Reverse Epidemiology: Dialysis Paradox

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In this population, high BMI, BP, and cholesterol seem to be associated with better survival.

While obesity, hypertension and hypercholesterolemia are well-established harbingers of poor cardiovascular health and death, so-called reverse epidemiology holds that these physiological states actually increase the chance of survival in many people—including dialysis patients.

That's the controversial theory being put forth by a group of maverick researchers led by Kamyar Kalantar-Zadeh, MD, PhD, associate professor of medicine and pediatrics at the University of California in Los Angeles.

According to Dr. Kalantar-Zadeh, reverse epidemiology seems to apply to several populations that comprise between 20 million and 40 million Americans. Renal & Urology News recently spoke with Dr. Kalantar-Zadeh about his provocative theory.

What first made you think that obesity, elevated cholesterol, and hypertension might be protective in some patients?

It was the consistent and repeated observation that in some populations traditional CVD risk factors do not appear to be good predictors of death. For a long time, it was taken for granted that the poor survival rates seen in dialysis patients were based on the presence of traditional CVD risk factors, such as high blood pressure and obesity. But studies failed to show this. At the same time, research began to find high BMI and high serum albumin and lipid levels are consistently associated with better survival. All of these observations led, finally, to a unifying hypothesis.

Could you summarize the evidence in favor of reverse epidemiology?

The studies are mostly observational. This doesn't mean that interventional studies would show the opposite, it's just that there is a paucity of interventional studies. There have, however, been a few. For example, a study performed at the University of Würzburg in Germany two years ago showed that dialysis patients who took statins received no survival benefit at four years' follow-up compared with patients who received placebos. Many people were surprised, even shocked, by these results.

You've said there may be distinct populations in which obesity may be an advantage. Which populations are these and how might extra fat tissue be helpful?

In addition to dialysis patients, obesity seems to improve survival in patients with chronic heart failure, rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), cancer, and adults over age 80. All of these populations have some important commonalities: In all of them, wasting syndrome and malnutrition become more important markers for mortality than conventional risk factors.

Fat is a natural protective mechanism; the human body can store fat for the days of hardship when it needs nourishment, and it is therefore an asset for short-term survival. Until 30 or 40 years ago, being "chubby" was a surrogate for being considered healthy; in the past, some cargo ships selected staff by seeking out obese men because people with more fat tissue can better overcome infectious diseases.

In short-term survival, long-term risk factors become irrelevant; most people with end-stage renal disease, heart failure, cancer, and so on won't live long enough to succumb to the consequences of obesity, high blood pressure and high cholesterol. Looking at populations in which reverse epidemiology applies, we can better understand why humanity tends toward obesity; we are genetically programmed in a way that protects us against short-term threats, such as famine.

Chronic disease states are, in effect, a return to conditions that prevailed prior to the 20th century, when mankind had to focus on short-term survival. One might even say that traditional epidemiology is an emergence of a new association, and that reverse epidemiology is more natural.

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