Fitsum Guebre-Egziabher

Body mass index, muscle and fat in chronic kidney disease: questions about survival

The human body can be roughly divided into two major compartments, fat mass and lean body mass. Adipose tissue is now considered to be a highly active tissue and, in addition to storing calories as triglycerides, it also secretes a large variety of compounds, including cytokines, chemokines and hormone-like factors such as leptin, adiponectin and resistin. On the other hand, muscle plays a central role in whole-body protein metabolism by serving as the principal provider for amino acids to maintain protein synthesis in vital tissues and organs and by providing hepatic gluconeogenic precursors. Although not a good indicator of body composition, the Quetelet index, also called body mass index (BMI), is often used for practical reasons. It is well known that high BMI predicts mortality and cardiovascular disease (CVD) in the general population. However, observational reports in the dialysis population have suggested that obesity is associated with improved survival, a phenomenon that is not well understood and subject to controversies. This review describes the characteristics of BMI in the general population and in chronic kidney disease (CKD) patients, as well as the respective role of muscle, whole body fat and fat distribution towards mortality, with particular emphasis on patients with CKD.

Accuracy of GFR Estimation in Obese Patients

BACKGROUND AND OBJECTIVES Adequate estimation of renal function in obese patients is essential for the classification of patients in CKD category as well as the dose adjustment of drugs. However, the body size descriptor for GFR indexation is still debatable, and formulas are not validated in patients with extreme variations of weight. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study included 209 stages 1-5 CKD obese patients referred to the Department of Renal Function Study at the University Hospital in Lyon between 2010 and 2013 because of suspected renal dysfunction. GFR was estimated with the Chronic Kidney Disease and Epidemiology equation (CKD-EPI) and measured with a gold standard method (inulin or iohexol) not indexed (mGFR) or indexed to body surface area determined by the Dubois and Dubois formula with either real (mGFRr) or ideal (mGFRi) body weight. Mean bias (eGFR-mGFR), precision, and accuracy of mGFR were compared with the results obtained for nonobese participants (body mass index between 18.5 and 24.9) who had a GFR measurement during the same period of time. RESULTS Mean mGFRr (51.6 ± 24.2 ml/min per 1.73 m(2)) was significantly lower than mGFR, mGFRi, and eGFRCKD-EPI. eGFRCKD-EPI had less bias with mGFR (0.29; -1.7 to 2.3) and mGFRi (-1.62; -3.1 to 0.45) compared with mGFRr (8.7; 7 to 10). This result was confirmed with better accuracy for the whole cohort (78% for mGFR, 84% for mGFRi, and 72% for mGFRr) and participants with CKD stages 3-5. Moreover, the Bland Altman plot showed better agreement between mGFR and eGFRCKD-EPI. The bias between eGFRCKD-EPI and mGFRr was greater in obese than nonobese participants (8.7 versus 0.58, P<0.001). CONCLUSIONS This study shows that, in obese CKD patients, the performance of eGFRCKD-EPI is good for GFR ≤ 60 ml/min per 1.73 m(2). Indexation of mGFR with body surface area using ideal body weight gives less bias than mGFR scaled with body surface area using real body weight.

Short-Term Administration of a Combination of Recombinant Growth Hormone and Insulin-Like Growth Factor-I Induces Anabolism in Maintenance Hemodialysis

CONTEXT Resistance to GH and IGF-I is a significant complication of severe chronic kidney disease, which contributes to muscle wasting. Pharmacological doses of recombinant human (rh) GH or rhIGF-I have been proposed to treat this catabolic condition. OBJECTIVE This study was undertaken to examine the potential additive anabolic effects of rhGH + rhIGF-I compared with rhIGF-I. DESIGN We studied eight well-nourished hemodialysis patients in a random crossover design and compared the metabolic effects of a 3-d administration of moderate dose of rhIGF-I (40 microg/kg per 12h) with an association of rhIGF-I + rhGH (50 microg/kg/d). Leucine kinetics, plasma amino acids (AAs), serum insulin, and IGF binding proteins (IGFBP)-1 and -3 were measured. RESULTS The net protein balance was not affected by rhIGF-I alone, whereas serum insulin and IGFBP-3 decreased (P < 0.05) and IGFBP-1 increased (P < 0.01). With the combination rhGH + rhIGF-I, an increase of IGFBP-3 (P < 0.01) and insulin (P < 0.01) as well as a decrease of IGFBP-1 (P < 0.01) occurred. Plasma essential AAs (P = 0.01) as well as the essential to nonessential AA ratio (P < 0.001) decreased. Whole-body protein net balance increased significantly (P < 0.05) with a 22% decrease in leucine oxidation and a 15% increase in nonoxidative leucine disposal. CONCLUSIONS In dialysis patients, rhIGF-I administration at a moderate dose has no protein metabolic effect, but the association with a moderate dose of rhGH is followed by a significant anabolic response.

Endocrine Role of Stomach in Appetite Regulation in Chronic Kidney Disease: About Ghrelin and Obestatin

The stomach may play an important role in central feeding regulation because it produces two peptides, ghrelin and the recently identified obestatin. These peptide hormones exert opposite actions on weight regulation. Whereas ghrelin is orexigenic, obestatin seems to be anorexigenic. Studies on feeding regulation are of particular importance for patients with chronic kidney disease (CKD), because anorexia and weight loss are associated with wasting and increased morbidity and mortality. This review discusses recent information about ghrelin and obestatin and their potential role in CKD. In addition, it seems important to consider not only single values but also their ratios, because both compounds could be affected disharmoniously by CKD.

Do Low-Protein Diets Work in Chronic Kidney Disease Patients?

Patients with chronic kidney disease have been advised for many years to reduce their protein intake. This review addresses the biochemical, pathophysiologic, and nutritional background that underlies this recommendation. The clinical and therapeutic evidence for prescribing such diets is addressed, as well as the potential caveats. A proposed method for managing and monitoring patients also is provided.

Insulino résistance et inflammation en insuffisance rénale

Resume L’insulinoresistance et l‘inflammation sont frequentes chez les patients ayant une maladie renale chronique. Ces deux anomalies metaboliques sont predictives d’evenements cardiovasculaires et sont egalement associees a un mauvais etat nutritionnel. Les donnees recentes experimentales, epidemiologiques et cliniques montrent qu’il existe une relation entre l‘inflammation et le developpement du syndrome metabolique ou les complications qui y sont associees en particulier dans le contexte d’obesite et de diabete de type II, faisant emerger l’hypothese de « metainflammation » ou inflammation induite par des anomalies metaboliques, avec le tissu adipeux jouant un role cle. Chez les patients insuffisants renaux qu’ils soient dialyses ou non, d’autres facteurs lies a l’uremie peuvent en partie expliquer ces anomalies, mais les concentrations anormales des cytokines et adipokines secretees par le tissu adipeux, laissent penser qu’une dysfonction adipocytaire pourrait egalement jouer un role initiateur de l’insulinoresistance et inflammation chez ces patients. Les therapeutiques visant les facteurs de risques cardiovasculaires traditionnels n’ont pas montre un gain majeur de survie en insuffisance renale. Des etudes futures visant a etudier l’impact de l’insuffisance renale sur la fonction adipocytaire et les voies metaboliques impliquees pourraient permettre des approches therapeutiques ciblant la dysfonction adipocytaire et l’inflammation.

Inflammation et insulino-résistance : particularités liées à la maladie rénale chronique

Chronic renal disease is a state of microinflammation and insulin resistance. They both impact on the patients outcome with an increased cardiovascular morbi-mortality and malnutrition. Current evidence suggests that there is a link between these two abnormal conditions. Recent data show a multiple organ regulatory pathway with a key role of bone, adipose tissue, immune system and central nervous system in energy balance control and glucose homeostasis. Thus, in searching for effective therapies, we should use an integrated approach aimed at modifying integrated outcomes rather than targeting single molecules.Resume Un etat inflammatoire chronique et une insulinoresistance sont frequemment presents au cours de la maladie renale chronique, et sont associes a une prevalence de pathologie cardiovasculaire et une denutrition accrue. Ces deux etats sont presents avant le stade de dialyse suggerant que l’etat d’uremie elle-meme est source potentielle d’inflammation et d’insulinoresistance. Les avancees dans la comprehension du mecanisme physiopathologique du diabete permettent de penser actuellement un lien entre l’inflammation et l’insulinoresistance et qu’il existe une regulation etroite entre le tissu adipeux, l’os, le systeme immunitaire et nerveux central dans le controle de la balance energetique et l’homeostasie glycemique.