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Resolved Combination treatment for ADPKD?

  1. Kidney Guy
    Kidney Guy
  2. Polycystic Kidney Disease
  3. Wednesday, February 17 2016, 11:04 AM
  4.  Subscribe via email
Many of the clinical trials are negative or minimally effective (mTOR inhibitors, somatostatin, water therapy, HALT PKD blood pressure control) - even tolvaptan is only modestly effective. However, in your opinion might a combination strategy be better than a single agent alone. Are there any efforts underway to test this?
Responses (4)
Daniel Bichet
Daniel Bichet Accepted Answer
There is no combination therapy tested so far and no combination therapy in clinical research studies as far as I know. However, he combination of tolvaptan and somatostatin would be of interest.

Dr. Daniel Bichet
  1. more than a month ago
  2. Polycystic Kidney Disease
  3. # 1
Dr. Jordan Weinstein
Dr. Jordan Weinstein Accepted Answer
Hi All,

There is a Nature paper on this issue, with the following taken from its abstract:

A combination of the vasopressin type 2 receptor antagonist tolvaptan and the somatostatin analogue pasireotide synergistically reduces cyst progression in a PKD1 mutant mouse model of autosomal dominant polycystic kidney disease (ADPKD). Both drugs indirectly inhibit adenylyl cyclase 6 activity, leading to a reduction in levels of 3', 5'-cAMP, which are decreased to those of wild-type controls by combination therapy. The dual therapy also results in smaller cystic and fibrotic volume, suggesting that it might be an effective treatment for ADPKD.

Dr. Jordan Weinstein
References
  1. http://www.nature.com/nrneph/journal/v10/n9/full/nrneph.2014.130.html
  1. more than a month ago
  2. Polycystic Kidney Disease
  3. # 2
Joel Topf
Joel Topf Accepted Answer
Coming off the stinging results of dual ACEi/ARB therapy that were so promising in theory, I would be very cautious extrapolating from animal data and mouse models. If it hasn't been tested in humans we should probably restrict it to protocols.
Attachments (1)
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References
  1. http://www.nejm.org/doi/full/10.1056/NEJMoa1303154
  1. more than a month ago
  2. Polycystic Kidney Disease
  3. # 3
Dr. Jordan Weinstein
Dr. Jordan Weinstein Accepted Answer
Coming off the stinging results of dual ACEi/ARB therapy that were so promising in theory, I would be very cautious extrapolating from animal data and mouse models. If it hasn't been tested in humans we should probably restrict it to protocols.


Thanks Joel,

You're right that combination therapy didn't work in that setting, but I'm thinking along the lines of the STENO Trial in diabetes which tested whether multiple interventions targeting different risk factors could improve outcomes in diabetes. And fortunately, that trial was positive.

Jordan
References
  1. http://www.nejm.org/doi/full/10.1056/NEJMoa0706245
  1. more than a month ago
  2. Polycystic Kidney Disease
  3. # 4
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