Nephrol Dial Transplant (2001) 16 wSuppl 6x: 111113
Pathogenesis and management of malnutrition in
chronic peritoneal dialysis patients
N. V. Dombros
Peritoneal Dialysis Unit, AHEPA University Hospital, Thessaloniki, Greece
Introduction
Protein-energy malnutrition is common (1855%)
among dialysed uraemic patients w1,2x. A variety of
factors may cause or contribute to the development of
malnutrition in chronic renal failure (CRF), haemo-
dialysis (HD), and peritoneal dialysis (PD) patients w3x.
These include: (i) inadequate nutrient intake due
to inadequate dialysis, dietary restrictions, old age,
poverty, depression and suppressed appetite because
of the increased intraperitoneal pressure, absorption
of glucose from the dialysate, various medications,
gastroparesis etc. (ii) Loss of proteins and amino acids
from the peritoneum. On average, the daily loss of
protein via the dialysate is in the order of 69 guday;
however, there is a large inter-individual variation
from 3 to 20 guday w4x. During or after peritonitis this
quantity may be increased by 50100%. Daily total
amino acid losses average 2.5 g (range 1.23.4) w5x;
and (iii) increased catabolism due to co-existing sys-
temic diseases, infections such as peritonitis, chronic
inflammation, underdialysis, metabolic acidosis or
other hypercatabolic diseases w3x. In many PD patients
many of these factors exist in combination. As a
result, in only a few PD patients an increase in the
recommended protein and energy intake is effective in
controlling malnutrition.
Assessment of malnutrition
So far, we do not have a single definite test by which to
assess nutritional status in CRF patients. Therefore, a
plethora of tests have been applied for that purpose.
Nutritional assessment relies on medical history,
physical examination, evaluation of nutrient intake,
anthropometric measurements, biochemical monitor-
ing, assessment of lean body mass and per cent body
fat, and hand-grip strength. Newer methods include
Correspondence and offprint requests to: Nicholas V. Dombros,
Peritoneal Dialysis Unit, AHEPA University Hospital, 32, Ethnikis
Aminis Street, Thessaloniki 54636, Greece.
# 2001 European Renal AssociationEuropean Dialysis and Transplant Association
bio-electrical impedance, dual-emission X-ray absorpt-
iometry, nuclear magnetic resonance, computerized
tomography, total body nitrogen, and total body
potassium. Subjective global assessment is based on a
history of weight loss and symptoms such as anorexia,
nausea and vomiting and has been shown, in many
studies, to be a simple and reliable method for assess-
ing the nutritional status in uraemic, pre-dialysis, HD,
and PD patients. Of all biochemical markers used
to evaluate nutritional status, serum albumin, so far,
is the most common. However, as shown in various
reviews, serum albumin is, rather, a poor nutritional
marker in healthy subjects, pre-dialysis and dialysis
patients w6,7x. Serum albumin level is regulated by
several factors, especially protein malnutrition, protein
losses and inflammation. The latter can lead to a
more marked hypoalbuminaemia than pure insuffi-
cient protein intake, because it suppresses albumin
synthesis and causes transfer of albumin from the
vascular to the extravascular space. Of course, the
combination of malnutrition and inflammation will
lead to a significant reduction in serum albumin
concentration w7x.
The role of inflammation in malnutrition and
atherosclerosis
There are several causes of inflammation in uraemic
patients. Causes related to chronic renal failure per se
include: reduced renal clearance of cytokines, and
advanced glycation products, congestive heart failure
(CHF), the atherosclerotic process per se, various
inflammatory diseases, as well as unrecognized persis-
tent infections, e.g. Chlamydia pneumoniae, Helicobacter
pylori, or dental anduor gingival infections. Additional
causes in HD are: graft and fistula infections, bio-
incompatibility of artificial membranes and exposure
to endotoxins and other cytokine-inducing substances
from contaminated dialysate. Finally, additional causes
of inflammation in PD patients include peritonitis, exit-
site infection, bio-incompatibility of dialysis solutions
and exposure to endotoxins, plasticizers, and other
112 N. V. Dombros

cytokine-inducing substances from contaminated increased dialysis, and nutritional support. In most PD
dialysate w8x. patients these two types of malnutrition overlap. It is
Recently, attention has been focused on the asso- interesting that serum albumin concentration below
ciation of malnutrition, inflammation, and athero- 3.5 gudl is only found in type-2 malnutrition. Thus, in
sclerosis (MIA syndrome) in CRF patients w7,11x. PD patients, hypoalbuminaemia most likely reflects
Chronic inflammation, is evidenced by increased the combination between malnutrition and inflamma-
levels of C-reactive protein (CRP) and other acute tion. In addition to CRF patients, type-2 malnutrition
phase reactants, such as fibrinogen, serum amyloid, is common among patients with CHF, rheumatoid
transferrin, serum albumin and pre-albumin, pro- arthritis, AIDS, advanced cancer and chronic
calcitonin, and others. Major mediators of acute respiratory insufficiency.
phase protein induction are various pro-inflammatory
cytokines such as interleukin (IL)-1, IL-6 and tumour
necrosis factor-a (TNF-a) w7,9x. Dialysis patients have Management of malnutrition
a high prevalence of increased both CRP and pro-
inflammatory cytokines. An increased CRP level is a
Standard treatment of malnutrition include meas-
strong risk factor for cardiovascular (CV) mortality,
ures such as early and adequate dialysis, nutritional
hospitalization and hypoalbuminaemia in dialysis
counselling, nandrolone maleate, oral protein and
patients. High levels of pro-inflammatory cytokines
amino acid supplements, enteral supplementation
may cause muscle wasting (by stimulating protein
and intraperitoneal administration of amino acids.
catabolism, reducing albumin synthesis, and inhibit-
However, all these interventions cannot restore the
ing appetite) and muscle protein catabolism (by
normal nutritional status in all malnourished dialysis
stimulating branched-chain ketoacid dehydrogenase,
patients. In a recent analysis, it was found that data
which leads to greater oxidation of branched-chained
supporting the use of intradialytic parenteral nutrition
amino acids). As a result, increased plasma levels of
in patients with CRF are weak w13x. Obviously, in some
pro-inflammatory cytokines predict hypoalbumin-
patients, inflammation plays a much more important
aemia and mortality in dialysis patients w7x. Although
role in the pathogenesis of malnutrition (type-2) than
inflammation and hypoalbuminaemia predict mortal-
other non-inflammatory factors. Therefore, it becomes
ity in dialysis patients, malnutrition per se accounts
very important to identify these patients by measuring
for -5% of deaths w12x, while atherosclerotic CV
CRP, which is very simple. Patients with an elevated
disease is very common in these patients. Available
CRP anduor other acute phase reactants should receive
evidence suggests that the increased mortality rate
appropriate attention and treatment for the manage-
observed in dialysis patients may be associated with
ment of chronic inflammation. New treatment strat-
inflammation rather than low serum albumin levels
egies, based on the theory of MIA syndrome, include
which often are caused by other mechanisms. Inflam-
administration of angiotensin-converting enzyme inhi-
mation has been shown to be associated with endo-
bitors, which, not only improve cardiac function and
thelial dysfunction, insulin resistance and increased
reduce mortality, but also are shown to be associated
oxidative stress, all of which may accelerate athero-
with a better nutritional status and lower levels of
sclerosis. Congestive heart failure is very common in
TNF-a in chronic renal failure patients w14x. Vitamin C
PD patients and very often (50%) is accompanied by
might be helpful in improving endothelial dysfunction,
muscle wasting and elevated serum levels of TNF-a
but should be avoided in doses )100 mguday, for
and IL-6 w7x. Altogether, nutritional and inflam-
fear of hyperoxalaemia. Antibacterial, and antiviral
matory markers are closely linked to CV disease and
therapy will be most helpful, as they may improve both
mortality in PD patients. Hence, it seems likely that
the cardiovascular and the nutritional status. Finally,
elevated levels of pro-inflammatory cytokines could
anti-cytokine therapy, e.g. anti-TNF-a antibodies, solu-
be the link between the high prevalence of mal-
ble TNF-a receptors, IL-1 receptor antagonists and
nutrition, inflammation and CV disease in these
thalidomide (a TNF-a inhibitor), hold great promise
patients w7,8x.
for the near future w15x.
It has been suggested that there are two types of
malnutrition in CRF patients w7,8x. Type-1 malnutri-
tion (usually without co-morbidity) is characterized
by the absence of inflammation, normalulow serum Conclusions
albumin, decreased protein catabolism, low food intake,
normal resting energy expenditure, and increased Protein-energy malnutrition, common in CRF, con-
oxidative stress. This type of malnutrition could be tributes to the exceptionally high CV and total mor-
reversed by adequate dialysis and nutritional support. tality of dialysed patients. Chronic inflammation, as
Type-2 malnutrition (associated with co-morbidity) is evidenced by increased levels of pro-inflammatory
characterized by the presence of inflammation. This cytokines and CRP, is also common in CRF patients
cytokine-driven type of malnutrition has low serum and, through several pathogenetic mechanisms, may
albumin, increased protein catabolism, lowunormal cause anduor aggravate pre-existing malnutrition and
food intake, elevated resting energy expenditure, atherosclerotic CV disease, thus, contributing to the
markedly increased oxidative stress and resistance to high mortality rate. Therefore, as, in malnourished
Pathogenesis and management of malnutrition in chronic PD patients
PD patients, an elevated CRP concentration indicates
chronic inflammation, our efforts should focus on
controlling the inflammatory state first. Only in the
absence of inflammation, could a malnourished PD
patient benefit from the traditional interventions, such
as nutritional counselling, adequate dialysis, enteral
or parenteral supplementation and intraperitoneal
administration of amino acids.
References
1. Marckmann P. Nutritional status of patients on hemodialysis
and peritoneal dialysis. Clin Nephrol 1988; 29: 7578
2. Cianciaruso B, Brunori G, Kopple JD et al. Cross-sectional
comparison of malnutrition in continuous ambulatory peritoneal
dialysis and hemodialysis patients. Am J Kidney Dis 1995;
26: 475483
3. Dombros NV, Digenis GE, Orepoulos DG. Malnutrition in
continuous ambulatory peritoneal dialysis and use of intra-
peritoneal amino acids. In: Berlyne GM, ed. The Kidney Today.
Selected Topics in Renal Science. Contributions to Nephrology.
Karger, Basel, 1992; 100: 188206
4. Lindholm B, Bergstrom J. Protein and amino acid metabolism in
patients undergoing continuous ambulatory peritoneal dialysis.
Clin Nephrol 1988; 30: S59S63
5. Dombros NV, Oren A, Marliss EB et al. Plasma amino acid
profile and amino acid losses in patients undergoing CAPD.
Perit Dial Bull 1982; 2: 2732
113
6. Dombros NV, Digenis GE, Oreopoulos DG. Nutritional
markers as predictors of survival in patients on CAPD. Perit
Dial Intern 1995; 15 wSuppl 5x: S10S19
7. Stenvinkel P, Heimburger O, Lindholm B, Kaysen GA,
Bergstrom J. Are there two types of malnutrition in chronic
renal failure? Evidence for relationships between malnutrition,
inflammation and atherosclerosis (MIA syndrome). Nephrol Dial
Transplant 2000; 15: 953960
8. Stenvinkel P. Malnutrition and chronic inflammation as risk
factors for cardiovascular disease in chronic renal failure. Blood
Purif 2001; 19: 143151
9. Arici M, Walls J. End-stage renal disease, atherosclerosis and
cardiovascular mortality: is C-reactive protein the missing link?
Kidney Int 2001; 59: 407414
10. Ikizler TA, Wingard RL, Harvell J, Shyr Y, Hakim RM.
Association of morbidity with markers of nutrition and
inflammation in chronic hemodialysis patients: a prospective
study. Kidney Int 1999; 55: 19451951
11. Bistrian BR. Interaction between nutrition and inflammation in
end-stage renal disease. Blood Purif 2000; 18: 333336
12. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of
cardiovascular disease in chronic renal failure. Am J Kidney Dis
1998; 32 wSuppl 5x: S112S119
13. Foulks CJ. An evidence-based evaluation of intra-
dialytic parenteral nutrition. Am J Kidney Dis 1999; 33: 186192
14. Stenvinkel P, Andersson P, Wang T et al. Do ACE-inhibitors
suppress tumor necrosis factora production in advanced
chronic renal failure? J Intern Med 1999; 246: 503507
15. Elliot MJ, Maini RN, Feldmann M et al. Randomised double-
blind comparison of chimeric monoclonal antibody to tumor
necrosis factor alpha (cA2) versus placebo in rheumatoid
arthritis. Lancet 1994; 344: 11051110