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Nutrition and Hypoalbuminuria
Figure 1: The Phosphatidylinositol 3-kinase/Akt Pathway
and muscle atrophy that occurs in uraemia, diabetes mellitus and other
conditions associated with insulin resistance.
problems, the dialysis procedure per se can stimulate muscle protein
catabolism. Interestingly, the negative protein balance stimulated by
the dialysis procedure is transiently corrected by intra-dialytic
paranteral nutrition (IDPN), but the benefits are not sustained and net
muscle catabolism re-appears when IDPN is discontinued even after
the dialysis procedure has finished.
These findings demonstrate
that the dialysis procedure stimulates muscle catabolism through
mechanisms not yet understood.
proteolytic pathway and
caspase-3 We do not dismiss the possibility that CKD patients can develop true
malnutrition because CKD can induce a decrease in appetite, especially
when the SUN is high and/or with a large numbers of medicines. In the
case of uraemia, it is ironic that the implementation of a low-protein diet
may decrease the levels of retained uraemic products and this, in turn,
Loss of muscle protein
would improve a patient’s appetite. The cause of anorexia is complex,
however, because there is evidence for circulating factors in CKD that
Chronic kidney disease (CKD) and other catabolic conditions activate a common proteolytic
pathway leading to muscle protein catabolism. Malnutrition rarely leads to a loss of lean
act via the central nervous system to decrease appetite.
For this reason,
body mass in CKD. The underlying mechanism of how the dialysis procedure causes muscle
the protein and caloric intakes of patients with CKD should be regularly
atrophy is unclear.
monitored. If intake is adequate, the term malnutrition should be used
with caution and other causes for muscle wasting should be sought,
activated independently of dietary intake. Unfortunately, the including the activation of proteolytic cellular pathways in muscle.
erroneous term of malnutrition is used for two reasons: there is
concern that hypoalbuminaemia is due to an insufficient protein
intake; and certain clinical features of CKD mimic the problems
For over a century, the implementation
associated with malnutrition.
of a protein-restricted diet has been
For example, hypoalbuminaemia is commonly seen in patients with shown to yield improvements in blood
CKD, especially those on dialysis. However, a decrease in serum
pressure control, uraemic symptoms
albumin is likely due to the presence of circulating cytokines and
inflammation, not from an inadequate diet (i.e. malnutrition).
and the harmful metabolic profile seen
weight loss, fatigue and muscle wasting seen in CKD have often been
with advanced kidney failure.
misdiagnosed as malnutrition, but it is the metabolic consequences of
CKD, not dietary insufficiency, that cause muscle wasting in CKD
Increasing protein intake in such patients will only lead to Conclusion
the detrimental metabolic consequences of CKD, rather than The medical community must use all safe therapeutic strategies to improve
increasing muscle mass. the overall health of CKD patients, slow the progression of their renal
insufficiency and stall the need for renal replacement therapy. Dietary
Specifically, increasing protein intake can lead to the development management is an integral strategy in managing patients with CKD. For
of acidosis, which has been shown to accelerate the destruction of over a century, the implementation of a protein-restricted diet has been
muscle protein through activation of the ubiquitin–proteasome shown to yield improvements in blood pressure control, uraemic
proteolytic (UPP) system, in conjunction with caspase-3.
The UPP symptoms and the harmful metabolic profile seen with advanced kidney
has been identified as the proteolytic system that causes muscle failure. There are suggestive results indicating that low-protein diets may
protein catabolism in a number of catabolic states, including burns slow the progression of kidney failure in some subjects. Any therapeutic
and traumatic injury.
Metabolic acidosis has been demonstrated to intervention that forces a significant change in patient lifestyle may be met
cause negative nitrogen balance and a loss of protein stores.
with resistance and therapy non-compliance. Low-protein diets are no
Correcting acidosis can suppress the UPP and lead to an increase different, but several studies have shown that a well-designed diet in
conjunction with a strong dietary counselling programme and support
structure are acceptable and tolerated by patients. More importantly, a
A major consequence of CKD is insulin resistance, and defects in protein-restricted diet is safe and does not lead to diminished muscle
insulin and insulin-like growth factor (IGF-1) signalling will activate mass, fatigue or malnutrition, as some would suspect. The term
muscle breakdown. The mechanism involves suppression of the malnutrition is used erroneously when describing these findings in patients
phosphatidylinositol 3-kinase (PI3K)/Akt pathway, leading to activation with CKD. In fact, more recent experimental data show that the muscle
of caspase-3 and UPP. This pathway is suppressed in the muscle of atrophy and decreased protein stores associated with CKD are due to
experimental models of uraemia/CKD, diabetes mellitus and other activation of proteolytic pathways and not to diminished caloric/protein
catabolic conditions (see Figure 1), suggesting that the suppression of intake. More studies are necessary to reveal other pathways associated
the PI3K/Akt pathway is the trigger for the muscle protein degradation with the anorexia of CKD or dialysis-related muscle catabolism. ■
44 EUROPEAN RENAL DISEASE 2007