NSF and GDD. There are more unanswered questions with NSF. The missing links.

I am interested about the intracellular presence of Gd for all different agents.

The work we and others have done with GDD, reveals by contrast that there are much larger gaps in knowledge about NSF than GDD. GDD is fairly simple: a Tcell dysregulation, as you know my theory is of tissue resident memory Tcells, essentially then a Tcell allergy - to something that persists in the body. Simple concept in the general rubric that: the host reacts to foreign antigens, like peanuts or bee stings. Straightforward: Gd even as an intact chelate is a foreign antigen and some people react to it, with the added problem that the foreign antigen remains imbedded in the body.

With NSF we just accept as sacrosanct that patients in renal failure eliminate GBCA more slowly, more time to break apart, and as a result the agents that are less stable cause NSF in renal failure patients. But we now know that in normorenal function patients if you have received a number of GBCA injections then you have a lot of Gd still left behind, and if that Gd is omniscan/optimark/magnevist a fair amount will be dissociated. So why does NSF not occur in these normals if it is simply a function of Gd hanging around in the body? Then next: which species of Gd is responsible for causing NSF, for the omniscan/optimark/magnevist that is broken down.

There are two huge missing links for NSF.

My theory, the various toxic tissue effects of chronic renal failure lead to dysfunction of bone marrow (and other cells) and with dysregulated bone marrow cells - they are then frazzled and react to Gd with exuberant tissue fibrosis. Then the other missing link, which of the Gd species is the inciting offender to the stimulus for fibrosis? My hypothesis is that it probably is Gd bound to macromolecules.. but then the sub-question, which macromolecule?

This is not to say that in any way I am disputing the existence of NSF (Gad Caused Systemic Fibrosis - Renal Failure), but rather the formal medical community readily has embraced the concept of NSF, unfortunately to the detriment of GDD suffers (mainly normal renal function) because the mantra is: if you don't got renal failure, you don't got anything wrong with you - just drink water and walk it off, or see a psychiatrist. There is much less experimental science in humans for NSF, than has been done for GDD. Certainly nothing about effective treatment: no effective treatment for NSF, very effective treatment for GDD. By the way, modifying what we do for GDD would also work for NSF. The acceptance of NSF is essentially pure observation science, which I am fine with, the vast majority of the papers I have written are observational. But purists snub their nose on the observational nature of much of the published work on GDD. But wait a minute, what is sauce (proof) for the goose should also be sauce for the gander. Besides that, we and others have done much more experimental work on GDD in humans than has ever been done on NSF in humans > so that is Michelin 3 star sauce.

Richard Semelka, MD