title: Genetic susceptibility of the donor kidney contributes to the development of renal damage after syngeneic transplantation.
abstract: Solitary kidneys, especially in rats, appear vulnerable to develop functional and structural damage. However, differences in susceptibility exist between strains. It is not clear whether this is intrinsic to the kidney or due to environmental factors. Therefore, the aim of the present study was to investigate possible differences in genetic susceptibility for renal damage. By transplanting different rat donor kidneys into a normotensive, histocompatible recipient, the kidneys were exposed to the same blood pressure profiles, metabolic and hormonal environment. Kidneys from young adult hypertensive fawn-hooded (FHH) rats, a strain showing early onset renal damage, normotensive, renal damage-resistant August x Copenhagen-Irish (ACI), and (ACI x FHH) F1 donors were transplanted into male F1 recipients. The native kidneys of the recipients were removed 1 week after transplantation. The results were mutually compared and to their unilaterally nephrectomized littermates. Systolic blood pressure (SBP) and albuminuria (UaV) were determined at the time of transplantation and at 8 and 16 weeks. The histomorphologic analysis included the incidence of focal glomerulosclerosis (FGS), and determination of chronic transplant dysfunction according to the BANFF criteria. A negative impact of the transplantation technique in this syngeneic situation could not be detected as F1 transplants did not differ functionally and morphologically from their UNx controls. Transplanting an ACI kidney did not result in significant changes of SBP, UaV, and incidence of FGS compared to F1 transplants and ACI-UNx. In contrast, FHH kidneys did show a progressive increase of UaV and glomerulosclerosis and a significantly higher BANFF score, whereas the SBP did not differ from F1 transplants. The moderate hypertension seen in FHH did not travel with the kidney. Compared to the FHH-UNx rats, transplantation of a FHH kidney did significantly attenuate the increase of UaV and FGS. The susceptibility of the donor kidney appears to be an important factor in the development of chronic renal damage. This may play a role in the long-term functional changes seen after clinical renal transplantation.
authors.affiliation: Department of Surgery, Erasmus University, Rotterdam, The Netherlands. Kouwenhoven@heel.fgg.eur.nl
authors.forename: E A
authors.initials: EA
authors.lastname: Kouwenhoven
authors.forename: R P
authors.initials: RP
authors.lastname: van Dokkum
authors.forename: R L
authors.initials: RL
authors.lastname: Marquet
authors.forename: U W
authors.initials: UW
authors.lastname: Heemann
authors.forename: R W
authors.initials: RW
authors.lastname: de Bruin
authors.forename: J N
authors.initials: JN
authors.lastname: IJzermans
authors.forename: A P
authors.initials: AP
authors.lastname: Provoost
mesh_terms: D000419:Albuminuria / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight; D005923:Glomerulosclerosis, Focal Segmental; D006977:Hypertension, Renal / Q000235:genetics; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014019:Tissue Donors; D014185:Transplantation, Isogeneic