Indeed, there is only one pharmacological treatment currently available that slows the progression of PKD, but it does not stop progression, let alone reverse it. So, the bar for PKD treatments is relatively low right now.
Everyone thinks that the deterioration of the kidneys in PKD is irreversible. And that’s, unfortunately, what is seen in clinical practice. Nobody ever gets better.
But is it POSSIBLE that PKD kidneys could get better with the right treatment? Has anyone ever tried this at least in the laboratory using animals with PKD?
It turns out that the answer is “yes”. Read on.
A recent paper in Nature Genetics (1) by Dr. Stefan Somlo’s group at Yale University used genetically engineered mice in which the PKD1 or PKD2 genes could be turned off first, and then turned on again. This genetic “flip-flop” had never been tried before.
What did they find? As one would expect, when the researchers turned off the PKD genes, the mice developed polycystic kidneys. Nothing new here. This has been done many times in many labs. But when the researchers turned the PKD genes back on – after the mice already had polycystic kidneys – the kidneys got better again. A lot better. The cysts shrank, fibrosis improved, and the kidneys functioned better. So, it is possible to reverse PKD, at least in mice and with some genetic trickery that “fixes” the “broken” PKD genes in all the kidney cells.
This is great news.
The researchers, however, also found that the disease reversal works best if the broken PKD genes are “fixed” relatively soon after kidneys became polycystic. If they waited too long, then the scarring in the kidneys became permanent.
Can the “genetic treatment” that was used in mice be applied to humans with PKD to reverse their disease?
Unfortunately, the answer is “no”. At least not for a very long time, perhaps never. Replacing the broken PKD genes with intact genes would be a form of gene therapy. Gene therapy is very promising for certain genetic diseases but not for PKD. There is really no method on the horizon that can achieve the gene replacement for every single kidney cell in a patient.
Have other treatments been shown to reverse PKD in rodents?
Here, the answer is “yes”. Reversal of PKD has already been shown by other groups previously. The group of Thomas Weimbs at the University of California in Santa Barbara already showed in 2010 that treatment of PKD mice with the drug rapamycin caused reversal of renal cysts and greatly improved kidney function (2). Unfortunately, rapamycin is a drug that has too many side effects to be useful in a chronic disease like PKD (3).
More recently, however, the same group at UCSB also showed that a ketogenic diet was able to reverse the disease in rats with PKD (4). Wait, a diet? Really? Yes, really. No drugs were needed in this dietary study (4, 5).
So, an exciting picture emerges: the new study (1) confirms that PKD is reversible with the right kind of treatment, at least in rodents.
How about humans? Could PKD be reversible in patients?
A clinical retrospective case series study was recently published – again by the Weimbs lab at UCSB (6). These researchers showed that PKD symptoms, including pain, hypertension and kidney function improved in a large fraction of the 131 individuals with PKD who had switched to ketogenic diets (6). While this study is preliminary and needs to be repeated, it is the first human study that showed that individuals with PKD can experience improvement of their disease.
Improvement? In humans with PKD? Yes, improvement in Homo Sapiens. This goes against long-standing dogma and against everything that patients have always been told.
With the new paper in Nature Genetics (1), now we have another mouse study that shows that improving PKD may not be such a crazy idea.
Importantly, this paper strongly suggests that interventions in PKD should start as early as possible before the scarring in the affected kidneys becomes so widespread that it cannot be reversed.
Bottom line: If you have PKD and your doctor tells you that there is nothing you can do about it, let them know about these studies.
The bar has been raised.