Metabolic Syndrome

In this issue of CJASN, no fewer than three articles deal with different aspects of the metabolic syndrome (MS) and its impact on the kidney—testimony to the fact that the MS is a topic of considerable current interest and of intense investigation. Obesity and the associated MS have become a scourge to the Western world. It has even been argued that the spectacular continuous increase in life expectancy and general health during the past decades may come to a halt or even be reversed by the ongoing epidemic of obesity, particularly in the young (1). The concept of risk factor clustering has a longstanding history going back to the early 20th century (2), but the idea of linking such clustering to insulin resistance was raised in the famous Banting lecture of G. Reaven (3). Among the numerous current definition(s) of the MS (World Health Organization, European Group for the Study of Insulin Resistance, American Association of Clinical Endocrinologists, and International Diabetes Federation), the one proposed by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [NCEP-ATPIII]) (4) is most widely used. With good arguments, it has been criticized that some components in the NCEP definition are loosely, if at all, linked to insulin resistance as the assumed unifying pathomechanism (5). The “father” of the original idea, G. Reaven, even wrote a paper with the sarcastic title “The Metabolic Syndrome: Requiescat in Pace” (6). The shortcomings of the MS as defined by NCEP-ATPIII are obvious: The individual traits that compose the MS cluster have no tight relation to insulin resistance; predictive power is lost by omitting powerful predictors of cardiovascular risk, particularly age and smoking, and by adopting categorization (yes/no) for continuous variables (e.g., diagnosis of hypertension instead of using BP values [7]). This may explain the following findings: In the Groningen study, the Framingham score and microalbuminuria were superior to NCEP criteria as predictors of cardiovascular events in the general population, and in the Pittsburgh study (8), microalbuminuria was more predictive of events than the MS score in patients with type 1 diabetes—an outcome not shocking to the nephrologist who is already convinced that kidney function is a most powerful indicator of cardiovascular malfunction and risk. Despite all of these critiques, the lumping of the cluster of risk factors into one MS formula has remained popular. Although defective as a scientific tool, MS has the merit to have raised awareness of the obesity problem in the medical community and in the general population. The concept of the MS was originally created to predict cardiovascular risk. Given the link between cardiovascular and renal risks (as we know today, this cuts both ways), it is little surprising that obesity, particularly visceral obesity (9), and MS are related to renal malfunction (i.e., microalbuminuria and low estimated GFR [eGFR] [10–12]). This relationship is apparently also found in individuals with renal disease: In type 1 diabetes, the MS score was higher the more advanced the stage of diabetic nephropathy (13), and obesity (presumably also MS) is a risk factor for deterioration of renal function in primary renal