Remote Ischemic Preconditioning Fails to Improve Early Renal Function of Patients Undergoing Living-Donor Renal Transplantation

The shortage of donor organs has greatly limited the development of organ transplantation. In the United States, on 31 December 2009, 52,503 active patients were waitlisted for kidney transplantation; 45% of them had been waiting at least 2 years and 11% had been waiting more than 5 years (1). Consequently, elderly or marginal donors trend to be included in the donor pool, which increases the risk of reduced renal function and impaired graft survival (2, 3). Approaches helping to avoid or alleviate ischemia-reperfusion injury (IRI) might improve the outcomes of renal transplantation with these vulnerable grafts (4). Remote ischemic preconditioning (RIPC) has shown protective effects against IRI in various target organs, including the kidney (5–9). However, clinical trials concerning renal protective effects of RIPC are still limited (10–12). The aim of this study is to investigate whether RIPC improves early renal function of patients receiving living-donor renal transplantation. From May 2010 to November 2011, 60 pairs of adult patients undergoing elective living-donor renal transplantation in our hospital were finally enrolled in this study. Exclusion criteria included emergency surgery, diabetes mellitus, severe peripheral vascular diseases, and history of solid organ transplantation. Anesthetic and surgical profiles as well as perioperative treatment were kept comparable in all patients. Patients were allocated to three groups randomly: RIPC was performed on the donor in group D and on the recipient in group R and no preconditioning was performed in group C. RIPC was conducted with a 12 cm wide blood pressure cuff encircling the upper part of the leg. The cuff was inflated to a pressure of 300 mmHg for 5 min and deflated for 5 min, and the whole procedure consisted of three cycles of inflation and deflation. Renal function and biochemical markers of renal IRI were assessed within 72 hr after transplantation. Baseline data of all patients and outcomes of the donors were similar among groups (see Table S1 and S2, SDC,https://links.lww.com/TP/A754). Five of the 60 recipients (one in group C and two in groups D and R, respectively) experienced delayed graft function and recovered within 1 month. There were no statistical significant differences between groups in urine volumes, plasma creatinine, and neutrophil gelatinase-associated lipocalin concentration of the recipients at any time point observed (P>0.05). Moreover, changes in urine retinol binding protein concentration and N-acetyl-D-glucosaminidase activity and plasma superoxide dismutase activity and malondialdehyde concentration did not show any statistically significant differences among the three groups (P>0.05), although median superoxide dismutase levels in the two RIPC groups were slightly higher than those in the control group at 1, 4, and 24 hr after transplantation (Table 1). The median postoperative hospitalization days in group D (15 days) and group R (14.5 days) were relatively shorter than the control group (17 days), but the difference was not statistically significant (P>0.05). Total costs during hospitalization were also comparable in the three groups. No severe adverse effects occurred, except that two patients had slight erythema and one patient felt constriction in their treated leg, which was relieved in 1 day with physical therapy.TABLE 1: Outcomes and the renal function of the recipients (median, interquartile range)RPIC was found to protect against renal IRI in rats in several experiments (8, 9, 13), but it seems unavailing in our clinical trial. Several factors might underlie our result. First, Wever et al. (9) demonstrated recently that preconditioning with only one hind limb was less effective in renal protection than with bilateral hind limbs, indicating that the mass of the remote tissue/organ might influence the intensity of protection. Thus, preconditioning with one leg of the patient in our study might not exert adequate effect on the graft. Second, clinical transplantation is different from any existing animal model. In animal experiments, preconditioning and ischemia-reperfusion take place in the same individual. Therefore, protective mediators (adenosine, opioids, and nitric oxide, et al) (14, 15) could act on the target organ all along, whereas, in allotransplantation, the graft is transferred from the donor to the recipient after perfusion and cold preservation, so that unilateral preconditioning of the donor or the recipient does not protect the graft throughout the procedure and might be insufficient. Simultaneously applying RIPC on both the donor and the recipient may yield different results. Our study has a relatively small sample size and the power of the test is insufficient. However, it is the first report of applying RIPC in renal transplantation and we found that the procedure could be easily fulfilled with few adverse reactions. It can be considered a pilot test of this novel preconditioning method and more elaborate and well-designed projects could be conducted later according to this. Yeling Chen Hua Zheng Xueren Wang Zhiqiang Zhou Ailin Luo Yuke Tian Department of Anesthesiology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, China ACKNOWLEDGMENTS The authors thank Qiong Shen (chief nurse, Tongji Hospital, Wuhan, China) who coordinated with the research team and conducted the RIPC protocol; Daniel Pöpping, M.D. (Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany) who assisted in grammatically revising and editing the article; Susanne Amler, Dipl.-Biomath. (Institute of Biostatistics and Clinical Research, University Hospital Münster, Münster, Germany) who helped complete the statistical analysis; and the colleagues in the Department of Transplantation of Tongji Hospital for their sincere cooperation.