Defining chronic kidney disease at the genetic level | Science Translational Medicine

Good morning all,

In our last two lectures of this third unit of the course, we are considering renal function and the often overlooked role of the kidneys in our health and well-being.  During lecture on Thursday, I mentioned several facts related to kidney disease and failure that some recent science news can inform.

We discussed conditions such as diabetes and hypertension that can induce kidney damage and failure, and the third items on that list was genetic bases for kidney ailments.  One of the reasons that we did not elaborate on the topic is that the specific genetic causes of kidney disease (like that of so many other of our diseases) is very nebulous - there are many genes involved, often with very weak effects, and their interactions with each other and with environmental influences are poorly understood.  In these situations, patients often recognize that they are part of a family history of disease (suggesting its genetic basis), but typically the genes involved are not identified, or their function is not characterized. 

Recently, several research teams have made progress on this issue.  Using exome sequencing (a DNA sequencing method that focuses only upon the protein-coding regions of our DNA), researchers recently have described with greater detail the number of different genes involved in a small sample of patients with chronic kidney disease.  They identify over 60 different genes, some with identified roles as membrane transporters or regulators of gene expression.  Most of these were associated with a tiny number of disease cases.

http://stm.sciencemag.org/content/11/474/eaaw0532

As is often the case, studies like this are useful if only because they reveal how much we have yet to learn, and offer a potential method forward.  It's a very long (and expensive) pathway from gene identification, to functional investigation, to testing of therapeutics, to useful treatments, and most avenues of exploration do not yield breakthroughs.  But, we now know more than we did, and there is great interest in finding ways to abate kidney disease.  There are still a great number of people awaiting kidney transplants, and many die while they wait.  Inequities of access to donated organs may be part of the problem.  Perhaps we should pay people for organ donation - or would that be more problematic than useful?

https://www.washingtonpost.com/opinions/the-us-organ-transplant-system-is-broken-but-the-latest-fix-will-make-it-worse/2019/04/02/41ef2b1c-555b-11e9-8ef3-fbd41a2ce4d5_story.html

https://www.washingtonpost.com/opinions/what-if-we-paid-people-to-donate-their-kidneys-to-strangers/2019/01/08/6f397a0c-1391-11e9-b6ad-9cfd62dbb0a8_story.html


Have a great weekend -
Dr. Nealen