- And the frequent hemodialysis network
actually was involved with two separate studies
that had similar outcomes and similar protocols.
I was a clinical investigator for the Wake Forest site
for the frequent daily study
where dialysis was done in center
for a short period of time, six times per week
on average, between one and a half and three hours.
And I was also the overall principal investigator
for the nocturnal study where patients did dialysis
for six nights a week for an average
of 30 to 36 hours per treatment.
They're two complementary studies.
They're both looked at providing much more dialysis
than a typical patient does.
This is an extension of the hemo study
which showed that more dialysis was not necessarily
beneficial on a three times a week basis.
The thought process of the investigators was that
if you do dialysis more frequently,
you don't have the same fluctuations in terms of
interdialytic weight gains, and the patients accumulate
less fluid between dialysis treatments,
and at least on a theoretic basis,
you would think that would improve
left ventricular hypertrophy,
that would help improve blood pressure control,
and then with the more frequent dialysis,
you also have more removal of urinal toxins,
and there could be certain potential benefits
from that, also.
The study was designed to look at
a large number of outcomes.
The two primary outcomes were looking at
change in left ventricular hypertrophy
and also looking at change in a measure
of a quality of life called the physical health component.
And both of these have been shown
in larger studies to be predictive of mortality rates.
Neither of the studies were designed to look at mortality.
For a mortality study, you would need
several thousand patients, and clearly,
there are not the patients, nor the resources
to do a study of that size, so these secondary outcomes
were chosen, and then there were an additional
group of secondary outcomes which looked
at areas of interest for nephrologists,
the menia management, management of hypophosphatemia
and secondary hypoparathyroidism, depression,
cognitive function, and nutrition.
The main results for the daily study
were published in New England Journal
in December, 2010, and the main results
from the nocturnal trial were published
in November of 2011, and for these trials,
for the daily trial, there was a benefit
in terms of both left ventricular mass
and also in terms of the physical health component.
The nocturnal trial was a smaller trial
and we saw a decrease in LV mass,
but it was not statistically significant.
In terms of the physical health component,
both arms of the nocturnal trial showed a small,
non-significant improvement in the physical health component
and we discussed why that might have been
and it was thought that the patients actually
going home to do dialysis treatment
may have provided a small benefit in both arms of the trial.
So even though the nocturnal trial was a negative trial,
we certainly learned quite a bit
about the nocturnal dialysis, too.
Both studies, patients who were doing short daily,
or patients who were doing nocturnal,
showed improvement in blood pressure control,
required fewer blood pressure medications
to keep their blood pressure under control,
and also had improvement in treatment of hypophosphatemia.
In fact, the removal of phosphorous in the nocturnal study
was so large that some of our patients
actually had to add phosphorous to the dialysis
so they would not get hypophosphatemia.
And there's no other form of dialysis
that can claim that large of a removal of phosphorous.
So, certainly there were benefits
of both of the more frequent studies.
This has to be tempered with an increase
in vascular access events, and if you think about
doing dialysis more frequently,
that means you're using your access more frequently.
So, one of the concerns was whether patients
had more complications with access,
and that turned out to be true.
There are benefits for more frequent dialysis.
I believe the clinician has to look
at the individual patient, has to individualize therapy,
look at the potential benefits
of more frequent dialysis, balance those against
the risks of more frequent dialysis,
and then inform the patient so the patient
can make an informed decision.
Now one of the reasons I think
there was a difference in the left ventricular hypertrophy
between the two studies is that in the daily study,
most patients had little to no residual renal function,
whereas in the nocturnal study,
a fair number of the patients, about 50%,
had been on dialysis for less than a year,
still had a good amount of urine output,
and those patients in the daily study
who had no residual output, were the ones
who most often had a decrease in their
left ventricular mass over time.
Clearly, another thing that we learned from the study
is another reason why it's important
to protect residual renal function.
We know that residual renal function
is important to help improve mortality,
but perhaps we understand why that is,
because residual renal function
is preventing that LV hypertrophy.
Certainly, one of the suggestions is that patients
may benefit from more frequent dialysis
once they start losing residual renal function
to help prevent the LV hypertrophy
which in turn should help to decrease mortality risk.
Now this is, of course, all post hoc analysis of the study,
but it certainly, from a theoretical viewpoint,
makes sense that this would be the mechanism
of how we're seeing one of the benefits
of more frequent dialysis.
In terms of the application of the dialysis research
and clinical practice, it gets back to
the individual patient, and finding out
what is best for the individual patient.
And that's what's so very important about this research.
It's not only looking at overall trends
and what are some benefits and what are some risks
of the therapy, but looking at the individual patient
and saying, this is a patient who has
a very high phosphorous level, so they're going to
benefit from more frequent dialysis
despite some of the risks that may be
associated with more frequent dialysis.
It helps us better explain to the patient
how they can choose a dialysis modality,
and what might be the best modality for the patient.
It helps the patient make an informed decision
an informed decision that hopefully
will lead to a better quality of life and better outcomes.