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Cross-sectional assessment of nutritional and immune

status in renal patients undergoing continuous ambulatory


peritoneal dialysis1’3
Leoc’adia Pa/op ciiicl J A Ifredo Ivlart#{237}nez

ABSTRACT Malnutrition prevalence and imrnunocompe- anthropometnic. biochemical, and immunologic determina-
tence were assessed in urernic patients undergoing continuous tions have been studied in different groups of patients and
ambulatory peritoneal dialysis (CAPD). Forty-two males and have been correlated with dietary intakes and clinical cx-
twenty-four females with kidney disease treated with CAPD aminations (10-13).
were distributed into three groups according to the length of The interactions between nutrition and morbidity in patients
time they had been undergoing dialysis. Group 0 included with renal failure are well documented: these patients fre-

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patients beginning dialysis: group 1 , patients undergoing CAPD quently suffer from wasting and malnutrition (3, 14-17). Thus,
for < 30 trio: and group 2, patients undergoing CAPD for > 30 when renal failure appears. uremia as well as several nutritional
trio. Body weight and body mass index were greater in patients
problems related to the kidney’s inability to excrete waste
who had been undergoing CAPD for longer periods of time
products, conserve nutrients, regulate fluid and electrolyte hal-
(ll% in males and 14% in females), which was accompanied
ance, produce hormones. and perform other metabolic func-
by higher fat stores and muscle mass when assessed through
tions may develop (18). The cause of malnutrition in mainte-
triceps skinfold thickness and arm muscle measurements. These
nance dialysis patients has been attributed to unbalanced
differences were more apparent in females than in males. Im-
nutrient intake, infections or underlying illnesses, metabolic
rnunoglohulin M values were lower in patients in groups 1 and
and endocrine disorders accompanying uremia. blood and nu-
2 than in group 0, whereas retinol binding protein. fibronectin,
trient losses into dialysate. and the impairment of renal metab-
and C4 were higher. Estimated protein intake was higher in
predialysis patients ( I .3 1 g ‘ d . kg ‘ ) than in the other olism (3. 14).
groups ( 0.95 g #{149}
d ‘ kg ‘ ). The percentage of B cells de- The treatment of chronic renal failure may require dialysis
creased with time on dialysis. Although no changes in total or therapy to remove undesirable substances by diffusion, which
helper T cells were found. a significant rise was noted for the T may involve the semipermeable membrane of the artificial
cell suhpopulation with assumed suppressor and cytotoxic ac- kidney (hemodialysis) on the patient’s penitoneum (penitoneal
tivities and for natural killer cells in those patients undergoing dialysis). Continuous anibulatory penitoneal dialysis (CAPD) is
longer periods of CAPD treatment. Alterations in immune cell a type of dialysis (19) in which the dialysate is left in the
numbers in itnmunoglobulins and complement proteins might peritoneum and exchanged manually four to five times daily
be responsible for immunologic disturbances and infectious with increased selective applications in cardiac and diabetic
processes occurring in patients with chronic renal failure and patients (20). The present investigation, an 8-y cross-sectional
undergoing CAPD. A,n J Cliii Nuir 1997;66:498S-503S. study. was performed to further define the disturbances in
anthropometric and biochemical status in different cohorts of
KEY WORDS CAPD. continuous ambulatory penitoneal CAPD maintenance patients and also to characterize the long-
dialysis, chronic renal failure, immunity, nutrition, nutritional term evolution of immune function in a population with
status, penitoneal dialysis. uremia. complement, T cell
chronic renal failure, in which nutrition, dialysis adequacy, and
infection (peritonitis) are involved in the risk of morbidity and
mortality.
INTRODUCTION

The mutual interactions among nutrition, immune func-


tion. and the pathologic condition are multidirectional ( 1)’
I From the Nephrology Unit. Nuestra Se#{241}oradel Pino Hospital. Las
Thus, first. nutritional intake and status influence host im-
Palmas, Canarian Islands, Spain. and the Department of Physiology and
munocompetence and the body’s response to illness or in-
Nutrition, University of Navarra. Pamplona. Spain.
fection (2-4); second, immune impairments bring about
2 Presented at the symposium Nutrition. liiimunity. and Inkction, held in
detrimental effects on nutrient utilization and affect the Madrid, October 24-25. 1994.
outcome of disease and infectious challenges (5, 6): and 3 Address reprint requests to JA Martinez, Department of Physiology
third, some pathogenic microorganisms or sicknesses may and Nutrition. C/Irunlarrea s/n, liniversidad de Navarra, 31(8)8 Pamplona.
induce malnutrition and immunodeficiency (7-9). Hence. Spain.

498S Ant J Cli,, Nuir l997:66:498S-503S. Printed in USA. 0 1997 American Society fr Clinical Nutrition
NUTRITION AND IMMUNITY IN RENAL CAPD PATIENTS 499S

SUBJECTS AND METHODS surements were compared with adequate geographic norms of
reference (23).
Subjects Blood samples were collected to quantify serum total pro-
The survey was conducted in the nephrology unit of a tein, albumin. prealbumin, netinol binding protein. and plasma
tertiary care hospital (Nuestra Se#{241}oradel Pino, Las Palmas, fibronectin, which were measured with a conventional auto-
Spain). Sixty-six patients with chronic renal failure undergoing analyzer and nephelometnic methods (10, 24). Immunoglobu-
CAPD, and who gave their informed consent according to lins and complement factors were determined by radial immu-
national regulations. participated in the study. nodiffusion (25).
The forty-two males and twenty-four females (mean age: Protein catabolic rate was calculated from four direct mea-
52.9 ± I 2.6 y) were distributed into three groups according to surements (urea and protein in dialysate and urine) and two
the length of time they had been undergoing dialysis. Thus, estimates (amino acids in dialysate and losses of nonurea
group 0 (ii = 16) included predialysis uremic patients: group I nitrogen) according to an accepted formula for CAPD patients
(!1 = 26), patients undergoing CAPD for < 30 mo (: 16.3 ± (26), which has been correlated with daily protein intake (27)
7.4 mo: range: 7-30 mo): and group 2 (ii = 24), patients and was also normalized pen kilogram of body weight as
undergoing CAPD for > 30 mo (: 51.0 ± 19.7 mo; range: described previously ( 2 1 ). The glucose absorbed per day was
31-94 iiio). obtained once the penitoneal pattern was established (28)..
The cause of renal disease before the start of the dialysis Plasma amino acids were quantitatively assessed by HPLC
procedure was glonierulonephnitis (9.1%). polycystic kidney through a standardized protocol (29).
(7.6%), diabetes (39.4%), tubular and interstitial disorders Lymphocytes were counted by routine automated analytic
(12.1%). or other unidentified processes (31.8%). Exclusion procedures (Coulter STKR, Hialeah. FL). Percentages of lym-

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criteria were age < I 8 y or > 75 y, malignant disease. unsuc- phocyte subsets were determined by flow cytometry with use
cessful hemodialysis, intestinal disease, or terminal heart dis- ofthe following commercially available monoclonal antibodies
ease. Patients were also excluded if they had contracted pen- (Coulter Scientific and Becton Dickinson, Onangehung. NY) as
tonitis within the past 2 mo. Four dialysis exchanges were follows: antibody to CD3 (pan T cells), antibody to CD4
performed daily with commercial dextrose solutions with a (helper T cells), antibody to CD8 (cytotoxic-supressor T cells).
volume of 1500 mL (ii 54) and 2000 mL (n 12) according antibody to CDI9 (B cells), and antibody to CD57 (natural
to needs and penitoneal capacity (2 1 ). Diabetic patients were killer cells). Fluorescence from fluonescein isothiocyanate-
administered insulin to maintain glycemia within physiologic labeled immunoglobulins was analyzed with a fluorescence-
levels. activated cell sorter (EPICS profile II: Coulter Electronics Inc).
Forward and perpendicular light-scatter signals were gated by
Methods using appropriate software (25). Data were analyzed with sta-
tistical comparisons widely used in nutritional research: anal-
Height was measured to the nearest 5 mm with a wall-
ysis of variance and the Dunnett I test.
mounted anthropometer and weight was measured to the near-
est 0.1 kg with a calibrated beam balance. The heights and
weights of the patients were measured while the patients were RESULTS
dressed in indoor clothes and no shoes. Body mass index
(Quetelet index) was calculated as weight (in kg) divided by Body weight and body mass index were greaten in patients of
the square of the height (in m). Triceps skinfold thickness was both sexes who had been undergoing CAPD for longer periods
assessed twice with a caliper (Holtain Ltd. Crymych, United oftime (ll% greater in males and 14% in females). This was
Kingdom) over the left triceps muscle, midway between the accompanied by higher fat stores and muscle mass when as-
acromion and olecranon processes and the mean value was sessed through triceps skinfold thickness and muscle arm mea-
recorded. Midarm muscle circumference was derived from surements. these compositional changes being more apparent
triceps skinfold thickness and midarm circumference, which in female than in male patients (Table 1).
was obtained by encircling the upper arm at the midpoint mark The estimated protein intake obtained from calculations of
with flexible, nonstretchable tape (22). Anthropometric mea- protein catabolic rate was higher in predialysis patients

TABLE I
CrosssectionaI anthropornetric measurements in male and female chronic renal failure patients receiving continuous ambulatory peritoneal dialysis’

Male patients Female patients

Group 0: Group I: Group 2: Group 0: Group I: Group 2:


admission 7-30 ili() 3 1-94 tao admission 7-30 010 3 I -94 110

Variables (ii = 9) (a I7 ) (a 16) (a 7) (a 9) ( ii 8)

Weight (kg) 65.9 77 74.5 ± I 1.2 75.5 15.6 54.0 ± 4.3 62.5 4.3 71.5 5.02

BMI (kg/rn2) 22.6 1.9 25.5 ± 3.6 25.7 t 3.6 21.9 t 2.4 25.1 ± 4.8 28.1 ± 5.12

TSF (mm) 9.5 t 3.5 I 1.3 ± 3.8 1 1.3 ± 6.4 16.1 ± 8.7 16.2 t 7.9 23.7 t 7.3
MAMC (cm) 24.1 2.9 27.1 i 3.4 26.3 ± 3.1 20.9 2.4 23.3 t 3.3 25.)) it 2.52

‘ .r ± SD. TSF. triceps skinfId thickness: MAMC. midarm muscle circumference.


2 Significantly different from admission patients. P < 0.05.
500S PALOP AND MARTINEZ

TABLE 2 tion from the dialysate, protein and amino acid losses, poor
Cross-sectional determinations of amino acid, urea. and glucose appetite, and recurrent episodes of peritonitis (30). Thus, mal-
utilization iii chronic renal failure patients receiving continuous
nutrition is present 20-40% of the time in different populations
aillbulatOry peritoneal dialysis’
of uremic patients receiving CAPD when assessed by using
Stages anthropometnic and biochemical approaches (14, 31). Variables
that have been correlated with the degree of malnutrition in
Group 0: Group I: Group 2:
dialyzed patients include body mass index, midarm muscle
adnissioii 7-30 nio 3 1-94 tiio
Variables (‘1 = I 6) (‘1 = 26) (n 24) circumference as an index of muscle mass, triceps skinfold
thickness as marker of subcutaneous fat, and also serum albu-
E:NE 0.64 ± 0.10 0.56 ± 0.082 0.56 ± 0.092
mm and other plasma proteins such as retinol binding protein,
Blood urea (gIL) 1 .67 0.46 1 .57 ± 0.33 1 .64 ± 0.50
PCR (g/d) 78.6 ± 17.5 66.6 ± 13.1’ 66.6 ± I4.8 immunoglobulins, and complement (14-17, 32).
NPCR (g d ‘ kg ‘ ) I .3 1 ± 0.3 0.9S 0. 1 53 0.92 ± 0.24’ In both male and female subjects with chronic renal failure,
GU (g/d) 18.2 ± 4.8 14.3 ± 353 13.9 ± 443 weight gains were greater in those who had been receiving
GAD (g/d) 68.6 t 20.7 71.8 ± 14.4 81.2 ± 17.0 CAPD for longer lengths of time. This was significant for the
‘ .r :t: SD. E:NE, ratio of essential to nonessential amino acids: PCR, female group with a longer duration of CAPD. Body weight
protein catabolic rate: NPCR. normalized protein catabolic rate: GU. gains could be ascribed in part to the absorption of glucose
getleratiOil of urea: GAD. glucose absorption per day. from the dialysate. which may represent 20% of basal energy
2 Out of the laboratory reference interval. needs (3).
3 Significantly different from admission patients. P < 0.05.
Because norms for healthy subjects are apparently adequate

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for individual dialysis patients (33), the reference norms used
(l.3lgd’ ‘kg’)and was reduced(to 0.95 gd’ ‘kg) to compare anthropometric measurements were selected from a
in groups 1 and 2. Also, the ratio of essential to nonessential geographically suitable population. This comparison indicated
amino acids decreased with time. whereas glucose absorption
that ‘20% of the patients under study were at least moderately
from the dialysate and blood urea remained stable during the
malnourished (23). Body composition changes accompanying
studied periods (Table 2).
the CAPD treatment were influenced not only by time on
Total protein and albumin were similar in all groups but out
dialysis, but also by sex. Female subjects with renal insuffi-
of the laboratory reference interval. whereas retinol binding
ciency had more evident increases in muscle mass and fat
protein and fibronectin were higher as a consequence of the
stores as a consequence of the dialytic therapy than did male
stay in dialysis (Table 3). Immunoglobulin M values were
patients. Previously, sex differences were found for anthropo-
lower in male ( I .0 ± 0,5 g/L) than in female ( 1 .4 ± 0.6 g/L)
metric measurements in patients on hemodialysis (16): muscle
patients. whose values were near normal (Table 4).
and fat stores were depleted distinctively in male and female
Additional information concerning immune status was ob-
tamed by measuring different lymphocyte subsets (Table 5). patients.
The percentage of CD19 cells decreased with time on dialysis. In stable renal cases, the protein catabolic rate (g/d) can be

On the other hand. although no significant changes in CD3 or estimated from data of nitrogen losses by using appropriate
CD4 cell phenotypes on in the ratio of CD4 to CD8 cells was equations for CAPD (26). Furthermore, the normalized protein
found, significantly higher percentages of CD8 cells, a T cell catabolic rate by body weight (g ‘ d ‘ kg I) has been pro-

subpopulation with assumed supressor and cytotoxic activities, posed as a useful measure of protein intake, although this value
and CD57 cells were found in group 2 compared with group 0. has not consistently predicted nutritional outcome in patients
with kidney disease (3 1 ). Estimated protein intake (ranging
between 1.31 and 0.95 g ‘ d’ ‘ kg) was reduced with time in
DISCUSSION
both male and female chronic renal failure patients. to a value

Penitoneal dialysis in patients with chronic renal failure is similar to those reported by others (2 1). The urea generation
associated with metabolic and nutritional abnormalities due to rate, obtained from data of urinary and dialysate urea losses
the combined effects of uremia, underdialysis. glucose absorp- (34), decreased with length of treatment and was higher in

TABLE 3
Cross-sectional plasma variables in chronic renal failure patients receiving continuous ambulatory peritoneal dialysis

Stages

Group 0: Group I: Group 2:


admission 7-30 115) 3 1-94 nio
Variables Reference interval (a 16) (a 26) (ii 24)

Total protein (gIL) 65-85 63.0 ± 7.0/2 64.0 ± 7.02 62.5 ± 7.22
Albumin (gIL) 35-55 34.1 ± 452 34.1 ± 4.62 34.0 ± 5.02
Prealhuniin (gIL) 0.2S-().3S 0.44 t 0.102 0.42 ± 0.092 0.40 ± 0.122
Retinol binding protein )111g/L) 30-6() 134 ± 352 ISO ± 372 144 ± 412
Fibronectin (mg/L) 25()-40() 371 ± 30 41 1 ± 892 450 ± 1212

‘ .r ± SD.
2 Out of the laboratory reference interval.
NUTRITION AND IMMUNITY IN RENAL CAPD PATIENTS 50 1S

TABLE 4
Cross-sectional humoral and innate immunity in chronic renal failure patients receiving continuous ambulatory peritoneal dialysis

Stages

Group 0: Group I: Group 2:


admission 7-30 mo 3 1-94 010

Variables Reference interval (ii - 16) (a 26) (a 24)

C3 (mg/L) 550-12(X) 646 ± 170’ 692 ± 160 676 159


C4 (mgfL) 2()0-S00 328 ± 108 376 ± 132 391 ± 95
Immunoglobulin G (g/L 8-18 10.8 ± 2.5 12.3 ± 4.8 I 1.8 ± 2.6
Imniunoglobulin A (gIL) 0.9-4.5 2.6 ± 1.2 2.5 ± 1.2 2.7 t 1.6
Inimunoglohulin M (gIL)2 0.6-2.S 1.4 ± 0.7 1.2 t 0.7 0.9 ± 0.6

‘ SD.
2 Significantly different in male ( I .0 ± 0.5) and female ( I .4 ± 0.6) patients. P < 0.05.

males than in females. although no changes in blood urea was also reduced with longer CAPD treatment as described in
nitrogen associated with duration of CAPD were found. situations of malnutrition that were ascribed mainly to meta-
Serum protein concentrations are often difficult to interpret bolic and nutritional alterations rather than to amino acid losses
in renal failure patients because shifts in intravascular volume in the dialysate (3, 30, 42).
status affect their measurement (35). However, the assessment Furthermore, nutritional status and dietary intake have been

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of visceral protein through measurement of total plasma protein shown to predict clinical outcome and peritonitis incidence in
and albumin revealed that mean values were not within the CAPD patients (19). Thus, peritoneal dialysis provides glucose
reference intervals, suggesting some prevalence of malnutrition in the dialysate solution, which may result in an imbalance in
(10). Hypoalbuminemia has been suggested as a risk factor for the distribution of energy intake (3). Protein supplementation.
peritonitis in CAPD, attributable to insufficient dialysis and zinc and vitamin B-6 intakes, and the protein catabolic rate
protein intake (36). Other indicators of protein metabolism have been associated with nutritional status in uremic patients
such as prealbumin and retinol binding protein, which are (21, 43, 44).
commonly measured to evaluate malnutrition. have been Some studies have described controversial alterations in
shown to be affected in chronic renal failure patients undergo- leukocyte and B cell functions, immunoglobulin and lympho-
ing CAPD as well as in subjects with uremia (35). Thus, kine production, complement activity, T cell activation. and the
prealbumin and netinol binding protein were markedly elevated ratio of CD4 to CD8 cells in CAPD uremic patients (40.
in our patients. On the other hand. fibronectin, considered to be 45-48). Other reports showed no marked changes in immuno-
an acute indicator of starvation and repletion, also increased in phenotypes of peripheral B and T lymphocytes over time (49.
the CAPD patients with time (37). 50). The role of peritoneal lymphocytes in host immunity for
Hypogammaglobulinemia (38) and reduced serum immuno- CAPD patients is just beginning to be understood, although
globulin titers after vaccination (39) have been found in pen- some signs of activation with time have been shown (50),
toneally dialyzed subjects, accompanying the complement particularly during peritonitis episodes (51).
activation associated with uremia (40). However, our determi- The distribution of patients into three groups according to
nations showed that immunoglobulin G and immunoglobulin A duration of CAPD showed that lymphopenia is present in
as well as C3 remained stable during the study whereas C4 was patients receiving CAPD, accompanied by a reduction in the
significantly increased after an average of 16 mo on dialysis, numbers of suppressor-cytotoxic (CD8) and B (CD19) cells
which could be associated with the molecular weight of this with length of time on CAPD, with no apparent changes in the
protein (4 1 ). The ratio of essential to nonessential amino acids helper T (CD4) subtype.

TABLE 5
Cross-sectional determinations of immune cell subpopulations in chronic renal failure patients receiving continuous ambulatory peritoneal dialysis

Stages

Group 0: Group 1: Group 2:


admission 7-30 mo 31-94 1110
Variables Reference interval (a 16) (0 26) (n 24)

Lyniphocytes (C/c) 20-40 28.2 ± I 1.3’ 25.5 ± 8.5 23.0 6.7


CDI9 (C/c) 2-IS 8.1 ± 4.8 7.6 ± 3.3 6.2 3.3
CD2 (C4) 65-90 79.5 ± 10 74.0 ± 14 72.1 9.2
CD4 ((/) 35-65 53.5 ± 13.4 54.7 ± 14.4 58.3 ± 8.1
CD8 %) 2()-3S 29.5 ± 12.3 34.2 ± 12.4 45.7 ± 14.32?
CD57 (C/c) <9 9.6 ± 543 13.7 ± 743 18.3 ± 10.72?
CD4:CD8 1.1-3 2.0 ± 0.8 1.8 ± 0.9 1.4 ± 0.6
‘ .t ± SD.

2 Significantly different from admission patients. P < 0.05.

3 Out of the laboratory reference interval.


502S PALOP AND MARTINEZ

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