I’m a sucker for cross-disciplinary, cross-age demographic topics, and Grand Rounds today was given by Martina Brueckner, M.D., a pediatric cardiologist and scientist from Yale.
She talked about how cilia are responsible for generating the left-right asymmetry in mammals. The most obvious of these asymmetries are organ position: the liver is on the right, the spleen and the stomach are on the left. But major organs themselves are asymmetric: the left side of the heart is much more muscular than the right side, for example, and the left side of the brain is usually bigger than the right in most people.
It has been known that primary cilial dyskinesia can be associated with situs inversus totalis (in Kartagener’s syndrome but also with other heterotaxies such as situs ambiguus that is more frequently associated with congenital heart disease.
Cilial dysfunction is also associated with polycystic kidney disease. While the cilia themselves may be normal, what is abnormal are either of two genes: polycystin-1 or polycystin-2. Interestingly, these are mechanosensitive cation channels which regulate the flow of calcium. Even more interesting, these types of channels can be inhibited by gadolinium.
My addled brain made this immediate jump: cilia are everywhere in the body, gadolinium is thought to cause nephrogenic systemic fibrosis, maybe it these mechanosensitive/strech-activated cation channels that mediate this serious adverse affect?
Now, granted, it’s certain to be much more complicated than that. The toxicity of free gadolinium ions has not been really looked at specifically, although some effects are known from exposure to the class of rare earth metals. One of the proposed mechanisms of NSF is that, since in renal failure, the gadolinium-chelate complex hangs around for quite a while, there’s enough time for the free gadolinium ion to dissociate.
Another paper talks about an association between the development of NSF in the setting of a pro-inflammatory condition. This would actually make sense, since it is known that cytokines promote fibrosis and scar formation.
The study of NSF is still in its infancy. In the mean time, it’ll be difficult to get any sort of imaging done in anyone with seriously boxed kidneys.