Donor hypertension increases graft immunogenicity and intensifies chronic changes in long-surviving renal allografts.

BACKGROUND

Marginal donor organs are used increasingly for transplantation. To define the influences of donor hypertension, we compared the behavior of kidney allografts from hypertensive and normotensive donors in an established rat model of chronic rejection.

METHODS

Donor hypertension was induced by partial occlusion of the right renal artery with a silver clip. After 10 weeks, the left kidney was removed and transplanted. Normotensive animals served as controls. All recipients were treated with a low dose of cyclosporine for 10 days (1.5 mg/kg). Blood pressure and proteinuria were determined weekly four times after transplantation. To examine the effects of donor hypertension on late events, grafts (n=6/time point) were examined morphologically and by quantitative reverse transcriptase-polymerase chain reaction analysis at serial intervals.

RESULTS

Recipients of kidneys from hypertensive donors developed systemic hypertension in contrast with normotensive controls (P<0.05). Allografts from hypertensive animals showed accelerated deterioration in structure and function after transplantation. Proteinuria became significantly elevated as early as 6 weeks (P<0.05) compared with controls and increased progressively thereafter (P<0.005). Grafts from hypertensive donors, histologically normal at the time of engraftment, developed significant morphologic deterioration after 12 weeks (P<0.01). Changes in allografts from normotensive donors remained minor. mRNA of proinflammatory mediators in hypertensive donor grafts (P<0.01) was up-regulated before transplantation and increased progressively over time (P<0.01).

CONCLUSIONS

Donor hypertension intensifies the chronic injury associated with allogeneic kidney transplantation in the rat model used. This condition also leads to induction of recipient hypertension and may be a more important risk factor for chronic graft dysfunction than previously appreciated.