were significantly increased in comparison with other patients (normal IDWG). We also found in these patients a significant increase in systolic BP before HD and diastolic BP before and after HD (159.3 ⫾ 25.1 v 146.3 ⫾ 24.1; P ⬍ .002, 79.0 ⫾ 13.7 v 71.8 ⫾ 12.0; P ⬍ .0001, and 69.9 ⫾ 13.9 v 65.7 ⫾ 12.7 mm Hg; P ⬍ .005, respectively). In contrast, the systolic BP after dialysis was unchanged (132.6 ⫾ 25.8 v 132.1 ⫾ 24.9 mm Hg; P ⫽ NS). There were no changes in sodium intake and SL.
Discussion
Figure 1. Correlation between IDWG and PCR in 32 patients (IDWG v PCR r ⫽ .85; P ⬍ .0001).
In dialysis patients, the pathogenesis of hypertension, a well-known risk factor for cardiovascular complications, is multifactorial.12 It seems that a major role is played by fluid retention because the majority of HD patients become normotensive after dialysis treatment is initiated
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and the excess volume is removed. This practice assumes a direct relationship between IDWG and increased BP.13 Indeed, IDWG has been charged in HD patients with a negative clinical connotation with regard to cardiovascular mortality and morbidity.14 However, it has recently been suggested that this relationship may not be so clear cut in either normotensive or hypertensive patients5,6 and that IDWG did not modify the association of mortality risk with the level of predialysis BP.15 As previously shown, we reported no correlation between IDWG and predialytic and postdialytic BP, confirming that there is no major influence of interdialytic fluid load on BP control in elderly, well-nourished HD patients studied over a long period (1 year). Other factors, such as an activated renin angiotensin system, increased vasopressin, endothelin, cathecolamine, and perhaps decreased nitric oxide activity, seem to influence the BP levels in HD patients and could explain why a different percentage of HD patients remain hypertensive despite vigorous ultrafiltration.16-19 The differences in predialytic systolic and diastolic BP in the group of patients with regularly high IDWG could be explained by the presence of different pressor systems in hypertensive patients, confirming that in dialysis patients, hypertension has a complex and intriguing pathophysiology.12 The role of salt ingestion as a determinant of weight gain in dialysis patients remains contradictory. IDWG can be considered the result of the accumulation of water, which if distributed across total body water, would be expected to have a minimal effect on circulating volume. In our study, we chose to determine the sodium balance by indirect measurements; mass balance studies would have provided more powerful significance, but they are difficult to assess clinically.19 Despite this limitation, the lack of relationship between sodium intake, SL, and IDWG suggests that weight gain is a poor surrogate for changes in intravascular volume. The sodium balance could be a far more important determinant of changes in extracellular volume and compliance with salt restriction associated with a moderate reduction of sodium dialysate and may, therefore, be a more important influence on BP than fluid restriction in hypertensive HD patients without altering dry body weight.20 Indeed, our data, obtained in patients who underwent dialysis regularly with
moderately low sodium dialysate (138 mEq/L) and with dietary salt restriction (ⱕ5 g/day), suggest a contrast with the classical relationship of high IDWG, high sodium intake, and high circulating volume. As has been recently shown, we confirm a close relationship between IDWG and PCR.3 In patients with a regularly high IDWG (⬎5%), levels of PCR, DPI, and CI were found to be higher than in controls. Our results suggest that in HD patients who are at risk of malnutrition, the stability of IDWG may be a useful clinical index, in association with other factors, to prevent inadequate nutritional intake. The excessive pressure exerted by medical staff on HD patients to limit IDWG and to avoid fluid overload may result in inadequate caloric and protein intake, confirming that a large IDWG may be accounted for by the consumption of beverages or solid food with nutritional value, and indirectly reflects a good nutritional status rather than a lack of compliance. Our study shows a negative correlation among age, IDWG, and PCR. This result suggests that a low interdialytic fluid gain found in elderly patients should be viewed with concern. If low IDWG persists in this population, the nutritional status should be the object of special monitoring. CRP is a well-known nonspecific marker of inflammatory response in multiple patient populations. CRP is reported to be elevated in patients with end-stage renal disease. This has been linked to multiple factors, including effects of the HD procedure and the biocompatibility of the dialysis membrane, as well as multiple hospitalizations due to infections and/or other factors.21 It has been suggested that proinflammatory cytokines (TNF-␣ and interleukins) induce an acute-phase response in the liver, resulting in an increase in the degradation of albumin. In malnourished HD patients, high concentrations of acute-phase reactant proteins, such as CRP, are correlated with low serum albumin.22 It is of interest that, in our well-nourished patients, this relationship is still present (data not shown) and that CRP seems to influence other nutritional parameters such as PCR and IDWG. These results suggest a synergism among different mechanisms contributing to the generation of malnutrition in HD patients.23 Compliance with medical treatment of HD patients is associated with improved outcomes
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and survival.24 Clearly, compliance is a multifactorial phenomenon that involves several types of behavior, such as dietary and medical regimens, and treatment schedules. IDWG and other biologic and clinical parameters have usually been used to estimate and quantify HD patients’ behavior.25 We found that both mean serum potassium and phosphate concentrations did not correlate with IDWG. In patients with regularly high IDWG, the mean concentration of these 2 ions varies differently than in controls. This confirms that, as we previously suggested, there is a need to discriminate between noncompliant patients and those patients in whom high IDWG simply reflects good food intake.3 It is our opinion that IDWG, as serum ion concentrations, may be affected by multiple variables that reduce their usefulness as an objective measurement to estimate the compliance in HD population. To our knowledge, this is the first time that IDWG, sodium balance, and nutritional intake were simultaneously investigated in a clinically stable HD population over a long period of time. Despite the fact that this observational study was ruled out because it did not have a control group, we were able to confirm that in HD patients there is a strong association between IDWG and nPCR. The hypothesis that IDWG can be used as useful clinical marker, in association with other factors, to detect an adequate calorie and protein intake was confirmed. In addition to previous studies, we also show that salt balance, investigated by SL and sodium intake, does not seem to influence IDWG in both normotensive and hypertensive HD patients, and that there is a lack of direct relationship between IDWG and predialysis and postdialysis BP, even in hypertensive patients. On one hand, this suggests that the relationship between salt balance and IDWG is difficult to assess in HD patients and, on the other hand, it emphasizes the role of additional factors in the control of BP in this population.
Acknowledgment The authors thank the head nurse and the staff of the Expansion des Centres d’Hemodialyse de l’Ouest (ECHO, Monfort) for their help in performing this study. The authors also appreciate the help of Dr Nguyen Vo for careful reading of the manuscript.
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