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?
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?
[QUOTE=Jane;19384]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?[/QUOTE]
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.
Peter Laird, MD
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.
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.
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.
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.
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.
Sounds good. Seems like this thread has resolved favourably for you.
I completely forgot to mention that alk. phos came down 50 points!
Although my elevated alk. phos soared down 50 points when I got a slightly higher dose of vitamin D months back, it then remained in a holding pattern, still elevated but much less. There has been no change all this time until this week when I could not dialyze 2 out of 6 nights due to a machine issue. We did labs at the end of the week and my alk phos had come down another 23 points. Wondering if there is any relationship between the loss of dialysis time and the lowered alk phos.? I did not get my PTH result yet, but I am guessing it is up another level considering the last time we did PTH it was heading upward, but it had been decided not to increase the dose yet.
I come back to the same issue we have dealt with before …
Lab numbers are not the be-all and end-all!
You have to understand … try to and please try to grasp this concept … that there is a measure of laboratory error in a every measurement we use … be it a creatinine, a haemoglobin, a calcium, a PTH, an alkaline phosphatase, an anything, an everything!
For a simple example … and this is NOT meant to represent every lab measurement we make but it is just an example … at a creatinine of 110, the reading may read as much as 3-4 umol/L higher or lower than the true creatinine … so … yes … the MACHINES and the METHODS do have error!!!
However, the degree of variance depends … (if we take the simple example of a creatinine measurement, though I COULD use any biological measurment) … on the creatinine measuring method used for that measurement. As regards measurement techniques, there are several commercial kits and/or methods out there and, there is an additional fact that even for any one specific method, there is also an error!.
People think that a creatinine is a creatinine … No … this is NOT SO!
It is a biological measurement.
As such … it has error.
The same applies for an alkaline phosphatase too. And to an Hb. And a calcium. And an ‘anything’.
Back to the example of a creatinine … that means that for at a TRUE creatinine of 110, the same sample of blood measured 10 times may give 10 different values … reading as low as 106 or 107 and/or as high as 113 or 114.
You can see from this that it is possible that a true creatinine might have been 110 on both occasions and the 106 (1.2) and 114 (1.3) were just spectral error ends of the same actual creatinine.
In this example, the 1.2 (106) and 114 (1.3) are, indeed the same creatinine!
I hope you can understand from this that this makes interpretation difficult! A creatinine, an alkaline phosphatase … an anything … is not immutable … it is not sacrosanct! It is a movable feast!
What this is meant to do is infuse into you the possibility that any ONE reading must be taken in context with ‘trends’ … with ‘circumstance’ … with medication changes … and NOT taken as sacrosanct within the context(s) of a range of different factors.
So … one reading … like one swallow … doth not make a summer!
I interpret biological measurements within the context of the patient. None are taken or interpreted in isolation. Rarely is a changing measurement taken as ‘to be acted upon’ unless it is in overall ‘contextual’ or ‘makes sense’.
So … your question … wait for the next measurement!
Don’t act precipitously.
Or … to use an Australian-ism … don’t get your knickers in a knot!
I’d not be doing anything … other than waiting for the next 2-3 monthly bloods!
I hope that helps … So … in brief, I’d not be getting too paranoid over one reading … be it Alk Phos or any other … I (and most f my nephrology colleagues) … would, note, think, remember, but not act.
So … you, as patients, need to understand that one reading may NOT be an absolute. It may be a ‘pointer’ … a heads up … but is rarely a call to arms!
Watch … and, yes, be interested, be involved … but … don’t be paranoid … things change … often for reasons we don’t understand … or even need to ! … and for lots of reasons … so, in your example, I’d watch, repeat in 2 months and … this time? … do nothing!
I am very observant of what affects my labs. If the difference is only a few points either way it means little to me. But if a see a more significant change of, in this case, about 23 points, or the previous time 50 points, then I look to see if anything was different. My labs stay pretty much the same within a few points unless something has changed. It doesn’t mean I am going to run out and do something. No, I just continue to observe and act accordingly should my team and I see a trend. We know a more sizable jump can be due to a lab error as well. By being observant and acting at the appropriate time, I have gotten various labs under control thus less medication or the correct dose of medication and problems like bone pain or yo-yoing Hgb don’t occur anymore.
Dear Dr. Agar,
It has been some time since I have posted as things are going well on nocturnal txs. In my first year of doing nocturnal, had to decrease my 8 hr txs 6x to 7 hr. txs. as there was no solution in sight for the over-removal of phos and potass. using NxStage technology. I thought surely NxS would address this issue so that other home patients and I could get back up to 8 hr+ txs, but years later the co. has still not done anything with it. At the same time, my alkaline phos. became very elevated with the initial 8 hr txs. It was not until I switched to 7 hr txs months later that I began to see my alkaline phos begin to decrease and come back into normal range. Phos, cal, PTH and potass. all balanced out as well although cal now runs on the high side of normal. Either my neph or corp. feels that current studies show that calcium should not exceed 9.5. Mine usually runs around 9.8 and sometimes jumps up to the 10’s. Was taking a daily antacid product containing 400mgs of cal., but discontinued it just recently when there was a recall of the product. Found a different product that contains no calcium. It is too soon to tell the affects. Wondering what your thinking is over there about appropriate calcium levels for those doing nocturnal txs?
Nice to hear from you again. I am thrilled that your absence from posts has been largely due to the fact that things are going so well on nocturnal. It means, I think, that you have your life back, that your thoughts are now reaching out away from your dialysis treatments to other things … and that can only be good.
One thing I would say about bone metabolism is that it is slow. Bone takes its time. Cut your skin and it heals in a few days. Break a bone and it will take several weeks - or more! Bone metabolism turns round rather slowly too - so look for changes over weeks and months not hours or days as you might expect when trying to correct a sodium or a potassium level.
One things we still don’t know enough about is what is the right calcium level to aim at in dialysis patients where the phosphate is low and the overall calcium x phosphate product is low … an uncommon or rare situation in conventional dialysis where the phosphate tends to always be high and the calcium:phosphate product is too. In the earlier work done by our own unit - my Renal Fellow at the time, Nigel Toussaint, was 1st author …
see (Agar CV: #106). Toussaint ND, Polkinghorne KR, Kerr PG, Somerville CA, Agar JWM. Comparison between different dialysate calcium concentrations in nocturnal hemodialysis. Hemodialysis International. 11(2) pp 217-224, April 2007
… and in published work by Andreas Pierratos from Toronto, we both developed the view - Andreas 1st, me subsequently - that a high dialysate calcium was optimal to avoid a negative calcium balance and bone resorption.
Andreas showed that even with a post dialysis serum Ca++ of 2.6-2.65 mmol/l (ie: mild clinical hypercalcaemia) which had been purposefully driven upwards during dialysis by a high calcium dialysate, that - importantly - this was in the presence of a post dialysis phosphate which was low at around 0.65 mmol/l. Thus the calcium x phosphate product was low - commonly around 2 (using SI units (mmol/l) for both calcium and phosphate). He also showed that even with post dialysis mild hypercalcaemia, resorption of extra-osseous calcium deposits occurred. Thus we both believe that a mild post dialysis hypercalcaemia (your levels, I believe) is fine, given and provided the (still unusual) concurrence of a low phosphate and a low calcium x phosphate product - findings that are still a little unusual and unfamiliar and which can be ‘challenging’ to those not used to nocturnal dialysis.
NB: I am sorry about the SI units - you can find a conversion table and do your own conversions but I find that I can’t think in the old US units any more.
There is a rebound rise in the post dialysis phosphate within only a short 1/2-1 hour after dialysis … but, too, there is a rebound fall in post dialysis calcium in the same time frame, leaving the calcium x phosphate product essentially unchanged. Our patients typically start dialysis with a calcium of 2.4 mmol/l rising to 2.6 - 2.65 mmol/l during dialysis and dropping back again post dialysis … this results from a planned positive calcium balance enforced by a high dialysate calcium. Our patients typically start dialysis with a phosphate of 1.3 - 1.4 mmol/l, falling to 0.65 - 0.70 mmol/l during dialysis and rebounding up again post dialysis. Their calcium x product typically remains <3.0 throughout the inter-dialytic period and bottom at about 2.0 post dialysis.
This commonly results in a PTH which falls into the desired range spontaneously without drugs and a with normalising Alkaline Phosphatase (if previously abnormal).
But, remember again, when it comes to bone, Rome wasn’t built in a day. Bone moves slowly … so, have patience. We don’t ‘rush stuff’. We try to ‘let it happen’. We try to stay cool and we try not to fiddle too much. And, in my experience, that tends to be the best policy.
Thanks for the review John, I don’t write much on the mineral bone disease of dialysis since it seems to me to be the least settled issue of dialysis as compared to dialysis dose and frequency issues. The talk I believe by Dr. Miller if I remember his name correctly at the ADC Home Hemo conference was quite interesting showing that the higher Ca+ level of 3.5 vs the standard 2.5 improved PTH. (US Ca+ numbers) I know that there is a connection between PTH and Alk Phos, is that a potential issue.
I Can’t remember if you already addressed this issue in the thread previously. But the data from Pierratos was quite impressive showing the resolution of calciphylaxis with higher nocturnal Ca+ levels in the dialysate, quite paradoxically to a reasoned thought on lowering Ca+ prescription in that situation. In any case, since returning from the ADC, I was wondering if there could be a connection between nocturnal dialysis and increased Alk Phos by worsening secondary hyperparathyroidism from a Ca+ level too low, by what ever SI or US parameters we would use.
Glad to have your comments on this issue once again since this is such an unsettled area in dialysis that once it gets settled by the big boys, perhaps I can start writing about it myself. The entire Vit D issue is quite unsettled as well with some data suggesting we need to increase Vit D in addition to the Vit D analogs as well as other data showing that this strategy will only increase extra-osseous, i.e. tissues other than bone, calcification leading to higher vascular calcification and increased cardiovascular events and death.
Are there any current large studies to address these mineral bone disorders other than the ubiquitous binder studies from the pharmaceutical companies?
I think one of the things that we don’t say often enough (either to ourselves or to our patients) is that we still do not understand, as well as we should or as well as we might, the whole calcium : phosphate : calcium x phosphate product : PTH : bone metabolism : bone alkaline phosphatase : vitamin D (and which vitamin D) inter-reactions and how any/all of these impact on the up-regulation and down-regulation of parathyroid and bone metabolism.
One of the main be-devilments in this whole ugly slough of hormones and biochemistry is the multitude of things that are all inter-reacting, impacting, altering, stimulating, suppressing and contributing to each other – all at once and together. All, like Dr Doolittle’s ‘push-me pull-you’ creature, seem to be pulling and tugging and urging in different directions.
[li]There is calcium in by mouth – either by food or by binders – and how much is absorbed … its absorption being dependent on Vitamin D (and what is the level of Vitamin D and does this mean active Vit D (as in paracalcitriol or calcitriol) or vitamin D as in cholecalciferol … or both (‘yes’ to all)
[li]There is calcium by dialysis – what dialysate calcium level is needed and does this vary with the status of the blood calcium and/or the blood PTH level (‘yes’ to both) … and does this vary with the duration or frequency of dialysis (‘yes’ again)
[li]There is phosphate in by mouth – and how much is absorbed … and does this vary with the binder used and whether the patient is also taking proton pump inhibitors (PPIs) and other agents (‘yes’ to all)
[li]There is PTH – and what are the effects of calcium (ionised or not) on PTH and is that influenced by the dose of Vit D (cholecalciferol or 1:25 di(OH) as calcitriol or paracalcitriol (‘yes’ to all) and do other things also impact PTH (‘yes’, and several)
[li]There is bone responsiveness to PTH (poorly understood in CKD and dialysis) – and does this vary with age, sunlight, activity, gender, inter-current medications (‘yes’ to all)
[li]There is (importantly) the time (hrs) and frequency per week of dialysis – with the shifts (+ve and –ve) that occur inter- and intra- dialysis, the dimensions of those shifts (dependent upon blood levels, dialysis membrane, transmembrane flows and Qb [blood flow rate] and Qd [dialysate flow rate] along with the dialysate calcium level itself) … again (‘yes’ to all)
[li]Then there are all the commonly used medications that up and down regulate calcium, phosphate, PTH and alkaline phosphatase, and the inter-reactions of each and all of these between, for and against each other and within the dialysis milieu – itself a constantly changing and swinging biochemical morass
[li]Then – underpinning all this is the lead-in time of CKD, the duration (vintage) of dialysis and the degree and duration of any pre-existing or stimulated hyperparathyroidism (or, at the other end of the bone metabolism spectrum, of adynamic bone disease) and the impact that may have on any or all of the above.
Oh, and did I say that that list of variables only just scratches the surface … no, I didn’t - I just got tired of listing them.
So, to answer what are, to any one individual patient, a seemingly simple question about calcium, phosphate, PTH, alkaline phosphatase or Vitamin D is
(a) commonly impossible without knowing the intimate details of that individual patient’s medication and history
(b) commonly impossible even if all those details are known.
Why? … because the simple truth is that we nephrologists are often just as blind to the right answers as is the patient. We try to do what we think is right, in any given circumstance, but the area is so misunderstood or just plain not understood that it remains one of the least understood and thus one of the most contentious areas in all of medicine, not just of nephrology.
That may sound a very worrying answer (or reality) to patients … What? are you telling me that my nephrologist doesn’t know what he’s doing? … well, no, not exactly. We do understand most (not all) of the interactions and most (not all) of the effects of the measures we take … it is more that the whole ‘mix’ is dynamic - it moves and changes - and thus we tweek and we modify, we change dose or agent, and we adjust constantly, sometimes to the bewilderment of the patient.
It is important in good cooperative patient management that the patient realises and understands that the reasons behind such a tweeking, adjusting process and that it is a necessary reaction and effort to maintain balance in what is a constantly changing biochemical environment.
But, the key word in that last sentence is ‘reaction’. We try to be proactive - to intervene before, rather than to react after - in most of what we do … but in the minefield that is PTH and bones, so much of what we do is ‘reactivity’ rather than ‘proactivity’. Would that it not be so.
To answer your question about trials … yes … trials are in progress but, to my mind, most of those in progress are – while well intentioned - likely to provide only yet more murk, more debate and no right answers.
Sorry to be so gloomy – but it IS important to now and again state is as I think it is.
So … don’t hold your breath.
All I know is … that more and more frequent dialysis does normalise – or tend to normalise – most of these aspects over time. Is that a surprise? … no, as more and more frequent dialysis moves the goal posts (just a bit) towards what normal kidneys do to keep control of this complex inter-reactive morass … and to my mind, that is a plus, not a negative
John, thank you for your explanation on the mineral bone research state of affairs, you listed several factors I have not really seen before in a concise statement. Until we have more definitive guidelines, I do not want to be on record in any posts giving out information that might not be correct a year or two or three from now. I tread very carefully when it comes to mineral bone issues.
There is still much to learn and elucidate from basic research on this topic. I will simply stay tuned for now and perhaps one of these days, we will actually know the right direction to take with these very basic questions.
Thank you again,
No … I think we should try to respond and answer … it is just so important that patients understand the lack of certainty, the multitude of inter-playing, inter-reacting factors and the individuality of their specific case when trying to find a non-explosive course through the minefield. I would still give it my best shot - just be prepared for unexpected incursions through your seemingly organised defenses!
[QUOTE=John Agar;20858]Dear Peter
No … I think we should try to respond and answer … it is just so important that patients understand the lack of certainty, the multitude of inter-playing, inter-reacting factors and the individuality of their specific case when trying to find a non-explosive course through the minefield. I would still give it my best shot - just be prepared for unexpected incursions through your seemingly organised defenses![/QUOTE]
Great point John, but what a minefield it is. You are right, I will give it my best shot. Certainly not an area where we can be dogmatic at this point in time, but you are right, sometimes it is quite important to put the uncertainty before the patients. Sometimes doctors are quite unfairly criticized over different issues because of this uncertainty and I am sure many of us docs shy away from these areas because of that.
I agree that there is, sometimes, some unfair criticism of doctors for what is seen as their uncertainty …
and it is uncertain … for there are so many variables, so few certain road maps and so many possibiities and combinations of clinical situations in the calcium/phosphate/PTH/bones area as no two patients are alike.
or for what seems like a constant ‘chopping and changing’ of therapy …
and we do ‘chop and change’ therapy … which always suggests that the doctor doesnt know what he/she is doing … when in fact, due to the reactive rather than proactive nature of treatment in this area, the doctor is reacting to blood results and is trying, always, to drive back towards the middle ground.
Calcium/phosphate/PTH/bones is really and truely such a difficult area … so, may I plead for the nephrologists on this one and ask that you try to give some leeway to your doc as he/she fights a guerilla war against the calcium/phosphate/PTH/bones axis … I do believe that they try to do their best to run a very difficult gauntlet and thet they run it with you, and not against you.