Interdialytic weight gain and nutritional parameters in chronic hemodialysis patients

Interdialytic Weight Gain and Nutritional Parameters in Chronic Hemodialysis Patients Richard A. Sherman, MD, Ronald P. Cody, EdD, Mary Ellen Rogers, RN, and Joan C. Solanchick, MSW, RN 0 The extent of interdialytic weight gain (IDWG) in chronic hemodialysis patients is usually attributed to the level of compliance with fluid restriction. However, in view of the substantial water content of food (and caloric content of beverages), IDWG also may be a function of calorie and protein intake and may reflect the nutritional state of patients. To investigate this theory, the relationship between P-day IDWG and body weight, normalized protein catabolic rate (nPCR), serum albumin, and delivered KW urea was assessed in a prospective, randomized study of 860 chronic hemodialysis patients in 56 dialysis units. Compared with patients having <2 kg IDWG (n = 378), patiints with >3 kg IDWG (n = 138) weighed more (dry weight, 76.8 v 61.7 kg), had higher nPCR (1.15 Y 0.98 g/ kg/d), and had higher serum albumin levels (3.96 v 3.79 g/dL) (all P < 0.601) but did not have different levels of KW (1.04 v 1.06). When IDWG was assessed as a function of dry weight, patients with IDWG > 4.5% of dry weight (n = 151) had higher nPCR (1.17 v 0.94 g/kg/d) but weighed less (60.1 Y 70.0 kg) and had a higher KW (1.14 v 1.01) than patients with IDWG < 3% of dry weight (n = 355) (all P < 0.001). Artiiactual association between IDWG and nPCR attributable to an accentuated two-pool effect from diiering ultrafiltration requirements was unlikely as assessed by the relationship between modeled KW and prescribed KW determined using an anthropometdc urea volume. A patient with an IDWG OF 1 to <2 kg was almost twice as likely (59.6% v 30.4%) as a patient with an IDWG of 3 to <4 kg to have an nPCR < 1 g/kg/d. The authors conclude that IDWG is an important nutritional parameter. The possibility exists that patient compliance with dialysis staff advice to limit IDWG may have an adverse nutdtional impact. 0 1995

by the

National

Kidney

Foundation,

Inc.

INDEK WORDS: Hemodialysis;

nutrition;

malnutrition;

albumin;

T

From the Departments of Medicine and Environmental and Community Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick and Piscataway; and the Trans-Atlantic Renal Council, East Brunswick, NJ. Received August 17, 1994; accepted in revised form November 22, 1994. The analyses on which this publication is based were performed under contract number 500-91-0008, entitled “ESRD Network Organizations, ” awarded by the Health Care Financing Administration, Department of Health and Human Services, Baltimore, MD, and supported by a grant from the Health Promotion Program, New Jersey State Department oj Health, Trenton, NJ. Address reprint requests to Richard A. Sherman, MD, Division of Nephrology, Department vf Medicine, UMDNJ-Robert Wood Johnson Medical School, One Robert Wood Johnson Place, CN-19, New Brunswick, NJ 08903. 0 1995 by the National Kidney Foundation, Inc.

METHODS From March thru June 1992, a dialysis prescription study was undertaken by the Trans Atlantic Renal Council in the of Kidney Diseases, Vol 25, No 4 (April),

rate.

dialysis programs it oversees. Eight hundred sixty patients receiving chronic hemodialysis were randomly selected (using computer-generated random numbers and social security numbers) to undergo formal two-point urea kinetic modeling. In addition to kinetic modeling, data were abstracted from the chart and collected prospectively on each patient. These data included serum albumin levels, IDWG for the three dialysis treatments preceding the modeled session, and current “dry” weight. Only patients dialyzed more than 1 year (to minimize the effect of residual renal function) and treated thrice weekly were included in the study. Serum albumin was determined by the bromcreosol green method in all but two dialysis programs, which used the bromcreosol purple method. In those units, the value was adjusted upward by

0 LIMIT interdialytic weight gain (IDWG), fluid restriction is prescribed for end-stage renal-disease patients treated with chronic hemodialysis. Excessive IDWG is often interpreted as evidence for noncompliance with the prescribed fluid restriction.‘-’ However, “solid” food has a substantial fluid content, and fluid intake often consists of beverages with substantial caloric value. Therefore, IDWG may be a significant correlate of calorie and protein intake. The importance of nutrition to the health of chronic hemodialysis patients has been noted increasingly in recent years8 Protein intake in these patients has a strong relationship to morbidity and mortality.9-12 The concentration of albumin in serum, believed to reflect nutritional state, is closely related to the mortality rate of these patients.13.14Because of the growing importance of nutritional issues in chronic hemodialysis patients and the potential for IDWG to serve as a nutritional marker, we sought to examine the relationship between IDWG and albumin, body weight, protein catabolic rate (nPCR), and Kt/ V urea in a large number of randomly selected patients in 56 dialysis units in New Jersey and Puerto Rico.

American Journal

protein catabolic

0272~6386/95/2504-0008$3.00/O 1995:

pp 579-583

579

SHERMAN

580

Table 1. Interdialytic IDWG (kg) 24 3-<4 2-<3 l-<2
Weight Gain Versus Dry Weight, nPCR, Serum Albumin,

N

%

Dry Wt

nPCR WWd)

27 112 296 319 59

3.6 13.8 36.4 39.2 7.3

80.0a 75.8b 67.7 61.8~ 61.4d

1.24 1.13e 1.05f 0.97 0.86

NOTE: P < 0.05 for differences in dry weight, that a versus b, c versus d, e versus f, j versus h differed significantly; for KW, no differences

KW Urea, and Prediaiysis

ET AL

BUN

nPCR
Alb (s/W

KW

PreBUN OWW

7.4% 30.4% 46.0% 59.6% 83.3%

3.85 3.999 3.78 3.79 3.74h

1.01 1.05 1.06 1.08 0.98

88.6 81.8j 77.2k 71.21 67.0m

nPCR, nPCR < 1 .O, and pre-BUN among the five IDWG groups, except k, k versus I, and I versus m, P = NS. For serum albumin, only g versus were significant.

0.5 g/dL.” Urea kinetic modeling was performed using a proprietary system (Kinetic Information System, Compumod Software version 2.6). PCR was normalized to actual dry weight. The 2-day IDWG was calculated by multiplying the sum of the IDWG values for the week preceding the modeled session by 0.2857 (two-sevenths). In the remainder of this article, IDWG will refer to this calculated, 2-day IDWG. Urea kinetic modeling data (delivered Kt/V) were available in 8 19 patients, current dry weight in 813 patients, and serum albumin levels in 767 patients. Basic descriptive statistics and frequency distributions were generated for all continuous variables. Pearson correlation coefficients were computed to test relationships between continuous variables, and linear regession was performed where a prediction equation was required. Comparisons of means between two groups was accomplished using Student’s t-test. All statistical tests were two-tailed. SAS software (SAS Institute, Cary, NC) was used for all statistical analysis.

RESULTS

IDWG was 2 kg or more in 53.8% of patients (Table 1 and Fig 1A) and 3% or more of dry weight in 56.4% of patients (Fig 1B). As groups, patients with larger IDWG weighed more than those with smaller IDWG (Table 1). The mean dry weight for patients with IDWG < 2 kg (mean, 1.41 kg, n = 378) was 61.7 kg compared with 76.8 kg for patients with IDWG > 3 kg (mean, 3.6 kg, n = 138) (P < 0.0001) (Table 2). However, the mean dry weight of patients with an IDWG < 3% of their dry weight (n = 355) was 70.0 kg compared with 60.1 kg for patients with an IDWG > 4.5% of their dry weight (Table 2). Thus, although IDWG increased with increasing body weight, the rate of increase was slower than that of the increase in body weight. The regression line for IDWG versus dry weight was 0.86 kg + 0.020 X dry weight. (P = 0.0001, correlation coefficient = 0.35).

IDWG showed a significant relationship with nPCR (P = 0.0001, correlation coefficient = 0.3 1) as shown in Table 1 and Fig 2. The mean nPCR for patients with IDWG < 2 kg was 0.96 g/kg/d compared with 1.15 g/kg/d for patients with IDWG > 3 kg, a difference of 20% (Table 2). A patient with an IDWG of 1 to < 2 kg was almost twice as likely to have an nPCR < 1 g! kg/d as a patient gaining 3 to <4 kg (59.6% v 30.4% likelihood) (Table 1). The mean nPCR of patients with IDWG < 3% of ,dry weight was 0.94 g/kg/d compared with 1.17 g/kg/d for patients with IDWG > 4.5% of dry weight, a difference of 24.5% (P < 0.0001) (Table 2). Regression analysis showed that, on average, nPCR increased by 0.072 g/kg/d for each 1% increase in IDWG as a percentage of dry weight. A

Percent

B

Percent

~1.5%

1.5%-~3%

3%-~4.5%

4.5%-<6%

6%+

Weight Gain as % of Dry Weight Fig 1. Distribution of P-day interdialytic weigM gain in 813 chronic hemodialysis patients in kg (A) and as a percentage of dry weight (B).

WEIGHT

GAIN,

NUTRITION,

AND

DIALYSIS

Table 2. Dry Weight, nPCR, Serum Albumin,

581

and

Kt/VUrea inPatients WiihHigh andLow Interdialytic Weight Gains (Absolute and as a Percentage of Dry Weight) IDWG <2 >3

kg kg

<3% >4.5%

N

Dry wt (kg)

nPCR WWd)

Albumin (g/dL)

KW

378 138

61.7 76.8

0.96 1.15

3.78 3.96

1.06 1.04’

355 151

70.0 60.1

0.94 1.17

3.78 3.83

1.01 1.14

* P = NS. All other

differences,

P < 0.001.

Serum albumin values were obtained predialysis and would be expected to correlate negatively with IDWG because of the substantial dilutional effect of varying levels of IDWG. Despite this confounding factor, a slight, statistically significant, positive correlation was found (Table 1). The mean serum albumin in patients with IDWG < 2 kg was 3.78 g/dL, significantly lower (P = 0.0002) than the 3.96 g/dL value found in patients with IDWG > 3 kg (Table 2). Kt/V urea did not correlate with IDWG (Table 1). For patients with IDWG < 2 kg, the mean Kt/V was 1.06 compared with 1.04 for patients with IDWG > 3 kg. However, the mean Kt/V for patients with IDWG > 4.5% of dry weight was 1.14, substantially higher (P < 0.0001) than the Kt/V of 1.01 seen in the patients with IDWG < 3% of dry weight. With differing nPCR and similar Kt/V, predialysis blood urea nitrogen (BUN) values would be expected to differ among the groups. This was indeed the case, with the predialysis BUN in the z4-kg IDWG group being 32% higher than that in the
The relationship between IDWG and nPCR seen in Tables 1 and 2 is striking, even more so when one notes that both increasing dry weight and increasing nPCR (ie, protein intake per kg) are associated with higher IDWG. This dual association indicates that the protein intake per patient (rather than per kilogram) associated with increasing IDWG is even more remarkable than that shown. A correlation analysis confirmed the independence of dry weight and nPCR (r = -0.05). Only a small (though statistically significant)

positive association between IDWG and serum

albumin wasfound. However, thisassociation is likely to be clinically significant when the effect of dilution is taken into account. The predialysis serum albumin in a patient with a 3-kg IDWG reflects dilution by an additional 2 L compared with that in a patient with a l-kg IDWG. The exact effect on serum albumin depends on the distribution of the additional fluid, a function of the nature and content of the salt in the fluid as well as vascular oncotic and hydrostatic pressures. If 350 mL of this 2 L were to distribute intravascularly, the serum albumin in a patient with a plasma volume of 3.5 L would be diluted by an additional 10% (0.4 g/dL for a patient with a serum albumin of 4.0 g/dL). Thus, in the absence of the dilutional effect of the additional IDWG, predialysis serum albumin in the patients with large IDWG would probably be substantially higher than the values observed. The possibility that our findings were artifactual must be considered. Patients with high IDWG require high ultrafiltration during dialysis. This could result in an enhanced “two-pool” effect caused by peripheral vasoconstriction or other factors. If this were the case, a greater postdialysis urea rebound might occur in patients with large IDWG, resulting in an artifactually high nPCR. If this were the case, however, one would expect that the relationship between modeled Kt/V and prescribed Kt/V would be altered, with the modeled V being relatively smaller in the patients with high IDWG compared with the modeled V in patients with low IDWG. As a result, for any given amount of prescribed dialysis (using an anthropometrically determined V), delivered dialysis (using a kinetically determined V) would be higher in patients with high IDWG. It

Mean Two Day Weight

Gain (kg)

Pig 2. Mean nPCR (g/kg/d) among 813 chronic hemodialysis patients as a function of their P-day interdialytic weight gain.

SHERMAN ET AL

582

would follow that the difference between prescribed and delivered dialysis would decline with increasing IDWG. We did this analysis and found nothing to support an artifact& cause for the association of IDWG and nPCR. The differences between delivered and prescribed (using manufacturer’s clearance data and V determined from Watson’s method) dialysis were 0.21 (24 kg IDWG), 0.16 (3 to <4 kg), 0.14 (2 to <3 kg), 0.12 (1 to < 2 kg), and 0.20 (< 1 kg). Only the difference between the >4 kg and 1 to <2 kg IDWG group was statistically different, with the direction of the difference being the opposite of that predicted from the “enhanced two-pool effect” theory. Although Kt/V did not correlate with IDWG, it strongly correlated with IDWG as a percentage of dry weight. This association may indicate that better dialysis (Kt/V) is associated with better nutritional parameters. However, it may be explained by other factors. The mean dry weight of the patients with IDWG > 4.5% of dry weight was 9.9 kg less than that of patients with IDWG < 3% of dry weight. We have previously demonstrated that dry weight is an important determinant of delivered dialysis, with large patients receiving a lower Kt/V than small patients.16 In addition, larger IDWG as a percentage of dry weight requires greater ultrafiltration as a percentage of body water and, as a consequence, provides greater ultrafiltrative (convective) urea clearance. This clearance is included in the modeled Kt/V but is not reflected in the urea reduction ratio (a common means of prescribing dialysis) nor in the dialysis prescription (dialyzer, blood flow, treatment time). Thus, although the higher Kt/V in patients with large IDWG as a percentage of dry weight may have played a causative role, the association may instead be attributable to other factors. That IDWG should be a marker for nutritional indices is not surprising. A substantial portion of dietary water is not in a fluid form. Table 3 shows the water content of a 2,100~calorie (nonrenal) diet. Of the 1,260 g water it contains, only 333 g (orange juice and skim milk) would be classified as fluid by the usual criteria. In addition, fluid itself usually makes a significant contribution to total calorie and protein intake. Although IDWG may be merely another nutritional parameter, there is a disturbing alternative possibility. Patients are instructed to limit their

Table 3. A 2,100~Calorie

Diet Water Content

Breakfast ‘4 cup orange juice “/4 cup corn flakes 2 slices whole wheat toast 1 Tbls margarine 1 cup skim milk Lunch 3 ‘4 ounces roast beef 2 slices whole wheat bread ‘4 Tbls mayonnaise 6 saltine crackers apple Snack 3 graham crackers Dinner 3 ‘4 ounces chicken 1 ‘4 cup pasta ‘/4 cup spaghetti sauce 1 slice whole wheat bread 1 cup tossed salad 1 Tbls Italian dressing 1 cup cooked broccoli Fresh orange Snack 1 slice bread 1 ounce turkey breast 1 tsp mustard ‘4 cup pineapple Total Data from Pennington JAT (ed): Food Values of Portions Commonly Water from oxidation is not included 20 mu100 calories).

(g)

110 0.5 19.2 2 222.5 60 19.2 1 0.6 115 0.03 64 138 47 9.6 52 5.6 140 121 9.6 20 4 104 1,265.l Bowes & Church’s Used, ed 16. 1994. in these figures (lo-

IDWG, typically to less than 2 kgl’; those that do so receive positive reinforcement. These compliant patients have, on average, nPCR values far below those of “noncompliant” patients and may, as a result of following the advice of dialysis staff, be at increased risk for malnutrition and its complications. One piece of evidence in this study supports this hypothesis. Feedback to patients usually comes in response to absolute IDWG rather than the more appropriate IDWG as a percentage of dry weight. As a result, heavier patients may be subjected to more pressure to reduce IDWG than patients of lower body weight. We found that the mean dry weight was lower in patients with greater weight gains (expressed as a percentage of dry weight) than in patients with lower weight gains. Efforts to minimize absolute IDWG may have been less vigor-

WEIGHT

GAIN,

NUTRITION,

AND

DIALYSIS

ous in patients with low body weight than in

thosewith higherbodyweight,resultingin the observed difference. This suggests the impact of counseling on IDWG and suggests further that the poor nutritional parameters in patients with low IDWG may be a result of attempts to limit IDWG rather than IDWG being merely a marker for poor nutrition. Other data also support this hypothesis. O’Brien” found that in hemodialysis patients, noncompliant behavior (including noncompliance with fluid restriction) was associated with better survival than was compliant behavior. In view of the relationship between IDWG and nutrition and the dilutional effect of IDWG on serum albumin, it may be appropriate for other investigators to consider obtaining equilibrated postdialysis serum albumin values when the nutritional status of hemodialysis patients is studied. If this is not done, serum albumin will be influenced by IDWG, an independent nutritional parameter, in a way that obscures the impact of changes in nutritional state on serum albumin. We do not believe that this study should be interpreted as indicating that a large IDWG in a chronic hemodialysis patient is typically beneficial and should go unchallenged. Rather, we believe that these data suggest that the interpretation of, and reaction to, the finding of a large IDWG needs to be modified. The distinction should probably be made between large IDWG attributable to excessive nonnutritive fluid intake and that caused by nutritionally valuable food and fluid intake. The latter may well result in a better nutritional state and outcomes that are better than they would be if such patients were “compliant.’ ’ ADDENDUM Recently published dataI from 42,341 patients in the Japanese dialysis registry showed that gross mortality rates (GMR) were increased in patients whose average rate of weight loss during dialysis (reflecting IDWG) was less than 4% of predialysis body weight. GMRs were 10.7% and 8.5% for weight losses of 1% to <2% and 2% to <3% of body weight, respectively, compared with GMRs of 4.9% and 4.7% for weight losses of 4% to <5% and 5% to <6% of body weight, respectively. As expected for a parameter that correlates with PCR, the association of low weight loss and GMR was not present in a multivariate analysis that included PCR.

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