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Advanced glycation products are proteins whose structural and functional properties have been modified by a process of oxidative glycation. The accumulation of advanced glycation products in most tissues and the oxidative stress and inflammatory reactions that accompany it, account for the multi-systemic impairment observed particularly in the elderly, diabetics and in chronic renal failure. The advanced glycation products endogenous production is continuous, related to oxidative stress, but the most important source of advanced glycation products is exogenous, mainly of food origin. Exogenous advanced glycation products are developed during the preparation of food and beverages. The advanced glycation products content is higher for animal foods, but it is mainly the preparation and cooking methods that play a decisive role. Dietary advice is based on the selection of foods and the choice of methods of preparation. Several randomized controlled studies have confirmed the favorable effect of these recommendations on serum advanced glycation products concentrations. In humans, as in animals, regular physical activity also results in a reduction of serum and tissue concentrations of advanced glycation products. There is a need for prospective clinical study to confirm the effects of hygienic and dietary recommendations that have only been appreciated, so far, on biological markers.

The acid production of endogenous origin depends mainly on the metabolism of the food and varies with the nature of these. Of the order of 1mEq/kg/day for contemporary food in industrialized countries, it is reduced by more than one third among vegetarians and close to neutrality among vegans. The dietary acid load is eliminated by the normal kidneys, thus maintaining the acid-base equilibrium. In the setting of CKD, it will overflow the capacities of the nephrons, generating a retention of H+ ions, promoting subclinical acidosis. This tissue retention of H+ ions was confirmed by direct techniques in animal models and indirect techniques in humans. The systemic retention of H+ ions and the accompanying compensatory mechanisms have negative consequences on bone tissue, skeletal muscle, cardiovascular risk and renal function. In the animal, the substitution of casein (acid) by soy (alkaline) prevents metabolic acidosis and slows the progression of renal insufficiency. In man, various prospective studies have confirmed that the risk of renal insufficiency was positively correlated with the dietary acid load. Conversely, bicarbonate supplementation and/or a diet enriched with fruits and vegetables, have a favorable effect on renal insufficiency, including in subjects with normal bicarbonate. These results lead to reconsider the K/DOQI recommendations to correct acidosis when the bicarbonate level falls below 22mEq/L, since tissue retention of H+ ions and its negative consequences appear at higher or even normal levels of bicarbonates.

Restricted protein diets in patients with chronic kidney disease have been debated for several decades. In chronic kidney disease as in other chronic diseases, the modulation of the nutritional intake is the object of a certain renewal. It is supported by recent studies that highlight the importance of modulating nutrient intake by diets that are healthier, less rich in animal proteins and richer in plants. The recent reintroduction in France of amino acid supplements and ketoanalogs of amino acids allows the prescription of a very restricted diet. Historical studies have only focused on the relationship between protein intake and renal function degradation. Recent studies on acid loading, bone metabolism or potassium intake allow revisiting the interest of restricted diets. As with any change in eating habits, the selection of patients, information, education and monitoring during the diet are very important and help prevent undernutrition: this is the purpose of this short review.

The gradual loss of weight and function of muscle in patients with chronic kidney disease as in the elderly impacts the quality of life. Early management should help slow the functional limitation. Physical activity is the first therapy to propose that ensures stability of muscle mass and improved function. Resistance training programs have proven effective but are not yet widely available in nephrology units. The nutritional management should not be forgotten because there is a resistance to anabolism and protein intake should be involved in physical activity program. Associated treatments should not be neglected: vitamin D, anti-inflammatory, androgens. Some are still under evaluation. Therapeutic option, tomorrow, could be anti-myostatin antibodies and glitazones.

Chronic kidney disease (CKD) patients often exhibit a low muscle mass and strength, leading to physical impairment and an increased mortality. Two major signalling pathways control protein synthesis, the insulin-like growth factor-1/Akt (IGF-1/Akt) pathway, acting as a positive regulator, and the myostatin (Mstn) pathway, acting as a negative regulator. Mstn, also known as the growth development factor-8 (GDF-8), is a member of the transforming growth factor-β superfamily, which is secreted by mature muscle cells. Mstn inhibits satellite muscle cell proliferation and differentiation and induces a proteolytic phenotype of muscle cells by activating the ubiquitin–proteasome system. Recent advances have been made in the comprehension of the Mstn pathway disturbance and its role in muscle wasting during CKD. Most studies report higher Mstn concentrations in CKD and dialysis patients than in healthy subjects. Several factors increase Mstn production in uraemic conditions: low physical activity, chronic or acute inflammation and oxidative stress, uraemic toxins, angiotensin II, metabolic acidosis and glucocorticoids. Mstn seems to be only scarcely removed during haemodialysis or peritoneal dialysis, maybe because of its large molecule size in plasma where it is linked to its prodomain. In dialysis patients, Mstn has been proposed as a biomarker of muscle mass, muscle strength or physical performances, but more studies are needed in this field. This review outlines the interconnection between Mstn activation, muscle dysfunction and CKD. We discuss mechanisms of action and efficacy of pharmacological Mstn pathway inhibition that represents a promising treatment approach of striated muscle dysfunction. Many approaches and molecules are in development but until now, no study has proved a benefit in CKD.

Advanced glycation products are proteins whose structural and functional properties have been modified by a process of oxidative glycation. The accumulation of advanced glycation products in most tissues and the oxidative stress and inflammatory reactions that accompany it, account for the multi-systemic impairment observed particularly in the elderly, diabetics and in chronic renal failure. The advanced glycation products endogenous production is continuous, related to oxidative stress, but the most important source of advanced glycation products is exogenous, mainly of food origin. Exogenous advanced glycation products are developed during the preparation of food and beverages. The advanced glycation products content is higher for animal foods, but it is mainly the preparation and cooking methods that play a decisive role. Dietary advice is based on the selection of foods and the choice of methods of preparation. Several randomized controlled studies have confirmed the favorable effect of these recommendations on serum advanced glycation products concentrations. In humans, as in animals, regular physical activity also results in a reduction of serum and tissue concentrations of advanced glycation products. There is a need for prospective clinical study to confirm the effects of hygienic and dietary recommendations that have only been appreciated, so far, on biological markers.

Often underestimated or misunderstood in chronic renal failure (CRF), muscle wasting is nevertheless common and concerns about 50% of dialysis patients. The consequences of this myopathy on quality of life and outcomes of patients are unfavorable, identical to those observed in sarcopenia in elderly subjects with sarcopenia. The similarities between the two situations also concern the symptoms, the underlying muscle damages and the pathogenic mechanisms and may be partly explained by the frequently high age of ESRD patients. Skeletal muscle involvement should be systematically investigated in the IRC patient as in the elderly with sarcopenia to propose as early as possible a treatment of which physical activity and nutritional interventions are the mainstay.

While dietary restriction of protein intake has long been proposed as a possible kidney-protective treatment, the effects of changes in the quality of ingested proteins on the prevalence and risk of progression of chronic kidney disease (CKD) have been scarcely studied; these two aspects are reviewed in the present article. The prevalence of hypertension, type 2 diabetes and metabolic syndrome, which are the main causes of CKD in Western countries, is lower in vegetarian populations. Moreover, there is a negative relationship between several components of plant-based diets and numerous factors related to CKD progression such as uraemic toxins, inflammation, oxidative stress, metabolic acidosis, phosphate load and insulin resistance. In fact, results from different studies seem to confirm a kidney-protective effect of plant-based diets in the primary prevention of CKD and the secondary prevention of CKD progression. Various studies have determined the nutritional safety of plant-based diets in CKD patients, despite the combination of a more or less severe dietary protein restriction. As observed in the healthy population, this dietary pattern is associated with a reduced risk of all-cause mortality in CKD patients. We propose that plant-based diets should be included as part of the clinical recommendations for both the prevention and management of CKD.

International audience; Traditional dietary management of chronic kidney disease (CKD) focuses on the quantity within the diet of energy and protein, and the restriction of single micronutrients, with little mention of dietary quality. Dietary patterns that are more plant-based, lower in meat (including processed meat), sodium and refined sugar, and have a higher content of grains and fibres are now included in multiple clinical guidelines for chronic disease prevention. The Mediterranean diet (MD) has been associated with reduced cardiovascular disease incidence in both observational and interventional studies. A wealth of evidence links MD with other beneficial effects on chronic diseases such as diabetes, obesity or cognitive health. This review examines each constituent of the classical MD and evaluates their suitability for the management of patients with CKD. We also evaluate the potential hyperkalaemia risk of increasing fruit and vegetable intake. Overall, a decrease in net endogenous acid production and increase in fibre may lead to a better control of metabolic acidosis. This, together with other putative favourable effects of MD on endothelial function, inflammation, lipid profile and blood pressure, provide mechanistic pathways to explain the observed reduced renal function decline and improved survival in CKD patients adhering to an MD.

The acid production of endogenous origin depends mainly on the metabolism of the food and varies with the nature of these. Of the order of 1mEq/kg/day for contemporary food in industrialized countries, it is reduced by more than one third among vegetarians and close to neutrality among vegans. The dietary acid load is eliminated by the normal kidneys, thus maintaining the acid-base equilibrium. In the setting of CKD, it will overflow the capacities of the nephrons, generating a retention of H+ ions, promoting subclinical acidosis. This tissue retention of H+ ions was confirmed by direct techniques in animal models and indirect techniques in humans. The systemic retention of H+ ions and the accompanying compensatory mechanisms have negative consequences on bone tissue, skeletal muscle, cardiovascular risk and renal function. In the animal, the substitution of casein (acid) by soy (alkaline) prevents metabolic acidosis and slows the progression of renal insufficiency. In man, various prospective studies have confirmed that the risk of renal insufficiency was positively correlated with the dietary acid load. Conversely, bicarbonate supplementation and/or a diet enriched with fruits and vegetables, have a favorable effect on renal insufficiency, including in subjects with normal bicarbonate. These results lead to reconsider the K/DOQI recommendations to correct acidosis when the bicarbonate level falls below 22mEq/L, since tissue retention of H+ ions and its negative consequences appear at higher or even normal levels of bicarbonates.

Cohort studies, mainly US, show that vitamin D deficiency is more common in African-American population. Social and environmental factors play a role but the difference in skin color is essential. Despite low 25-hydroxyvitamin D concentrations, a lower risk of fragility or fracture exists in these populations. Vitamin D deficiency is a contributing factor in many chronic diseases. There is a relationship between vitamin D deficiencies, progression of chronic kidney disease and increased relative risk of mortality. If the ethnicity of patients is now taken into account to estimate renal function, probably specific recommendations for vitamin D deficiency are needed.

The changes in eating habits and decreased physical activity have been responsible for part of the high prevalence of chronic diseases such as hypertension or diabetes, currently observed in the so-called civilized societies. These diseases are less prevalent in previous civilizations and several decades of nutrition research have enabled better understanding of the eating habits of our ancestors, and have demonstrated the value of diet called "Mediterranean or Paleolithic". This review provides an update on the latest research. What dietary changes since the Paleolithic period, and finally how can we adapt our current diet? Several animal studies or human clinical demonstrate the value of historical research and nutrition.

The gradual loss of weight and function of muscle in patients with chronic kidney disease as in the elderly impacts the quality of life. Early management should help slow the functional limitation. Physical activity is the first therapy to propose that ensures stability of muscle mass and improved function. Resistance training programs have proven effective but are not yet widely available in nephrology units. The nutritional management should not be forgotten because there is a resistance to anabolism and protein intake should be involved in physical activity program. Associated treatments should not be neglected: vitamin D, anti-inflammatory, androgens. Some are still under evaluation. Therapeutic option, tomorrow, could be anti-myostatin antibodies and glitazones.

The risk of non-traumatic fractures is greatly increased in kidney disease patients and well demonstrated in dialysis patients. If osteoporosis plays a major role in the general population, in chronic kidney disease renal osteodystrophy is associated with neurological and muscular disorders, which probably worsen the risk. The decrease in physical activity is a factor contributing to the loss of bone mass and the initiation of a rehabilitation program improves the prognosis. Despite the association between chronic renal disease and sedentary lifestyle, the relationship between physical inactivity and bones in dialysis patients and the effect of increased activity programs, are not well documented in the literature.

Background: The consequences of a supplemented very-lowprotein diet remain a matter of debate with regard to patient outcome before or after the onset of renal replacement therapy. Objective: We evaluated the long-term clinical outcome during maintenance dialysis and/or transplantation in patients who previously received a supplemented very-low-protein diet. Design: We assessed the outcome of 203 patients who received a supplemented very-low-protein diet for .3 mo (inclusion period: 1985–2000) and started dialysis after a mean diet duration of 33.1 mo (4–230 mo). Results: The survival rate in the whole cohort was 79% and 63% at 5 and 10 y, respectively. One hundred two patients continued with chronic dialysis during the entire follow-up, and 101 patients were grafted at least once. Patient outcomes were similar to those of the French Dialysis Registry patients for the dialysis group and similar to the 865 patients who were transplanted in Bordeaux during the same period for the transplant group. There was no correlation between death rate and duration of diet. Conclusions: The lack of correlation between death rate and duration of diet and the moderate mortality rate observed during the first 10 y of renal replacement therapy confirm that a supplemented very-low-protein diet has no detrimental effect on the outcome of patients with chronic kidney disease who receive renal replacement therapy. Am J Clin Nutr 2009;90:969–74.

Insulin resistance is characterized by a lesser biological response to a standard level of insulin. Currently the most popular method used to quantify insulin resistance is the homeostasis model of assessment of insulin resistance (HOMA-IR). A state of insulin resistance is present from the early stages of chronic renal failure (CRF). Defects in glucose utilization observed during CRF concern both nonoxidative metabolism (storage in the form of glycogen) and oxidative metabolism. Resistance to the action of insulin during the CRF concerns traditionally peripheral tissues, particularly skeletal muscle. The mechanisms are multiple: retention of nitrogenous waste, metabolic acidosis, hypovitaminosis D or inflammation. The insulin resistance is associated with a disturbance of endothelial function and is involved in increased vascular risk and aggravates muscle metabolic disorders. Recent studies demonstrated a link between insulin resistance and progression of renal failure. Physical activity is known to improve insulin resistance status, the correction of metabolic abnormalities and attempts to reduce the inflammatory syndrome are potential targets of treatment. Thiazolidinedione have recently shown their interest, but in CRF the balance between risk and benefit remains to be evaluated.

Skeletal muscle is frequently impacted in uraemic patients with both mechanical and metabolic consequences. Muscle wasting, weakness and structural changes, fundamentally as atrophy of type II muscle fibers, but also insulin resistance are common and however readily overlooked. Beyond a negative effect on physical activity and quality of life, skeletal muscle loss was reported to be also a powerful and independent predictor of survival, at least partly in relation with insulin resistance. Muscle loss in uraemic patients appears to be multifactorial. Among the different mechanisms liable to contribute to muscle wasting vitamin D deficiency, which is present in 50–80 % of incident dialysis patients, is a well-known factor of reduction of muscle mass, strength, physical performance and of increased risk of falls.

Background Three-day food recall and normalized protein nitrogen appearance calculation from pre- and postdialysis plasma urea are the most commonly used techniques to assess nutritional intake, but a 7-day dietary recall is probably more accurate to approach dietary intake in clinical practice. Methods A total of 99 hemodialyzed patients from two units were analyzed in a 7-day dietary record with a large range of age and without having any signs of malnutrition. Dietary protein intake was estimated from the recall and calculated (normalized protein catabolic rate) from urea kinetic modeling. Calorie intake and quality and repartition of nutrients were estimated from diaries. Results Repartition of nutrients was close to that of a reference population except for a lower glucidic contribution (glucide 47%, lipid 36%, protein 16%). Normalized protein catabolic rate and dietary protein intake were well correlated (R2 = 0.4), but a large variability existed from day to day, according to age (older patients are less variable) and day of dialysis (long or short interval). Conclusion A large variation in alimentary intake exists from patient to patient and day to day. A 7-day evaluation of nutrient intake, dialysis adequacy, and nutritional parameters seems to be a good solution to guide dietetic counseling.

Often underestimated or misunderstood in chronic renal failure (CRF), muscle wasting is nevertheless common and concerns about 50% of dialysis patients. The consequences of this myopathy on quality of life and outcomes of patients are unfavorable, identical to those observed in sarcopenia in elderly subjects with sarcopenia. The similarities between the two situations also concern the symptoms, the underlying muscle damages and the pathogenic mechanisms and may be partly explained by the frequently high age of ESRD patients. Skeletal muscle involvement should be systematically investigated in the IRC patient as in the elderly with sarcopenia to propose as early as possible a treatment of which physical activity and nutritional interventions are the mainstay.

Background Thanks to advancements in immunosuppression, patients are living longer with kidney transplants, and nonimmunologic factors (particularly nutritional) have become a major source of morbidity and mortality after successful kidney transplantation (KTx). In this current study, we have prospectively assessed, in a cohort of kidney transplant recipients (KTR), the course of some nonimmunologic factors liable to hinder the long-term outcome of KTR. Methods Forty-four consecutive KTR with stable functioning grafts received dietary recommendations and were on the lowest effective dose of steroids. Biochemical nutritional markers, C-reactive protein, lipid profile, and body composition determined by dual-energy X-ray absorptiometry were studied over the first year, 2 years, and 5 years after KTx. Results No patients died during the follow-up. All patients but 2 were considered normotensive. Clinical diabetes developed in 3 patients. Visceral proteins stabilized at a normal range after the first year. Most of the patients normalized their inflammatory status. A significant improvement in lipid profile was observed. Female patients had a significant increase of weight (13.5%), mainly because of an increase in fat mass: 3.4 kg (19.4%) at 1 year and 5.6 kg (29.7%) at 2 years. In male patients, body composition remained stable and close to baseline values. The evolution of bone mass varied according to gender, total corticoid doses, and calcineurin inhibitors. Patients on low doses of steroids normalized their Z-score over the 5-year period. The increase in bone mass (paired t-test, P = .006) was only significant in patients treated with tacrolimus (analysis of variance for repeated measures, P Conclusions Simple measures and dietary intervention to prevent or correct nonimmunologic disorders should permit improvement of long-term morbidity and mortality of KTR without compromising the functional outcome of their transplant.

Leptin is a 16-kd protein that is thought to be a regulator of food intake and body weight. Many previous studies have reported elevated serum leptin levels in renal failure. In this study, we investigated the outcome of serum leptin and its relationship to body fat (BF), dietary intake, nutritional, and inflammatory markers after kidney transplantation (KTx). A total of 41 kidney transplant recipients were followed-up prospectively during 6 months posttransplantation. Serum leptin, albumin, transferrin, and C-reactive protein (CRP) were measured at KTx, 15 days, 3, and 6 months later. Dietary intake and BF were determined at KTx, 3, and 6 months later. A decrease in serum leptin was observed early at day 15 after KTx; this decrease was significant only in patients with BF/= 30% of body weight. The decrease was maintained at 3 and 6 months after KTx. In multivariate analysis, an independent impact of higher percentage BF at KTx on the decrease of serum leptin was observed. Serum leptin correlated positively with BF. Conversely, no correlation was found between changes of serum leptin and changes of dietary intake. Leptin correlated positively with CRP at KTx, but not after normalization of renal function. Changes of serum leptin levels were not correlated with those of serum albumin levels. In summary, hyperleptinemia at KTx is manifest in patients with a high percentage of BF. An early and maintained correction follows KTx. Serum leptin levels did not appear to affect alimentary intake at and after KTx.

Resume Le metabolisme proteique est affecte par l’insuffisance renale chronique, quel que soit le stade de celle-ci ou ses modalites de traitement substitutif, hemodialyse, dialyse peritoneale ou transplantation renale. Plus que l’insuffisance renale par elle-meme, ce sont les conditions qui lui sont associees, en premier lieu l’inflammation chronique, l’acidose metabolique et l’insulinoresistance peripherique qui entrainent des phenomenes responsables de catabolisme proteique. Les parametres nutritionnels proteiques sont frequemment affectes chez l’insuffisant renal, avec des consequences deleteres en termes de morbidite et mortalite. La correction de ces anomalies doit permettre le maintien d’un etat nutritionnel satisfaisant, et un meilleur devenir clinique des insuffisants renaux.

Background: It has been reported that patients on a very-low-protein diet (VLPD) maintain a satisfactory nutritional status because of a conserved adaptive metabolic response. However, only few studies have examined the course of nutritional status and body composition in the long term (2 years). Methods: Thirteen stable patients (8 men; age, 55 ± 12 years; glomerular filtration rate (GFR), 15 ± 5 mL/min) receiving a VLPD (0.3 g/kg/day protein) supplemented with amino acids and ketoanalogues (SVLPD) were studied for 2 years. A joint visit with a physician and a dietitian and routine blood and urine analyses were performed every month. Dual-energy x-ray absorptiometry (DEXA), which was used to assess modification of body composition, and GFR (urinary 51 Cr-EDTA) and urinary urea and creatinine excretion, which were used to assess nutritional status and compliance to the diet, were assessed every 3 months. Results: GFR, albumin, and prealbumin levels remained stable. Urea urinary excretion decreased at 3 months and then slightly increased at 2 years, but the calculated protein intake remained low at 0.38 ± 0.1 g/kg/day. Energy intake remained close to 30 kcal/kg/day. No significant change was observed for total fat mass or percent fat mass. After an initial decrease, lean body mass stabilized at 6 months and then increased significantly from 6 to 24 months ( P = .02, paired t -test); the mean increase during this period was of 2 kg, that is, 4.6%. Urinary creatinine excretion showed the same profile. Total bone mass, lumbar or hip site bone mass, and Z-score significantly decreased from T0 to 1 and 2 years ( P Conclusion: This study confirms that a supplemented VLPD is nutritionally safe for a long period, but attention must be paid to bone mass.

Nutrition in hemodialysis patients previously on a supplemented very low protein diet.BackgroundNutritional safety of protein-restricted diets in patients with chronic renal failure is controversial. In the present study, we have assessed the evolution of nutritional status after initiation of hemodialysis in patients previously treated by a supplemented very low protein diet (SVLPD).MethodsNutritional data were prospectively collected during the first year of hemodialysis from 15 consecutive patients treated with a SVLPD (0.3 g protein/kg/day supplemented with essential amino acids, calcium, iron, and vitamins) and compared to 15 age- and gender-matched end-stage renal disease (ESRD) patients previously on a less-restricted diet (0.90 ± 0.21 g protein/kg/day) who started hemodialysis during the same period. Dual-energy x-ray absorptiometry (DEXA) was used to assess body composition at 0, 6, and 12 months. Hemodialysis prescriptions, biologic data and 3-day food records were collected every 3 months.ResultsProtein intake was higher than 1.2 g/kg/day in both groups as soon as 3 months after the start of hemodialysis. Albumin and prealbumin increased significantly during the first 6 months in all patients. Body mass index (BMI) increased in all patients (+0.97 ± 1.31 kg/m2; P < 0.001) reflecting a gain in fat mass in the overall population (+2.36 ± 2.94 kg/m2; P < 0.001) while lean body mass remained stable overall.ConclusionOnce on hemodialysis, SVLPD patients rapidly increased protein intake. Nutritional status improved in all patients, with a gain in fat mass in all, and a gain in lean body mass in SVLPD men only. These data indicate that treatment with a SVLPD prior to hemodialysis initiation is nutritionally safe.

Resume Introduction. – La gemcitabine est un analogue nucleosidique utilise dans les tumeurs solides depuis 1987. Sa toxicite principale est hematologique. Elle peut aussi etre responsable dˈinsuffisance renale aigue par microangiopathie thrombotique. Nous rapportons un nouveau cas et suggerons une possibilite de depistage precoce. Exegese. – Un patient âge de 71 ans traite au long cours par gemcitabine pour un adenocarcinome pancreatique metastatique a presente plusieurs poussees dˈhemolyse a bas bruit precedant un syndrome hemolytique et uremique avec insuffisance renale aigue qui a necessite une seance dˈhemodialyse. Lˈenquete etiologique etait negative et la responsabilite de la gemcitabine a ete etablie. La gemcitabine est une nouvelle cause de microangiopathie thrombotique. Cette toxicite est cumulative, survient preferentiellement sur un rein fragilise et le diagnostic est souvent retarde. Le traitement doit etre interrompu definitivement. Conclusion. – La surveillance de la reticulocytose, de lˈhaptoglobine serique et du sediment urinaire pourrait permettre un depistage precoce de cet effet indesirable meconnu et sous-declare.

In a cross-sectional study of more than 30% of French dialysis patients (N = 7,123), we evaluated the relationships between predialysis plasma bicarbonate concentration and nutritional markers. Data including age, gender, cause of end-stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were collected. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) were computed from pre- and postbicarbonate-dialysis urea and creatinine levels according to the classical formulas of Garred. Average values (+/- 1 SD) were age 61 +/- 16 years, BMI 23.3 +/- 4.6 kg/m2, dialysis time 12.4 +/- 2.7 h/week, HCO3 22.8 +/- 3.5 mmol/L, albumin 38.7 +/- 5.3 g/L, prealbumin 340 +/- 90 mg/L, Kt/V 1.36 +/- 0.36, nPCR 1.13 +/- 0.32 g/kg BW/day, and LBM 0.86 +/- 0.21% of ideal LBM. A highly significant negative correlation was observed between predialysis bicarbonate levels (within a range of 16-30 mmol/L, 95% of this population) and nPCR confirmed by analysis of variance using bicarbonate classes (p < 0.0001). Bicarbonate was also negatively correlated with albumin, prealbumin, BMI, and LBM. No relationship was noted between bicarbonate and Kt/V despite a positive correlation between Kt/V and nPCR. It is likely that a persistent acidosis observed despite standard bicarbonate dialysis was caused by a high dietary protein intake which results in an increased acid load, but also overcomes the usual catabolic effects of acidosis.

We have previously shown that a ketoacid-supplemented very-low-protein diet (KSVLPD), which has been proposed to slow down the rate of progression of chronic renal failure (CRF), improves tissue insulin sensitivity and decreases hyperinsulinemia in predialytic uremic patients. However, this diet may interfere with nutritional status. The aim of this study was to study basal energy expenditure (EE) and EE after an oral glucose load in patients with CRF before and during a KSVLPD (0.3 cal x kg wt(-1) x d(-1) supplemented with aminoacid and ketoanalogs) using oral glucose loading in combination with indirect calorimetry. We also monitored body weight and analyzed body composition by dual-energy x-ray (DEXA) during KSVLPD. In the third month of KSVLPD, no significant change in total body weight was observed, but DEXA showed a decrease in lean tissue mass (LTM; 46.2 +/- 3.6 kg before v 44 +/- 3.4 kg in the third month; P.01) and an increase in body fat mass (20.1 +/- 2.4 kg before v 21.3 +/- 2.4 kg on KSVLPD; P.05). Postabsorptive plasma glucose level was significantly lower, and glucose oxidation and energy expenditure per LTM were significantly increased (EE, 20 +/- 0.8 cal x kg LTM(-1) x min(-1) before diet v 21.9 +/- 1.1 cal x kg LTM(-1) x min(-1) after 3 months on KSVLPD; P.01). Plasma glucose and serum insulin levels were significantly lower after glucose loading, and glucose oxidation increased. EE values were significantly higher after the oral glucose load, and cumulative EE after oral load increased from 20.7 +/- 0.7 cal x kg LTM(-1) x min(-1) before the diet to 22.9 +/- 1.1 cal x kg LTM(-1) x min(-1) in the third month of KSVLPD; P.001). Glucose oxidation was higher and cumulative glucose storage was decreased after diet (29.6 +/- 4.2 g v 20.9 +/- 3.4 g on KSVLPD; P.01). We conclude that KSVLPD increases EE in the postabsorptive state and after an oral glucose load with an adaptation of lean tissue mass in the third month of the diet. Therefore, during KSVLPD, strict monitoring of dietetic management is necessary to maintain energy requirements at high levels appropriate to the new EE.

Chronic renal failure (CRF) is often accompanied by hyperleptinemia caused by deficient renal metabolism of leptin and possibly increased leptin production, which in turn may result from the hyperinsulinemia and increased proinflammatory cytokine levels in patients with CRF. The hyperinsulinemia and insulin resistance observed in patients with CRF improve on supplemented very low protein diets (SVLPDs). The goal of our study is to determine whether the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is accompanied by improvement in hyperleptinemia. Thirteen patients were studied before and 1 year after following SVLPDs providing 0.3 g/kg/d of protein, supplemented with amino acids and ketoanalogues. After 1 year, patients showed markedly less hyperinsulinemia (7.4 +/- 1.6 versus 13.8 +/- 2 microU/mL at the start of diet; P: = 0.05) and insulin resistance, whereas serum leptin levels remained unchanged (16.1 +/- 4.7 versus 19.1 +/- 7.4 ng/mL at start of the study; P: = not significant). The initial correlation between serum leptin level and percentage of body fat persisted during follow-up. No correlation was found between insulin and leptin levels or between the variation of these two parameters during the study. Our study shows that the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is not accompanied by improvement in hyperleptinemia, which consequently does not appear to result from changes in carbohydrate metabolism.

Reduced parathyroid functional mass after successful kidney transplantation.BackgroundChronic uremia is responsible for secondary hyperparathyroidism (HPT II). Parathyroid secretion usually tends to normalize after kidney transplantation (KT), but the parameters of the reversibility of HPT II remain poorly defined, particularly the intrinsic mechanisms underlying the improvement of parathyroid function.MethodsThe kinetic functional parameters of the ionized calcium (iCa)/parathormone (PTH) relationship curve were studied in 11 patients with mild to moderate HPT II one and six months after successful KT. Hypercalcemia and hypocalcemia were induced, respectively, by CaCl2 and Na2-ethylenediaminetetraacetic acid (Na2-EDTA) infusions.ResultsThe mean glomerular filtration rate remained stable during follow-up. Basal PTH decreased from 195 ± 54 pg/ml before KT to 70 ± 12 pg/ml six months later (P < 0.005). During the tests, mean PTH levels decreased significantly between the two measured times for all iCa levels, indicating an improved parathyroid function. An analysis of the kinetic parameters of the curves showed significant decreases of the mean maximal and minimal PTH levels, respectively, from 340 ± 91 to 220 ± 30 pg/ml (P = 0.03) and from 25 ± 6 to 15 ± 5 pg/ml (P = 0.005). On the other hand, no change was noted in the parathyroid-cell calcium-sensitivity parameters (slope, set point) assessed using two different approaches, either the entire curve or the limited calcium-mediated suppression curve.ConclusionImprovement of the parathyroid function between the first and sixth months post-KT seems mainly attributable to a reduction of the parathyroid functional mass.

Background. Despite the severity and the prognosis value of undernutrition in haemodialysed patients, no large study is available as yet in Europe. Hence, this French National Cooperative Study aimed to determine the prevalence of undernutrition and its relationship to dialysis efficacy. Methods. Nutritional status was determined in 7123 patients (i.e. one-third of the French haemodialysis population) using body mass index (BMI), predialysis haemoglobin, albumin, pre-albumin, cholesterol, and also normalized protein catabolic rate (nPCR) and lean body mass (LBM) calculated from pre- and postdialysis urea and creatinine. Dialysis treatment was estimated from weekly dialysis time and KtV determination. Results. Dialysis time was 12.4±2.7 h/week and KtV 1.36±0.36. BMI was below 20 kg/m 2 in 24% and the observed/expected LBM ratio below 90% in 62%. Albumin, pre-albumin and nPCR were below the high-risk thresholds of 35 g/l, 300 mg/l and lg/kg/day in 20%, 36% and 35% of patients, respectively. Pre-albumin was the most representative nutritional parameter. Albumin, pre-albumin and LBM correlated with nPCR. A dialysis time above 12 h/week was associated with higher BMI, albumin, pre-albumin and LBM. LBM was higher in patients with a KtV value > 1.1. Conclusion. This study showed life-threatening undernutrition in 20-36% of the studied population, according to nutritional parameters. Protein intake (estimated by nPCR) and dialysis efficacy (estimated by dialysis time and KtV) appeared to be major determinants of nutritional status in this population.

OBJECTIVE We investigated whether loss of bone is detectable during follow-up of diabetic patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS In 40 initially non-dialysed diabetic patients with CKD (isotopic glomerular filtration rate 30 mg/24 h), body composition (DEXA scan) and glomerular filtration rate (GFR determined from (51)Cr-EDTA clearance) were measured at a 2-year interval, and compared by paired t-tests. RESULTS The 40 patients, mainly with Type 2 diabetes (n = 28), were men (n = 28), aged 65 +/- 11 years, with diabetes duration 18 +/- 11 years. GFR was initially 38.0 (range 8-89) ml/min/1.73 m(2). CKD progressed during follow-up: eight started haemodialysis and GFR declined in the 32 others (P < 0.05 vs. initial). T-scores for total body (initial -0.61 +/- 1.11, final -1.11 +/- 1.40; P < 0.001) and femoral neck (initial -1.88 +/- 0.15, final -2.07 +/- 0.15; P < 0.05) declined. Ten patients were osteopaenic at baseline (no osteoporosis), whereas most were osteopaenic (n = 21, P < 0.05) and five were osteoporotic at final assessment. The 16 patients who became osteopaenic or osteoporotic during follow-up did not differ from the others for the type of diabetes, age, GFR, albumin excretion rate, HbA(1c), GFR reduction and the requirement for dialysis during follow-up. They were all men (P < 0.01 by chi-squared test), with reduced initial total body T-score (-1.20 +/- 0.82, others -0.32 +/- 1.13; P < 0.05) and a lower body mass index (24.6 +/- 4.3; others 27.7 +/- 4.3; P < 0.05). CONCLUSION Bone loss, especially in the femoral neck, is progressive in diabetic patients with CKD.

Resume Une denutrition proteino-calorique n'est pas exceptionnelle a un stade evolue de l'IRC, elle conditionnera la morbidite et la mortalite des premiers mois du traitement dialytique. La diminution de l'apport energetico-protidique qui accompagne la progression de l'IRC est en rapport avec la retention de molecules anorexigenes et constitue le principal facteur de denutrition auquel s'associent l'acidose metabolique, facteur d'hypercatabolisme, et des anomalies portant sur le metabolisme des principaux nutriments. L'apport proteique et energetique doit etre regulierement surveille, la persistance de troubles nutritionnels malgre le suivi medical et dietetique doit faire commencer sans tarder le traitement dialytique.

A low-protein, low-phosphorus diet (LPD) has been shown to improve insulin sensitivity in uremic patients; however, this improvement has not been studied at low physiologic concentrations of plasma insulin, and the metabolic pathways concerned with this improvement have not been located. We used the glucose clamp technique at a low (0.25 mU kg -1 . min -1 ) level of hyperinsulinemia associated with the infusion of D[6,6- 2 H 2 ] glucose to assess the insulin sensitivity of endogenous glucose production (EGP). Eight nondialyzed uremic patients were studied before and after 3 mo on an LPD providing 0.3 g/kg protein, 5-7 mg P/kg, and 146 kJ/kg (67% of energy as carbohydrates and 30% as lipids) per day, supplemented with ketoanalog amino acids. Postabsorptive plasma glucose and insulin declined after 3 mo of the diet (plasma glucose: 5.0 ± 0.1 mmol/L before compared with 4.7 ± 0.1 mmol/L after the LPD, P < 0.05; plasma insulin: 82.4 ± 20.7 pmol/L before compared with 48.8 ± 6.0 pmol/L after, P < 0.05). Postabsorptive glucose turnover rates did not change with the diet (2.06 ± 0.14 mg. kg -1 . min -1 before compared with 2.11 ± 0.17 mg. kg -1 . min -1 after LPD; NS). The insulin metabolic clearance rate was enhanced after the diet, so a lower level of hyperinsulinemia was obtained during the clamp (168.8 ± 28.1 pmol/L before compared with 115.2 ± 14.7 pmoVL after; P < 0.05). However, EGP was more easily inhibited after the diet (0.90 ± 0.31 mg. kg -1 . min -1 before compared with 0.30 ± 0.17 mg.kg -1 .min -1 after; P < 0.05), providing evidence of an improved insulin sensitivity of this parameter. This beneficial influence takes place at a physiologic level of hyperinsulinemia, and it probably plays an important role in the better glucose tolerance that has been reported in uremic patients on an LPD. An abnormal insulin sensitivity of EGP may participate in the disturbances of glucose metabolism in chronic renal failure.

Low protein diet in uremia: Effects on glucose metabolism and energy production rate. Low-protein diets (LPD) increase insulin-mediated glucose disposal in chronic renal failure (CRF), but the fate of the better utilized glucose and the effect on energy production rate are unknown. Using a two-step (1 and 5mU · kg−1 · min−1) euglycemic hyperinsulinemic clamp combined with indirect calorimetry, we studied the effects of a LPD (0.3g · kg−1 · day−1, supplemented with essential amino acids and ketoanalogs) in six patients suffering from chronic renal failure. After three months of diet, no significant change was observed concerning glomerular filtration rate, body wt, or arterial pH. In the postabsorptive state, plasma glucose and insulin levels were significantly lower, and energy production rose from 15.72 ± 0.48 to 17.16 ± 0.67Cal · kg−1 · min−1 (P < 0.05). Insulin-stimulated glucose oxidation (2.36 ± 0.29 vs. 3.37 ± 0.35mg · kg−1 · min−1; P < 0.05 at first clamp step) and nonoxidative disposal (P < 0.05 at both clamp steps) increased after LPD. This confirms that LPD ameliorates insulin sensitivity in CRF, even for low plasma insulin concentrations. Since energy production rate is increased by LPD, the caloric intake should be increased when protein intake is restricted.

Increased peroxidation of lipids in red blood cells (RBC) in patients with advanced chronic renal failure (CRF) reflects increased generation of reactive oxygen species (ROS), which may contribute to the metabolic damage induced by CRF and to its progression. We have evaluated parameters indicative of lipoperoxidation (LPO) of RBC at baseline in patients with CRF compared to controls, and the effects of a very low protein diet supplemented with amino and keto acids and vitamins A, C, E (VLPD) over a 6-month period. The presence of peroxidation damage in CRF patients before the administration VLPD was demonstrated by elevated levels of free malondialdehyde (MDA) (p.0003) and decreased levels of polyunsaturated fatty acids (PUFA), particularly C20:4 (p.001), C22:4 (p.0001) and C22:5 (p.0001) when compared to controls. Similarly, RBC vitamin E content was significantly decreased (p.0001) while enzymatic activities were unalterated. VLPD reduced erythrocyte LPO as suggested by (a) decreased levels of free and total RBC MDA (p.003 and p.03, respectively), (b) increased levels of PUFA, particularly C22:4 and C22:5 (p.003 and p.03, respectively), and (c) increased levels of vitamins A and E (p.001 and p.04, respectively) as compared to prediet results. Antioxidant enzyme activities were not modified. These results suggest that VLPD has a protective role against LPO of erythrocytes in patients with CRF.

Early versus later start of dialysis is still a matter of debate. Low-protein diets have been used for many decades to delay dialysis initiation. Protein-restricted diets (0.3-0.6 g protein/kg/day) supplemented with essential amino acids and ketoanalogues (sVLPD) can be offered, in association with pharmacological treatment, to motivated stage 4-5 chronic kidney disease (CKD) patients not having severe comorbid conditions; they probably represent 30-40% of the concerned population. A satisfactory adherence to such dietary prescription is observed in approximately 50% of the patients. While the results of the studies on the effects of this diet on the rate of progression of renal failure remain inconclusive, they are highly significant when initiation of dialysis is the primary outcome. The correction of uremic symptoms allows for initiation of dialysis treatment at a level of residual renal function lower than that usually recommended. Most of the CKD-associated complications of cardiovascular and metabolic origin, which hamper both lifespan and quality of life, are positively influenced by the diet. Lastly, with regular monitoring jointly assumed by physicians and dietitians, nutritional status is well preserved as confirmed by a very low mortality rate and by the absence of detrimental effect on the long-term outcome of patients once renal replacement therapy is initiated. On account of its feasibility, efficacy and safety, sVLPD deserves a place in the management of selected patients to safely delay the time needed for dialysis.

Vegetarian diet is a very old practice that is liable to confer some health benefits. Recent studies have demonstrated that modification of the dietary pattern with a reduction of animal protein intake and increased consumption of plant-based foods could influence cardiovascular risk profile and mortality rate. Moreover, phosphate bioavailability from plant proteins is reduced. These statements could lead to some benefits for chronic kidney disease (CKD) patients. This review summarizes the characteristics and benefits of vegetarian diets in the general population and the potential beneficial effects of such a diet on phosphate balance, insulin sensitivity, and the control of metabolic acidosis in CKD patients. Potential drawbacks exist when a vegetarian diet is associated with protein intake that is too restrictive and/or insufficient energy intake, justifying an early and regular nutritional follow-up jointly assumed by a nephrologist and a renal dietitian.

R'esume Quarante cas de purpura rhumatoide de l'adulte (21 femmes, 19 hommes, d'âge moyen: 39 ans) sont etudies, issus d'un service de nephrologie (28 cas) et de medecine interne ( 12 cas). Les signes cutanes sont quasi constants (39 cas), sans particularite clinique ou histologique par rapport a ceux de l'enfant. Les manifestations digestives (23 cas) sont essentiellement des douleurs abdominales et des troubles du transit, les hemorragies restant rares. Elles sont, dans cette serie comme dans la litterature, moins graves que chez l'enfant. L'atteinte articulaire (22 cas)evolue parallelement au purpura et guerit sans sequelle. Le pronostic de l'affection est finalement le fait de l'atteinte renale, objectivee chez 33 de nos patients (82.5 %). Cette frequence elevee s'explique probablement par l'importance du recrutement nephrologique. Dans un tiers des cas elle est decouverte tardivement (jusqu'a 24 mois) ce qui souligne la necessite d'un suivi prolonge de ces patients. Comme chez l'enfant, l'hematurie et la proteinurie sont quasi constantes. La biopsie renale montre dans 58 % des cas une glomerulonephrite proliferative segmentaire et focale, avec depots mesangiaux d'igA 16 fois sur 21. En dehors du repos toujours preconise, le traitement est constitue par la corticotherapie seule dix fois, les corticoides et les immunosuppresseurs huit fois, l'association corticoides-immunosuppresseurs-plasmaphereses deux fois, la dapsone une fois. L'evolution de la nephropathie est connue chez 26 patients suivis en moyenne 37 mois: 11 guerissent completement, sept gardent des anomalies du sediment urinaire sans insuffisance renale, et huit developpent une insuffisance renale chronique terminale en 3 mois a 13 ans. Les facteurs de mauvais pronostic, dans notre serie, sont l'insuffisance renale initiale, l'HTA, et le jeune âge. Cette evolution pejorative peut s'expliquer par l'importance du recrutement nephrologique. Elle contraste avec le caractere aigu de l'affection chez l'enfant.

Cohort studies, mainly US, show that vitamin D deficiency is more common in African-American population. Social and environmental factors play a role but the difference in skin color is essential. Despite low 25-hydroxyvitamin D concentrations, a lower risk of fragility or fracture exists in these populations. Vitamin D deficiency is a contributing factor in many chronic diseases. There is a relationship between vitamin D deficiencies, progression of chronic kidney disease and increased relative risk of mortality. If the ethnicity of patients is now taken into account to estimate renal function, probably specific recommendations for vitamin D deficiency are needed.

The changes in eating habits and decreased physical activity have been responsible for part of the high prevalence of chronic diseases such as hypertension or diabetes, currently observed in the so-called civilized societies. These diseases are less prevalent in previous civilizations and several decades of nutrition research have enabled better understanding of the eating habits of our ancestors, and have demonstrated the value of diet called "Mediterranean or Paleolithic". This review provides an update on the latest research. What dietary changes since the Paleolithic period, and finally how can we adapt our current diet? Several animal studies or human clinical demonstrate the value of historical research and nutrition.

*Department of Nephrology, Centre Hospitalier Universitaire et Universitea Bordeaux II, Bordeaux, France.†Nephrology Dialysis and Renal Transplantation Unit, University Hospital ‘‘S. Giovanni di Dio e Ruggi d’Aragona’’, Salerno, Italy.‡Department of Nephrology, Hopital Pellegrin, Bordeaux, France.§Aurad-Aquitaine, Gradignan, France.{Nephrology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy.**Division of Nephrology, Department of Internal Medicine, Istanbul School of Medicine, Istanbul University, Capa, Istanbul, Turkey.††Departement de Nephrologie, H^opital E. Herriot, Lyon Cedex, France.‡‡‘‘Dr. Carol Davila’’ Teaching Hospital of Nephrology, Bucharest, Romania.§§Chinese Society of Nephrology, International Society of Nephrology, and Division of Nephrology, Huashan Hospital, Fudan University,Shanghai, People’s Republic of China.{{Division of Nephrology, Baylor College of Medicine, Houston, Texas.***Department of Nephrology, Institute for Clinical and Experimental Medicine and Institute for Postgradual Education, Prague, CzechRepublic.‡‡‡Dialysis Center No. 9, Health Care Service PLC, Euro Care Hungary, Szekesfehervar, Hungary.§§§The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China.FinancialDisclosure:TheauthorsbelongtotheFreseniusKabiKetoanalogueAdvisoryBoardandparticipatedinthe5thInternationalAdvisoryBoardMeeting,Vevey,Switzerland,May29,2010.ConsultancyfeesandtravelgrantswerereceivedfromFreseniusKabi.Thearticleswerepub-lished as part of a supplement sponsored by an unrestricted educational grant from Fresenius Kabi.AddressreprintrequeststoPhilippeChauveau,ServicedeNephrologie,HopitalPellegrin,CHUdeBordeaux,PlaceAmelieRabaLeon,33000,Bordeaux, France.

Hemodialysis with complement-activating membranes, such as cuprophane, induces neutropenia and expression of the granulocyte adhesion receptor Mac-1 (CD11b/CD18), while hemodialysis with noncomplement-activating membranes does not. Increased expression of CD11b by neutrophils may mediate cuprophane-induced leukopenia. However, the rebound granulocytosis that follows leukopenia is not fully understood. Ten patients on regular hemodialysis were included in a cross-over study. Hemodialysis was performed for 2 weeks with cuprophane and 2 weeks with polyamide, a high-flux noncomplement-activating membrane. At the end of each period, the following parameters were determined during a hemodialysis session: C5a concentration by enzyme immunoassay and the neutrophil expression of CD11b, LFA-1 (CD11a/CD18), and the antigen recognized by MoF11 (MoF11 Ag), a monoclonal antibody that recognizes activated neutrophils, by immunofluorescence flow cytometry. Hemodialysis with cuprophane induced an increase in C5a concentration and in the expression of CD11b and MoF11 Ag, which were maximal after 15 minutes of hemodialysis, at the nadir of neutropenia. CD11 b expression was maintained throughout hemodialysis, despite the reversal of neutropenia. Conversely, after peak expression, C5a and MoF11 Ag decreased as the neutrophil count increased to baseline values. Polyamide hemodialysis did not induce variations in C5a concentration, nor in CD11 b and MoF11 Ag expression. CD11a/CD18 expression remained stable during hemodialysis with both membrane types. Neutrophil activation, as determined by MoF11 Ag expression, was correlated with the evolution of neutrophil count and C5a concentration during cuprophane hemodialysis, while CD11 b expression was not correlated with neutrophil count throughout dialysis. A decrease in neutrophil activation could explain in part the detachment of neutrophils previously bound to endothelium and, therefore, the reversal of neutropenia. Hemodialysis with polyamide did not induce variations in either C5a levels, neutrophil count, or neutrophil membrane expression of CD11b and MoF11 Ag.

Actinobacillus actinomycetemcomitans (Aa) is a fastidious Gram-negative coccobacillus that belongs to the HACEK group w1x. It grows slowly and optimally at 378C as small colonies on blood or chocolate agar, and blood cultures need to be incubated in CO2 and maintained for 2–3 weeks. These characteristics of Aa may retard the diagnosis. Aa is well known as the causative agent of localized juvenile periodontal disease, but the most common severe infections caused by Aa are endocarditis and soft-tissue abscesses w1x. Less common are Aa brain abscesses, pneumonia, osteomyelitis and urinary tract infections. We describe a patient who developed Aa septicaemia mimicking c-ANCA (cytoplasm-labelling anti-neutrophil cytoplasm antibodies)-positive small-vessel vasculitis with kidney and nerve damage.

Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction.

The risk of non-traumatic fractures is greatly increased in kidney disease patients and well demonstrated in dialysis patients. If osteoporosis plays a major role in the general population, in chronic kidney disease renal osteodystrophy is associated with neurological and muscular disorders, which probably worsen the risk. The decrease in physical activity is a factor contributing to the loss of bone mass and the initiation of a rehabilitation program improves the prognosis. Despite the association between chronic renal disease and sedentary lifestyle, the relationship between physical inactivity and bones in dialysis patients and the effect of increased activity programs, are not well documented in the literature.

The efficacy and safety of protein-restricted diets in chronic kidney disease (CKD) is still a matter of debate. However, several studies have clearly demonstrated the beneficial effects of such diets on the outcome of patients with stage 3-4 CKD. This point has been confirmed by 4 recent studies. In 2009, a meta-analysis showed that protein restriction significantly delayed the time to renal death with a substantial economic benefit for the health service. Although toxicity of urea has since long been considered as negligible, an experimental model in rats has shown a direct role of urea in the development of oxidative stress and insulin resistance, which are among the leading mechanisms of cardiovascular complications in CKD. These latter results confirm an interest in studying reduction in blood urea levels as observed in patients kept on a low-protein diet (LPD) or on a supplemented very-low protein diet (SVLPD). A reduction in proteinuria, which is associated to a LPD, has the following prognostic value: the more important the reduction in proteinuria, slower is the decline in renal function. This effect, which is additive to the one of an angiotensin-converting enzyme inhibitor (ACEI), is higher with SVLPD than with conventional LPD. Safety of a reduced protein intake has been confirmed by the study on the long-term outcomes (11 years) of patients already on SVLPD. The difference between these results and those from the extended follow-up of the modification of diet in renal disease (MDRD) study, in which no recommendations were made after the completion of the trial, confirms the importance of a close nutritional survey of patients with CKD who are put on a protein-restricted diet.