A mysterious substance in cyst fluid
So we have looked at injury of kidney cells earlier in this book (page5) and we have concluded that injuring a kidney cell in a PKD patient increases the chances of this cell becoming cystic as it switches to fermentation. The next question would be: is this always the case? Or is there an instance where injuring cells over and over does not lead to cyst growth and instead the cells retain the ability to heal and revert back to their healthy state? Yes, such cases have been described in several studies and they are highly intriguing. The question then becomes, what differentiates a cell that reacts to injury with uncontrolled growth from a cell that does not?
To elucidate this, I will take you down the path of some exciting research. As long ago as 1970, Darmady and colleagues had hypothesized that the expression of cysts in PKD might be connected to a specific toxin since the changes in renal structure were found at points where toxins were ‘maximally concentrated’.1 This was followed in 1995 by experiments using extracted cyst fluid from PKD patients, applied to healthy non-PKD tissue. The researchers found that this fluid stimulated ‘fluid secretion, cyclic adenosine monophosphate accumulation, and cell proliferation’, which are hallmarks of PKD, even though there was no mutation present. The toxins themselves were enough to exhibit the same effect.2
In the same year, a group of researchers led by JJ Grantham tried to dig deeper and used mass spectrometry to narrow the constituents of the cyst fluid down to a single substance that actually was responsible for triggering cyst growth. While they were able to concentrate the fluid to a point where its secretory activity was 48-fold above that of the original substance, meaning its ability to produce fluid that could fill a cyst was 48 times higher, they could not narrow it down to a single substance and described it as a fraction of lipids enriched in monoglycerides.3
Nine years before that, Avner had led a study in which he showed that complete regression of cystic changes was possible, after only 120 hours, when he removed the cell culture from its environment, thereby removing all of the present toxins as well.4
Endotoxin
Even though the mass spectrometry study didn’t yield conclusive results and bears repeating now that our technology has evolved further, we might still be able to look at other analyses of cyst fluid from PKD kidneys to shed more light on the issue.
Miller-Hjelle and colleagues in 1997 found the substance lipopolysaccharide (LPS), al