NephMadness 2015: Nephrology and Nutrition Region

Joel Topf, MD; Allon N. Friedman, MD

Disclosures

March 02, 2015

Editorial Collaboration

Medscape &

In This Article

Obesity: ESRD Risk Factor vs Obesity: ESRD Survival Factor

At no point in his career did Shaquille O'Neal's points per game (career 24.6, highest season average 28.1 in '97-'98) exceed his BMI (35), but what a career he had, spanning 18 years. So could these two factors be linked? Could increased BMI drive a long career, and could the same go for dialysis patients?

Obesity: ESRD Risk Factor

One large weakness in the reverse epidemiology theory is how can it just disappear after transplant. But study after study finds that obesity is no longer protective but harmful for kidney transplant recipients.

Meier-Kriesche et al looked at patient and graft survival after transplant based on the BMI at transplant, examining 52,000 transplants from 1988 to 1997. The authors found a U-shaped curve, similar to the one found for the normal population, with increased risk of death/graft loss at a BMI below 20 and ever-increasing risk as BMIs rise over 26. Similar results were seen in a surgical study that looked at both delayed graft function and non-death censored graft survival. For both outcomes, increasing BMI was harmful.

Additionally, while much of the increased BMI is due to fat, when attempts were made to look into what drove survival, patients with increased muscle mass driving the increased BMI did better than patients with fat driving the increased muscle mass. In fact, the high BMI group with low muscle mass actually did worse than the normal BMI and high muscle mass (14% higher all-cause and 19% cardiovascular death).

A second group looked at the same question but instead of using 24-hour urine creatinine clearance at the onset of dialysis (a potentially suspect methodology) they used dual X-ray absorptiometry to look at body composition. Not surprisingly BMI was positively correlated with both lean mass index (LMI) and fat mass index (FMI). After 54 months of follow-up they found the familiar finding of lowest mortality in the highest BMIs but they then had data which separated out fat and lean body mass:

Patients in the highest FMI tertile had the lowest risk for all-cause mortality, although it was not statistically significant (P = 0.134). The patients in the highest FMI tertile showed a significantly reduced risk for non-CVD mortality (P = 0.004).

Similar analyses were performed for LMI, although no significant univariate association was found between the LMI tertiles and the risk of death from all-cause, CVD, or non-CVD events.

So, this data doesn't seem to be consistent with the CrCl data. Another team used near infrared (NIR) interactance technology to determine the percentage body fat. They also used the Short Form 36 quality of Life Scoring System to expand the research beyond survival. And they tried to correlate the data with inflammatory markers.

Interestingly, CRP and TNF-alpha concentrations were significantly higher in the lowest body fat percentage group than in the other 3 groups. (P=0.06). Quality of life scores worsened as percentage body fat went up. However the benefits of obesity still shined through with increased fat percentage being associated with better survival.

And once again, when investigators looked at weight loss, they found the same concerning findings uncovered in other trials: loss of at least 1% body composition fat resulted in a 30-month mortality HR of 1.98.

Though the bulk of data seems to be in line with obesity, the weight-loss data should be stratified for intentional versus unintentional weight loss. In total this theory is being driven by epidemiologic data and association does not indicate causation. It is time for a trial of intentional weight loss so we can get some real answers.

Obesity: ESRD Survival Factor

Everyone feels like they know health when they see it. And everyone knows that obesity is not good for you. It is common sense that if you are obese you need to lose weight. Strangely, these seemingly immutable laws break down in the topsy-turvy world of dialysis. Obesity, which is a potent risk factor for death in normal populations, becomes a survival factor in dialysis.

How can a condition called "morbidly obesity" be a survival factor? From Kalantar-Zadeh's analysis of weight and survival, "Both all-cause and cardiovascular mortality showed almost strictly decreasing rates across increasing BMI categories, ie, morbidly obese MHD patients had the greatest survival rates." Reading that article you can almost feel the authors' frustration at their inability to find an association of mortality with obesity: "Obesity, including morbid obesity, was associated with improved survival and decreased cardiovascular mortality, even after exhaustive adjustment for time-varying laboratory markers. These associations were independent of changes in BMI over time."

Kalantar-Zadeh then looked at patients with low and high protein intake, obesity was still protective, right up to and including the morbidly obese. Probably most troubling was the data on patients who changed weight. Half the cohort maintained a stable weight, the other half of the cohort gained or lost more than 1% of their baseline weight.

Gaining weight had a higher mortality than a stable weight but losing weight was the most dangerous of all. Consider that, the next time the transplant team recommends your patient lose weight to become transplant eligible. The obesity paradox persists regardless of dialysis vintage or patient age.

As perplexing as that is, it is not unique to ESRD; obesity has been described as a survival factor in congestive heart failure.

COPD also has increased survival with increased BMI, as has rheumatoid arthritis. But the story truly takes a turn for the weird if you believe the results of Kovesdy et al, who looked at pre-dialysis CKD and found a survival advantage for obesity. And the advantage got larger the greater the BMI, with the best survival being reserved for patients with BMI over 36.7. The pattern was stronger in non-diabetic patients than diabetic patients, but the pattern was still there, even in diabetics.

However, other researchers have found obesity to be a potent risk factor for developing ESRD. Alan Go's team used Kaiser Permanente data to demonstrate a strong BMI dependent risk of increased ESRD. One possible limitation of that data is, if obesity is actually a survival factor, one would expect more ESRD with obesity because fewer patients would be dying of other illnesses, leaving them alive and at continued risk of ESRD. Thinner patients with higher risk of death would be less likely to survive to dialysis.

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