Reverse epidemiology, obesity and mortality in chronic kidney disease: modelling mortality expectations using energetics.
OBJECTIVE
Obesity is a predisposing factor for chronic illnesses such as type 2 diabetes, heart disease and cancer. In chronic kidney disease (CKD), the effect of obesity on mortality is reversed. Obese patients appear protected. Two ideas have been advanced to explain this 'reverse epidemiology'. First, obesity may buffer patients from wasting. Second, fat may sequester uraemic toxins leading to a systematic error in the prescription of dialysis. Our aim was to use data on the scaling of daily energy expenditure, fat and lean tissue mass to predict the pattern of variation in mortality with obesity under the contrasting hypotheses.


METHODS
We used data on daily energy demands measured using the doubly labelled water technique and body composition collected on a cohort of 503 individuals to model the expected impacts of wasting and fat sequestration/underdialysis on mortality.


RESULTS
A model predicting mortality due to wasting replicated the mortality pattern of the obesity paradox. However, quantitatively the beneficial effect of being fat was predicted to be much larger than that observed in the actual CKD population. Similar results were found for the fat sequestration/underdialysis hypothesis, but in this case the discrepancy was smaller.


CONCLUSIONS
These models tend to support the fat sequestration and underdialysis idea more than the wasting hypothesis. In part (or in whole) this may be because of inadequacies in the model construction which are currently based on rather crude assumptions. Refinement of the models may enable better tests between alternative ideas for the obesity paradox.
Speakman
John R
JR
Aberdeen Centre for Energy Regulation and Obesity, Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, UK. j.speakman@abdn.ac.uk
Westerterp
Klaas R
KR
D000273:Adipose Tissue / Q000378:metabolism*; D001823:Body Composition; D001834:Body Water; D001835:Body Weight; D002100:Cachexia / Q000209:etiology / Q000378:metabolism; D002908:Chronic Disease; D015331:Cohort Studies; D015897:Comorbidity; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000401:mortality* / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000401:mortality / Q000628:therapy; D008297:Male; D008954:Models, Biological; D008957:Models, Genetic; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics; D011379:Prognosis; D006435:Renal Dialysis / Q000379:methods*; D012641:Selection, Genetic; D013217:Starvation / Q000235:genetics / Q000401:mortality; D014118:Toxins, Biological / Q000378:metabolism
D014118:Toxins, Biological; C026865:uremia middle molecule toxins