Renal manifestations of the metabolic syndrome.

The metabolic syndrome is defined by a constellation of risk factors, including abdominal obesity, impaired glucose tolerance in association with hyperinsulinaemia and insulin resistance, dyslipidaemia characterized by low high-density lipoprotein (HDL)-cholesterol and high triglyceride levels, and hypertension. The World Health Organization (WHO) and the Adult Treatment Panel (ATP) III of the National Cholesterol Education Program have developed clinical criteria for metabolic syndrome (Tables 1 and 2) [1]. Although these organizations have provided somewhat different criteria, the overarching theme from each is aimed at describing the key features. Metabolic syndrome has gained a great deal of attention because it is a precursor to type 2 diabetes and also because it increases cardiovascular disease (CVD) risk, even with levels of glycaemia below that used to define diabetes [1]. The connections between chronic kidney disease (CKD) and CVD are increasingly evident. Indicators of CKD, albuminuria (microor macro-) and loss of glomerular filtration rate (GFR) are independently associated with increased CVD risk in the general population, as well as high-risk subgroups [2–7]. These connections are exceedingly complex and include a number of shared traditional risk factors (notably diabetes and hypertension), development of non-traditional risk factors (anaemia, hyperparathyroidism with disordered mineral metabolism, high levels of homocysteine and others) and more severe atherosclerosis. Accordingly, relationships between indicators of CKD and metabolic syndrome have also gained increasing interest. Microalbuminuria is a clinical criterion for metabolic syndrome by the WHO classification [1]. The frequency of microalbuminuria increases across the spectrum from those with normal glucose tolerance (5–10%), to metabolic syndrome (12–20%), to type 2 diabetes (25–40%) [3,8–10]. CVD risk parallels the escalating frequency of microalbuminuria. Endothelial dysfunction is a hallmark of vascular injury associated with atherosclerosis. Loss of albumin in the urine is believed to reflect endothelial dysfunction expressed in the glomerulus that, in turn, reflects the status of the circulation at large. In support of this concept, elevated levels of albuminuria (even within the conventional normal range) are related directly to impaired brachial artery reactivity and to severity of angiographically defined coronary artery disease [11,12]. The aetiologies of endothelial dysfunction and CKD in metabolic syndrome are likely to be multifactorial. Prevalence or probability of microalbuminuria and/or low GFR is progressively amplified by increasing numbers of metabolic syndrome risk factors (Figure 1) [8,13,14]. Such observations have been made in a variety of different groups, including the general population, Native Americans, Australian Aboriginals and treated hypertensives, among others [8,13–16]. Associations were found between various individual risk factors or combinations and indicators of CKD, suggesting that the various components of metabolic syndrome have an important impact. Recent data indicate that fat itself, particularly in the abdomen, is a source of cytokines that produce endothelial damage [17]. In addition, adiponectin, an adipocytederived hormone that has antiatherogenic and antiinflammatory properties, is reduced in those with metabolic syndrome and increased intra-abdominal fat [17].