Kidney International, Vol. 58, Suppl. 76 (2000), pp.

S-133–S-139

Nutritional aspects in hemodialysis

MAURICE LAVILLE and DENIS FOUQUE
Department of Nephrology, Claude-Bernard University, Edouard-Herriot Hospital, Lyon, France

Nutritional aspects in hemodialysis. The results of cross sec- min are strongly correlated with body composition and
tional studies throughout the world indicate that maintenance dialysis outcomes and represent suitable surrogates to
hemodialysis patients are at risk of malnutrition. Longitudinal
studies show that malnutrition is associated with a reduced life follow-up closely the nutritional status of the patients [2].
expectancy mainly because of cardiovascular and infectious According to threshold values of 35 g/L for albumin and
complications. Several factors are responsible for malnutrition 300 mg/L for prealbumin, recent data from France on
of hemodialysis patients. Protein-energy intake is often reduced
more than 7000 hemodialyzed patients indicated that 20
because of inappropriate dietary restrictions, anorexia, and
taste alterations, promoting malnutrition in most patients en- or 36%, respectively, of them suffered from malnutrition
tering dialysis. Intercurrent illnesses and frequent hospitaliza- despite satisfying dialysis adequacy (mean Kt/V 1.36 ⫾
tions add to meal disturbances. A state of persistent catabolism 0.36). In this study, the mean normalized protein nitro-
may result from acidosis, resistance to anabolic factors such as
growth hormone, insulin, and insulin-like growth factor-1, as
gen appearance (nPNA) was 1.13 ⫾ 0.32 g/kg/day; how-
well as a chronic inflammatory state caused by dialysis mem- ever, 35% of patients had a nPNA below 1 g/kg/day [3].
brane and fluid bioincompatibility. In addition, losses of nutri-
ents, including glucose, amino acids, proteins, and vitamins,
occur during the dialysis treatment. Careful monitoring of di- CONSEQUENCES OF MALNUTRITION ON
etary intakes is mandatory even in predialysis patients. In he-
modialysis patients, the dose of dialysis should be adapted to
DIALYSIS OUTCOMES
correct acidosis and to relieve anorexia caused by accumulation While reported annual mortality rates range from
of uremic toxins and hyperleptinemia. When malnutrition is 23.6% in the United States in 1993 [4], to 10.7% in
established, active therapeutic interventions should take place,
including intradialytic parenteral nutrition if oral supplementa- Europe [5], and to 9.5% in Japan in 1994 [6], a common
tion has failed to improve nutritional status. Anabolism has factor of increased death risk in these populations is
been observed during the administration of recombinant growth malnutrition [7]. Serum albumin below 35 g/L [2, 8–10]
hormone and insulin-like growth factor-1. Emerging therapeu- and serum prealbumin below 300 mg/L (abstract; Chiap-
tic strategies against malnutrition may also involve a short
period of daily dialysis. pini et al, Nephrol Dial Transplant 5:699, 1990) [2, 11–13]
have been shown to be independent predictors of in-
creased morbidity and mortality.
End-stage renal disease (ESRD) patients treated by An early report from 98 nondiabetic hemodialysis pa-
maintenance hemodialysis (MHD) are at risk of malnu- tients followed for 12 months showed an inverse relation-
trition, as shown by several cross sectional studies in the ship between the protein nitrogen appearance and the
United States, Japan, and Europe. In fact, virtually every frequency of hospitalizations and mortality rate [14]. In
study examining the nutritional status of hemodialysis 1990, Lowrie and Lew showed that in over 12,000 MHD
patients indicates that such patients frequently manifest patients followed for 12 months, of various predialysis
protein calorie malnutrition [1]. The clinical evidence serum chemistries, the serum albumin exhibited the most
for malnutrition includes decreased relative body weight, striking odds ratio for survival [15]. The multicenter Ca-
skinfold thickness, arm muscle circumference, and low nadian Hemodialysis Morbidity Study reported a direct
growth rates in children (Table 1). Body composition correlation between the serum albumin level and the
measurements using total body nitrogen, bioelectrical morbidity and mortality risk in 486 hemodialysis patients
impedance measurements, and dual-energy x-ray absorp-
[16]. Two other recent studies also confirm that a low
tiometry (DEXA) also reveal a high incidence of protein
serum albumin concentration is a strong predictor of
calorie malnutrition. Serum levels of albumin and prealbu-
high death rates [17, 18].
A follow-up from the large French multicenter study
Key words: malnutrition, diet and dialysis, growth factors, uremia. on a representative subset of more than 1600 patients
 2000 by the International Society of Nephrology reported a survival of 90 and 78% at one and two years,

S-133
S-134 Laville and Fouque: Hemodialysis and nutrition

Table 1. Nutritional parameters in chronic hemodialysis patients Table 2. Factors of malnutrition in chronic hemodialysis patients

Clinical Biological Previous malnutrition

Reduced protein-energy intakes
Body weight Serum urea/creatinine Inadequate diet counseling
Skinfold thickness nPNA Anorexia
Arm muscle circumference Serum albumin Taste disturbances
Subjective Global Assessment Serum prealbumin Digestive side-effects of drugs
Growth rate (children) Transferrin Frequent hospitalizations
Cholesterol Primary/intercurrent illnesses
IGF-1 Reduced dietary intakes
Total body nitrogen
Catabolic state
Bioelectrical impedance Chronic inflammation
Dual energy x-ray absorptiometry
Endocrine and metabolic disorders
Acidosis
Anemia
Uremic toxins
Hyperparathyroidism
respectively, and confirmed a significant influence of se- Hyperleptinemia
rum levels of albumin and prealbumin on survival (ab- Growth hormone and IGF-1 resistance
Dialysis-related events
stract; Combe et al, J Am Soc Nephrol 10:239A, 1999) [3]. Inadequate Kt/V
It should be emphasized that these findings do not Bioincompatible membranes
indicate that improving nutritional status by increasing Chronic inflammation
Endotoxin back-filtration
nutritional intake or other maneuvers will reduce mor- Amino acid and protein losses
bidity or mortality. Malnutrition by itself is rarely re- Vitamin losses
ported as a cause of death in ESRD patients. In fact,
malnutrition itself may be detrimental on outcomes of
infectious and cardiovascular complications. It is also
possible that the same illnesses that engender malnutri- either referred for checkup or following surgery overall
tion will independently cause the high morbidity and received only 80% of the scheduled meals, thus resulting
mortality, therefore reducing the pathogenetic weight of in a weekly deficit of about 2800 kcal per patient. The
malnutrition per se. reasons for those missed meals were, for example, fasting
states before diagnosis procedures or surgery, modified
schedule of dialysis sessions, postdialysis fatigue, and
FACTORS OF MALNUTRITION IN inadequacy between meals and patient’s preferences. It
HEMODIALYSIS PATIENTS is therefore not surprising that in the French cohort,
A high prevalence of protein calorie malnutrition is malnutrition was observed significantly more often in
observed in patients commencing hemodialysis (Table 2) patients with diabetic and vascular kidney disease, even
[19]. Those hemodialysis patients who are malnourished after adjustment for age [3]. Before starting maintenance
at the onset of dialysis therapy are likely to stay malnour- dialysis therapy, low-protein and low-phosphate diets
ished one to two years later. Conversely, those individu- are routinely prescribed. These diets may be sometimes
als who are well nourished at the onset of maintenance hypocaloric [27, 28] and therefore may be deleterious to
dialysis therapy are likely to remain well nourished. the patient’s nutritional status, if not adequately moni-
Malnutrition can result from several factors that can tored by skilled dietitians.
be found in different combinations in selected patients, The most important cause of inadequate nutrient in-
and it involves reduced dietary intakes, metabolic disor- take is almost certainly anorexia. Anorexia may be
ders, and inadequate dialysis [20] in terms of dose [21, 22] caused by many factors, including: uremic toxins; gastro-
or membrane biocompatibility [23, 24]. intestinal disorders such as peptic ulcers, gastritis, or
esophagitis; unpalatable medicines; and psychosocial dis-
orders [20, 29, 30].
DIETARY NUTRIENT INTAKE Recent evidence suggest that protein calorie malnutri-
There are many possible causes for protein calorie tion often begins incipiently when the glomerular filtra-
malnutrition in patients receiving maintenance dialysis tion rate (GFR) is about 28 to 35 mL/min/1.73 m2 or
therapy. These patients are chronically exposed to the even higher (abstract; Kopple et al, J Am Soc Nephrol
risk of inadequate diet counseling or self-designed re- 5:335, 1994) and continues to fall gradually as the GFR
strictions, and repeated hospitalizations (abstract; Young decreases below these values [31, 32]. However, patients
et al, J Am Soc Nephrol 10:259A, 1999) [25], which dis- usually do not become frankly malnourished until the
turb dietary habits and reduce dietary nutrient intake, GFR is 4 to 5 mL/min/1.73 m2 or lower. As a result, pre-
and superimposed acute or chronic illnesses [26]. We ESRD patients often have critically low levels of protein
have observed in our unit that hemodialysis patients and energy intakes, and the spontaneous nutrient intake
 Laville and Fouque: Hemodialysis and nutrition S-135

does not normalize when maintenance dialysis treatment benefits of maneuvers designed to enhance the removal
is started. Jacob et al reported that 45% of 61 MHD of uremic toxins through increased dialysis elimination
patients had a protein intake less than 1.0 g/kg body or adsorption. A specific goal should be to lower plasma
weight/day [33], whereas Bergström et al found that 12% leptin by increasing dialysis clearance or decreasing its
of 117 unselected hemodialysis patients had a protein overproduction, which is likely associated with chronic
intake below 0.8 g/kg body weight/day [30]. A recent inflammation [44].
report of the HEMO pilot study in hemodialysis patients
entering dialysis showed a low energy intake (22.8 kcal/kg
NUTRITIONAL CONSEQUENCES OF
body weight/day) and a protein intake of 0.94 g/kg body
CHRONIC INFLAMMATION
weight/day, much less than the 35 kcal/kg body weight/
day usually recommended for hemodialysis patients or In patients with chronic renal failure (CRF), chronic
normal individuals [34, 35]. These protein energy intakes inflammation may be associated with immunologically-
may strongly affect early outcomes of renal replacement mediated primary renal diseases, treated by corticoste-
therapy and explain why long-term hemodialysis patients roids, which in turn induces a well-known catabolic state.
are frequently malnourished. However, an important factor is likely repeated in-
A progressive decrease in protein calorie intake may flammatory bursts caused by bioincompatibility of dial-
also depend on taste disturbances. The neuroregulation ysis membranes and fluids. The quality of dialysis water
of appetite is far from well understood in patients with and dialysis fluid backfiltration play a major role, as sug-
chronic renal failure [36]. Zinc deficiency contributes to gested by cross-sectional studies in which plasma C-reac-
taste disturbances [37, 38]. It has also been suggested tive protein levels are significantly higher in patients treated
that, in addition to factors such as delayed gastric empty- by low-flux hemodiafiltration than in patients treated
ing, poorly palatable diets enhanced by salt and electro- by either high-flux hemodiafiltration, paired filtration
lyte restrictions, and postdialysis malaise, some uremic dialysis, or conventional hemodialysis [46]. C-reactive
toxins appear to affect appetite directly. Anderstam et protein is an acute phase reactant protein synthesized by
al recently infused uremic ultrafiltrate into the peritoneal the liver in response to inflammatory processes leading to
cavity of rats. Compared with rats infused with saline or an increase in IL-6 production. As a result, synthesis of
plasma ultrafiltrate from healthy humans, the rats in- acute phase reactants by the liver is associated with a
fused with uremic ultrafiltrate demonstrated a net reduc- decreased albumin production [47]. Moreover, chronic
tion in their spontaneous food intake [39]. Ultrafiltrate inflammatory status likely increases lipid and protein
fractionation studies suggest that the molecular weight oxidation, and probably contributes to vascular disease
of compounds that may induce anorexia is between 1000 and tissue amyloid deposition [48, 49].
and 5000 D [39]. Another compound called leptin, a 15 kD
polypeptidic hormone synthesized by adipocytes, has
DIALYSIS-RELATED NUTRIENT LOSSES
been shown to decrease appetite in rats and to induce
weight loss when administered as a recombinant product The hemodialysis procedure itself may promote wast-
in obese humans [40]. Leptin is abnormally high in hemo- ing by removing nutrients and also by stimulating protein
dialysis patients as a consequence of reduced renal clear- catabolism. Hemodialysis increases the urea nitrogen ap-
ance, elevated insulin levels, and possibly chronic inflam- pearance (UNA or net urea generation), enhances net
mation [41–44]. protein breakdown, and promotes negative nitrogen bal-
These observations suggest that more intensive dial- ance [50]. During sham hemodialysis in normal volun-
ysis therapy might increase appetite by removing uremic teers, Guttierez et al reported an increased release of
toxins. Lindsay and Spanner increased the dose of dial- amino acids from the leg, indicating enhanced net muscle
ysis in a group of hemodialysis patients and observed a protein breakdown [51]. The bioincompatible nature of
spontaneous increase in proteic catabolic rate without dialyzer membranes may stimulate the release of cyto-
evidence of catabolic events, suggesting that patients had kines, such as interleukin-1, which may be the cause of
increased their protein intake [45]. On the other hand, the enhanced protein catabolism.
in many patients, the proteic catabolic rate does not During a routine hemodialysis treatment using a low-
become normal when the Kt/V is increased. Although flux cuprophane membrane, 4 to 9 g of free amino acids
this might reflect the fact that Kt/V is not sufficiently are lost through the dialyzer during fasting and 8 to 10 g
high in these patients, it is possible that comorbid factors, if patients are eating during the procedure [52, 53]. Pep-
poorly dialyzable compounds, or other factors may con- tides are also removed in a range of 2 to 3 g per dialysis
tribute to the anorexia and that a high dose of dialysis, [53], thus leading to a net amino acid of 10 to 13 g per
within a range that is attainable routinely may improve dialysis [30]. With high-flux dialyzers in fasting patients,
but not eradicate anorexia in many patients. about 8 g of free amino acids are removed during a
Further studies are needed to evaluate the nutritional routine hemodialysis treatment [54]. However, the use
S-136 Laville and Fouque: Hemodialysis and nutrition

of high-flux membranes with an increased permeability Table 3. Therapeutic nutritional interventions

to protein may result in albumin losses as high as 25 g Interventions
per session when highest ultrafiltration rates are used Adequate dialysis dose
during hemodiafiltration (abstract; Hillion et al, J Am Daily dialysis
Soc Nephrol 10:283A, 1999). Correction of acidosis
Oral/enteral dietary supplements
Reuse of dialyzers is a routine procedure in the United Parenteral nutrition
States [55]. Although usually small amounts of protein Interdialytic
are lost during a single hemodialysis, Kaplan et al re- Intradialytic rHu-EPO
rHu-GH
ported markedly increased protein losses when polysul- rHu-IGF
fone membranes were reprocessed many times with
bleach or formaldehyde [56]. After 20 to 25 reuses, up
to 17 g of protein were lost during one hemodialysis
session. Protein losses do not seem to increase markedly failure patients, increases protein catabolism [73, 74].
until reprocessing exceed 10 times. Interestingly, when Metabolic acidosis impairs protein metabolism by mainly
the use of bleach for dialyzer reprocessing was discon- increasing protein catabolism through a stimulation of
tinued, the patients underwent a significant increase in the ubiquitin-proteasome pathway. In addition, acidosis
serum albumin, from 3.6 to 3.8 g/dL, which was consid- increases insulin resistance and impairs the effects of
ered to be due to reduced protein leakage through the insulin on glucose and amino acid utilization. Acidosis
dialyzers [56]. is also partially corrected by a low-protein diet [75].
During hemodialysis with glucose-free dialysate, an
average of 20 to 30 g of glucose is lost into the dialysate
[57, 58]. If a dialysate containing 200 mg/dL (11 mmol/L) PERSPECTIVES FOR
of glucose monohydrate (180 mg/dL of anhydrous glu- NUTRITIONAL INTERVENTIONS
cose) is used, there is a net absorption of 10 to 30 g of In face of numerous causes for malnutrition, it is not
glucose during each dialysis [57, 58]. unexpected to find many different treatments for malnu-
Deficiency of water-soluble vitamins in hemodialysis trition. Some are still experimental, although pilot stud-
patients results primarily from insufficient intake, losses ies appear promising (Table 3).
into dialysate, or altered vitamin synthesis or metabolism A low serum bicarbonate level may be associated with
or possibly the presence of inhibitors to the actions of higher protein intakes [3], and it is unclear from clinical
the vitamins. Water-soluble vitamins and other bioactive studies whether those patients have a higher benefit of
compounds are removed by both hemodialysis and peri- larger protein intakes as compared with the detrimental
toneal dialysis [59–62]. These losses may be reduced by catabolism induced by acidosis per se. However, since
decreased urinary excretion and may be partially re- dietary protein intake is not easy to assess routinely and
placed by the vitamins provided in a normal diet [63–68]. because nPNA may not be a valid marker of protein
If patients have low nutrient intakes, these losses may intake in acidosis (for example, a nonstable metabolic
enhance malnutrition. In fact, the content of several vita- state), acidosis control should be advised, through oral
mins in typical meals ingested by MHD patients is less or dialytic route, to reach a minimum predialytic serum
than the Recommended Dietary Allowances of the Food bicarbonate level of 22 mmol/L.
and Nutrition Board. However, the need of water-solu- Oral and enteral dietary supports are generally not
ble vitamins may vary with the new types of dialyzers largely prescribed because of moderate taste acceptabil-
used. The more porous, high-flux dialyzers remove greater ity, patients getting tired of them, and products overcost.
quantities of vitamins. Some of the detrimental effects In addition, a number of patients may present gastroin-
of losses of water soluble vitamins and other compounds testinal discomfort or disease and may not benefit from
might be alleviated by either intradialytic supplementa- these compounds. However, oral supplements may pre-
tion [69] or convective dialysis methods associated with vent the setting of malnutrition particularly due to low
reinfusion of regenerated ultrafiltrate. energy intakes and should therefore be proposed system-
atically before any intravenous nutrition therapy, be-
cause of almost no side effects and potential benefits. In
IMPAIRED UTILIZATION OF NUTRIENTS particular states of severe malnutrition, we and others
Endocrine and metabolic disorders are frequently ob- have observed unexpected recoveries after gastrostomy
served during chronic renal failure. There is a state of and sustained enteral nutrition.
resistance to many anabolic hormones, including insulin, Parenteral nutrition, either predialytic (IDPN) or con-
growth hormone, and insulin-like growth factor-1 (IGF-1) tinuous (TPN), has been proposed in response to the
[70–72]. failure of increasing oral nutrients intake. Except during
Acidemia, a condition frequently observed in renal specific conditions such as surgery, trauma, severe sepsis,
 Laville and Fouque: Hemodialysis and nutrition S-137

or chronic digestive disease where this intravenous sup- 4. Held PJ, Brunner FB, Odaka M, Garcia JR, Port FK, Gaylin
DS: Five-year survival for end-stage renal disease patients in the
port will maintain an optimal intake, there are no con- United States, Europe, and Japan, 1982 to 1987. Am J Kidney Dis
vincing randomized controlled studies supporting the use 15:451–457, 1990
of long-term intravenous nutrition [76]. Furthermore, 5. Valderrabano F, Berthoux F, Jones E, Mehls O: Report on
management of renal failure in Europe, XXV, 1994: End stage
side effects may occur such as nausea, malaise, liver test renal disease and dialysis report. Nephrol Dial Transplant 11(Suppl
abnormalities, and sepsis, and in one study, IDPN has 1):2–21, 1996
been associated with outcome worsening in patients with 6. Shinzato T, Nakai S, Akiba T, Yamazaki C, Sasaki R, Kitaoka
T, Kubo K, Shinoda T, Kurokawa K, Marumo F, Sato T, Maeda
a serum albumin of greater than 35 g/L [77]. However, K: Survival in long term haemodialysis patients: Results of the
the fact that nutrients could be delivered without extra annual survey of the Japanese society for dialysis therapy. Nephrol
hospitalization and venous access during a regular dial- Dial Transplant 12:884–888, 1997
7. Bergström J: Nutrition and mortality in hemodialysis. J Am Soc
ysis, that new delivery systems and solutions (all-in-one) Nephrol 6:1329–1341, 1995
are proposed, and new formulas are under development 8. Iseki K, Kawazoe N, Fukiyama K: Serum albumin is a strong
still represent a large potential for future treatments, predictor of death in chronic dialysis patients. Kidney Int 44:115–
119, 1993
which should be adequately validated through clinical 9. Goldwasser P, Mittman N, Antignani A, Burrell D, Michel
trials of best quality. MA, Collier J, Avram MM: Predictors of mortality in hemodialy-
In order to stimulate protein synthesis, anabolic com- sis patients. J Am Soc Nephrol 3:1616–1622, 1993
10. Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC,
pounds have been administered during limited pilot trials Barre PE: Hypoalbuminemia, cardiac morbidity, and mortality in
in maintenance dialysis patients. It is now well accepted end-stage renal disease. J Am Soc Nephrol 7:728–736, 1996
11. Oksa H, Ahonen K, Pasternak A, Marnela KM: Malnutrition
that recombinant growth hormone (rhGH) exerts a in hemodialysis patients. Scand J Urol Nephrol 25:157–161, 1991
strong anabolic effect in chronic renal failure children, 12. Avram MM, Mittman N, Bonomini L, Chattopadhyay J, Fein P:
and benefits on growth and body composition have Markers for survival in dialysis: A seven-year prospective study.
Am J Kidney Dis 26:209–219, 1995
largely overcome limited side effects and high costs of 13. Sreedhara R, Avram MM, Blanco M, Batish R, Avram MM,
treatment [78]. In chronic renal failure adults, rhGH has Mittman N: Prealbumin is the best nutritional predictor of survival
been associated with anabolic response during acute and in hemodialysis and peritoneal dialysis. Am J Kidney Dis 28:937–
942, 1996
chronic administration [79–81]. Since IGF-1 is the active 14. Acchiardo SR, Moore LW, Latour PA: Malnutrition as the main
compound released by growth hormone, rhIGF-1 has factor of morbidity and mortality in hemodialysis patients. Kidney
also been administered in adult chronic renal failure Int 24(Suppl 16):S199–S203, 1983
15. Lowrie EG, Lew LN: Death risk in hemodialysis patients: The
patients and showed anabolic properties as well [82]. predictive value of commonly measured variables and an evalua-
Long-term administration of these compounds in adult tion of death rate differences between facilities. Am J Kidney Dis
MHD patients are still lacking, but it seems reasonable 5:458–482, 1990
16. Churchill DN, Taylor DW, Cook RJ, Laplante P, Barre P,
to try to boost the nutritional response by a short-term Cartier P, Fay WP, Goldstein MB, Jindal K, Mandin H: Cana-
growth factor treatment combined with optimal protein dian hemodialysis morbidity study. Am J Kidney Dis 3:214–234,
and energy intakes. 1992
17. Owen WF, Lew NL, Liu Y, Lowrie EG, Lazarus JM: The urea
Finally, recent data from short daily dialysis programs reduction ratio and serum albumin concentrations as predictors
seem to offer a strong and rapid renutrition response by of mortality in patients undergoing hemodialysis. N Engl J Med
enlarging to almost unrestricted diets patients nutrient, 329:1001–1006, 1993
18. Collins AJ, Ma JZ, Umen A, Keshaviah P: Urea index (Kt/V)
salt, and beverage intakes. This last issue, debatable in and other predictors of hemodialysis patient survival. Am J Kidney
terms of costs and patient comfort, deserves attention, Dis 23:272–282, 1994
at least as a rescue therapy (abstract; Traeger et al, J Am 19. Blummenkrantz MJ, Kopple JD, Gutman YK: Methods for as-
sessing nutritional status of patients with chronic renal failure. Am
Soc Nephrol 10:197A, 1999). J Clin Nutr 33:1567–1585, 1980
20. Bergström J: Why are dialysis patients malnourished? Am J Kid-
Reprint requests to Maurice Laville, M.D., Department of Nephrol- ney Dis 26:229–241, 1995
ogy, Claude-Bernard University, Edouard-Herriot Hospital, 69437 21. Hakim RM, Breyer JA, Ismail NM, Schulman GM: Effect of
Lyon Cedex 03, France. dose of dialysis on morbidity and mortality. Am J Kidney Dis
E-mail: [email protected] 23:661–669, 1994
22. Held PJ, Port FK, Wolfe RA, Stannard DC, Carroll CE,
REFERENCES Daugirdas JT, Bloembergen WE, Greer JW, Hakim RM: The
dose of hemodialysis and patient mortality. Kidney Int 50:550–556,
1. Wolfson M, Strong CJ, Minturn D, Gray DK, Kopple JD: Nutri- 1996
tional status and lymphocyte function in maintenance hemodialysis 23. Parker TF III, Wingard RL, Husni L, Alp Ikizler T, Parker RA,
patients. Am J Clin Nutr 39:547–555, 1984 Hakim RM: Effect of the membrane biocompatibility on nutritional
2. Cano N, Fernandez JP, Lacombe P, Lankester M, Pascal S, parameters in chronic hemodialysis patients. Kidney Int 49:551–
Defayolle M, Labastie J, Saingra S: Statistical selection of nutri- 556, 1996
tional parameters in hemodialysed patients. Kidney Int Suppl 24. Hakim RM, Held PJ, Stannard DC, Wolfe RA, Port FK, Daug-
22:S178–S180, 1987 irdas JT, Agodoa L: Effect of the dialysis membrane on mortality
3. Aparicio M, Cano N, Chauveau P, Azar R, Canaud B, Flory of chronic hemodialysis patients. Kidney Int 50:566–570, 1996
A, Laville M, Leverve X: Nutritional status of haemodialysis 25. Carlson DM, Duncan DA, Naessens JM, Johnson WJ: Hospital-
patients: A French national cooperative study. Nephrol Dial Trans- ization in dialysis patients. Mayo Clin Proc 59:769–775, 1984
plant 14:1679–1686, 1999 26. Grodstein GP, Blumenkrantz MJ, Kopple JD: Nutritional and
S-138 Laville and Fouque: Hemodialysis and nutrition

metabolic response to catabolic stress in chronic uremia. Am J phagocyte oxidative metabolism detected in vivo and in vitro within
Clin Nutr 33:1411–1416, 1980 microamounts of whole blood. Kidney Int 28:158–167, 1985
27. Fouque D, Joly MO, Laville M, Beaufrere B, Goudable J, 49. Miyata T, Wada Y, Cai Z, Iida Y, Horie K, Yasuda Y, Maeda
Pozet N, Chatelain P: Zech Increase of serum insulin-like growth K, Kurokawa K, van Ypersele de Strihou C: Implication of an
factor I (IGF 1) during chronic renal failure is reduced by low- increased oxidative stress in the formation of advanced glycation
protein diet. Miner Electrolyte Metab 18:276–279, 1992 end products in patients with end-stage renal failure. Kidney Int
28. Ciancaruso B, Capuano A, D’amaro E, Ferrara N, Nastasi A, 51:1170–1181, 1997
Conte G, Bellizzi V, Andreucci VE: Dietary compliance to a low 50. Borah M, Schoenfeld PY, Gotch FA, Sargent JA, Wolfson M,
protein and phosphate diet in patients with chronic renal failure. Humphreys MH: Nitrogen balance in intermittent hemodialysis
Kidney Int Suppl 27:S173–S176, 1989 therapy. Kidney Int 14:497–500, 1978
29. Evans RW, Manninen DL, Garrison LP Jr, Hart LG, Blagg 51. Guttierez A, Alvestrand A, Wahren J, Bergstrom J: Effect of
CR, Gutman RA, Hull AR, Lowrie EG: The quality of life of in vivo contact between blood and dialysis membranes on protein
patients with end-stage renal disease. N Engl J Med 312:553–559, catabolism in humans. Kidney Int 38:487–494, 1990
1985 52. Giordano C, DePascale C, De Cristofaro D, Capodicasa G,
30. Bergström J: Nutrition and adequacy of dialysis in hemodialysis Balestrieri C, Baczyck K: Protein malnutrition in the treatment
patients. Kidney Int Suppl 41:S261–S267, 1993 of chronic uremia, in Nutrition in Renal Disease, edited by Berlyne
31. Ikizler TA, Greene JH, Wingard RL, Parker RA, Hakim RM: GM, Baltimore, Williams and Wilkins, 1968, p 23
Spontaneous dietary intake during progression of chronic renal 53. Kopple JD, Swendseid ME, Shinaberger JH, Umezawa CY: The
failure. J Am Soc Nephrol 6:1386–1391, 1995 free and bound amino acids removed by hemodialysis. Trans Am
32. Pollock CA, Ibels LS, Zhy FY, Warnant M, Caterson RJ, Soc Artif Intern Organs 19:309–313, 1973
Waugh DA, Mahony JF: Protein intake in renal disease. J Am 54. Ikizler TA, Flakoll PJ, Parker RA, Hakim RM: Amino acid
Soc Nephrol 8:777–783, 1997 and albumin losses during hemodialysis. Kidney Int 46:830–837,
33. Jacob V, Le Carpentier JE, Salzano S, Naylor V, Wild G, 1994
Brown CB, el Nahas AM: IGF-1, a marker of undernutrition in 55. Levin NW: Dialyzer reuse: A currently acceptable practice. Semin
hemodialysis patients. Am J Clin Nutr 52:39–44, 1990 Dial 6:89–90, 1993
34. Dwyer JT, Cunniff PJ, Maroni BJ, Kopple JD, Burrowes JD, 56. Kaplan AA, Halley SE, Lapkin RA, Graeber CW: Dialysate
Powers SN, Cockram DB, Chumlea WC, Kusek JW, Makoff protein losses with bleach processed polysulphone dialyzers. Kid-
R, Goldstein DJ, Paranandi L: The hemodialysis pilot study: ney Int 47:573–578, 1995
Nutrition program and participant characteristics at baseline: The 57. Wathen RL, Keshaviah P, Hommeyer P, Caldwell K, Comty
HEMO Study Group. J Ren Nutr 8:11–20, 1998 CM: The metabolic effects of hemodialysis with and without glu-
35. National Kidney Foundation DOQI guidelines in nutrition. Am J cose in the dialysate. Am J Clin Nutr 31:1870–1875, 1978
Kidney Dis 2000 (in press) 58. Gutierrez A, Bergström J, Alvestrand A: Hemodialysis-associ-
36. Astback J, Fernstrom A, Hylander B, Arvidson K, Johansson ated protein catabolism with and without glucose in the dialysis
O: Taste buds and neuronal markers in patients with chronic renal fluid. Kidney Int 46:814–822, 1994
failure. Perit Dial Int 19(Suppl 2):S315–S323, 1999 59. Kopple JD, Swenseid ME: Vitamin nutrition in patients undergo-
37. Atkin-Thor E, Goddard BW, O’Nion J, Stephen RL, Kolff WJ: ing maintenance hemodialysis. Kidney Int Suppl 2:S79–S84, 1975
Hypogueusia and zinc depletion in chronic dialysis patients. Am 60. Andersen KEH: Folic acid status of patients with chronic renal
J Clin Nutr 31:1948–1951, 1978 failure maintained by dialysis. Clin Nephrol 8:510–513, 1977
38. Mahajan SK, Bowersox EM, Rye DL, Abu-Hamdan DK, Prasad 61. Rostand SG: Vitamin B12 levels and nerve conduction velocities
AS, McDonald FD, Biersack KL: Factors underlying abnormal in patients undergoing maintenance hemodialysis. Am J Clin Nutr
zinc metabolism in uremia. Kidney Int Suppl 27:S269–S273, 1989 29:691–697, 1976
39. Anderstam B, Mamoun AH, Södersten P, Bergström J: Middle- 62. Sullivan JF, Eisenstein AB, Mottola OM, Mittal AK: The
sized molecule fractions isolated from uremic ultrafiltrate and nor- effect of dialysis on plasma and tissue levels of vitamin C. Trans
mal urine inhibit ingestive behavior in the rat. J Am Soc Nephrol Am Soc Artif Intern Organs 18:277–281, 1972
7:2453–2460, 1996 63. Sullivan JF, Eisenstein AB: Ascorbic acid depletion during he-
40. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner modialysis. JAMA 220:1697–1699, 1972
R, Hunt T, Lubina JA, Patane J, Self B, Hunt P, McCamish 64. Whitehead VM, Comty CH, Posen GA, Kaye M: Homeostasis
M: Recombinant leptin for weight loss in obese and lean adults: of folic acid in patients undergoing maintenance hemodialysis.
A randomized, controlled, dose-escalation trial. JAMA 282:1568– N Engl J Med 279:970–974, 1968
1575, 1999 65. Sullivan JF, Eisenstein AB: Ascorbic acid depletion in patients
41. Merabet E, Dagogojack S, Coyne DW, Klein S, Santiago JV, undergoing chronic hemodialysis. Am J Clin Nutr 23:1339–1346,
Hmiel SP, Landt M: Increased plasma leptin concentration in 1970
end-stage renal disease. J Clin Endocrinol Metab 82:847–850, 1997 66. Descombes E, Hanck AB, Fellay G: Water soluble vitamins in
42. Fouque D, Juillard L, Lasne Y, Tabakian A, Laville M, Joly chronic hemodialysis patients and need for supplementation. Kid-
MO, Laville M: Acute leptin regulation in end-stage renal failure: ney Int 43:1319–1328, 1993
The role of growth hormone and IGF-1. Kidney Int 54:932–937, 67. Dobbelstein H, Korner WF, Mempel W, Grosse-Wilde H, Edel
1998 HH: Vitamin B6 deficiency in uremia and its implications for the
43. Meyer C, Robson D, Rackovsky N, Nadkarni V, Gerich J: Role depression of immune responses. Kidney Int 5:233–239, 1974
of the kidney in human leptin metabolism. Am J Physiol 36:E903– 68. Kopple JD, Mercurio K, Blumenkrantz MJ, Jones MR, Tallos
E907, 1997 J, Roberts C, Card B, Saltzman R, Casciato DA, Swendseid
44. Stenvinkel P, Lonnqvist F, Schalling M: Molecular studies of ME: Daily requirement for pyridoxine supplements in chronic
leptin: Implications for renal disease. Nephrol Dial Transplant renal failure. Kidney Int 19:694–704, 1981
14:1103–1112, 1999 69. Cristol JP, Bosc JY, Badiou S, Leblanc M, Lorrho R, Descomps
45. Lindsay RM, Spanner E: A hypothesis: The protein catabolic rate B, Canaud B: Erythropoietin and oxidative stress in hemodialysis:
is dependent upon the type and amount of treatment in dialyzed Beneficial effects of vitamin E supplementation. Nephrol Dial
uremic patients. Am J Kidney Dis 13:382–389, 1989 Transplant 12:2312–2317, 1997
46. Panichi V, Migliori M, De Pietro S, Taccola D, Metelli MR, 70. De Fronzo RA, Tobin JD, Rowe JW, Andres R: Glucose intoler-
Palla R: Plasma C-reactive protein in haemodialysis. Blood Purif ance in uremia: Quantification of pancreatic beta cell sensitivity
17:142–148, 1999 to glucose and tissue sensitivity to insulin. J Clin Invest 62:425–435,
47. Kaysen GA: Biological basis of hypoalbuminemia in ESRD. J Am 1978
Soc Nephrol 9:2368–2376, 1998 71. Fouque D: Insulin-like growth factor-1 (IGF-1) resistance in renal
48. Nguyen AT, Lethias C, Zingraff J, Herbelin A, Naret C, Des- failure. Miner Electrolyte Metab 22:133–137, 1996
camps-Latcha B: Hemodialysis membrane-induced activation of 72. Fouque D, Peng S, Kopple JD: Impaired metabolic response to
 Laville and Fouque: Hemodialysis and nutrition S-139

recombinant human insulin-like growth factor-1 in dialysis patients. insufficiency, end-stage renal disease and following renal trans-
Kidney Int 47:876–883, 1995 plantation: Update 1997. J Pediatr Endocrinol Metab 10:361–370,
73. May RC, Kelly RA, Mitch WE: Mechanisms for defects in muscle 1997
protein metabolisms in rats with chronic uremia. J Clin Invest 79. Ikizler TA, Wingard RL, Flakoll PJ, Schulman G, Parker RA,
79:1099–1103, 1987 Hakim RM: Effects of recombinant human growth hormone on
74. Reaich D, Channon S, Scrimgeour CM, Daley SE, Wilkinson plasma and dialysate amino acid profiles in CAPD patients. Kidney
R, Goodship THJ: Correction of acidosis in humans with CRF Int 50:229–234, 1996
decreases protein degradation and amino acid oxidation. Am J 80. Iglesias P, Diez JJ, Fernandez-Reyes MJ, Aguilera A, Burgues
Physiol 265:E230–E235, 1993 S, Martinez-Ara J, Miguel JL, Gomez-Pan A, Selgas R: Recom-
75. Rigalleau V, Combe C, Blanchetier V, Aubertin J, Aparicio binant human growth hormone therapy in malnourished dialysis
M, Gin H: Low protein diet in uremia: effects on glucose metabo- patients: A randomized controlled study. Am J Kidney Dis 32:454–
lism and energy production rate. Kidney Int 51:1222–1227, 1997 463, 1998
76. Wolfson M: Use of intradialytic parenteral nutrition in hemodialy- 81. Johannsson G, Bengtsson BA, Ahlmen J: Double-blind, placebo-
sis patients. Am J Kidney Dis 23:856–858, 1994 controlled study of growth hormone treatment in elderly patients
77. Chertow GM, Ling J, Lew NL, Lazarus JM, Lowrie EG: The undergoing chronic hemodialysis: Anabolic effect and functional
association of intradialytic parenteral nutrition administration with improvement. Am J Kidney Dis 33:709–717, 1999
survival in hemodialysis patients. Am J Kidney Dis 24:912–920, 82. Fouque D, Peng SC, Shamir E, Kopple JD: Recombinant human
1994 IGF-1 induces an anabolic response in malnourished CAPD pa-
78. Fine R: Growth hormone treatment of children with chronic renal tients. Kidney Int 57:646–654, 2000