Date of publication: February 1, 2016

Expert Perspectives

Expert Round Table (Part 7): When to Start Proactive Management of Phosphate in Non-Dialysis Patients

In the last of our expert round table videos, recorded prior to the ERA-EDTA 2015 Congress, our experts debate at what point proactive phosphate management should start in non-dialysis CKD patients. Topics discussed include:

  • The significance of high PTH levels in pre-dialysis patients
  • Testing for phosphaturia in CKD patients
  • Studies that are underway which might provide further clarity on this issue

The COMPACT expert panel comprises Drs Stuart Sprague, Kam Kalantar-Zadeh, Angel De Francisco & Adrian Covic.

It’s not until we get down to GFRs around 20, when you have all these other hormones way out of control, that the phosphate actually goes up in the blood. So I actually am a strong advocate of starting phosphate binders in patients as soon as I can see an increase in their parathyroid hormone as a practical level.

– Dr Stuart Sprague

Video: https://player.vimeo.com/video/146621106

Transcript

Dr De Francisco

One frequent question that the young fellows ask is “If I have a patient with a normal serum phosphate and GFR of (let’s say) 35, should I control this normophosphatemia?”

When do you think we should educate everybody in order to start treatment of hyperphosphatemia in normophosphatemic patients?

Dr Sprague

I think what you’re asking is an extremely important question. I’m glad young clinicians and fellows are thinking that way, but we don’t have a clear-cut answer. There are some studies going on right now that will hopefully address the impact of that.

If I’m not involved in the study, my normal approach, based on my understanding of the pathophysiology, is that I start relatively early when patients are normophosphatemic.

Generally, when the GFR gets below 40 to 50, we will check the PTH level. If that PTH level is above the upper limit of normal, I believe they have an imbalance in phosphate metabolism.

Granted, they may have some vitamin D deficiency, but again, if we look, the mechanisms are phosphate detaching, followed by production of FGF 23 followed by a decrease in calcitriol production followed by an increase in parathyroid hormone.

It’s not until we get down to GFRs around 20 when you have all these other hormones way out of control that the phosphate actually goes up in the blood. So I actually am a strong advocate of starting phosphate binders in patients as soon as I can see an increase in their parathyroid hormone as a practical level.

Sometimes I could go as far as measuring FGF 23, but generally that’s not really practical to do clinically now based on the assays, or we can measure a 24-hour urine phosphate to see if that’s decreased or look at the fraction excretion of phosphate to see if that’s increased. That would be another marker.

The truth is, from a practical sense, I just start with a phosphate binder at that point in time.

Dr De Francisco

You don’t see any role in the phosphaturia as a marker of . . .

Dr Sprague

Oh, I think it’s a marker. I do believe it’s a marker, but I don’t really—

Dr De Francisco

But nobody records phosphaturia in their patients?

Dr Adrian Covic

No, we don’t.

Dr Kalantar-Zadeh

We don’t, but if we can’t educate ourselves with younger and other nephrologists that management of phosphorous should start early, not to wait until patients are on dialysis and to start it also when the phosphorous appears to be within normal range. That’s an important . . .

Dr De Francisco

But this is very difficult to convince the young nephrologists, the fellows, to prescribe and to control phosphate when the phosphate is still in normal.

Dr Kalantar-Zadeh

The two criteria that Stuart mentioned, I think that’s important and it’s amazing and at least one of them is readily available, is high PTH. I think you’re suggesting that once PTH starts going up, that’s already the first alarm that here you may have a phosphorous problem.

The second one that I think maybe is not frequently done, is measuring urinary phosphorous and/or to measure phosphorous clearance.

Dr Sprague

Now, hopefully we will actually have an answer to this in a couple of years. There is a big study sponsored by the NIH looking at patients with CKD and actually taking patients with normal phosphates and measuring 24-hour urines, FGF 23, and then placing them on phosphate binders for a year in a randomised, double-blind fashion and then measuring it at the end.

It’s actually looking at hard endpoints such as both progression of cardiovascular disease and progression of the renal disease during that.

Now, this is a pilot study for hopefully a larger study. I think the science supports it. I do believe that we ultimately need some good studies to prove it which are now finally being done.

In short of that, I think there’s enough information out there that we probably should be treating these patients early or aggressively. As far as I can tell, there’s very little evidence that you can cause harm by putting a patient on a phosphate binder early on.

Dr De Francisco

Adrian, what do you think?

Dr Covic

I am a little bit more reluctant because . . . I’m glad that you mentioned that the NIH finally is having a study. I have the approach of a cardiologist and I have this specialty, as well, because, you see, in cardiology, cholesterol, we talked about cholesterol, is related to worse outcome but also they’ve proved that by bringing cholesterol down, outcomes are indeed . . . are going to be better.

We didn’t prove that. I think we have only the first leg of these associations. We should prove that by bringing, by whatever means, the levels into the normal range, it’s actually beneficial.

You mentioned correctly that they don’t produce any harm, but on the other hand, it’s another pill and another pill. So, as it sits, I am not really supporting the idea of keeping . . .

Dr De Francisco

You would focus probably better on nutrition…

Dr Covic

And monitoring the patients. If the patient is getting a high phosphorous, then yes, of course I am going to do something. Other than that . . .

Dr De Francisco

Normal phosphorous with high PTH, you still are . . . ?

Dr Covic

I am not bothered by the PTH. I mentioned that before. I think that PTH, PTH, we don’t know how to measure it. It’s variable. It’s a late molecule in the pathophysiology. It hasn’t been associated, in my mind, with clear-cut outcomes. I am a younger nephrologist and I’m not an old PTH guy!

Dr De Francisco

What seems to be very rational is just do a correct approach and then offer good nutrition able to control phosphate.

Dr Covic

Absolutely.

See also the previous expert round table publications:

September 9th, 2015; Expert round table (Part 1): what are the biggest challenges clinicians face in controlling serum phosphorus in dialysis patients?

September 16th, 2015; Expert round table (Part 2): the importance of adherence, nutrition and treatment individualization

September 22nd, 2015; Expert round table (Part 3): role of new markers of mineral & bone metabolism

November 24th, 2015; Expert round table (Part 4): optimizing protein and phosphorus intake in dialysis patients?

December 1st, 2015; Expert round table (Part 5): the importance of an integrated renal team approach, supported by the nephrologist, when managing CKD-MBD patients

December 9th, 2015; Expert round table (Part 6): CKD-MBD management – top tips for young nephrologists

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