Paradoxical Effect of Risk Factors in Dialysis

[stauffenberg]

In the general populaton, mortality increases if people are obese, have high blood lipids, and have high blood pressure.  But the curious fact is that all three of these risk factors for the general population operate as protectors of health in the dialysis population and correlate significantly with better survival rates.  Why this is remains a mystery, but it indicates how radically strange the physiology of the dialysis patient is compared with that of people who do not have endstage renal failure.

One of the many sources discussing this phenomenon is K. Kalantar-Zadeh, et al, "Reverse Epidemiology of Cardiovascular Risk Factors in Maintenance Dialysis Patients" KIDNEY INTERNATIONAL, vol. 64, no. 3 (September, 2003) 1138.

[spacezombie]

Wait... so I should eat more fatty food and drink tons of coffee?

I thought being obese was a risk factor for many complications. This is not true on dialysis?

[annabanana]

I think the issue is that people who have very little fat don't do as well. There's a lot of people inbetween "skinny" and "obese".

[Sunny]

Good to know. Now I have an excuse to gain lots of weight, keep my blood pressure at minimum acceptability, and not exercise.
So now I've just got to get my doctors to agree. I've already got them thinking red wine is good for me.

[jbeany]

I thought the studies showed that an overweight dialysis patient had better outcomes, not an obese dialysis patient?  An advantage to being a bit chubby would make sense - anyone stick thin on dilaysis would have no reserves when they get sick and can't eat. 
The higher blood pressure makes sense in the same way.  If you have really low bp, it's going to be really hard to pull enough fluid off - you would crash while the fluid was trying to shift from your tissures into your blood stream where it could be removed.  I was still on bp meds when I started NxStage and had to go off them to keep from constantly crashing.  My bp runs a tiny bit higher the rest of the time, but if I take meds to drop it, then I never get the fluid off.

[Bajanne]

Hmmmmm... Interesting, says an overweight dialysis patient with  hypertension and fairly high triglicerides!

[devon]

I will forward a copy of this thread to my doc!

Thank you!

-Devon

[okarol]

The article is quite lengthy, but you can read it here: http://www.nephrology.rei.edu/RevEpi_03.htm Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients

I have included the conclusion only, below:

CONCLUSION

The reversal of certain key risk factors in dialysis patients poses serious questions. Is the increasing prevalence of obesity and its detrimental impact to health in the general population of any relevance in dialysis patients? Do overnutrition, obesity, hypertension, or hypercholesterolemia that promote atherosclerosis and mortality in the general population prevent poor outcome in dialysis patients, and if so how? Should dialysis patients be advised to increase their nutrient intake in order to gain weight and to increase their serum cholesterol, creatinine, and homocysteine levels? Should their target blood pressure be higher? Can these reversed relationships be used to establish therapeutic goals?

Publication bias may have handicapped or delayed reporting such paradoxical findings in dialysis patients as the association between plasma homocysteine and cardiovascular disease in dialysis patients, since the investigators' first impression upon encountering results with inversed association may be to consider them erroneous or flawed and hence be reluctant to report them [131]. However, as more reports indicative of reverse epidemiology in ESRD have been published recently, more investigators may be encouraged to report their similar findings. This may explain why more frequent reports and publications consistent with the reverse epidemiology have emerged only recently.

It is important to appreciate that some of the discussed risk factors may represent different biologic or medical phenomena in ESRD patients as compared to the general population. Serum creatinine, for instance, is a reflection of renal function in the general population, whereas it is essentially representative of skeletal muscle mass and/or meat ingestion as well as the dose of dialysis in ESRD patients. Similarly, a pre-dialysis blood pressure measurement may represent a different underlying disease processes in hemodialysis patients who are often volume overloaded. Thus, a low predialysis blood pressure in patients who are likely to be volume expanded is more probably due to a sick heart, whereas in the general population it may more likely indicate excellent circulatory homodynamics. Hence, the etiology of "reverse epidemiology" in dialysis patients may be quite different for various risk factors, and the term "reverse epidemiology" may be a misnomer. Nevertheless, it is important to first exhaust the possibility of a single unifying entity to be accounted for all or most of the above-mentioned risk factor reversals. We believe that PEM and inflammation (MICS) are the best candidates.

Despite all these concerns, the evidence is strong that a risk factor paradox indeed exits in those who reach ESRD and who continue to have an unacceptably high rate of mortality, currently approximately 20% in the United States. This high mortality rate has not substantially been changed in the recent years despite aggressive efforts toward an optimal management of traditional risk factors in these individuals. Hence, it is important to explore the causes of reverse epidemiology and to ascertain how best to reverse these associations in dialysis patients. We believe that in dialysis patients more attention should be focused on optimal management of under-nutrition and inflammation based on the mechanisms responsible for the reverse epidemiology. However, premature or radical conclusions to discontinue antihypertensive or antihyperlipidemic treatment should be avoided until such information is forthcoming. For instance, the antihypercholesterolemic agent, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor or such antihypertensive agents as angiotensin-converting enzyme inhibitors may have an anti-inflammatory effect, which can be beneficial in the management of the elements of MICS and improved outcome in dialysis patients irrespective of the existence of reverse epidemiology [132-135]. It is also important to appreciate that most of the examples of reverse epidemiology do not apply to renal transplant recipients, in whom obesity and hyperlipidemia are still reported to be quite common and strong risk factors for cardiovascular disease and poor outcome [136].

Although data presented in this review suggest that a higher body mass, hypertension, and hypercholesterolemia are associated with reduced morbidity and mortality in the vulnerable population of ESRD, it is possible that, in the long run, overweight patients may suffer from more cardiovascular consequences if they could survive sufficiently long [137]. Therefore, extended observations with sequential measurement of BMI, blood pressure, and serum levels of cholesterol, creatrinine, homocysteine and other relevant markers should be helpful to identify different subgroups of dialysis patients who may have traditional epidemiology as well as those who have reverse epidemiology. As more effective treatments for ESRD patents become available, it is possible that there may be a reversal of the reverse epidemiology and a return of the traditional epidemiology to many subgroups of dialysis patients, as is currently found in kidney-transplant patients. The question may remain unanswered as to what is indeed the normal epidemiology and what is reverse. Randomized, prospective, controlled clinical trials to examine the reversal of the traditional associations or the paradoxic risk factors will be most beneficial to the maintenance dialysis patients.
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