elevated alkaline phosphatase

[Jane]

Hi Dr. Agar.

Trust you had a good vacation. My question today is what does it mean if alkaline phosphatase becomes very elevated with nocturnal txs and what causes it?

[PeterLairdMD]

Hi Dr. Agar.

Trust you had a good vacation. My question today is what does it mean if alkaline phosphatase becomes very elevated with nocturnal txs and what causes it?

Let me jump in while Dr. Agar is out and about. Alkaline phosphatase is an enzyme found in bone and liver tissues primarily. There are many conditions that can cause the alkaline phosphatase level to become elevated. In dialysis patients, the mineral-bone disease brought on by secondary hyperparathyroidism is the usual cause of an elevated alkaline phosphatase caused by increase bone turn over. Going to nocturnal hemodialysis and extended treatments in many cases improves the mineral-bone metabolism lessening PO4 elevations and it usually reduces the need for phosphate binders as well as reduced need for vitamin D analogs that help control the vitamin D deficiency that is caused by renal failure. In such, PTH levels usually improve with switching to nocturnal dialysis regimens.

There are several simple tests that your medical team can look at to see if the elevation is related to bone or related to the liver. The first place to start with a dialysis patient is observing the relationships between PTH, PO4, Ca and alkaline phosphatase to see if it fits into a pattern associated with hyperparathyroidism. Many patients will eventually not respond to Vitamin D analogs or Sensipar and need to undergo parathyroidectomy to correct the underlying disorder of mineral bone disease. Once again, your nephrologist and your medical team should be able to observe the relationships between the factors listed above.

The difficult observation to make when faced with a clinical situation where we might expect elevations related to the renal disease is to always understand that there may be another process causing the elevation unrelated to the renal disease issue. Testing for liver enzyme abnormalities, obtaining liver imaging tests and other specific blood tests to exclude these rare entities should always be considered when evaluating elevations of alkaline phosphatase especially if modifying the renal related mineral-bone disease factors does not correct the elevation.

Fortunately, the majority of evaluations for an elevated alkaline phosphatase do not reveal any significant findings. Nevertheless, due to the many causes of an elevated alkaline phosphatase, a complete and thorough evaluation in every case should be completed expeditiously to identify what the specific cause is. Once again, the first place that the evaluation begins is determining whether it is an elevation due to liver or due to bone which is determined by a simple blood test.

I hope that this gives you some information to bring to your medical team for discussion of where to look further. I am sure that Dr. Agar can add further to this discussion.

Most sincerely,

Peter Laird, MD

[John Agar]

I couldn't have said it better, Peter.

Yes, though an elevated alkaline phosphatase may clearly mean persisting hyperparathyroidism and, yes, while many patients - despite the medical 'advances' of PTH suppression with Vit D and/or cinacalcet - do come to parathyroidectomy, it is important to exclude other sources of alkaline phosphatase.Pprimary liver and primary (unrelated) bone disease, like Pagets disease of bone and other bone-related problems do occur in renal patients and there are tests to exclude these, some of which Peter has already described.

Your doctor can methodically check for these and, if it is a problem unrelated to CKD and dialysis, then can take you down the path of appropriate treatment. If these other non-CKD problems are excluded and, by so excluding, the focus returns to the to CKD and unrepentant parathyroid disease, then if PTH cannot be suppressed by all the 'tricks' we now have available - and remember, no intervention works in ever patient - a parathyroidectomy may be the final solution.

Thank you, Peter, for your help. Keep it up. I need it!

And: PS, Jane ... thank you forasking just a single-barrelled question. It really is easier than a list.

John Agar

[Jane]

Nice to meet you Dr. Laird. TY for subbing for Dr. Agar. The tag team approach is great! Looking back over my lab reports, it seems my alk. phos began to increase the first month i went to nocturnal txs. That is a yr. ago now. Each month it would climb a little higher.

With nocturnal, my pre-PO4 decreased as I expected it would. It has been on the low side of normal ranging from 3.2 to 3.6 and I take a post phos 2 hrs post tx which has ranged from 2.2- 2.8. Calcium has been a little too elevated at around 9.8 - 10.0.

About 3-4 months ago, I went to 7 hr nocturnal txs having previously been on 8 hr txs. Right around in here was when my alk phos started a steeper increase.

Two months ago my PTH started climbing, going first to 400 and then to 600. I was on just one Vit D analog pill a week for months with PTH in range, but at this juncture my dietitian had me go to 2x/wk.. When she saw the PTH continuing to climb, she upped the dose to 4/week. At that point the PTH went back down to 400 and my current dose is 3x/week. I will be getting labs soon so will know if my PTH has come down some more. It did respond to the Vitamin D analog when the dose was increased to 4 as you can see.

I don't know why my PTH started climbing when I went to 7 hr txs., but overall, I am wondering if the lower PO4 and higher cal. I have had for a year now has anything to do with the elevated alk. phos.? When I went to 4x Vit D, my alk phos dropped a little , but it is still about 93 points elevated over scale.

Would the fact that my PO4 has been on the low side while my cal has been on the high side since starting nocturnal txs, be the likely reason alk. phos has steadily gone up? If I was able to take a supplement to get my PO4 up higher, do you think that would be the way to go?

Also, what is the name of the simple blood test you spoke of Dr. Laird? TY for helping me figure this out so I can bring this info back to my neph. He does not know what my alk phos is doing, but he has always told me that PTH changes show up quarterly when something shifts in the balance.

[PeterLairdMD]

Dear Jane, the blood test I was referring to is a fractionated alkaline phosphatase with can show where the major component of the elevated alkaline phosphatase is coming from with liver and bone the two major determinants of an elevated alkaline phosphatase but it can also come from other sites as well.

With an elevated Ca, low PO4 and high PTH and elevated alkaline phosphatase, as a patient, I would want to know what is precisely the cause which should be fairly easily determined with the appropriate tests by your medical team to offer you the best treatment options. The issue of mineral bone disease and the impact that nocturnal dialysis has on it is not a settled issue at this point that I can see from my review of the studies I have read to date.

Once again, with the varied causes of these elevations, sorting out the precise cause would be one of my priorities if I faced that issue myself. Establishing whether it is primarily liver or bone alakline phosphatase elevation is usually the first decision point in most protocols involved in looking at these issues.

Once again, Dr. Agar has much more direct experience in this in the dialysis and nocturnal dialysis population than I do and I am sure he has much more to add to this.

[John Agar]

Jane

There really isnt much I can add to the discussion. Alkaline Phosphatase has several origins. Not all are to do with the kidney or with kidney disease. For example, it can be elevated in all sorts of bone diseases - Pagets disease of bone is but one that quickly comes to mind. Liver disease needs consideration too. And, Peter is right - it is usually reasonable simple to work this out. Maybe this is the 1st simple step to take.

In addition ... and I cannot stress this enough ... a doctor (and his/her patient) must always be careful, in medicine, not to just 'treat a test'. It really should be incorporated into the Hippocratic Oath!

OK, OK - I know I am being a bit tongue-in-cheek there - but it really can be misleading, and even dangerous, to treat a test. It is the patient that must be treated. A test result must be interpreted, not in isolation, but in the context of the patient as a whole. Sadly, the medical defensiveness that is sometimes forced by insurance and litigation can bias and warp this simple tenet ... 'don't treat a test, treat the patient'.

Please don't misinterpret what I am saying here ... laboratory tests are beaut, but only up to a point. We have come to depend on them enormously ... as we should ... but this dependence must, in the end, always be tempered by a combination of wisdom and sane, careful thought. 'First, do no harm ..etc''

Not every abnormal test or change in test results will indicate a problem.

So, as I tell my students ... test and check, by all means ... but always, always bring common sense and wisdom to the table when interpreting the result you find.

John Agar
http://www.nocturnaldialysis.org

[Jane]

A little progress has occurred as I had hoped it would. This was the 2nd month to take vitamin D analog 3x. My PTH climbed from 420 to 484, but the ratio went from 2.1 to 1.6, indicating that the high bone turnover has slowed down and is right where it should be. In other words, a # of 1.6 shows a normal rate of bone turnover. My dietitian is keeping me at Vitamin D analog 3x.

Since I have been right in range for PTH and ratio for many months now, apparently PTH just took off a little bit and needed more Vitamin D analog then just the 1x week. I would think this larger dose will now bring things back under control and we will wind up tapering down the dose again. Thank you very much for your help here to see how to approach the matter. It appears the problem was simply related to PTH and with next month's labs we will see if we are still on the right track. Apparently, PTH can behave itself for a long period and then decides to go awol. Hope all that is involved here is leashing it back in again.

[John Agar]

Jane

Sounds good. Seems like this thread has resolved favourably for you.

Cheers

John Agar
http:www.nocturnaldialysis.org

[Jane]

I completely forgot to mention that alk. phos came down 50 points!