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Anorexia and protein malnutrition, occasionally associated with obesity, are frequently observed in peritoneal dialysis (PD) patients. Both are recognized risk factors for cardiovascular (CV) morbidity and mortality. Leptin is produced by adipocytes and regulates body-fat mass through a satiety central effect. Leptin accumulates in the uremic state. We analyzed the relationship between plasma leptin levels, nutritional status, obesity, CV risk factors, and atherosclerosis in PD patients. Leptin was determined using a polyclonal antibody [radioimmunoassay: Linco Research, St. Louis, MO, U.S.A.]. The normal range was 1-7.8 ng/mL. We studied 38 PD patients. Mean leptin levels were 59.1 +/- 57.5 ng/mL (elevated in 32 patients). Women (n = 21) showed higher leptin levels than did men (80.4 +/- 60 ng/mL vs. 32.3 +/- 43.3 ng/mL, p < 0.01), in spite of both groups having a similar body mass index (BMI). A statistically significant direct correlation was found between leptin and BMI (r = 0.7, p < 0.01) and triceps skin-fold measurement (r = 0.77, p < 0.01). Leptin levels and renal creatinine clearance (CCr) showed no significant correlation. Independent of BMI, higher leptin levels were associated with parameters considered to be CV risk factors (Framingham study), such as serum triglycerides < 150 mg/dL (n = 29) as compared with > 150 mg/dL (44.2 +/- 53.2 ng/mL vs. 80 +/- 58.4 ng/mL, p < 0.05), cholesterol < 250 mg/dL (n = 28) as compared with > 250 mg/dL, (50 +/- 55.6 mg/dL vs. 84.7 +/- 57.7 mg/dL, p < 0.05), uric acid < 7 mg/dL (n = 28) as compared with > 7 mg/dL (47 +/- 53.7 mg/dL vs. 93.1 +/- 56.6 mg/dL, p < 0.05), and the presence or lack of presence of left ventricular hypertrophy [68.8 +/- 60 (n = 30) vs. 29.5 +/- 23.7 (n = 5), p < 0.05]. The patients were classified into two groups according to a clinical atherosclerosis score (CAS). Nineteen patients had low CAS scores, and they showed higher plasma leptin values than did the other patients (82.4 +/- 65.7 ng/mL vs 35.8 +/- 36.6 ng/mL, p < 0.05). Twelve patients with anorexia had lower leptin values than did patients with normal appetite (19.2 +/- 15.8 ng/mL vs. 91.3 +/- 58.8 ng/mL, p < 0.001). In non obese patients (BMI < 25 and CCr < 3 mL/min, n = 14), leptin had a statistically significant direct linear correlation with markers of nutrition, including albumin (r = 0.63, p < 0.05), transferrin (r = 0.4, p < 0.05), cholesterol (r = 0.65, p < 0.05), and triglycerides (r = 0.6, p < 0.05). Finally, plasma leptin levels were notably increased in the PD population, indicating increased production (possibly by chronic hyperinsulinism), or uremic retention, or both. By multivariate analysis, we confirmed the association between leptin levels and sex, leptin and BMI, and leptin levels > 40 ng/mL and sex and LVH. All of those features suggest that plasma leptin levels could be considered a marker of CV risk and food intake in non obese PD patients without inflammation.
Adv Perit Dial 2002
PMID:Leptin as a marker of nutrition and cardiovascular risk in peritoneal dialysis patients. 1240 21

The approach to patients with "complex" permanent hemodialysis (HD) access problems remains poorly defined. The purpose of this review is to outline our current algorithm for patients presenting for dialysis access and to address the management of specific problems that complicate this objective of establishing permanent access. The key components of the algorithm include noninvasive imaging in the diagnostic vascular laboratory to determine all the possible access configurations and invasive imaging with both venography and arteriography to confirm the optimal choice. The specific access-related problems addressed include inadequate ipsilateral vein, inadequate arterial inflow, central vein stenosis/occlusion, multiple previous access failures, and obesity. Despite the label of "complex" access problems, it is possible to construct native arteriovenous fistulas (AVFs) in almost all patients presenting for access using the standard principles of vascular surgery that are based on establishing adequate arterial inflow, adequate venous outflow, and selecting an appropriate conduit.
Semin Dial
PMID:Approach to patients with "complex" hemodialysis access problems. 1253 97

Obesity and hyperhomocysteinaemia are found very frequently after kidney transplantation (Tx). They may independently represent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored, over a period of 24 months, a total of 118 obese transplant patients [body mass index (BMI) > or =30 kg/m(2)] with hyperhomocysteinaemia. We compared the findings of a new therapeutic regimen at 1 year (start of the study) and 2 years after renal transplantation. Based on a Subjective Global Assessment Scoring Sheet, we started at the end of the first year with an individualized hypoenergic-hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was supplemented regularly with orlistat at a dose of up to 3 x 120 mg/day, statins (pravastatin 10-40 mg), folic acid 5 mg/day and vitamin B6 50 mg/day, and followed-up for up to 2 years. All patients were on a regimen of cyclosporin A and mycophenolate mofetil. During the study period, there was a significant decrease in BMI (P < 0.025) and total homocysteine level (P < 0.001). Long-term therapy was associated with a significant decrease in serum leptin (P < 0.001) and lipid metabolism parameters (P < 0.01). The mean values of serum folate and vitamin B6 also increased significantly (P < 0.01); creatinine clearance, mean blood pressure, proteinuria, lipoprotein(a) and apolipoprotein E isoforms did not differ significantly. Based on our results, we assume that obesity and hyperhomocysteinaemia after renal transplantation can be treated effectively by modified immunosuppression (corticosteroid withdrawal), long-term diet (IHHD), folic acid and vitamin B6 supplementation, and drugs suppressing digestion or absorption to reduce atherosclerotic and chronic allograft nephrop-athy processes.
Nephrol Dial Transplant 2003 Jul
PMID:Obesity and hyperhomocysteinaemia after kidney transplantation. 1281 77

Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lpa) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lpa levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 95.6 +/- 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein a (Lpa), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side-effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement in general well-being and increased performance were experienced by 44 of 45 patients. The present data demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe even in long-term application.
Ther Apher Dial 2003 Aug
PMID:Low-density lipoprotein apheresis: an overview. 1288 19

Eating and appetite disorders are frequent complications of the uremic syndrome which contribute to malnutrition in dialysis patients. The data suggest that uremic anorexia may occur with or without abdominal and visceral fat accumulation despite a lower food intake. This form of obesity (i.e., with low food intake and malnutrition) is more common in dialysis patients than obesity with high food intake. This article reviews the current knowledge regarding mechanisms responsible for appetite regulation in normal conditions and in uremic patients. Anorexia in dialysis patients has been historically considered as a sign of uremic toxicity due to "inadequate" dialysis as judged by uncertain means ("middle molecule" accumulation, Kt/V, "peak-concentration hypothesis," and others). We propose the tryptophan-serotonin hypothesis, based on a uremia-induced disorder in patients' amino acid profile--low concentrations of large neutral and branched-chain amino acids with high tryptophan levels. A high rate of tryptophan transport across the blood-brain barrier increases the synthesis of serotonin, a major appetite inhibitor. Inflammation may also play a role in the genesis of anorexia and malnutrition. For example, silent infection with Helicobacter pylori may be a source of cytokines with cachectic action; its eradication improves appetite and nutrition. The evaluation of appetite should take into account cultural and social aspects. Uremic patients showed a universal trend to carbohydrate preference and red meat refusal compared to healthy people. In contrast, white meat was less problematic. Uremic patients also have a remarkable attraction for citrics and strong flavors in general. Eating preferences or refusals have been related to the predominance of some appetite peptide modulators. High levels of cholecystokinin (CCK) (a powerful anorexigen) are associated with early satiety for carbohydrates and neuropeptide Y (NPY) (an orexigen) with repeated food intake. Obesity and elevated body mass index often falsely suggest a good nutritional status. In uremic patients (a hyperinsulinemia state), disorders in the regulation of fat distribution (insulin, leptin, insulin-like growth factor [IGF]-1, fatty acids, and disorders in receptors for insulin, lipoprotein lipase, mitochondrial uncoupling protein-2, and beta 3 adrenoreceptors) may cause abdominal fat accumulation without an increase in appetite. Finally, appetite regulation in uremia is highly complex. Disorders in adipose tissue, gastrointestinal and neuropeptides, retained or hyperproduced inflammatory end products, and central nervous system changes may all play a role. Uremic anorexia may be explained by a hypothalamic hyperserotoninergic state derived from a high concentration of tryptophan and low branched-chain amino acids.
Semin Dial
PMID:Eating behavior disorders in uremia: a question of balance in appetite regulation. 1471 11

We tested the agreement between classifications of the weight status of patients on peritoneal dialysis (PD) by body mass index (BMI) and by body fat (BF) content (BF/W, where W = actual weight), when BF was computed as BF = W - V/0.73 from the Sahlgrenska, Watson, or Hume anthropometric formulas estimating body water (V) in 933 patients on PD and 7,737 outpatients without hydration disorders. We used currently accepted cut-off values for classifying subjects as underweight, normal-weight, overweight, and obese by BMI and BF/W. We obtained these values: BMI: men on PD (n = 555), 25.5 +/- 4.3; men with normal renal function [NRF (n = 5,906)], 27.7 +/- 5.1; women on PD (n = 378), 25.9 +/- 6.1; women with NRF (n = 1,831), 28.3 +/- 6.5; BFSahlgrenska/W--men on PD, 0.238 +/- 0.063; men with NRF, 0.274 +/- 0.052; women on PD, 0.342 +/- 0.89; women with NRF, 0.366 +/- 0.075. We obtained these regressions: Women on PD BMI = 12.0832 + 38.9550 (BFSahlgrenska/W) -92.9252 (BFSahlgrenska/W)2 +254.0675 (BFSahlgrenska/W)3, r2 = 0.917; Men on PD BMI = 19.4729 - 29.1310 (BFSahlgrenska/W) +213.7045 (BFSahlgrenska/W)2, r2 = 0.888. From those regressions, the BMI value corresponding to the BFSahlgrenska/W cut-off for underweight was similar to the National Institutes of Health (NIH) BMI cut-off for underweight. The BMI value corresponding to the BFSahlgrenska/W cut-off for obesity was substantially lower than the NIH BMI cut-off for obesity. The kappa ratios of the classifications of weight status by BMI and BFSahlgrenska/W varied between 0.142 and 0.304 (poor agreement), with more than 50% of the subjects classified in a more obese weight category by BFSahlgrenska/W than by BMI. Classification of the subjects by BMI and by BFSahlgrenska/W in quintiles or quartiles led to much higher kappa ratios, particularly in women. The results were similar in subjects with NRF and with the use of the Watson and Hume formulas to estimate BF. The use of arbitrary cut-off values of BMI or anthropometric BF/W to classify PD patients or patients without edematous states as underweight, normal-weight, overweight, or obese leads to substantial disagreement between the two classifications. Classification of weight status by BMI or BF/W in quintiles or quartiles improves substantially the agreement between the two classifications and should be preferred.
Adv Perit Dial 2003
PMID:Weight status classification of patients on continuous peritoneal dialysis. 1476 66

The association of high body mass index (BMI) with better survival in chronic kidney disease (CKD) is considered a "risk factor paradox" or "reverse epidemiology." Since malnutrition is a powerful predictor of death and cardiovascular disease is its leading cause, it has been suggested that malnutrition and atherosclerosis must be associated. Thus the current paradigm is that malnutrition is a risk factor for atherosclerosis and obesity is protective in CKD patients. We recently showed that high-BMI patients with inferred high body fat have an increased prevalence of atherosclerosis and subsequent cardiovascular and all-cause mortality. Prior cross-sectional studies also showed that high BMI in CKD is associated with higher C-reactive protein (CRP) levels and increased coronary calcification on electron beam computed tomography (CT) scan. These apparently conflicting data on better survival but increased inflammation and atherosclerosis in high-BMI CKD patients could be explained as follows. It is hypothesized that nutrition exerts a much stronger influence on survival than atherosclerosis in CKD. Malnutrition strongly augments the hazard of death from coexistent diseases, while better nutrition has the opposite effect. Thus the risk of death is highest in malnourished patients (low muscle and low fat mass) and lowest in well-nourished patients (high BMI, high muscle mass). Obesity (high BMI, high fat mass) is associated with inflammation and atherosclerosis. The risk of death from obesity and atherosclerosis is increased, but not so much as occurs with malnutrition. Therefore high body fat patients have intermediate survival. Thus it is postulated that an association of obesity, inflammation, and atherosclerosis (OIA syndrome) might exist in CKD.
Semin Dial
PMID:The body mass index paradox and an obesity, inflammation, and atherosclerosis syndrome in chronic kidney disease. 1514 50

Obesity shortens survival in the general population. In hemodialysis (HD), obesity is associated with improved short-term survival (around 3 years). The discrepancy in the survival of obese patients between HD and the general population may be attributable to survival bias. (Only a small percentage of patients with renal failure survive until HD, and they may have certain survival advantages, including obesity.) Bias is introduced through the mixture of prevalent and incident HD patients in most studies, better nutrition in obese HD patients, malnutrition-inflammation complex syndrome causing weight loss, or other reasons. In studies of peritoneal dialysis (PD), obesity has been associated with decreased patient survival, no noticeable effect on survival, and increased survival. Potential reasons for the differences include bias in the selection of PD for obese patients, effects of race, chronic inflammation in obese PD patients, differences in nutrition and adequacy of PD, adverse effects of the increased PD dose needed to achieve adequate small-solute clearances, differences in body composition, and time discrepancies among risk factors having opposite effects on PD patient survival. Some evidence exists that in the long-term (> 10 years), obesity is a risk factor for death in both HD and PD. Further studies are needed to identify the short- and long-term risks and benefits of obesity in the two dialysis modalities.
Adv Perit Dial 2004
PMID:Obesity and patient survival in chronic dialysis. 1538 1

Anorexia-associated malnutrition is a severe complication that increases mortality in peritoneal dialysis (PD) patients. Ghrelin is a recently-discovered orexigenic hormone with actions in brain and stomach. We analyzed, in 42 PD patients, the possible relationship between ghrelin and appetite regulation with regard to other orexigens [neuropeptide Y (NPY), NO3] and anorexigens [cholecystokinin (CCK), leptin, glucose-dependent insulinotropic peptide (GIP), tumor necrosis factor alpha (TNFalpha)]. All orexigens and anorexigens were determined in plasma. Eating motivation was evaluated using a visual analog scale (VAS). The patients were divided into three groups: those with anorexia (n = 12), those with obesity associated with high intake (n = 12), and those with no eating behavior disorders (n = 18). A control group of 10 healthy volunteers was also evaluated. Mean plasma levels of ghrelin were high (3618.6 +/- 1533 mg/mL), with 36 patients showing values above the normal range (< 2600 mg/mL). Patients with anorexia had lower ghrelin and NPY levels and higher peptide-C, CCK, interleukin-1 (IL-1), TNFalpha, and GIP levels than did the other patients. Patients with anorexia also had an early satiety score and low desire and pleasure in eating on the VAS and diet survey. We observed significant positive linear correlations between ghrelin and albumin (r = 0.43, p < 0.05), prealbumin (r = 0.51, p < 0.05), transferrin (r = 0.4, p < 0.05), growth hormone (r = 0.66, p < 0.01), NO3 (r = 0.36, p < 0.05), and eating motivation (VAS). At the same time, negative relationships were observed between blood ghrelin and GIP (r = -0.42, p < 0.05), insulin (r = -0.4, p < 0.05), leptin (r = -0.45, p < 0.05), and creatinine clearance [r = -0.33, p = 0.08 (nonsignificant)]. Ghrelin levels were not related to Kt/V or to levels of CCK and cytokines. Ghrelin plasma levels are elevated in PD patients. Uremic patients with anorexia show relatively lower ghrelin plasma levels than the levels seen in obese patients or in patients with normal appetite. The role of ghrelin in appetite modulation is altered in uremic PD patients, and that alteration is possibly associated with disorders in insulin and growth hormone metabolism.
Adv Perit Dial 2004
PMID:Ghrelin plasma levels and appetite in peritoneal dialysis patients. 1538 25

Anthropometric and body composition assessments provide important information about the nutritional status of dialysis patients. Anthropometric measurements describe body size, fatness, and leanness in dialysis patients and have been collected in the Modification of Diet in Renal Disease (MDRD) and HEMO studies. Dialysis patients present special problems for anthropometry, including decreased functional status and increased comorbidity, that challenge nutrition assessment methodology. Recumbent anthropometric techniques are recommended and stature is estimated from knee height. Measures of weight, stature, calf circumference, arm circumference, and triceps and subscapular skinfolds have recently been reported for dialysis patients, who tend to be shorter, lighter, and have less adipose tissue than healthy persons of the same age. The HEMO study anthropometric data provide a clinical reference for assessing the nutritional status of dialysis patients. The most common body composition methods used with dialysis patients are dual energy X-ray absorptiometry (DEXA), bioelectrical impedance, total body water (TBW), and prediction equations, but they are not recommended for assessment of predialysis patients, as estimates are best obtained postdialysis. The TBW volume used in calculating the dose of dialysis has commonly been predicted from the limited, out-of-date equations of Watson, based on nonrepresentative samples. New prediction equations are available for white, black, and Mexican American children and adults. Watson's data are not representative of the TBW of U.S. men and women. The greater TBW in non-Hispanic black men and women and Mexican American women reflects the greater levels of obesity in the U.S. population.
Semin Dial
PMID:Anthropometric and body composition assessment in dialysis patients. 1566 May 77


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