bone health

[Jane]

Dear Dr. Agar,

My questions are:

1) Do nocturnal length txs improve bone health...should one doing nocturnal txs begin to notice any changes in the PTH, cal., phos balance and other bone issues for the better?

2) Does adjusting the hrs of tx to lets say from 8 hrs to 7 hrs have any affect on the PTH, cal, phos balance?

3) Also, I would like to know if in Australia, measurement of the PTH "ratio", along with PTH, is done as it is done by Scantibodies Labs in the U.S. for supposedly more accurate measurement of PTH? I find their website very informative. Our clinic uses their method, but I don't know any other patients whose nephs use Scantibodies. Not sure if Scantibodies is something we just have here in the U.S or if other countries have something similar.

I know, I know, I'm looking at the #s again, but I really do think like you, Dr. Agar, in that I believe dialysis should be individualized to the patient. If you had ever read any of my posts on this site you would know I have long advocated individualization/optimization and had attempted to get nocturnal txs for years before finally being given the opportunity about a year ago. This girl believes in optimal dialysis whatever that takes and I very much believe in starting with the best so it is possible to look at the big picture overall rather than having to focus on the #s. Unfortunately, that's not how dialysis has been typically done in the U.S. With barely adequate txs being the norm here for most of the patient population, is it any wonder we have been programmed to look at the #s ?!? I am most glad to be turning things around with my txs for the first time. THAT is a good feeling!

[John Agar]

1) Do nocturnal length txs improve bone health...should one doing nocturnal txs begin to notice any changes in the PTH, cal., phos balance and other bone issues for the better

There is conflicting evidence regarding the effect of NHD on bone. Early on in NHD – and this was our experience too – the Canadian team(s) found a sharp fall in bone mass density (BMD). BMD is not, mind you, a particularly accurate way of assessing bone ... but all/any of the method(s) available to us to measure bone metabolism are still very blunt and are, at best a very inaccurate science. Furthermore, dialysis patients are, in my experience, never very keen to enter studies that use bone biopsies - a fact neither surprising nor unexpected ... and nor can I blame them.

It was soon realized that to sustain a positive calcium balance and to improve calcium uptake from bone, a higher than usual dialysate calcium was needed in order that calcium could be moved 'in' rather than 'out' across the dialyser membrane. For most (not all) NHD patients in our program, we found that a dialysate calcium of between 1.5 and 1.75mmol/L seemed to be about right … so much so that Fresenius (Australia) now make a special NHD dialysate for us with a 1.6mmol/L calcium concentration – an amount we think is, for us, pretty much where it should be. There has also been debate (unsolved as yet) whether Vit D should or should not be given - and if so, in which form and how much - as PTH falls without calcitriol (or paracalcitrol). PO4 is also so well controlled that in the more frequent forms of NHD, PO4 must be given back via the dialysate and, in addition, as the calcium x phosphate product is so low, some mild low-level hypercalcaemia at the end of dialysis might not only be on no consequence but actually be seen as an advantage. We like to see our pre-dialysis Ca++ levels at ~2.40mmol/L - and this will rise such that, by the end of dialysis, the Ca++ is ~2.60-2.65mmol/L as the PO4 levels fall from a mean pre-dialysis level of ~1.35-1.45mmol/L to ~0.65-0.75 mmol/L by the end of dialysis - the calcium phosphate product throughout being commonly <3. Is this the right approach? Will bone benefit or not? In truth, no-one knows. It seems to be the right approach - to us. We think bone will benefit. But, do we know? ... no, in truth, we don't. Sadly, patients sometimes expect too much of us ... or too often think (or expect) all the answers to be known. They aren't. We can only do what we think is best. We must try to keep an open mind and learn along the way.

Jane, put simply - we still just dont know enough about all this - nor what is right, or right for most. And, as for 'noticing changes' ... we dont even know (or agree on) what changes we should notice. We can't agree how best to measure - your later question (Part 3) about the way to measure PTH is just such one case in point.

Bone metabolism in dialysis patients is a debated, uncertain and still largely unknown or poorly understood area (indeed, one of the most debated, the least known) - and all the wishing will not and does not change that. I suspect it will be thus for many years yet. It will be a long time before we really understand what happens to bone in renal failure or how our treatments (long, short, frequent, infrequent) influence it - either for the good or for the bad - and what exactly we should do, one way or the other. It is an area where there are more questions than answers - and much of what you have asked is just not known ... there are hot opinions, yes, but facts - few! Hot opinion does not equal knowledge ... and knowledge, we lack.

As all of this information (and debate) is in the medical literature and is still medically neither solved nor agreed, I think any ‘additional’ discussion is probably beyond the scope or need of most patients who read these pages.

2) Does adjusting the hrs of (treatments) to lets say from 8hrs to 7 hrs have any affect the PTH, cal, phos balance?

No … I doubt it … certainly not an effect that could be demonstrated nor one of likely clinical significance. Our current assessment techniques of bone metabolism are blunt, at best, and no statistical difference would be able to be shown with such a minor change.

3) Also, I would like to know if in Australia, measurement of the PTH "ratio", along with PTH, is done as it is done by Scantibodies Labs in the U.S. for supposedly more accurate measurement of PTH? I find their website very informative. Our clinic uses their method, but I don't know any other patients whose nephs use Scantibodies. Not sure if Scantibodies is something we just have here in the U.S or if other countries have something similar.

No. we do not, clinically, use the Scantibody assay. The majority (if not all) papers on this issue seem to suggest that there is little or no advantage. Again, you will no doubt be able to quote some who would disagree with me but most of the information I have seen on this subject is summed up (here paraphrased) by a UK group from Nottingham (Godber IM, Parker CR, Lawson L et al: Annals of Clinical Biochemistry) who concluded ... “the 'whole molecule' PTH assay (ie: the "Scantibodies” assay) is unable to discriminate and provides very little additional clinical information to that obtained from the intact PTH assays”.

I suspect their general conclusion underlines why, to my understanding, the ‘ratio’ process is not widely used. Again, it may be in the US and if it is, this maybe a US-centric phenomenon ... though I am unable to comment of the % of laboratories in the US who do or do not use the Scantibody process. It is probably too narrow a discussion to follow further with here.

John Agar

[kamalshah20]

Thanks so much for this thread, Jane and thanks so much for your response Dr. Agar. I have been struggling with severe bone pain for the last 2 months. I have had a very low phosphorus ever since I switched to daily nocturnal. No amount of oral phosphorus supplementation helped. I also tried adding a phosphate enema to the dialysate but stopped after about a week for other reasons. My PTH was very high at one point. I started cinacalcet for this and it came under control. My active Vit D was very low for which I started calcitriol about 2 months back. PTH is now normal (179). My inactive Vit D level is normal.

The bone pain however continues to get worse with every passing day. I am unable to walk properly. Even turning from one side to another on the bed while lying down is painful. The bone pain is in my back, my ribs and my feet. Any strain on any of these areas causes pain. There is no pain if I am just sitting still or lying still. Any movement that causes these areas to get some strain causes pain.

We have done the DEXA scan, several X Rays, an isotope bone scan and even a Serum protein electrophoresis. All of these have been normal or did not show anything other than secondary hyper parathyroidism (isotope bone scan showed this). My nephrologist has no other ideas about what the cause could be.

I am using a low Calcium dialysate and this is due to my Calcium becoming high about 2 years back. My Calcium is currently 7.5 mg/dl pre dialysis and 8.4 mg/dl post dialysis which after reading your response above I realize is lower than what it should be. My nephrologist has suggested switching to a regular Ca dialysate and I am doing that immediately.

Currently the bone pain is my biggest problem and I am really at a loss about what I could do. It is affecting my life in a very negative way as merely going about my daily activities has become difficult. Dr. Agar, do you have any suggestions on what the problem might be?

Thanks
Kamal

[kamalshah20]

I think I may have hit upon the reason for my bone pain!

Around October 2007, my Calcium went high - about 11.7 mg/dl (normal 8.5 to 10.5 mg/dl). At that point my nephrologist asked me to stop taking Calcitriol and asked me to switch to a low Ca dialysate. The normal dialysate here has 3 meq/l of Calcium. He asked me to switch to one with 2.25 meq/l. I did that. Initially I used to check the label on the Acid can and it was right. I checked the label on the acid can a few minutes back. Guess what - it is only 1.5 meq/l !!! I don't know when they started supplying these extremely low Calcium acid cans! This is far lower than what I had wanted.

I have not been checking the label from many months. I somehow feel that this is the reason for my bone pain. Too much calcium being pulled out from my blood and consequently from the bones. I am ordering a batch of normal Calcium acid cans immediately and will be switching to that from tonight.

I really hope my reasoning is correct!

Thanks
Kamal

[John Agar]

Dear Kamal

I am not surprised you have bone pain … and I think the problem is your calcium! As you say, your PO4 levels are in your boots but so are your calcium levels. No wonder your PTH is so high and, even though it has ‘responded’ to Cinacalcet, from what I can deduce from what you have told me, I think you need calcium … and a truckload of it.

You say you have had a Dexa scan but I don’t know your Z scores which, my guess is, would be minus – and lots minus too.

In my SI unit language, I have your pre- and post- calcium levels ranging 1.87 – 2.09 (that is if I understood the meaning of the numbers you gave – 7.5 – 8.4 - and if my conversion tables are right and the conversion = mg/dl x 0.2495). I would suggest that you need a bath (dialysate) calcium of 1.75 mmol/l and lots more calcitriol than your current dose too.

Admittedly, advising like this has lots and lots of traps and I neither know you nor your other circumstances but certainly, on the face of it, you are likely decalcifying bone at a great rate. No wonder you hurt ++++. You need to have that looked at – and quickly.

You will need to have your calcium levels monitored quite closely but that, I think, is the answer. I am not at all surprised you are in pain. It can be reversed but it needs hands on and careful monitoring. I think (and I know Andreas Pierratos thinks similarly) that when the phosphate is so low (as it is in frequent and overnight NHD), that modest post-dialysis hypercalcaemia is OK ... up to a Ca++ blood level post-dialysis of 2.7mmol/L or even up to 2.75mmol/L (provided the PO4 is low - which it is). That is probably, at least in the short term, where you should be aiming your post Ca++, at least until your pains settle ... and that may take a while as I suspect the rate of Ca++ leeching form bone has been quite high .... then, maybe, it would be time to drop the posts back to a 2.6 range thereafter.

As your PO4 is low (and in you, it seems to have been very low), I still think you will need PO4 supplementation in some format and as your CaxPO4 product is low, the risk of extra-osseous calcification (like calcifying your blood vessels) is also low ... if any risk is there at all (which I suspect there isnt). Pierratos has shown resorption of extraosseous calcification on NHD with high dialysate Ca++ concentration but a low phosphate and a low CaxPO4 product.

Go get some calcium!

John Agar

[kamalshah20]

Thanks so much Dr. Agar for your explanation. It all makes sense now! I am going to switch to the 1.75 mmol/l Ca acid right away.

Kamal

[kamalshah20]

Just wanted to post a quick update - after 4 days of using regular Calcium dialysate (3 mEq/l) and one day of nigh Calcium dialysate (3.5 mEq/l) - I got only 5 days of dialysis last week, was on a holiday - my Calcium is now 10.7 mg/dl or 2.675 mmol/l. My Phosphorus is at 1.7 mg/dl or 0.548 mmol/l. I had also doubled my dose of Calcitriol to 0.5 mcg/day from 0.25 mcg/day.

My Phosphorus has fallen a little. I have been adding the phosphate solution (100 ml) to each can for more than a month. Last week, pre dialysis Phosphorus was 4 mg/dl or 1.29 mmol/l. I wonder why it has fallen.

Dr. Agar, I just thought I would post the update here for you when you returned!

Thanks
Kamal
http://kamaldshah.com

[kamalshah20]

My post dialysis Calcium is 13.0 mg/dl (3.250 mmol/l) and post dialysis Phosphorus is 1.4 mg/dl (0.45 mmol/l). The Ca-P product is 1.46.
My pre dialysis Calcium is 10.7 mg/dl (2.675 mmol/l) and pre dialysis Phosphorus is 1.7 mg/dl (0.55 mmol/l). The Ca-P product is 1.47.

I guess the Calcium is way too high. This is after using a Calcium solution of 1.75 mmol/L for 2 nights. The second night is when these tests were done.

The best part is my bone pain is starting to get better - I would say about 10% after only a week of changing the acid cans to normal or high (high for the last 2 nights).

My question to you Dr. Agar (when you return from vacation) is how long would you say is it ok to have this high a Calcium without running into the risk of extra osseous calcification? I am checking my values every week.

Thanks so much for your help Dr. Agar! I couldn't have gone this far without you!

Thanks
Kamal
http://kamaldshah.com

[kamalshah20]

One more update:

After another week of regular Calcium dialysate (1.5 mmol/l of Ca) and 0.25 mcg/day of calcitriol in addition to 30 mg of cinacalcet every other day, my PTH has plummeted to 4.7 pg/ml (normal 7 to 53)!! This had at one point reached 1015! I think this proves that the low Calcium was the root of all the problems. I am stopping my cinacalcet completely and am continuing to use regular Calcium dialysate (3 mEq/l or 1.5 mmol/l) and continuing to use 0.25 mcg/day of calcitriol. I am not sure if I should continue the Calcitriol because that will further cause the PTH to go down. My calcium is currently 10.5 mg/dl (2.625 mmol/l). As always I am discussing all this with my nephrologist. But your thoughts on this would be greatly appreciated, both by my nephrologist and me because there is very little (no? ) experience of nocturnal dialysis available here.

Thanks
Kamal

[John Agar]

Kamal

I am not really back from leave till next Monday but have taken 2 days out of my holiday to go to the 3rd Australian and New Zealand Home Therapies workshop in Brisbane (http://www.hometherapiesworkshop.com.au for any who want to check the program) and I thought I'd drop you a line.

Yes ... I would back off the calcitriol entirely for the moment till your PTH drifts up a little though later, when it recovers to about the 15-20 range, a smidge of calcitriol should begin again, I think, though this needs to be run by your nephrologist and monitored by him/her.

Is the bone pain any better?

John Agar