MINERAL METABOLISM AND FRACTURES, PRURITUS, AND SLEEP DISTURBANCES
Bjorn Wikstrom, Uppsala, Sweden
 
Chair: F.K. Port, Ann Arbor, USA
N. Lameire, Ghent, Belgium

 

Prof. B. Wikstrom
Department of Medicine, Nephrology Section
University Hospital
Uppsala, Sweden

Slide 1

Prof Wikstrom: Mr Chairman, I want to thank the organising committee for inviting me to this DOPPS symposium. If you look at the title, it may seem that it could be difficult to link the different parts of it to one whole thing but I will do my best during this short presentation for that.

Slide 2

High phosphorous and calcium levels are very common in hemodialysis patients and there is much growing evidence now that this mineral metabolism abnormality is associated with high mortalities, especially cardiovascular mortality. We can also identify some clinical consequences of the high phosphorus and high calcium such as the cardiovascular events, maybe amputations, fractures, maybe pruritis we have seen, bad sleep quality and the high phosphorus and calcium can also influence the poietin doses and the correction of haemoglobin levels.

Slide 3

Now, let's start to look at the serum phosphorus levels. From DOPPS data we can see that high serum phosphorus levels are associated with a significant increased risk of cardiac death. This distribution of the relative risk is however, bimodal, so we can see the same thing with low phosphorus levels and you should also look at the range of this serum phosphorus falling into the KDOQI guidelines. As you can see, the majority of the levels are outside.

Slide 4

Now, if you turn to serum calcium, you can see a similar increased relative risk for cardiac death in the high range but contrary to serum phosphorus there is a decrease, a significant decreased relative risk of cardiac death in low, in hypocalcemia, in low levels of serum calcium and as for phosphorus, a very limited amount of the values are falling within the KDOQI guidelines.

Slide 5

If we look at the baseline calcium phosphate product levels, we can see that there is an increased, a weak increased relative risk of a new cardiovascular event such as myocardial infarction but if you look at heart failure, stroke and peripheral vascular disease, there's an increased relative risk of the new event for every level of raised calcium-phosphorus product.

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Slide 7

Now, amputation, we know that high levels of calcium and phosphate promote vascular calcification and in DOPPS we asked for new amputations and when analysing new amputations in diabetics as well as in non-diabetics and when analysing the data we found a significant increased relative risk of new amputation in diabetics as well as in non-diabetics, if we looked at the different calcium phosphate product levels. This was more marked in non-diabetic patients, but you have to be aware of the incidence of amputation in diabetics was almost ten fold higher.

Slide 8

There was a wide variation between the countries of the incidence of amputation, so with the United States as the reference we could see raised relative risk especially in Belgium, France and Germany. On the contrary, in Japan there was a decreased relative risk in the diabetics. Also so in the non-diabetics and the Japanese figures were somewhat similar to the UK figures.

Here we can notice that in non-diabetics there is no variation, no difference between the reference United States and the other countries in DOPPS. It's also worth to note that the prevalence of amputation, prevalence of amputation was around 15% among the diabetics in dialysis patients and among around 2% in the non-diabetic patients. The total, the overall figure was around 6 %.

Slide 9

Something about fractures.

Slide 10

In DOPPS too there was a question about the history of hip fracture for the patients. Hip fracture, typically is a complication of osteoporosis, however, when we analysed the DOPPS data we found an increased adjusted odds ratio for having a hip fracture when you had a serum calcium more than 10.2 mg/l and the overall odds ratio was 1.2mg/decilitre higher calcium. The reason is unclear maybe one can speculate about more brittle bones with the heavy calcium deposition.

Slide 11

Pruritis is a pain still existing, it's a pain for the hemodialysis patients and a problem in many centres. In the DOPPS too pruritis was defined by a patient reported itchiness during a 4-week period prior to the questionnaire completion.

Slide 12

It looked like that pruritis was very common among the DOPPS patients. 46% of the patients had moderate to extreme degree of itchiness pruritis.

Slide 13

Looking further into the data this pruritis was significantly associated with the higher serum levels and also with higher calcium levels.

Slide 14

If we look at the mortality and pruritis, we found a little bit surprising that pruritis was associated to mortality and in the extreme degree of pruritis there was a 23% greater relative risk of death. But when these data were adjusted for sleep quality, the relative risk of death decreased almost 10%.

Slide 15

So the interpretation of this will be that sleep quality is a confounding factor behind this phenomenon.

Slide 16

A simple algorithm then for pruritis and mineral metabolism abnormalities such as high calcium and phosphorus might be that hypercalcemia and hyperphosphatemia create pruritis, which gives in turn poor sleep quality, and sleep quality contributes to a higher mortality risk. We don't know for sure if pruiritis per se contributes to the higher mortality risk but it notes worth to remind you that almost 50% of the hemodialysis patients across this DOPPS report had moderate to extreme pruritis.

Slide 17

So my conclusion of looking at this data is that despite existing guidelines, high phosphorus

Slide 18

and calcium levels still are common among hemodialysis patients.

Slide 19

And that these mineral metabolism abnormalities create associated with the mortality especially cardiovascular mortality and the links in these cases may be these ones, the cardiovascular events, amputation fractures, pruritis and sleep quality and in this conclusion I also want to say we could also expect better outcome hopefully for hemodialysis patients when serum calcium and serum phosphorus values are kept within the KDOQI guidelines.

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Thank you for your kind attention.

 
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