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Part 4: Metabolic Syndrome and Nutrition in PD |
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China
Correspondence to: P.K.T. Li, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China. philipli{at}cuhk.edu.hk
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ABSTRACT |
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 TOP ABSTRACT DEFINITION AND CONSEQUENCES OF...TREATMENT OPTIONS FOR MetSCONCLUSIONSREFERENCES |
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Metabolic syndrome (MetS) occurs in about 50% of peritoneal dialysis
(PD) patients. It encompasses a cluster of major risk factors for
cardiovascular diseases. A modified National Cholesterol Education Program
Third Adult Treatment Panel guideline for the diagnosis of MetS in PD patients
has been proposed. Preliminary data suggest that PD patients with MetS in our
cohort have an increased risk of cardiovascular mortality. The proinflammatory
effects of adipose tissue are one of the reasons for poor outcome in obese PD
patients. Lifestyle modification, including appropriate dietary restriction
and exercise, especially reduction of fat mass in obese patients, has been one
of the major areas proposed for managing patients with MetS. Individual
therapeutic trials are treating hyperglycemia, hypertension, and dyslipidemia
in dialysis patients. Evidence in PD patients that interventions targeting
MetS can improve outcomes is still lacking. Large-scale studies with data on
the clinical outcome for MetS intervention in PD patients are needed.
KEY WORDS: Metabolic syndrome.
Peritoneal dialysis (PD) is a well-established treatment modality, and continuous ambulatory PD (CAPD) is actually the first-line treatment for end-stage renal failure patients in Hong Kong (1). Although we can achieve a 2-year CAPD patient survival rate of 91%, cardiovascular morbidity and mortality remain a major problem affecting our CAPD patients (2). Both traditional and nontraditional factors for cardiovascular disease and reverse epidemiology of the risk factors for cardiovascular disease exist in PD patients (2). Data recently published from our own center in the Prince of Wales Hospital showed the significance of residual renal function, inflammation, valvular calcification, and left ventricular hypertrophy as potential factors leading to cardiovascular diseases in PD patients.
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DEFINITION AND CONSEQUENCES OF METABOLIC SYNDROME |
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TOPABSTRACTDEFINITION AND CONSEQUENCES OF...TREATMENT OPTIONS FOR MetSCONCLUSIONSREFERENCES |
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We recently proposed using the modified NCEP–ATP III criteria for diagnosing MetS in PD patients (3). Those criteria require the patient to have 3 or more of the following 5 criteria to be diagnosed as having MetS:
1.7 mmol/L 130/85 mm Hg or hypertension on treatment 5.6 mmol/L or diabetes on treatment Notably, body weight for BMI in PD patients is measured either with a dry abdomen or with PD dialysate in the abdomen minus x kg (x being the volume in liters of PD dialysate infused). Fasting plasma glucose in PD patients is measured by means of a conventional method after an overnight fast, but with continuation of PD therapy with 1.5% dextrose dialysate.
We reviewed 212 unselected patients on PD at our center on 1 June 1999
(4). Of these 212 patients, 113
(53.3%) had MetS (3 criteria). The 8-year cardiovascular survival for
patients on PD with and without MetS were 64.0% and 73.8% respectively (log
rank test: p = 0.014). Thus, not only did we find a high prevalence
of MetS in PD patients, we confirmed the association of MetS with
cardiovascular mortality in our PD population. Two previous studies found MetS
prevalences of 50% in PD patients (Australia) and 69.3% in all dialysis
patients [94% hemodialysis, 6% peritoneal dialysis (United States)].
The key element of MetS is obesity. Obesity, especially central obesity, is
associated with increased visceral adipose tissue that, being metabolically
very active, releases substantial amounts of free fatty acids (FFAs) and hence
is associated with a high serum level of FFAs. Adipocytes produce a wide range
of signaling proteins and factors termed adipocytokines, including tumor
necrosis factor 
, interleukin-6, plasminogen activator inhibitor,
leptin, monocyte chemotactic protein 1, macrophage migration inhibitory
factor, and adiponectin. These factors serve as the signals for the effects of
adipocytes on insulin resistance, inflammation, dyslipidemia, hypertension,
endothelial dysfunction, and atherosclerosis. Racial differences are an
important consideration in diagnosing obesity. In young Caucasians, a BMI
cut-off of 25–29.9 kg/m2 is defined as overweight and
30 kg/m2 is defined as obesity. In Asians, the definition of
obesity should be adjusted so that a BMI 25 kg/m2 is defined
as obesity. This threshold is based on strong evidence that Asian people have
more body fat for the same BMI than do their Caucasian counterparts.
Central obesity is considered more important in MetS. Thus, waist circumference is considered to be a more important surrogate marker for the harmful effects of obesity than BMI is. However, in PD patients, waist circumference is affected by the presence of a catheter in situ, by lax skin condition after repeated distention of the abdomen by PD fluid, and by potential residual PD fluid in the abdominal cavity, and so this measurement may not reliably reflect abdominal visceral fat content. Thus, BMI remains a good and reliable anthropometric parameter to measure obesity in PD patients (3).
A raised BMI in the general population is associated with higher risk of mortality. However, it is unclear if obesity in PD patients results in better or worse survival outcome. At one time, studies showed improved survival in dialysis patients with a higher BMI, but other studies found that a higher degree of obesity led to worse survival in PD patients. This negative effect of obesity in PD results from higher hazard ratios for development of peritonitis, for PD technique failure, and for more rapid loss of residual renal function. This difference in the effect of obesity on PD survival can be partly explained by a study that showed worse survival in patients with a high BMI resulting from increased fat mass than in patients with a high BMI resulting from non-fat mass (5). Thus, PD patients with a high BMI and normal or high muscle mass have the best survival; hence, patients should be encouraged to gain muscle mass rather than fat mass.
In our previous study of 252 nondiabetic Chinese patients newly started on CAPD, fasting plasma glucose correlated significantly with baseline serum C-reactive protein (CRP). Most importantly, the results showed that even mild hyperglycemia after PD [fasting plasma glucose level greater than 5.6 mmol/L (100 mg/dL)] is associated with worse survival. By multivariate analysis using the Cox proportional hazards model, every 0.6 mmol/L (10 mg/dL) increase in fasting plasma glucose conferred a 1.6% excess hazard for all-cause mortality (6). These findings give further evidence to support the adverse effect of dysglycemia as a criterion for MetS in PD patients.
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TREATMENT OPTIONS FOR MetS |
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TOPABSTRACTDEFINITION AND CONSEQUENCES OF...TREATMENT OPTIONS FOR MetSCONCLUSIONSREFERENCES |
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In PD patients, general measures to reduce weight— preferably fat mass—are similar to those in the nondialysis population. A multidisciplinary approach to weight reduction is more likely to be successful and includes individualized meal plans according to energy and nutrition requirements and increased physical activity. Exercise to reduce fat mass and to improve muscle mass is obviously encouraged, especially in light of other beneficial effects of exercise on dialysis patients. Surgical approaches such as laparoscopic banding should be considered only for extreme obesity. Oral anti-obesity drugs are currently not an option for PD patients because of their limited safety profiles among patients on dialysis. In PD patients, avoiding or minimizing peritoneal dialysate glucose by using icodextrin and amino-acid solutions may aid weight control. A trial using icodextrin as compared with 2.5% dextrose PD fluid showed that patients receiving icodextrin had no increase in weight after 52 weeks, in contrast to a weight gain of almost 2 kg in the dextrose group.
Recommendations for weight reduction, especially fat mass, in PD patients with MetS have theoretical advantages. Unfortunately, there is little evidence so far that weight reduction is associated with improved patient survival in PD patients.
Glucose control in PD patients includes lifestyle changes, hypoglycemic
agents, and non–glucose-based dialysis solutions. As in managing
obesity, lifestyle modification works through diet, exercise, and body weight
control. Multiple hypoglycemic agents are available, and one group to note is
the thiazolidinediones. In addition to reducing insulin resistance, the
thiazolidinediones (peroxisome proliferator–activated receptor 
agonists) also have specific anti-inflammatory effects that may be beneficial
in patients with renal failure
(7). Our study of 52 PD
patients with type 2 diabetes who had previously been administered a constant
dose of subcutaneous insulin and achieved stable glycemic control randomly
assigned those patients to a fixed dose of rosiglitazone (RSG) plus insulin or
to insulin alone (7). After 24
weeks, the percentage reduction in insulin dose was significantly greater in
the RSG group than in the control group. At the same time, there appeared to
be an anti-inflammatory effect in the RSG group, who showed a significant
reduction in CRP level as compared with the insulin-alone group. Recent
studies have shown that the more biocompatible and non-glucose-containing
dialysis fluids, such as those containing icodextrin and amino acids, seem to
be associated with improvements in glycemic control in diabetic patients on
PD.
Many of our PD patients tend to have hypertension that usually requires treatment with antihypertensive agents. In our recent cohort of CAPD patients, 80% had hypertension. Elevation of BP in PD patients is obviously multifactorial, but is partly related to fluid status and salt intake. Restriction in salt and fluid intake is important. We still aim to achieve a BP of 130/85 mm Hg in our PD patients. Multidrug treatment is usually required to manage BP, and not uncommonly, many PD patients require 3 or more antihypertensive medications to control BP. Our previous study using an angiotensin converting-enzyme inhibitor in patients on PD showed the additional benefit of preservation of residual renal function, which is also important in overall outcome for PD patients (8).
Dyslipidemia can be treated with a reduction in the amount of dietary cholesterol or fats, exercise, and use of lipid-modifying drugs such as statins or fibrates. However, no large survival outcome studies have looked at the use of these drugs in PD patients. The Die Deutsche Diabetes Dialyse Studie conducted in Germany in patients with type 2 diabetes mellitus receiving maintenance hemodialysis created much controversy regarding the treatment of dyslipidemia in dialysis patients. In that study, 1255 subjects were randomly assigned to receive atorvastatin or placebo. However, after a median follow-up of 4 years, atorvastatin, despite reducing low-density lipoprotein (LDL) cholesterol by 42%, had no statistically significant effect on the composite primary endpoint of cardiovascular death, nonfatal myocardial infarction, and stroke.
The LANDMARK study (Longitudinal Assessment of Numerous Discrete Modifications of Atherosclerotic Risk Factors in Kidney Disease) was conducted in Australia with a mixed group of hemodialysis, PD, and pre-dialysis patients. With lifestyle modifications and drugs, the subjects showed significant improvement in serum LDL cholesterol, homocysteine, and systolic and diastolic BP as compared with controls. Despite the changes, no significant change was noted in carotid intima media thickness or brachial artery reactivity (outcome measures of atheroma burden and endothelial function respectively). A subgroup of these chronic kidney disease subjects with MetS were randomized to intensive risk-factor modification and showed no difference in composite cardiovascular survival as compared with patients on typical care (9).
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CONCLUSIONS |
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TOPABSTRACTDEFINITION AND CONSEQUENCES OF...TREATMENT OPTIONS FOR MetSCONCLUSIONSREFERENCES |
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ACKNOWLEDGMENTS |
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REFERENCES |
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TOPABSTRACTDEFINITION AND CONSEQUENCES OF...TREATMENT OPTIONS FOR MetSCONCLUSIONSREFERENCES |
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