Impact of Remote Ischemic Preconditioning Conducted in Living Kidney Donors on Renal Function in Donors and Recipients Following Living Donor Kidney Transplantation: A Randomized Clinical Trial.

Ji-Yeon Bang,Sae-Gyeol Kim,Seon-Ok Kim,Jimi Oh,Jun-Gol Song,Yon-Ji Go,Gyu-Sam Hwang

doi:10.3390/jcm8050713

Abstract

Although remote ischemic preconditioning (RIPC) has been shown to have renoprotective effects, few studies have assessed the effects of RIPC on renal function in living kidney donors. This study investigated whether RIPC performed in living kidney donors could improve residual renal function in donors and outcomes in recipients following kidney transplantation. The donors were randomized into a control group (n = 85) and a RIPC group (n = 85). The recipients were included according to the matched donors. Serum creatinine (sCr) concentrations and estimated glomerular filtration rate (eGFR) were compared between control and RIPC groups in donors and recipients. Delayed graft function, acute rejection, and graft failure within one year after transplantation were evaluated in recipients. sCr was significantly increased in the control group (mean, 1.13; 95% confidence interval (CI), 1.07–1.18) than the RIPC group (1.01; 95% CI, 0.95–1.07) (p = 0.003) at discharge. Donors with serum creatinine >1.4 mg/dL at discharge had higher prevalence of chronic kidney disease (n = 6, 26.1%) than donors with a normal serum creatinine level (n = 8, 5.4%) (p = 0.003) after one year. sCr concentrations and eGFR were similar in the RIPC and control groups of recipients over the one-year follow-up period. Among recipients, no outcome variables differed significantly in the RIPC and control groups. RIPC was effective in improving early renal function in kidney donors but did not improve renal function in recipients.

Highlights

Kidney transplantation (KT) is the most effective treatment for many patients with kidney failure [1], with living donor KT having a higher survival rate than deceased donor KT [2]
Donor nephrectomy may induce intrarenal structural changes and hemodynamic derangements for several days due to hyperfiltration, accompanying increases in serum creatinine (sCr) concentrations [6]. This is regarded as a physiological response, followed by an increase in glomerular filtration, we recently reported that a continuous increase in sCr after donor nephrectomy can lead to chronic kidney disease [30]
Our results show that Remote ischemic preconditioning (RIPC) was significantly effective in lowering creatinine level in donors compared to the control group during the acute postoperative phase, but at later times for up to one year

Summary

Introduction

Kidney transplantation (KT) is the most effective treatment for many patients with kidney failure [1], with living donor KT having a higher survival rate than deceased donor KT [2]. RIPC is known to exert protective effects using three different modes: a humoral, a neural, and a systemic generalized response [18] These protective effects have been attributed to several trigger factors, which include autacoids released into the systemic circulation (nitric oxide or nitrite) [19] along with other types of signaling molecules (endocannabinoids, stromal cell-derived factor-1α, microRNA-144) [20]. These molecules activate the signaling cascade that includes protein kinase and nuclear factor kB and leads to the synthesis of protective proteins, such as manganese superoxide dismutase and inducible nitric oxide synthase [21]. This results in attenuation of endothelial dysfunction, modulation of reactive oxygen species and proinflammatory mediator release after reperfusion, and decreased cell death [21,22]

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Conclusion