Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Kidney transplantation (KTx) is the optimal treatment for end-stage renal diseases. The surgical procedure of KTx inherently requires cold ischemic preservation and warm reperfusion of grafts, resulting in ischemia-reperfusion (I/R) injury. I/R injury is a major cause of delayed graft function, requiring dialysis or re-transplantation and carrying a high mortality rate if patients are not re-transplanted immediately. No pharmacological treatment for I/R injury is available. Prostacyclin (PGI2), an endogenous metabolite of arachidonic acid, promotes vasodilation and inhibits inflammation and platelet aggregation. Treprostinil, an FDA-approved PGI2 analog, has potent vasodilatory and anti-platelet aggregatory effects. Purpose: To examine the protective effects of treprostinil against renal I/R injury in rat.
*Methods: Male Sprague Dawley rats were randomly divided into: control, sham, I/R-placebo and I/R-treprostinil groups and subjected to bilateral renal ischemia followed by reperfusion for 1-48 hours. Placebo or treprostinil (100 ng/kg/min) was administered subcutaneously via a mini-pump. Blood and kidney tissue were collected to measure serum creatinine (SCr) and urea levels, histologic evaluations, and markers of kidney injury.
*Results: Pretreatment of rats before renal I/R injury with treprostinil significantly reduced (mean ± SEM) peak SCr levels at 24 hours post-reperfusion, from 1.79 ± 0.64 mg/dl in placebo to 0.53 ± 0.10 mg/dl (p<0.05), and serum urea levels from 199.67 ± 43.84 mg/dl in placebo to 38.34 ± 3.36 mg/dl (p<0.05) at 48 hours post-reperfusion. Histological evaluation indicates that treprostinil reduced I/R-induced renal proximal tubular necrosis. In addition, treatment with treprostinil reduced the magnitude of renal KIM-1 and NGAL mRNA induction by 2.8- and 2.7-fold compared to placebo at 48 hours post-reperfusion.
*Conclusions: Our results indicate that treprostinil administration ameliorates renal I/R injury by inhibiting renal necrosis in rat. Treprostinil has the potential to serve as a therapeutic agent to protect the kidney graft against I/R injury in patients receiving de novo kidney transplantation.
To cite this abstract in AMA style:Ding M, Tolbert E, Birkenbach M, Chung C, Gohh R, Akhlaghi F, Ghonem N. Treprostinil Attenuates Renal Ischemia-Reperfusion Injury in Rat [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/treprostinil-attenuates-renal-ischemia-reperfusion-injury-in-rat/. Accessed October 24, 2020.
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