PKD Life - Spring 2020 - 11


The Future of
PKD Treatment

Insights from nephrologist Fouad T. Chebib, M.D.
With Debra Gordon

T. Chebib, M.D., is a nephrologist at the
F ouad
Mayo Clinic in Rochester, Minnesota, where

he specializes in treating patients with ADPKD and
conducts basic and clinical research on the disease.

You worked to develop
a protocol to identify
patients most likely to benefit from tolvaptan, the first
FDA-approved treatment
for PKD. Can you explain
why this is necessary?
The Food and Drug Administration approved tolvaptan
for patients at risk of rapidly
developing progressive disease, but the agency didn't
define what that means.
As experts in the field,
we had to get together and
decide how to choose which
patients would benefit from
this long-term treatment.
We decided the most practical way to do that is to know
how big the kidneys are with
either CT scan or MRI of the
abdomen. This tells us how
severe the disease is and if the
patients would benefit from
being on tolvaptan to slow
the disease progression.


Where are we on
Q other treatments
for PKD?

There are several clinical
trials we're excited about.
One of these trials is testing
the effect of the compound

venglustat in slowing the
disease progression of
ADPKD. Venglustat inhibits
the enzyme glucosylceramide
synthase and lowers kidney
and plasma glucosylceramide,
a specialized lipid molecule
found in higher levels in the
kidneys of PKD patients and
in mouse models of PKD
as compared with those of
healthy controls. Preclinical
studies in animal models of
PKD demonstrated efficacy,
and a phase 1 trial in healthy
volunteers showed it was safe.
The manufacturer has now
launched a phase 2/3 clinical trial.
Another clinical trial is
evaluating the safety and
efficacy of bardoxolone,
which works through an
inflammatory pathway to
reduce kidney cell proliferation and inflammation. It has
been shown to be effective in
several small studies, with a
larger trial now underway.
These drugs are not cures,
but we hope they can slow
the progression toward endstage renal disease. It's like
treating high blood pressure
to prevent the long-term

effects of heart disease
and stroke.
There are also trials evaluating the effectiveness of
water treatment, in which
patients drink a certain
amount of water a day to suppress or stop the formation of
the thirst hormone, vasopressin, as well as studies on the
effects of intermittent fasting
and calorie restriction as a
means of reprogramming
kidney cell metabolism.
There are a few other
promising therapies that
are still in early phases of
research but have potential
in proceeding toward clinical trials.


When will there be
a cure?

That will come through gene
therapy. We are one of many
groups trying to identify a
gene therapy method in PKD.
It is challenging because the
protein made by the PKD1
gene is very large, so it is difficult to fit into a virus for

delivery. It is also challenging
to get it to the kidney.

What is the biggest
misconception that
people with PKD have
about the disease?


Because PKD runs in families, patient perception of the
disease is often affected by
the experience their parents
and grandparents had. So
if their parent had a severe
form of the disease, they
think they will also have a
severe form.
The key message for
patients is that each person
will have their own disease
trajectory, their own experience with the disease. Just
because your parent had a
severe form doesn't mean it
has to be the same for you.
Each child inherits genes
from the other parent that
could affect PKD. Also, environmental factors such as
how much you eat, exercise,
and drink water can make
a difference.



Answers to many questions can be found on the PKD
Foundation website ( or in UpToDate,
an evidence-based clinical resource for patients
and their families (

P K D C U R E .O R G

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3/23/20 11:12 AM http://www.PKDCURE.ORG

PKD Life - Spring 2020

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PKD Life - Spring 2020 - Contents
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