Second Hit
The second hit model for PKD is no longer a theory. It has long been proven to be a truth. It exists as the model for transmitting the expression of the PKD gene.
What is the significance of the the two-hit model for PKD?
PKD cystic organ inheritance comes through our genes. This loads the gun, so to speak. Yet it is actually something in the environment that pulls the
trigger; something else that fires the gun and begins the process of cyst expansion, growth and enlargement of polycystic organs.
This trigger could
be anything that might disrupt DNA - Greg Germino MD.
Greg Germino MD was named Deputy Director of NIH National Institute of Diabetes and Digestive and Kidney Diseases. Understanding the two hit model is important for those who strive for PKD health. This model helps explain why within a PKD family there are differences in the manifestation of PKD. As PKD is passed onto future generations, the severity of symptoms seems to increase, with symptoms onset occurring at an earlier and earlier age. Polycystic Kidney Disease or the PKD gene is inherited. This second hit comes about through environmental exposure to toxins, to carcinogens, to endocrine disruptors within the environment. This is the second hit, the missing trigger starting cyst production within our organs. Some have voiced the opinion that this is a theory. Correspondence with researchers has revealed compelling evidence to support the existence of the two hit model (2nd hit model) in ADPKD. There are now multiples of studies supporting this Second hit model in ADPKD. Data below from the pulldown menu of articles, supports a two-hit model in ADPKD. Data has come from studies of human tissues (both PKD1 and PKD2) and from PKD mouse models that have genetic mutations or the mouse equivalent of PKD1 and PKD2. The data does not exclude other factors from contributing to ADPKD gene expression, however most investigators agree that these published studies clearly show a role for the presence of a two-hit model present in the pathogenesis of PKD disease production.
