Does intra‐operative verapamil administration in kidney transplantation improve graft function

Abstract

The role of the calcium channel blocker (verapamil) in kidney transplant is controversial. Verapamil has been hypothesized to mitigate ischemia reperfusion injury (IRI) to the allograft. Herein, we evaluated the effect of intra-operative verapamil administration in a large cohort of kidney transplants. Total 684 transplants were performed during 2007-2017. Of these, 348 (50.9%) transplants received verapamil (2.5 mg) Ver (+), and 336 (49.1%) did not, Ver (−). Based on the donor type, the study was divided into three groups; living donor (LD) (N = 270), neurological determination of death (NDD) (N = 394), and donation after cardiac death (DCD) (N = 20). Ver (−) subgrouphad more diabetic recipients as compared to Ver (+) subgroup in LD and NDD groups (P < 0.05). No significant difference was found for delayed graft function in any of the group (P > 0.05). Cold ischemia time and dialysis requirement were significantly higher in Ver (+) LD and NDD groups, respectively. Except for DCD group, there was no significant difference in eGFR (mL/min) immediately and 6 months after kidney transplant in any of the groups. Furthermore, univariate and multivariate logistic regression analysis was performed to account for potential confounders, but verapamil administration did not improve graft function in any of the groups (P > 0.05) after transplant. K E Y W O R D Scalcium channel blocker, ischemia reperfusion injury, kidney transplantation

Intraoperative Verapamil Fails to Reduce Delayed Graft Function in Donation After Circulatory Death Renal Allografts

“… 16 , 18 A more recent single-center study failed to demonstrate that intraoperative verapamil reduced DGF. 21 However, this latter study did observe that only 60% of the DCD Ver (+) group had DGF, in contrast to 80% in the DCD Ver (–) group. 21 Unfortunately, the small sample size and short CIT in the DCD groups limited the generalizability of this conclusion.…”

“…A larger contemporaneous series comprised mainly living donor (39%) and DBD (58%) transplants failed to demonstrate a significant benefit with the use intraoperative verapamil. 21 In the latter report, the small DCD Ver (+) subgroup did have a lower incidence of DGF that did not achieve statistical significance because of sample size limitations. 21 Our single-center matched cohort study included a large Ver (+) DCD cohort (n = 27); however, we also did not demonstrate a significant reduction in DGF versus the Ver (–) DCD cohort.…”

“… 21 In the latter report, the small DCD Ver (+) subgroup did have a lower incidence of DGF that did not achieve statistical significance because of sample size limitations. 21 Our single-center matched cohort study included a large Ver (+) DCD cohort (n = 27); however, we also did not demonstrate a significant reduction in DGF versus the Ver (–) DCD cohort. In our cohort matched for donor age, KDPI, and DCD status, the only covariate independently associated with an increased risk of DGF on multivariate logistic regression analysis was CIT ( P = 0.005).…”

“…19 Other studies have used intraoperative renal artery verapamil injection immediately postreperfusion in a single-pass model in an attempt to mitigate calcium-mediated IRI. 16,18,21 Intra-arterial verapamil significantly reduced the incidence of DGF in early reports. 16,18 A more recent single-center study failed to demonstrate that intraoperative verapamil reduced DGF.…”

Performance of Renal Allografts Perfused With Verapamil-Treated Perfusion Solution

“…Their cohort included living donors, brain dead donors, and donation after circulatory death donors, and administration did not improve graft function after transplant in any group. 3 A 2008 study that evaluated the effects of Verapamil on recipients, that had their donated grafts flushed with a preservation solution prior to transplant, found that the addition of Verapamil can improve long-term graft function. 4 This study had limitations noted including the fact that it was not designed with a paired kidney framework.…”