Postprandial metabolic response to a fat- and carbohydrate-rich meal in patients with chronic kidney disease.

BACKGROUND: While chronic kidney disease (CKD) is associated with dysmetabolism including a marked insulin resistance, the postprandial response has not comprehensively been studied in CKD patients. METHODS: We conducted an intervention study comparing fasting and postprandial circulating biomarkers of glucose and lipid homeostasis, incretins, anabolic hormones, inflammation and oxidative stress in nine prevalent non-diabetic hemodialysis (HD) patients and 10 matched controls assessed after a standardized meal consisting of 75 g of milk fat, 80 g of carbohydrates and 6 g of proteins/m(2) of body surface area. RESULTS: Glucose and triglyceride increased in a similar manner following the meal, while insulin, C-peptide and glucose-dependent insulinotropic polypeptide increased more in HD patients. HDL and LDL cholesterol decreased slightly with no significant difference between the groups. The elevated baseline growth hormone (GH) in patients dropped, resulting in comparable levels in both groups 240 min after the meal; however, there was no change in insulin-like growth factor 1 (IGF-1) levels. No marked changes of interleukin 6 and tumor necrosis factor-α were observed in either group. An elevation in the DNA oxidative product 8-hydroxydeoxyguanosine was observed in HD patients. CONCLUSIONS: The postprandial state in CKD is characterized by impaired insulin sensitivity with increased incretin levels, along with GH/IGF-1 axis uncoupling and an elevation in an oxidative stress marker.

Hyperhomocysteinemia, malnutrition, and inflammation in ESRD patients.

Hyperhomocysteinemia is a risk factor for cardiovascular disease in the general population, but in end-stage renal disease patients some studies show a reverse association, i.e. higher levels of homocysteine are associated with better clinical outcome. In this brief review, we review the evidence that malnutrition, hypoalbuminemia, inflammation and diabetes mellitus may lower circulating levels of homocysteine. As these factors are strong predictors of clinical outcome, this may explain why lower homocysteine levels in end-stage renal disease patients are associated with worse clinical outcome. We conclude that these factors need to be taken into account in multivariate models evaluating the impact of hyperhomocysteinemia as a risk factor in end-stage renal disease patients.

Truncal fat mass as a contributor to inflammation in end-stage renal disease.

BACKGROUND: An activated inflammatory response is a common feature of end-stage renal disease (ESRD) and predicts outcome. Adipose tissue is an endocrine organ that may contribute to an inflammatory burden by secreting adipocytokines such as interleukin 6 (IL-6). OBJECTIVE: The objective was to relate plasma concentrations of IL-6 in ESRD patients to body composition, regional fat mass distribution, and blood lipid profiles. DESIGN: One hundred ninety-seven ESRD patients (123 men; +/- SE age: 52 +/- 1 y) were evaluated shortly before dialysis started. Lean body mass and truncal and nontruncal fat mass were estimated by dual-energy X-ray absorptiometry. Nutritional status was evaluated on the basis of subjective global assessment and handgrip strength. Inflammatory biomarker and blood lipid concentrations were also evaluated. RESULTS: Median IL-6 (8.5 compared with 4.5 pg/mL; P < 0.001) concentrations were significantly greater in malnourished than in well-nourished patients. Moreover, negative correlations were observed between IL-6 and serum creatinine (rho = -0.19, P < 0.01), handgrip strength (rho = -0.24, P < 0.001), and serum albumin (rho = -0.34, P < 0.001). A significantly higher truncal fat mass (12.8 +/- 0.7 compared with 10.5 +/- 0.4 kg; P < 0.005) was observed in ESRD patients with inflammation (C-reactive protein >/= 10 mg/L). Inverse correlations were observed between plasma IL-6 and HDL cholesterol (rho = -0.16, P < 0.05) and apolipoprotein A (rho = -0.23, P < 0.001). CONCLUSIONS: Plausible relations exist between inflammatory biomarkers, such as IL-6 and high-sensitivity C-reactive protein, and regional fat distribution in ESRD patients. Moreover, the strong inverse relations between HDL cholesterol and apolipoprotein A and biomarkers of inflammation suggest that the chronic inflammatory response observed in ESRD patients is an important contributor to the atherogenic lipoprotein profile in uremia.

Inverse relationship between the inflammatory marker pentraxin-3, fat body mass, and abdominal obesity in end-stage renal disease.

BACKGROUND AND OBJECTIVES: Pentraxin-3 (PTX3) belongs to the same pentraxin superfamily of acute-phase reactants as C-reactive protein (CRP). Abdominal fat accumulation in ESRD is considered a chronic inflammatory state, but the relationship of PTX3 to this phenomenon is unknown. This study assesses plausible associations between PTX3 and surrogates of fat mass deposits in dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Circulating levels of PTX3, CRP, and IL-6 were cross-sectionally analyzed in relation to anthropometric and nutritional surrogate markers of fat tissue in two cohorts comprising 156 prevalent hemodialysis (HD) and 216 incident dialysis patients. RESULTS: In both cohorts, PTX3 was negatively associated with body mass index (BMI) and fat body mass index (FBMI) derived from anthropometrics and leptin, whereas there was a positive association with adiponectin. In prevalent HD patients, those with larger waist circumference (above gender-specific median values) had lower PTX3, higher CRP, and higher IL-6 levels. This was also true in multivariate analyses. In both cohorts, multivariate regression analyses showed that PTX3 was negatively and CRP (or IL-6) was positively associated with FBMI. CONCLUSIONS: Although CRP and IL-6 were directly associated with body fat, PTX3 levels showed negative correlations with surrogates of adipose tissue in two independent cohorts of ESRD patients. Understanding the underlying reasons behind these opposite associations may have clinical relevance given the survival advantage described for obese patients on dialysis.