Protein metabolism

Protein metabolismIntroduction:

Among the different consequences of chronic renal failure (CKD), the alteration of protein metabolism is of particular importance, the kidneys having a major role in the metabolism of proteins:

– by their function of excretion of the products of protein catabolism;

– by their direct involvement in the metabolism of certain amino acids (AA);

– by their role in homeostasis, especially in the acid-base equilibrium that modulates protein catabolism.

Renal replacement therapies, which provide extended survival for patients with CKD, all have an impact on protein metabolism, whether it be hemodialysis, peritoneal dialysis, or renal transplantation. .

The metabolism of proteins is changed during the course of the CRI. Nutritional disorders affect almost half of patients at the initiation of the replacement therapy for CKD; this state thus constitutes a situation of hypercatabolism linked either to insufficient protein and / or energy supply, or to excessive protein degradation. The spontaneous reduction of protein-caloric intake and the alteration of the humoral regulatory mechanisms linked to the progressive loss of renal function can actually explain this state of protein-energy malnutrition, to which also contribute infectious, inflammatory and cardiovascular pathologies, which are all factors of degradation. Protein frequently associated with IRC. Finally, the substitution treatment of renal function, whatever its modalities, also interferes with protein metabolism.

An increased knowledge of the different abnormalities of protein metabolism and AA observed in CKD should allow better control and is essential in these patients for whom nutritional status is one of the major predictors of morbidity and mortality.

Protein metabolism of the normal subject:

In a normal adult adult, the total weight of the proteins is of the order of 9 to 10 kg, nearly half of which is part of the muscle mass. Protein synthesis is made from a restricted pool of free AA of a hundred grams fed in part by the daily food intake, but also by the degradation of proteins (proteolysis). Permanent exchanges between the AA pool and the protein mass result in the daily turnover of approximately 300 g of proteins, ie 2 to 3% of the total body protein mass.These exchanges are made according to a rhythm nycthéméral alternating the phases of fasting and meals.

During fasting, protein degradation is observed mainly concerning muscle proteins, releasing AA especially for hepatic neoglucogenesis. In postprandial, the protein reserves are restored, the protein syntheses are increased and especially the proteolysis is inhibited. The regular alternation of these two phases allows, in the normal subject, the maintenance of a balanced nitrogen balance and a satisfactory nutritional state.

Protein metabolism study in IRC:


Protein intake in CKD can, as in the normal subject, be evaluated by the dietary survey carried out for a minimum of 3 days.

Protein intake estimation is also frequently performed from the determination of the rate of protein catabolism from the elimination of urea.

In IRC subjects before the terminal stage:

In CKD subjects before the terminal stage, protein intake can be estimated as the sum of urinary urea and non-urea nitrogen excretion. Maroni et al. calculated that non-urea nitrogen accounted for 31 mg / kg / day. The measurement of urinary urea thus makes it possible to calculate the protein intakes, by assuming that the losses and the protein intakes are equal, and knowing that 1 g of nitrogen = 2 g of urea = 6.25 g of proteins. Protein intakes are estimated from the nPCR (normalized protein catabolic rate), ie in g / kg / day.

In patients treated with hemodialysis or peritoneal dialysis:

In patients treated with hemodialysis or peritoneal dialysis, modeling the urea kinetics allows to calculate the nPCR, and thus to estimate protein intake. Formulas that can be used are listed in the K / DOQI (Kidney Disease / Dialysis Outcome Quality Initiative) recommendations published by the National Kidney Foundation in the United States and in various modeling work. Other formulas of the same type have been developed, notably by Daugirdas.

These formulas have been used to estimate protein intakes in many epidemiological studies of end-stage and non-end stage CKD.


Different techniques make it possible to appreciate the body composition, in particular the lean mass which depends on the protein metabolism. Anthropometric measurements can be used to estimate lean body mass, but they pose problems of reproducibility. This can be estimated by different methods, which for the most part are reserved for clinical research conditions: neutron activation, electrical bioimpedance, biphotonic absorptiometry (DEXA). Only these last two methods seem applicable under relatively simple and reproducible conditions.


Serum markers are used to assess nutritional status, especially proteins. The two most useful proteins for assessing nutritional status are albumin and prealbumin.

Albumin is the main plasma protein, with a concentration of 42 Å} 2 g / l (reference dosage by the bromcresol technique), for a total amount of 5 g / kg of weight including 40% in the vascular sector. Its relatively long half-life of 20 days makes it unsuitable for monitoring rapid changes in protein metabolism, especially for renutrition phases.

Prealbumin is synthesized by the liver and metabolized by the kidney, its normal concentration is 300 mg / l. Its short half-life of 2 days is one of the factors contributing to its great interest in monitoring the nutritional status of proteins.

Protein Nutritional Markers at IRC:


The first studies that showed the high prevalence of protein-energy malnutrition in CKD were performed in patients treated with hemodialysis or peritoneal dialysis.

Serum markers:

Serum markers reflecting protein metabolism are frequently altered, and their decrease is predictive of mortality.

In a US study of more than 13,000 hemodialysis patients followed for 18 months, albumin was <40 g / l in 60% of cases. The relative risk of mortality was 1.48 for patients with albumin levels between 35 and 39 g / l, and 3.13 for albuminemia between 30 and 34 g / l. Several other studies in the United States and Europe have also shown the frequency of albumin decline and its prognostic importance. In a study conducted in France in 1996 in more than 7000 hemodialysis patients, albumin was less than 35 g / l in 20% of them. In a cohort of more than 1,600 of these patients followed for two and a half years, the relative risk of mortality decreased by about 5% per g / l of additional albumin.

Other markers of protein metabolism have a major prognostic importance, especially prealbumin. The short half-life of this protein makes it more sensitive to alterations in protein metabolism, which may explain its probably better prognostic value than that of albumin, whether in North American or European studies. .

Other markers:

Anthropometric markers reflecting the state of protein stocks have been studied in smaller cohorts because of the difficulty of their use. Nevertheless, the data from the different studies are consistent with the major epidemiological studies.

Anthropometric parameters, especially those reflecting protein masses such as the mediobrachial perimeter, are frequently altered in hemodialysis patients.

Nitrogen pool estimation by neutron activation shows a value below the 80th percentile in almost one third of cases, with higher mortality in patients with low protein stocks.

The lean mass estimated by DEXA or electrical bioimpedance is below normal reference values, in a large fraction of the population of hemodialysis patients in several studies.

Similarly, the lean mass estimated from creatinine generation was below the 90th percentile in more than 60% of patients in the French cohort, the decrease in lean mass having a prognostic impact in univariate analysis.

In studies that measured the impact of initiation of hemodialysis treatment on body composition, the change in protein masses is in minor rule.

In total, regardless of the markers used, all demonstrate the frequency of protein undernutrition in patients treated with hemodialysis. The alteration of these parameters is highly predictive of the mortality risk of these patients, as well as events reflecting morbidity such as hospitalizations.


Pre-terminal CKDs were much less studied than patients treated with hemodialysis or peritoneal dialysis, whereas it is well established that the quality of clinical follow-up before the end-stage determines the prognosis of these patients once they are treated with hemodialysis.

Ikizler et al. showed that different parameters were altered along with the degree of CKD, with a decrease in urinary creatinine excretion (thus a likely decrease in lean body mass), a decrease in transferrin. Nutritional biological markers such as albumin and prealbumin improve in the first few months after dialysis and persist in the first year. However, no study has shown an increase in lean body mass in patients after dialysis.

The prevalence of protein-energy malnutrition is important in CKD, either before the end stage or with the various locum treatments. It has a major impact on the future of these patients.


Few authors are interested in the evolution of the nutritional status of transplant patients, in which the factors of aggression are nevertheless multiple: the surgical act, the use of steroids in high dose, the occurrence of opportunistic infections are as many potential causes of protein catabolism. Our team has shown, in a cohort of 44 kidney transplant patients, an increase in lean body mass (and body fat) only in women. This increase in lean mass was all the more important as the use of steroids had been low.

Proteinergenic and CRI inputs:


Chronic renal failure before end stage:

Spontaneous protein intake decreases steadily with progression of renal failure, as the creatinine clearance falls below 50 ml / min. During the inclusion visit of the North American Study of Change in Renal Disease, protein intake was found to be 1.07 g / kg / day in patients with glomerular filtration rate of 70 m / min, decreased steadily with decreased renal function to only 0.8 g / kg / day in those with a glomerular filtration rate (GFR) of not more than 9 ml / min . This reduction in protein intake was associated with a simultaneous decrease in energy intake. These data confirmed those from previous studies. Thus, it was calculated that dietary protein intake was reduced by 0.06 g / kg / day for each 10 ml / min drop in creatinine clearance.

Although in CKD the energy expenditure is identical to that observed in normal subjects, the reduction of energy intake, frequently associated with that of protein intake, can only potentiate the nutritional risk. Indeed, if the caloric intake has little effect on the nitrogen balance when the protein intake is within the limits of the normal, its importance becomes determinant on the maintenance of the nitrogen balance when the protein intake is reduced. Thus, in pre-dialysis-grade CKD patients, whose protein intake is reduced to 0.6 g / kg / day, it has been calculated that an energy intake close to 35 kcal / kg / day was necessary for maintaining a balanced nitrogen balance. In fact, at this evolving stage of CKD, the spontaneous energy intake of these patients usually does not exceed 25 to 30 kcal / kg / d, which promotes protein catabolism. Any prescription of protein restricted diet in the IRC requires ensuring that caloric intake is sufficient, a necessary condition for the maintenance of nutritional status.

In summary, spontaneous protein and energy contributions decrease in proportion to the decline in renal function, with deleterious consequences on the nitrogen balance of CKD patients.

Chronic end stage renal failure:

Several studies have shown that protein and energy intake were insufficient in patients treated with hemodialysis: thus, in the first 1,000 patients included in the HEMO study in the United States, the protein intake was 0.93 Å} 0.36 g / kg / day, with a very insufficient energy intake of 22.9 Å} 8.4 kcal / kg / day, with the corollary low albumin of 36.5 Å} 3.8 g / l. It is notable that in this study, protein and energy inputs were strongly correlated (r = 0.74, p < 0.0001). Data of the same type were obtained in patients treated with peritoneal dialysis. However, the US results are not necessarily transferable to Europe. Thus, in the French multicentric study, the protein intake estimated by the nPCR was well above 1.13 Å} 0.32 g / kg / day.

In summary, in hemodialysis and peritoneal dialysis patients, protein and energy intake are frequently lower than the recommendations of 1.2 g / kg / day and 35 kcal / kg / day, respectively.


The weakness of protein and energy intake in CKD is largely explained by frequent anorexia in these patients. Several factors have been advanced to explain it.

Some medium-sized molecules, between 1,000 and 10,000 Da, normally found in urine, are found in the plasma of CKD patients; when after extraction and purification, they are injected into the animal, they induce a dose-dependent anorexia involving carbohydrates and proteins.

The responsibility for leptin, which is increased in concentration during CKD, has also been advanced but has not been clearly demonstrated. Indeed, leptin, product of the ob gene in mice, is a molecule that has anorectic effects. It is frequently elevated in CKD, but inconsistently and highly related to body composition, with the highest levels of leptin being observed in obese CKDs. This is in contradiction with a determining role of leptin in the genesis of anorexia of CKD.

Other anorectic molecules are at high concentrations, such as cholecystokinin, glucagon or serotonin, all of which are molecules of intermediate molecular weight. Proinflammatory cytokines must also have an appetite suppressing effect in CKD, but without the responsibility of any of them being formally demonstrated.

The alteration of taste and smell, the often excessive consumption of drugs, the socio-economic and psychological problems frequently found, especially in elderly patients, contribute to make these patients anorexic.

Factors Affecting Protein Metabolism During CKD

As in subjects with normal renal function, protein synthesis of renal insufficiency depends on proteinoenergetic inputs and regulatory mechanisms that control the intermediate metabolism. Protein catabolism factors are multiple during CKD, but are not specific to it.


IRC patients before the terminal stage:

Whatever the mechanisms, the only reduction in protein and energy intake can not explain the high prevalence of protein-energy malnutrition during CKD. Indeed, in the absence of a hypercatabolism situation, a daily protein intake of 0.6 g / kg is sufficient to ensure a balanced nitrogen balance in both normal and CKD patients (provided that the caloric intake are sufficient), the mechanisms of adaptation of the organism to the reduction of the protein intakes being preserved during the CRI. These mechanisms initially consist of a reduction in AA oxidation, ensuring AA availability for protein syntheses. In a second step, there is a reduction in protein degradation that is balanced with protein syntheses, allowing the subject to maintain a balanced nitrogen balance. When the daily protein intake falls below 0.6 g / kg, the adaptation mechanisms become insufficient, the nitrogen balance is negative, unless the patient receives supplementation of essential AA or its keto-analogues, a necessary condition to maintain a satisfactory nutritional status in patients to whom a greater protein restriction is prescribed, especially to slow the progression of CKD.

In summary, in CKD patients before the end stage, protein intake of 0.6 to 0.8 g / kg / day ensures a balanced nitrogen balance, provided that the calorie intake is greater than or equal to 35 kcal. / kg / day.

CKD patients treated with hemodialysis or peritoneal dialysis:

In these patients, protein intakes should be greater than 1.2 g / kg / day and energy intakes greater than 35 kcal / kg / day (30 kcal / kg / day in subjects over 60 years of age) to ensure the stability of the nitrogen balance. Indeed, various mechanisms secondary to the CKD and especially to the co-morbidities associated with it, as well as to the effects of the techniques used, require these higher intakes than those of normal subjects.

As mentioned above, such contributions are seen in a limited number of patients, whether they are European or American studies; Inadequate intakes are therefore a major factor of protein-energy malnutrition in these patients.


In addition to the reduction of protein-caloric intake, there are abnormalities in AA metabolism, the distribution and structure of which are altered during CKD. These abnormalities worsen along with the severity of CKD and contribute to altering protein synthesis.

The abnormalities of AA distribution are illustrated by the plasma and cellular aminograms, obtained by muscle biopsy, and can be explained by the metabolic disturbances that are found in particular at the renal, muscular and hepatosplanchnic levels.

The kidney plays an important role in the metabolism of AA. It is home to the extraction of glutamine used for ammoniogenesis and gluconeogenesis, proline, citrulline and phenylalanine. It also plays a role in the production of taurine, threonine, ornithine, lysine, arginine, serine and tyrosine, the latter two resulting respectively from the conversion of glycine and hydroxylation of phenylalanine. Alteration of renal function thus explains certain aminogram abnormalities, the most notable being the increase in proline and citrulline levels, while the serine and tyrosine levels are lowered, contrasting with the normal or high levels of glycine and phenylalanine.

The accumulation of some AAs such as hydroxyproline or 3-methyl-histidine is directly related to a decrease in their renal elimination.

At the muscular level, the most obvious alterations are observed during the fasting phase. During this phase, if the release of AA and in particular of glutamine is normal, on the other hand, that of branched AA: leucine, isoleucine and valine is reduced, because of their lower intracellular concentration.

At the hepatosplanchnic level, the percentage of AA captured by the liver is reduced by 50%. The increase in the total quantity of AA released after a synthetic meal preferably concerns non-essential AAs, whereas essential AAs, in particular leucine, which is fundamental for protein syntheses, have lowered levels.

These changes in the plasma aminogram are reminiscent of those observed in malnutrition states. This is particularly the case of the decrease in the ratio of AA essential / non-essential AA, to which are added more specific abnormalities of renal insufficiency.

The modifications of the intracellular aminogram are very close to those observed in the plasma. They have potentially more consequences since cells, especially muscle cells, constitute the major reservoir of AA. Low concentrations of branched AA are found, but also taurine, threonine, lysine and histidine, which is therefore considered essential AA in the course of CKD.

To these distributional anomalies are added biochemical changes of AA and proteins. This is the case, in particular, oxidative stress and carbamylation phenomenon. The latter consists of the binding of isocyanic acid, derived from urea, with AA, proteins and lipids; its importance therefore increases with the progression of renal failure. The molecular modifications that result from this binding are a priori likely to alter the synthesis and functions of certain proteins, both plasma and tissue.

These quantitative and qualitative abnormalities have a negative effect on cell reserves and protein synthesis. They therefore affect the nutritional state, as confirmed by correlations between the plasma and / or muscle concentrations of certain essential AAs, branched in particular, with nutritional markers.


CKD is often presented, referring to observations made in different models of experimental CKD, as being associated with excessive protein degradation. However, despite the high concentrations of many catabolic substances, parathyroid hormone, glucagon, cortisol, catecholamines, it does not seem that in the absence of acidosis or intercurrent pathology, the catabolism of these patients is increased. Many studies have shown that patients with advanced CKD are able to maintain a neutral or positive nitrogen balance despite reduced dietary protein intake.

The difference in blood levels at the level of a catheterized arterial and venous limb that allows to appreciate the AA muscle release, which increases with proteolysis, is identical in CKD and in subjects with renal function. normal. After studying marked phenylalanine fluxes at the level of the upper limb (which makes it possible to assess the levels of synthesis and protein degradation), Garibotto et al. confirmed the absence of excessive proteolysis of muscle origin in stable CKD patients.

The absence of abnormal protein catabolism during CKD was confirmed by the introduction of labeled leucine or glycine into the AA pool, which allows the measurement of protein degradation and synthesis as well as oxidation of AA. The measurement of these different parameters does not show a significant difference between control subjects and patients with advanced renal insufficiency, regardless of protein intake, and subjects being fasted or fed. V. Lim et al. confirmed, using the same stable isotope delivery technique, that in the CKD patient there was no increase in catabolism and that the protein turnover was, on the contrary, slowed down.

In summary, CKD itself is not a cause of excessive protein catabolism.


In addition to the reduction of protein-caloric intake and the biochemical changes of AA and protein, there are disruptions in the hormonal mechanisms that control the intermediate metabolism of proteins.

The hormonal regulation of protein metabolism is either anabolic hormones such as insulin or growth hormone, or catabolic as glucocorticoids.


Among the various abnormalities observed during CKD, peripheral resistance to insulin action, well demonstrated in the context of carbohydrate metabolism, is also likely to affect protein metabolism. Insulin exerts its action at different stages of protein metabolism: it promotes the cellular transport of AA to hepatic and muscular levels and stimulates protein synthesis, but its essential role is to reduce proteolysis and gluconeogenesis. Castellino et al. showed, by studying the effect of insulin on the protein metabolism of CRI, that the antiproteolytic action of insulin was preserved;in contrast, protein synthesis in response to AA infusion in the presence of insulin was reduced by about 30%, with the defect appearing to be beyond the membrane receptor of insulin. However, in recent work, protein syntheses in the presence of combined insulin and AA infusions have been found to be normally stimulated in patients with renal impairment.

In summary, the anabolic action on the protein metabolism of insulin appears to be reduced in CKD, due to the peripheral insulin resistance observed during CKD.

Growth hormone and IGF-1:

The abnormalities of the growth hormone-insulin-like growth factor-1 (IGF-1) axis also contribute to alterations in protein metabolism. High growth hormone levels due to impaired renal metabolism do not compensate for resistance to the hormone observed at the cellular level, and growth hormone supplementation potentiates in malnourished patients the effects Anabolic steroid protein supplementation.

In patients treated with hemodialysis or peritoneal dialysis, there is resistance to the anabolic action of IGF-1 administered at pharmacological doses; the use of higher doses of IGF-1 results in a net positivity of the nitrogen balance despite the absence of changes to dialysis doses or protein-caloric intake.


In normal rats, glucocorticoids promote the catabolic effect of protein metabolic acidosis, as well as other factors such as acute diabetes or prolonged fasting. Similar results have been obtained on cell culture systems that have demonstrated that glucocorticoids have a permissive effect on the stimulation of the stimulus-activated ubiquitin-protease system such as acidosis, by promoting the transcription of the protein genes involved in this process. ubiquitin-proteasome system.


Metabolic acidosis is a common complication of CKD, mainly related to the reduction of renal ammoniogenesis.

Experimentally, induction of metabolic acidosis is accompanied by growth retardation and increased muscle protein degradation. In CKD, it is a major factor in the alteration of protein metabolism, so it can be considered an authentic “uremic toxin”.

Protein synthesis:

Acidosis mainly plays a role in proteolysis, but it also has inhibitory activity towards protein synthesis, inducing insulin resistance and reducing the expression of IGF-1 and the hormone receptor. growth.

Protein catabolism:

Many studies have investigated the role of metabolic acidosis on protein metabolism in experimental situations.

Metabolic acidosis induces an increase in the degradation of proteins, in particular muscle. This increase in proteolysis is related to the increased activity of the ubiquitin-proteasome adenosine triphosphate (ATP) -dependent protein degradation pathway. After initial conjugation of the relevant proteins to ubiquitin, in the presence of ATP, the conjugate thus formed is degraded in a large proteolytic complex of more than 2000 kDa, the proteasome. The messenger ribonucleic acid (mRNA) encoding ubiquitin and the different subunits of the proteasome is increased in the muscles of rats in acidosis.

It is important to mention that corticosteroids participate in this catabolic effect of acidosis. The increase in proteolysis is also related to the increase in the production of branched AA deodrogenase which increases the oxidation and transamination thereof. High levels of mRNA encoding the different components of this enzyme have also been found in rat acidosis muscles.

Numerous studies have confirmed the increase in proteolysis in acidic CKD patients. Bergström et al. have reported an inverse correlation between plasma bicarbonate concentration and plasma AAA plasma levels, which normalize after 6 months of bicarbonate supplementation. Williams et al. have observed that the ratio of 3-methyl histidine / urinary creatinine, a control of the degradation of muscle proteins, is normalized after the intake of bicarbonates in patients with advanced renal insufficiency. Other authors have also observed a decrease in the degradation of AA branched after bicarbonate supply and an improvement in nitrogen and potassium balance. Because of its stimulating effect on protein degradation and oxidation of AA, acidosis counteracts the mechanisms of adaptation to the reduction of protein intake, which implies the need to normalize the plasma level of bicarbonates to 25 mmol / l at least before prescribing a restrictive protein diet.

The correction of the metabolic acidosis of patients on peritoneal dialysis by the intake of alkalis has significantly improved their nutritional status. The Mitch and Walls groups showed that this increase in weight was accompanied by an increase in plasma AA concentrations, and a decrease in ubiquitin im mRNA levels, and a decrease in concentration. serum tumor necrosis factor (TNF) – a .


The inflammation that is frequently observed during CKD also strongly influences protein metabolism. Elevated serum levels of markers of C-reactive protein (CRP) and serum-amyloid A protein (SAA) inflammation were found in almost 50% of patients at the time of dialysis, with a higher prevalence in older patients. Hepatic synthesis of these markers is stimulated by pro-inflammatory cytokines, interleukins 1, 6, and 8 and TNF- a whose rates are increased in IRC. These positive markers of the acute phase of inflammation are negatively correlated with markers of nutritional status, albumin and prealbumin in particular, whose hepatic synthesis is reduced. This chronic inflammation has antagonistic effects of dietary intakes on nutritional status; it is thus clear that part of the negative predictive effects of undernutrition on the outcome of hemodialysis-treated patients is in fact secondary to the existence of chronic inflammation. In addition, it is very frequently associated with progressive atherosclerosis, achieving a syndrome associating malnutrition, inflammation, and atherosclerosis called under the acronym of “MIA syndrome”. Cytokines can also interfere with protein metabolism by inhibiting appetite by direct stimulation of leptin production by adipocytes.

In summary, although it is not specific but associated with CKD, chronic inflammation is responsible for much of the protein catabolic phenomena observed during CKD.


In patients with nephrotic syndrome, proteinuria is an additional loss factor, and excess protein intake may have deleterious effects on renal function, justifying a protein restriction proportional to the degree of CKD. In these patients, a diet providing 35 kcal / kg / day and 0.8 g / kg / day of protein plus 1 g protein / g of proteinuria has been shown to maintain a stable nitrogen balance. the restriction of protein intake being retained.

Substitute treatments for CKD and protein metabolism:


As already detailed, protein-energy malnutrition is a major risk factor for death in hemodialysis patients. Its high incidence may be due to the different CKD-related abnormalities that we have already described, but may also be due to the dialysis procedure itself.

The dialysis session is accompanied by a loss of AA in the dialysate (on average 5 to 10 g per session) which can be increased by 10 to 30% with membranes of high permeability. Protein losses are negligible with non-reused membranes. Ikizler et al. have recently confirmed the catabolic role played by the dialysis session. In 11 patients dialyzed on high permeability biocompatible membranes, there was a decrease in plasma levels of 33% for essential AA and 38% for non-essential AA from the beginning to the end of the session. Plasma levels remain below baseline 2 hours after the end of the session. However, there is a decrease in the net AA balance at the muscle mass level, indicating increased tissue release of AA. The Bergström group has shown, during dummy dialysis performed in healthy volunteers, that the contact of the blood with a cellulosic membrane leads, presumably under the action of pro-inflammatory cytokines, an increase in the concentration of AA in the venous blood. lower limb catheterized arterial and venous. Thus, the decrease in circulating levels of AA observed in the hemodialysis during the session despite an AA output from the muscle mass testifies to the non-compensation of the high loss of AA in the dialysate.

The same team showed, again in healthy volunteers, with muscle biopsies performed before and after dialysis, that the dialysis session was accompanied by a reduction in protein synthesis capacity estimated by the number of intramuscular ribosomes. Data from Ikizler et al. go in the same direction by showing that the dialysis session is at the origin of a decrease in protein synthesis which, combined with a 10% increase in proteolysis, contributes to the negation of the net protein balance.

In addition, it is unclear whether or not dialysis is associated with increased energy expenditure. Although the first studies did not show an increase in energy expenditure in hemodialysis patients, more recent studies have shown an increase in energy expenditure during the hemodialysis session but also the days of no -dialysis, where it would be in the range of 8 to 16%.

In summary, the dialysis session results in a moderate decrease in protein synthesis, a stimulation of the muscle protein degradation with release of AA in the plasma and a loss of these AA in the dialysate. It is estimated that 7 to 8 g of protein disappear during each dialysis session, mainly related to a loss of AA in the dialysate.

While the dialysis session is a situation of hypercatabolism, the longitudinal follow-up of hemodialysis patients shows, provided the dialysis doses are sufficient, a frequent improvement of the nutritional parameters at least during the first years of treatment. These clinical results are confirmed by the study of protein turnover before and after 10 weeks of dialysis. While patients’ protein intake has remained unchanged, V. Lim et al. observed a normalization of protein turnover that was initially reduced compared to a control population. After 10 weeks of dialysis, the degradation and protein synthesis are increased, the latter more pronounced, while the oxidation rate of leucine is reduced compared to that observed in control subjects.

These different results confirm the long-term improvement of protein metabolism by hemodialysis, and are consistent with daily clinical observation.

Different therapies may be considered in dialysis patients with protein-energy malnutrition.

Currently, many teams use parenteral parenteral nutrition that appears to have some efficacy in malnourished patients, and its use is relatively simple in hemodialysis. The interest of this parenteral nutrition has recently been reinforced by the study of Pupim et al. Indeed, this treatment induces an increase in protein synthesis and a decrease in proteolysis during the dialysis session in the seven patients studied. In comparison, a dialysis session without associated nutrition leads to a catabolic state, while parenteral nutrition provides a state of anabolism in terms of protein metabolism. This is all the more interesting as this study concerned patients who were undernourished and who had adequate dietary protein and caloric intake.


In peritoneal dialysis, the daily losses in AA are of the order of 1 to 2 g, resulting in weekly losses close to those induced by hemodialysis. On the other hand, the protein losses are much greater than those observed in hemodialysis, of the order of 5 to 15 g / day, with however large individual variations. Albumin is the protein largely eliminated but it is not the only one. Fifteen percent of immunoglobulin G is present in protein losses by the dialysate.These losses can double during episodes of peritonitis and then remain at high levels for several weeks. In these circumstances, increased protein leakage can lead to malnutrition, which is sometimes major. Although there is a gradual reduction in active cell mass in patients after several years of peritoneal dialysis, the kinetics of labeled leucine show that these patients are also in a situation of protein anabolism.

Various authors prospectively followed the nutritional status of patients on peritoneal dialysis. Jager et al. studied 118 patients on peritoneal dialysis, and report an increase in persistent albuminemia after 2 years of treatment. This improvement in nutritional status is greater in patients with better treatment (creatinine clearance > 75 l / week), despite protein intakes of less than 1 g / kg / day. Currently, the recommended protein intake is 1.3 g / kg / day in patients on peritoneal dialysis (DP), slightly higher than those recommended for hemodialysis (HD) because of the greater protein losses with this technique. AA losses can also be partially offset by the use of AA-containing dialysis bags that will be absorbed through the peritoneal membrane.


Protein metabolism in renal transplant patients differs according to whether they are in the initial period of transplantation or later. Indeed, the immediate consequences of the graft are characterized by increased protein catabolism, due not only to surgery which is associated with an increase in energy and protein requirements, but also to the use of large doses of corticosteroids. A few years ago, Hoy et al. studied the rate of protein catabolism in 50 transplant patients, and showed that this rate increases during the first week after transplantation and stabilizes until at least the third week. All of these patients received 60 mg / day of prednisone, and in patients who had an acute rejection and then had an increase in corticosteroid therapy, this protein catabolism was significantly increased. The role of the corticosteroid dose is confirmed by a second study in 20 patients, showing a significant increase in the rate of protein catabolism in patients receiving 3 mg / kg / day of prednisone versus 1 mg / kg / day.

The increase in protein catabolism frequently leads to a negation of the nitrogen balance. Thus, our team found a decrease in albuminemia within 15 days of surgery in 44 kidney transplant patients. The rate then increases with the decrease in corticosteroid therapy on the one hand, but also thanks to adequate dietary intake. Protein intakes of 1.2 g / kg / day are required to maintain a positive nitrogen balance in these patients, but these intakes should be increased in the postoperative period and in those receiving high doses of corticosteroids. In late post-transplantation, protein metabolism is less influenced by corticosteroid treatment, which is weak or absent, than by the degree of impairment of renal function.


Various recommendations concerning the dietary intakes of CKD have been made by the learned European and American nephrology societies. All also insist on the need for a correction of acidosis, and a sufficient amount of extrarenal treatment.

These recommendations do not include patients with moderate CKD (GFR between 40 and 25 ml / min), for whom a moderate protein restriction (0.8 to 1 g / kg / day) with adequate caloric intake seems desirable. .


IRC is not in itself a catabolic situation, and while protein-energy malnutrition is common in CKD patients, it should be remembered that it spares more than half of all patients. There is no inevitability of malnutrition if a certain number of rules are respected: sufficient protein and energy supply, control of the uremic syndrome, including metabolic acidosis and sufficient dialysis doses. However, even when these instructions are well followed, some patients remain malnourished, catabolic, often as part of a chronic inflammatory syndrome. The identification of a curable cause for inflammation is sometimes possible. Ultimately, therapeutic anti-inflammatory strategies may improve the protein metabolism and nutritional status of these patients.