Role of genetic variants of the renin-angiotensin system in chronic renal allograft injury.
In the the vast majority of patients undergoing kidney transplantation, long-term success is markedly limited by a gradual decrease in graft function over time, often termed as "chronic rejection" or "chronic allograft injury." Although there have been no formal studies examining the role of genetic factors other than those related to histocompatibility for the development or progression of chronic allograft rejection, it is likely that genetic factors affecting blood pressure regulation, mesangial or vascular proliferation, or aspects of inflammatory response including thrombosis, chemotaxis, or fibrosis may play an important role in this complex syndrome. There is currently little hope that the responsible genes can be identified through sib-pair or linkage studies in families. Therefore, the study of candidate genes selected on the basis of our current understanding of the pathophysiological mechanisms involved in the chronic rejection response appears the only feasible approach. Thus far, studies have focused mainly on the role of functional genetic variants of the renin-angiotensin system on renal allograft funding. These studies, however, have not identified these variants as important determinants of renal allograft survival. Clearly, future studies will have to address the role of other variants of this system as well as genes encoding for other systems deemed to be of pathophysiological significance for the development and progression of chronic transplant injury.
Sharma
A M
AM
Department of Internal Medicine, Universitätsklinikum Benjamin Franklin, Free University of Berlin, Germany. sharma@zedat.fu-berlin.de
Beige
J
J
Distler
A
A
D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D002908:Chronic Disease; D014644:Genetic Variation / Q000502:physiology*; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology
D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A