Chronic Kidney Disease
Obesity
Abdominal or central obesity is the key component of metabolic syndrome.48 prerequisite.14
In the IDF definition of metabolic syndrome, obesity is a In concert with the obesity epidemic is the crescendo of
adults with ESRD, a population that is expected to double over the next decade.49
and for diabetes,52
Obesity is a well-recognised risk factor for hypertension50,51 the most common aetiologies of ESRD.53
Importantly,
in long-term observational studies a correlation between body mass index (BMI) and new onset of ESRD is present.54,55
Concordantly, waist-
to-hip ratio or waist circumference is gaining widespread acceptance as an important risk factor for CKD.56
Obesity is a cause of glomerular hyperfiltration, proteinuria, glomerulo- megaly, podocyte hypertrophy,
increased mesangial matrix and
proliferation, lesions of segmental sclerosis and food process effacement with interstitial fibrosis and impaired kidney function.57–59 Moreover, there is a continuous risk association between BMI and increased filtration fraction extending from normal to elevated BMI values.60
Hypertension
It has been reported that metabolic syndrome predicts future development of hypertension.61
By contrast, hypertension is not a
good predictor of the development of metabolic syndrome.62 Hypertension is extremely common in CKD patients and as GFR decreases the prevalence of hypertension rises significantly.26 hypertension was the second most common reason for ESRD.23
In 2008, A
representative study to illustrate the relationship between CKD risk and hypertension comes from the Multiple Risk Factor Intervention Trial (MRFIT). A clear relationship between the level of systolic and diastolic pressure over a 16-year follow-up period provided important information in the context of ESRD incidence.63
Further support for the
relationship between hypertension and risk of ESRD comes from an analysis of the Kaiser Permanente group in northern California. Investigators evaluated 316,675 men and women who participated in health check-ups between 1964 and 1985. After 8,210,431 person- years of follow-up it was concluded that even relatively modest elevation in blood pressure is an independent risk factor for ESRD.64
Insulin Resistance
Even though metabolic syndrome is predominantly associated with abdominal obesity, which is essential for the syndrome,
insulin
resistance and hyperinsulinaemia are key factors for development of these components of the metabolic syndrome. Insulin resistance is a good predictor, plays an important part in risk-factor clustering and contributes to many of the untoward outcomes attributed to metabolic syndrome. Recent progress and research on adipocytes showed that visceral obesity and associated conditions, including chronic inflammation and physical inactivity,65
play a critical role in the development of insulin resistance and hyperinsulinaemia.
Hyperinsulimaemia could potentially have deleterious effects on kidney function. It appears also to be an important link connecting obesity with CKD66
and other proinflammatory cytokines and hormones.67 Insulin
resistance results in an increase in insulin levels to maintain glycaemic control and this state can have deleterious effects, with early evidence of structural changes and glomerular hypertrophy in the kidney even before the onset of diabetes.68
antinatriuretic effect on tubular function,69
It is recognised that insulin has an while the relationship of
insulin resistance with glomerular function has not been completely
12
Some generic recommendations about healthy lifestyle in the general population that could also be applied to CKD patients are of great importance. Clinical guidelines from NCEP III and consequently from the AHA and Endocrine Society recommended two major therapeutic goals in patients with metabolic syndrome. The first is to treat underlying causes (overweight/obesity and physical inactivity) by intensifying weight management and increasing physical activity. Mediterranean diet may be beneficial, improve insulin resistance and lower levels of markers of inflammation and endothelial function.80 Prevention or reduction of abdominal obesity, which also improves insulin sensitivity, is the main therapeutic goal in patients with
EUROPEAN NEPHROLOGY
elucidated. It would appear reasonable to suggest that insulin resistance is also related to proteinuria based on the evidence provided that insulin resistance increases urinary excretion of albumin in diabetic patients without affecting systemic albumin permeability.70
Although the picture is not entirely clear, current data support the notion that insulin resistance induces hypertension. Although the precise mechanism for insulin-resistance-induced hypertension is largely unknown, it has been hypothesised that insulin can increase sodium reabsorption in the proximal tubes and stimulate sympathetic tone. One the other hand, hyperinsulinaemia increases blood pressure by inducing salt retention and central sympathetic overactivity.71 Obesity, the aforementioned key component of metabolic syndrome, also plays an important role. Obese insulin-resistant subjects with metabolic syndrome showed a higher fractional sodium reabsorbtion in the proximal tubules72
and often have salt-sensitive hypertension.73
Salt-sensitive hypertension is characterised by the same features as those characterising patients with metabolic syndrome, namely obesity,
microalbuminuria,
cholesterol, intraglomerular hypertension and high incidence of cardiovascular disease.73,74
Dyslipidaemia
Overall, current evidence shows that dyslipidaemia is a risk factor for cardiovascular disease in CKD patients.34
However, it is still uncertain
whether dislipidaemia itself causes progression of kidney disease or whether kidney impairment and proteinuria are responsible for both progression and dislipidaemia.75,76
A small series provides
evidence that these lipoprotein abnormalities of renal insufficiency contribute to the progression of kidney failure in CKD patients and have demonstrated an association between progression of renal disease and dyslipidaemia.77
Proposed mechanisms of lipoprotein
(very-low-density lipoproteins and triglycerides)-induced kidney damage include recruitment of inflammatory cells, stimulation of mesangial cell proliferation, extracellular matrix deposition and synthesis of inflammatory cytokines.78,79
Treatment of Metabolic Syndrome in Chronic Kidney Disease Patients
Diagnosis of an individual with metabolic syndrome somehow focuses attention on the need for lifestyle therapy and inspires patients to pay attention and to be more adherent to therapy. Even though we are making important progress in this direction, there are no large randomised, placebo-controlled trials that evaluate the progression of kidney dysfunction in patients with metabolic syndrome. As a result, there is no agreement on how metabolic syndrome should be treated in patients with renal failure; it is therefore unclear whether treating metabolic syndrome will prevent CKD.
insulin resistance, low serum HDL
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