Lower rate of delayed graft function is observed when epidural analgesia for living donor nephrectomy is administered.

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Wolfgang Baar, Ulrich Goebel, Hartmut Buerkle, Bernd Jaenigen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.101/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Mar, 2019 Read the published version in BMC Anesthesiology → Version 3 posted 4 You are reading this latest preprint version Show more versions Abstract Background The beneficial effects of epidural analgesia (EDA) in terms of pain control and postoperative convalescence are widely known and led to a frequent use for patients who underwent living donor kidney nephrectomy. The objective of this study was to determine whether general anesthesia (GA) plus EDA compared to GA only, administered for living donor nephrectomy has effects on postoperative graft function in recipients. Methods In this monocentric, retrospective cohort analysis we analyzed the closed files of all consecutive donor- recipient pairs who underwent living donor kidney transplantations from 2008 to 2017. The outcome variable was delayed graft function (DGF), defined as at least one hemodialysis within seven days postoperatively, once hyperacute rejection, vascular or urinary tract complications were ruled out. Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher exact test for categorical variables with a significance level of p<0.05, respectively. Results The study enclosed 291 consecutive living donor kidney transplantations. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. The groups showed balanced pretransplantational characteristics and comparable donors´ and recipients’ risk factors. 9 out of all 291 recipients needed renal replacement therapy (RRT) during the first 7 days due to delayed graft function; none of these donors received EDA. The observed rate of DGF in recipients whose kidney donors received epidural analgesia was significantly lower (0% vs. 4.6%; p=0.031). Conclusions In our cohort we observed a significantly lower rate of DGF when epidural analgesia for donor nephrectomy was administered. Due to restrictions of the study design this observation needs further confirmation by prospective studies. Internal Medicine Specialties kidney transplantation delayed graft function epidural analgesia donor nephrectomy Figures Figure 1 Figure 2 Background Living kidney transplantation showed superior results compared to deceased donor kidney transplantation in terms of graft survival, accessibility, waiting time and cost containment for public health services [1–3]. For patients undergoing surgical procedures for another one´s benefit, it is important to minimize perioperative risks and inconvenience. Furthermore, it is the healthcare providers’ duty to maximize the beneficial impact of the donation for the recipient. In numerous studies major outcome benefits like mortality of EDA could neither be confirmed nor denied[4, 5]. However, the beneficial effects of EDA in terms of intra- and postoperative pain control, intestinal motility, early mobilization and duration of ICU- hospitalization are widely known and find broad acceptance[6–9]. Therefore it is not surprising, that continuous EDA is a mandatory part of many surgical fast track programs [10–12]. In order to provide these advantages also for kidney donors and to increase their convalescence and speed up their reintegration in daily life, we offered EDA to patients for donor nephrectomy, if contraindications were ruled out and patients gave their informed consent. The primary intent of providing perioperative EDA for donor nephrectomy are the beneficial effects for the donor[13–15]. These EDA effects are mostly mediated by perioperative sympathicolysis which probably has effects on the kidney intended for transplantation[16, 17]. Potential effects on graft function of kidneys explanted from donors with EDA in terms of a two day follow up of glomerular filtration rate, microalbuminuria, or creatinine clearance have shown no differences in a small cohort [17]. Potential effects on the incidence of delayed graft function have not yet been reported. Therefore, the aim of this hypothesis generating study was to determine whether GA plus EDA compared to GA only, administered for living donor nephrectomy is associated with beneficial effects on postoperative graft function after transplantation. Methods This retrospective cohort study was approved by the local Institutional Review Board, University of Freiburg, Germany (approval number EK 555/17). The study was conducted at the Department of Anesthesiology and Critical Care and the Department of General and Visceral Surgery, Medical Center - University of Freiburg, Faculty of Medicine - University of Freiburg Germany. The study was planned and designed in accordance with the initiative for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), using the suggested checklist for epidemiological cohort studies [18]. The study was initiated and designed in March 2018; the retrospective data collection was conducted in June 2018. The onset of data collection is analogous to the existence of an electronic patient data management system on ICU which enabled data acquisition. As we enclosed only closed files and the data collection started in June 2018, cases after December 31th 2017 were not enclosed. The study cohort consists of all consecutive living donor kidney transplantations between October 2008 and December 2017 which determines the sample size. A priori sample size calculation is not applicable in this fully retrospective and observational study design. Figure 1 shows the protocol of data collection and statistical processing. Recipient and donor evaluation were based on a check-up examination which lead to confirmation of donor suitability. Ahead of transplantation all donor- recipient pairs were evaluated by an ethics committee of the District Medical Association Suedbaden, Germany. A positive vote of this ethics committee was mandatory for transplantation. Surgical procedure was standardized to a maximum as only two different surgeons contributed to the transplantations in this cohort. The donor nephrectomy was performed in supine position over an open anterior extraperitoneal minimal incision laparotomy. Transplantations were performed in the established technique, to the right iliac fossa of the recipient. Decision on epidural analgesia was based on the patients´ preference. All patients that received epidural analgesia gave their informed consent on that procedure. Epidural analgesia was performed directly preoperatively according a specific departmental standard operating procedure: Epidural catheter was placed between the 7th and the 11th thoracic intervertebral space, followed by an application of 25 g sufentanil and 10 ml ropivacaine 0.2 %. After the initial dose a continuous epidural application of 45 ml ropivacaine 0.2 % mixed with 25 g sufentanil (= ropivacaine 0.18 % and sufentanil 0.5 g/ml) with an infusion rate of 8 ml/h during the surgery was established. Anesthesia procedures for donor nephrectomy with and without epidural analgesia followed a unique mandatory standard operating procedure (SOP) which differed only regarding the administration of EDA and was performed by a specialized transplantation team. Our transplantation team consists of 8 to 10 attending anesthesiologists, who underwent special training (transplant fellowship) and are used to perform anesthesiology for kidney transplantation in accordance to our mandatory in-house standard operating procedure. Over the years the attending anesthesiologists in charge changed, so that in total a number of 25 anesthesiologists took care of the patients. Postoperatively all donors were transferred to a transplantation ICU. Patients who received epidural analgesia were visited daily by the acute pain service of our department. Epidural catheters were removed between the second and the fifth postoperative day by the acute pain service. Anesthesia for transplantation was performed without epidural analgesia for the recipient and followed a departmental SOP which was established and revised where necessary in close collaboration between the responsible surgeons and anesthetists The SOP addresses the need for 250 mg prednisolone and 10 g mannitol ahead of reperfusion. With the onset of reperfusion of the transplant kidney 125 mg furosemide were administered. Intraoperative fluid and catecholamine management was performed by the attending anesthetist referring to the SOP. Renal replacement therapy (RRT) was initiated when patients were threatened by volume overload or increased serum potassium levels. Delayed graft function was defined as any renal replacement therapy in the first postoperative week, once hyperacute rejection, vascular or urinary tract complications were ruled out [19–21] . Statistics: The data was collected in a MS Excel™ (Microsoft, Redmond, USA) datasheet. Further statistical processing was performed using SPSS™ (IBM, Armonk, USA). Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher Exact test for categorical variables with a significance level of p<0.05, respectively. Results The study enclosed 291 consecutive living donor kidney transplantations between October 2008 and December 2017. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. Table 1 shows the distribution of patients, the rate of EDA and the incidence of RRT and DGF for every year. For none of the years RRT or DGF rate are significantly increased. All recipients underwent kidney transplantation due to end stage renal disease. No mortality was reported in either group. In the EDA group no epidural catheter associated complications were found. The perioperative characteristics are shown in table 2. The two study groups showed no significant differences in several donors´ risk factors except a significantly shorter nephrectomy time (135 vs. 144 min, p<0.003). The intraoperative fluid consumption (1813 vs. 2191 ml; p=0.053) and maximum dose of vasopressor (0.03 vs. 0.06 g/kg/min; p=0.300) showed no statistically significant difference. None of the recipients´ pre- and intra-transplantation data showed a significant difference (table 2). After transplantation, 14 out of all 291 recipients needed renal replacement therapy during the first 7 days after transplantation, but only 9 cases due to delayed graft function. The other 5 recipients suffered humoral rejection, thrombosis of the iliac vessel or bleeding complications with the need of a surgical revision (table 3). All kidney donors to these 9 recipients received GA without epidural analgesia. The incidence of DGF was significantly higher in recipients whose donors did not receive epidural analgesia (4.6% vs. 0%; p=0.031) (figure 2). In line with this finding the serum creatinine level as well as the maximum serum potassium level within 7 days were significantly lower in the recipients whose donors received EDA (2.17 vs. 2.04 mg/dl, p=0.036; 5.15 vs. 5.11 mmol/l, p<0.001). Discussion The benefits of EDA regarding pain control, ICU stay, intestinal motility and early mobilization are frequently reported [22–27]. The beneficial effects of EDA in terms of pain control and return to normal daily activities specifically for kidney donors have also been reported in the past [28, 29]. This retrospective cohort study of 291 living donor kidney transplantations compared 99 cases whose donors received EDA with 192 cases that received GA only, with regard to DGF in the recipients. The main result is that DGF is significantly more frequent in patients whose kidney donors did not receive EDA. The incidence of DGF in cohorts of living kidney transplantations varies from 4 to 10% and increases morbidity, healthcare costs, hospitalization times and complicates post- transplantation care [30–33]. DGF predisposes for chronic rejection, chronic allograft nephropathy and seems to be causal for increased rates of graft failure and mortality [34, 35]. In line with the significantly lower rate of DGF in EDA group, we found that serum creatinine level, as well as the maximum serum potassium level within 7 days, were significantly lower in the EDA group. Although these findings are statistically significant, their measured levels and differences in numbers are clinically not of relevance. Even when looking at the decline of the serum creatinine levels over the first two days postoperatively no significant or clinically relevant difference can be found. The recipients of the no-EDA group start at a slightly higher level of serum creatinine which should be taken into account. Further baseline characteristics of donors and recipients showed no statistically significant difference or clinically relevant imbalance between the donors and recipients of both groups. An increased intraoperative fluid and vasopressor consumption in the EDA group could be associated with the EDA mediated inhibition of the sympatho- adrenal response with consecutive vasodilatation. However, neither intraoperative fluid nor vasopressor consumption showed a statistically significant difference in our study. The standard surgical technique for donor nephrectomy in our institution is an open anterior extraperitoneal minimal incision laparotomy. Open surgical technique for donor nephrectomy is associated with inferior cosmetic result, longer hospitalization and more intra- and postoperative pain with consecutively increased need for pain medication [36, 37]. However, the open surgical approach showed superior results in terms of warm ischemia period, surgical costs, length of operation, intraperitoneal complications, recovery of graft function, recipient anastomosis difficulties and incidence of acute tubulus necrosis [38–40]. It is reported that up to 25% of living kidney donors after open surgical technique nephrectomy suffer from chronification of postoperative pain [41]. A reduction of somatic pain within the first six postoperative weeks is associated with improved mental health of kidney donors [37]. These findings underline the need for EDA from the donors’ perspective. The described clinical benefits of EDA for the donor might lose their relevance and have to be reconsidered in case the surgical approach in our institution changes to laparoscopic technique. The reasons why kidney grafts fail to function immediately after transplantation when acute rejection, urological or vascular reasons are ruled out are associated with the transplanted kidney. DGF is modulated and caused by complex mechanisms of hypoxic and ischemic injuries and insufficient repair mechanisms [42]. These cascades seem to be induced by the operative trauma and the corresponding physiological stress response during donor nephrectomy. It is known that surgical procedures and the physiological stress response are associated with intra- and postoperative hypercoagulability which results in postoperative thromboembolic and vaso-occlusive events[43, 44]. Increased levels of tissue factor, tissue plasminogen activator, plasminogen activator inhibitor-1, and von Willebrand factor which all contribute to hypercoagulability are reported to be found proximately after surgical stimulus[45]. Due to inhibition of nociceptive and non-nociceptive pathways of sympathetic innervation of the adrenal glands, EDA with local anesthetics leads to a perioperative sympathicolysis[46]. Experimental reports on rats showed a significantly improved microcirculation in the areas of EDA mediated sympathetic blockage[47]. In an ovine model with artificially administered pulmonary embolism therapeutic EDA improved macrohemodynamic parameters[48]. It is also reported that EDA modulates postoperative hypercoagulability by normalizing antithrombin III- activity and a decrease of platelet aggregation [49–51]. We hypothesize that a decreased risk of thrombotic and vasoocclusive events which is mediated by therapeutic EDA could be one of the reasons that we found a significantly increased rate of DGF in the non-EDA group. The potential benefit of EDA performed for the transplantation could not be investigated by our study group. In our institution the transplantation itself is performed without EDA due to the mandatory immune suppressive therapy and the high incidence of platelet dysfunction in patients suffering from end stage renal disease[52, 53]. Hadimioglu and colleagues found improved clinical results and an attenuated stress response in kidney transplantations performed with EDA and general anesthesia compared to general anesthesia alone[54]. Against the background of these results and the results of our study, we will reconsider our previous approach with regard to the use of EDA in kidney transplants. The present study has several distinct limitations. First, the retrospective and non-randomized design implies that a study protocol which addresses randomization on who receives EDA is missing. It is speculative why patients opted for or against EDA, possibly the way whether EDA was offered by the visiting anesthesiologist or rather recommended plays an important role. Perhaps patients who opted for EDA were more trustful of their physicians and therefore had less anxiety or stress levels which may have influenced DGF of their donated kidney. The way EDA was offered to the donors might have been changed throughout the years. We have seen that EDA is more frequently performed in the last years of the program compared to the very early years of the observation period. However, this imbalance of EDA rates throughout the observational period was not associated with an accumulation of RRTs or DGF in the early or the late years of the observation. RRT was initiated by visiting nephrology specialists and the request of the attending ICU physician when patients were threatened by volume overload or increased serum potassium levels. We are fully aware that living donor kidney transplantation is a highly complex procedure. The outcome quality is affected by various confounding variables for which we have not adjusted in our study due to the limited number of cases with DGF. There are also several slightly different definitions on delayed graft function in literature. In our study DGF was defined as any renal replacement therapy in the first postoperative week, when hyperacute rejection, vascular and urinary tract complications were ruled out. More than 22 different definitions of DGF are described, the most common definition refers to any RRT within the first posttransplantational week [55, 56]. Due to the manageable size of our cohort we could screen every case of RRT for the underlying reasons. Knowing these reasons leading to RRT for every patient, we decided to choose a more specific definition of delayed graft function. Beyond the discussion about the definition we have to state, that in the EDA group none of the patients who received RRT showed graft associated reasons leading to RRT. In no case of the EDA group, graft perfusion deficits or insufficient otherwise unexplainable graft dysfunction led to RRT. Finally, we can report of an association between EDA for donor nephrectomy and a lower rate of DGF in our study. However, we are fully aware that correlation does not proof causality. Especially in a multifactorial context such as living kidney transplantations, larger numbers of prospectively randomized assigned patients are needed to provide stronger evidence. Conclusions In this retrospective cohort study, we found an association between epidural analgesia for living kidney donors and significantly less delayed graft function in the corresponding kidney recipients. These results favor not only the beneficial analgesic effect of epidural analgesia for donors, but also show significant beneficial effects for kidney recipients. As our analysis depends on the authors' experience, derived from a very low level of evidence with consecutive relevant shortcoming in terms of study design, number of index cases and adjustment of confounding variables, our findings have to be confirmed by prospective randomized trials. List of abbreviations DGF – delayed graft function EDA – epidural analgesia GA – general anesthesia RRT – renal replacement therapy SOP – standard operating procedure STROBE – Strengthening the Reporting of Observational Studies in Epidemiology Declarations Availability of data and materials The datasets generated and analyzed during the current study are not publicly available due institutional restrictions but are available from the corresponding author on reasonable request. Authors contributions: SH initiated the study, performed statistically processing, contributed to the writing of the manuscript, UG developed the study design, contributed to data collection and proofread the manuscript, HB advised the study design, is responsible for the anesthesia SOPs and proof read the manuscript, BJ operated most of the patients is responsible for the postoperative care of the patients and contributed to data collection, KK contributed to data collection and writing of the manuscript, WB contributed to data collection and wrote the manuscript. All authors contributed substantially to this work and all of them revised and agreed to the final version of the manuscript with full access to all data. Ethics approval and consent to participate The local ethics committee approved the analysis and publication of the data and confirmed that no specific patient´s consent was necessary because of the anonymous and observational design of the study (approval number EK 555/17). Ethics Committee University of Freiburg, Germany Engelberger Straße 21 79106 Freiburg Consent for publication Not Applicable. Acknowledgements Not Applicable. Competing interests The authors declare that they have no competing interests. Funding The article processing charge was funded by the German Research Foundation (DFG) and the University of Freiburg in the funding program Open Access Publishing. The funding body had no influence on study design, data collection, analysis, interpretation and writing the manuscript. References 1. Lionaki S, Kapsia H, Makropoulos I, Metsini A, Skalioti C, Gakiopoulou H, et al. 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Therapeutic administration of thoracic epidural anesthesia reduces cardiopulmonary deterioration in ovine pulmonary embolism. Crit Care Med. 2007;35:2582–6. 49. Fant F, Tina E, Sandblom D, Andersson S-O, Magnuson A, Hultgren-Hörnkvist E, et al. Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy. Br J Anaesth. 2013;110:747–57. 50. Grass JA. The role of epidural anesthesia and analgesia in postoperative outcome. Anesthesiol Clin N Am. 2000;18:407–28, viii. 51. Liu S, Carpenter RL, Neal JM. Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology. 1995;82:1474–506. 52. Pluta J, Nicińska B, Grzeszczyk M, Kołacz M, Jureczko L, Kwiatkowski A, et al. Assessment of the Hemostatic Parameters and Platelet Function on Thromboelastometry and Impedance Aggregometry in Hemodialysis Patients Qualified for Kidney Transplantation: Preliminary Report. Transplant Proc. 2016;48:1431–4. 53. Kaw D, Malhotra D. Platelet dysfunction and end-stage renal disease. Semin Dial. 2006;19:317–22. 54. Hadimioglu N, Ulugol H, Akbas H, Coskunfirat N, Ertug Z, Dinckan A. Combination of Epidural Anesthesia and General Anesthesia Attenuates Stress Response to Renal Transplantation Surgery. Transplant Proc. 2012;44:2949–54. 55. Decruyenaere P, Decruyenaere A, Peeters P, Vermassen F. A Single-Center Comparison of 22 Competing Definitions of Delayed Graft Function After Kidney Transplantation. Ann Transplant. 2016;21:152–9. 56. Yarlagadda SG, Coca SG, Garg AX, Doshi M, Poggio E, Marcus RJ, et al. Marked variation in the definition and diagnosis of delayed graft function: a systematic review. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2008;23:2995–3003. Tables Table 1: Year Number of patients With EDA (n/%) RRT within 7 days (n/%) DGF (n/%) 2008 7 0/0% 0/0% 0/0% 2009 31 1/3% 0/0% 0/0% 2010 33 0/0% 1/3% 1/3% 2011 34 6/18% 3/9% 3/9% 2012 35 15/43% 3/9% 1/3% 2013 32 14/44% 0/0% 0/0% 2014 35 8/23% 2/6% 1/3% 2015 31 14/45% 2/6% 2/6% 2016 30 25/83% 2/7% 1/3% 2017 23 16/70% 1/4% 0/0% Table 1: Distribution of patients, rate of EDA, incidence of RRT and DGF throughout the observation period. Table 2 without EDA (n=192) with EDA (n=99) significance Donor and nephrectomy data Donor male sex [n/(%)] 71 (37%) 32 (32%) 0.469 Donor BMI [kg/m²] 25.7 ± 4.1 25.5 ± 3.5 0.165 Donor age [years] 52 52 0.416 Donor preoperative hemoglobin [g/dl] 14.1 ± 1.2 14.1 ± 1.2 0.919 Crystalloid fluid for nephrectomy [ml] 1813 ± 907 2191 ± 1113 0.053 Max. dose of noradrenaline after cut [µg/kg/min] 0.03 ± 0.04 0.06 ± 0.05 0.300 Nephrectomy time (cut – suture) [min] 135 ± 38 144 ± 48 0.003 Recipient and transplantation data Recipient BMI [kg/m²] 24.8 ± 3.9 25.6 ± 4.2 0.168 Recipient male sex [n/(%)] 121 (62%) 61 (62%) 0.899 Recipient age [years] 44 ± 13 47 ± 13 0.853 Recipient rest diuresis [ml] 1098 ± 907 1134 ± 858 0.062 Recipient preoperative creatinine [mg/dl] 8.0 ± 2.8 7.6 ± 2.8 0.744 Duration of transplantation [min] 161 ± 55 145 ± 41 0.129 Warm ischemic period [min] 29 ± 9 26 ±7 0.138 MAP for anastomosis [mmHg] 93 ± 11 88 ± 16 0.165 Fluid intake during transplantation [ml] 2782 ± 1366 3477 ± 1233 0.559 Posttransplantation data Diuresis first hour [ml] 425 ± 430 383 ± 390 0.358 Diuresis 24 hours [ml] 9947 ± 5313 10871 ± 6419 0.062 Recipient creatinine 12-24 hours postoperative [mg/dl] 4.37 ± 2.2 4.09 ± 1.8 0.189 Recipient creatinine 36-48 hours postoperative[mg/dl] 3.15 ± 2.1 3.04 ± 1.7 0.404 Recipient creatinine 7 days postoperative [mg/dl] 2.17 ± 1.6 2.04 ± 1.1 0.036 Max. recipient serum potassium level within 7d 5.15 ± 0.6 5.11 ± 0.4 0.001 Renal replacement therapy first postoperative week [n/(%)] 11 (6%) 3 (3%) 0.312 Delayed graft function [n/(%)] 9 (4.6%) 0 (0%) 0.031 Table 2: Main results of the study. Continuous variables are given as mean ± standard deviation, categorical variables are given as absolute number and percentage. Table 3: Case Number Year EDA Underlying reason leading to RRT within 7 days DGF 507 2010 no graft perfusion deficit yes 581 2011 no insufficient graft function, later sepsis yes 588 2011 no critical potassium levels, good graft function later on yes 624 2011 no acute tubules necrosis yes 666 2012 yes humoral rejection no 692 2012 no bleeding complication, needed operative revision no 701 2012 no insufficient graft function yes 829 2014 no humoral rejection no 859 2014 no graft perfusion deficit yes 888 2015 no insufficient graft function, critical potassium levels yes 935 2015 no insufficient graft function yes 1017 2016 no insufficient graft function yes 1023 2016 yes humoral rejection no 1089 2017 yes thrombosis of recipients iliac vessel no Table 3: Underlying reasons for renal replacement therapy (RRT) and met definition of delayed graft function (DGF). Supplementary Files supplement1.docx Cite Share Download PDF Status: Published Journal Publication published 18 Mar, 2019 Read the published version in BMC Anesthesiology → Version 3 posted Editorial decision: Accept 11 Mar, 2019 Editor invited by journal 08 Mar, 2019 Editor assigned by journal 08 Mar, 2019 Submission checks completed at journal 09 Dec, 2018 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-101","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":7626,"identity":"f7b50b48-5eac-40f2-ad90-58abf42ba2b7","order_by":1,"name":"Wolfgang Baar","email":"","orcid":"","institution":"Universitatsklinikum Freiburg Anasthesiologische Klinik","correspondingAuthor":false,"prefix":"","firstName":"Wolfgang","middleName":"","lastName":"Baar","suffix":""},{"id":7627,"identity":"c573fcaf-84cf-4be0-ac6a-b1e0ee67a302","order_by":2,"name":"Ulrich Goebel","email":"","orcid":"","institution":"Universitatsklinikum Freiburg Anasthesiologische Klinik","correspondingAuthor":false,"prefix":"","firstName":"Ulrich","middleName":"","lastName":"Goebel","suffix":""},{"id":7628,"identity":"84ddd5d6-e517-47c5-ab17-50cf8dbe46bd","order_by":3,"name":"Hartmut Buerkle","email":"","orcid":"","institution":"Universitatsklinikum Freiburg Anasthesiologische Klinik","correspondingAuthor":false,"prefix":"","firstName":"Hartmut","middleName":"","lastName":"Buerkle","suffix":""},{"id":7629,"identity":"c6534a9b-3e4a-4bf9-9e03-6f269ca36314","order_by":4,"name":"Bernd Jaenigen","email":"","orcid":"","institution":"Universitatsklinikum Freiburg Klinik fur Allgemein- Viszeral- und Transplantationschirurgie","correspondingAuthor":false,"prefix":"","firstName":"Bernd","middleName":"","lastName":"Jaenigen","suffix":""},{"id":7630,"identity":"ff216784-16ea-4d36-8e7d-96d8fbb075a2","order_by":5,"name":"Kai Kaufmann","email":"","orcid":"","institution":"Universitatsklinikum Freiburg Anasthesiologische 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Freiburg","correspondingAuthor":true,"prefix":"","firstName":"Sebastian","middleName":"","lastName":"Heinrich","suffix":""}],"badges":[],"createdAt":"2018-12-12 13:46:57","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.2.101/v3","doiUrl":"https://doi.org/10.21203/rs.2.101/v3","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-019-0713-y","type":"published","date":"2019-03-18T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2606729,"identity":"5e62e112-330a-458c-99b5-15c9382d7bab","added_by":"dbe1c910-fa3f-4a3a-a5c6-af99624d3e99","created_at":"2020-09-25 20:49:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":54448,"visible":true,"origin":"","legend":"Flowchart showing the data collection of the study.","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-101/v3/figure_1.jpg"},{"id":2606734,"identity":"445a5dbd-8a69-45a4-9664-e4e8b5b16d83","added_by":"dbe1c910-fa3f-4a3a-a5c6-af99624d3e99","created_at":"2020-09-25 20:49:08","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":55278,"visible":true,"origin":"","legend":"The incidence of renal replacement therapy (RRT) with the first seven days and delayed graft function (DGF) depending on the anesthesia procedure for donor nephrectomy.","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-101/v3/figure_2.jpg"},{"id":13466263,"identity":"d22aa641-d911-4eb5-8289-d57d8a5d2b86","added_by":"auto","created_at":"2021-09-16 20:50:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3244351,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-101/v3/8b978318-9aa5-4edf-b5c9-4826c16d6cce.pdf"},{"id":2606732,"identity":"e45b3a96-b8dc-4c03-85af-d85bdc333da3","added_by":"dbe1c910-fa3f-4a3a-a5c6-af99624d3e99","created_at":"2020-09-25 20:49:08","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":30494,"visible":true,"origin":"","legend":"","description":"","filename":"supplement1.docx","url":"https://assets-eu.researchsquare.com/files/rs-101/v3/supplement_1.docx"}],"financialInterests":"","formattedTitle":"Lower rate of delayed graft function is observed when epidural analgesia for living donor nephrectomy is administered.","fulltext":[{"header":"Background","content":"\u003cp\u003eLiving kidney transplantation showed superior results compared to deceased donor kidney transplantation in terms of graft survival, accessibility, waiting time and cost containment for public health services [1–3]. For patients undergoing surgical procedures for another one´s benefit, it is important to minimize perioperative risks and inconvenience. Furthermore, it is the healthcare providers’ duty to maximize the beneficial impact of the donation for the recipient. \u003c/p\u003e\n\u003cp\u003eIn numerous studies major outcome benefits like mortality of EDA could neither be confirmed nor denied[4, 5]. However, the beneficial effects of EDA in terms of intra- and postoperative pain control, intestinal motility, early mobilization and duration of ICU- hospitalization are widely known and find broad acceptance[6–9]. Therefore it is not surprising, that continuous EDA is a mandatory part of many surgical fast track programs [10–12]. In order to provide these advantages also for kidney donors and to increase their convalescence and speed up their reintegration in daily life, we offered EDA to patients for donor nephrectomy, if contraindications were ruled out and patients gave their informed consent. The primary intent of providing perioperative EDA for donor nephrectomy are the beneficial effects for the donor[13–15]. These EDA effects are mostly mediated by perioperative sympathicolysis which probably has effects on the kidney intended for transplantation[16, 17]. Potential effects on graft function of kidneys explanted from donors with EDA in terms of a two day follow up of glomerular filtration rate, microalbuminuria, or creatinine clearance have shown no differences in a small cohort [17]. Potential effects on the incidence of delayed graft function have not yet been reported. Therefore, the aim of this hypothesis generating study was to determine whether GA plus EDA compared to GA only, administered for living donor nephrectomy is associated with beneficial effects on postoperative graft function after transplantation. \u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective cohort study was approved by the local Institutional Review Board, University of Freiburg, Germany (approval number EK 555/17). The study was conducted at the Department of Anesthesiology and Critical Care and the Department of General and Visceral Surgery, Medical Center - University of Freiburg, Faculty of Medicine - University of Freiburg Germany. The study was planned and designed in accordance with the initiative for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), using the suggested checklist for epidemiological cohort studies [18]. The study was initiated and designed in March 2018; the retrospective data collection was conducted in June 2018. The onset of data collection is analogous to the existence of an electronic patient data management system on ICU which enabled data acquisition. As we enclosed only closed files and the data collection started in June 2018, cases after December 31th 2017 were not enclosed. The study cohort consists of all consecutive living donor kidney transplantations between October 2008 and December 2017 which determines the sample size. A priori sample size calculation is not applicable in this fully retrospective and observational study design. Figure 1 shows the protocol of data collection and statistical processing. \u003c/p\u003e\n\u003cp\u003eRecipient and donor evaluation were based on a check-up examination which lead to confirmation of donor suitability. Ahead of transplantation all donor- recipient pairs were evaluated by an ethics committee of the District Medical Association Suedbaden, Germany. A positive vote of this ethics committee was mandatory for transplantation.\u003c/p\u003e\n\u003cp\u003eSurgical procedure was standardized to a maximum as only two different surgeons contributed to the transplantations in this cohort. The donor nephrectomy was performed in supine position over an open anterior extraperitoneal minimal incision laparotomy. Transplantations were performed in the established technique, to the right iliac fossa of the recipient. \u003c/p\u003e\n\u003cp\u003eDecision on epidural analgesia was based on the patients´ preference. All patients that received epidural analgesia gave their informed consent on that procedure. Epidural analgesia was performed directly preoperatively according a specific departmental standard operating procedure: Epidural catheter was placed between the 7th and the 11th thoracic intervertebral space, followed by an application of 25 g sufentanil and 10 ml ropivacaine 0.2 %. After the initial dose a continuous epidural application of 45 ml ropivacaine 0.2 % mixed with 25 g sufentanil (= ropivacaine 0.18 % and sufentanil 0.5 g/ml) with an infusion rate of 8 ml/h during the surgery was established. Anesthesia procedures for donor nephrectomy with and without epidural analgesia followed a unique mandatory standard operating procedure (SOP) which differed only regarding the administration of EDA and was performed by a specialized transplantation team. Our transplantation team consists of 8 to 10 attending anesthesiologists, who underwent special training (transplant fellowship) and are used to perform anesthesiology for kidney transplantation in accordance to our mandatory in-house standard operating procedure. Over the years the attending anesthesiologists in charge changed, so that in total a number of 25 anesthesiologists took care of the patients. Postoperatively all donors were transferred to a transplantation ICU. Patients who received epidural analgesia were visited daily by the acute pain service of our department. Epidural catheters were removed between the second and the fifth postoperative day by the acute pain service.\u003c/p\u003e\n\u003cp\u003eAnesthesia for transplantation was performed without epidural analgesia for the recipient and followed a departmental SOP which was established and revised where necessary in close collaboration between the responsible surgeons and anesthetists The SOP addresses the need for 250 mg prednisolone and 10 g mannitol ahead of reperfusion. With the onset of reperfusion of the transplant kidney 125 mg furosemide were administered. Intraoperative fluid and catecholamine management was performed by the attending anesthetist referring to the SOP. \u003c/p\u003e\n\u003cp\u003eRenal replacement therapy (RRT) was initiated when patients were threatened by volume overload or increased serum potassium levels. Delayed graft function was defined as any renal replacement therapy in the first postoperative week, once hyperacute rejection, vascular or urinary tract complications were ruled out [19–21] . \u003c/p\u003e\n\u003cp\u003e\u003ci\u003eStatistics:\u003c/i\u003e\u003c/p\u003e\n\u003cp\u003eThe data was collected in a MS Excel™ (Microsoft, Redmond, USA) datasheet. Further statistical processing was performed using SPSS™ (IBM, Armonk, USA). Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher Exact test for categorical variables with a significance level of p\u0026lt;0.05, respectively. \u003cb\u003e \u003c/b\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study enclosed 291 consecutive living donor kidney transplantations between October 2008 and December 2017. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. Table 1 shows the distribution of patients, the rate of EDA and the incidence of RRT and DGF for every year. For none of the years RRT or DGF rate are significantly increased. All recipients underwent kidney transplantation due to end stage renal disease. No mortality was reported in either group. In the EDA group no epidural catheter associated complications were found.\u003c/p\u003e\n\u003cp\u003eThe perioperative characteristics are shown in table 2. The two study groups showed no significant differences in several donors´ risk factors except a significantly shorter nephrectomy time (135 vs. 144 min, p\u0026lt;0.003). The intraoperative fluid consumption (1813 vs. 2191 ml; p=0.053) and maximum dose of vasopressor (0.03 vs. 0.06 g/kg/min; p=0.300) showed no statistically significant difference. None of the recipients´ pre- and intra-transplantation data showed a significant difference (table 2). After transplantation, 14 out of all 291 recipients needed renal replacement therapy during the first 7 days after transplantation, but only 9 cases due to delayed graft function. The other 5 recipients suffered humoral rejection, thrombosis of the iliac vessel or bleeding complications with the need of a surgical revision (table 3). All kidney donors to these 9 recipients received GA without epidural analgesia. The incidence of DGF was significantly higher in recipients whose donors did not receive epidural analgesia (4.6% vs. 0%; p=0.031) (figure 2). In line with this finding the serum creatinine level as well as the maximum serum potassium level within 7 days were significantly lower in the recipients whose donors received EDA (2.17 vs. 2.04 mg/dl, p=0.036; 5.15 vs. 5.11 mmol/l, p\u0026lt;0.001). \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe benefits of EDA regarding pain control, ICU stay, intestinal motility and early mobilization are frequently reported [22–27]. The beneficial effects of EDA in terms of pain control and return to normal daily activities specifically for kidney donors have also been reported in the past [28, 29]. This retrospective cohort study of 291 living donor kidney transplantations compared 99 cases whose donors received EDA with 192 cases that received GA only, with regard to DGF in the recipients. The main result is that DGF is significantly more frequent in patients whose kidney donors did not receive EDA. The incidence of DGF in cohorts of living kidney transplantations varies from 4 to 10% and increases morbidity, healthcare costs, hospitalization times and complicates post- transplantation care [30–33]. DGF predisposes for chronic rejection, chronic allograft nephropathy and seems to be causal for increased rates of graft failure and mortality [34, 35]. \u003c/p\u003e\n\u003cp\u003eIn line with the significantly lower rate of DGF in EDA group, we found that serum creatinine level, as well as the maximum serum potassium level within 7 days, were significantly lower in the EDA group. Although these findings are statistically significant, their measured levels and differences in numbers are clinically not of relevance. Even when looking at the decline of the serum creatinine levels over the first two days postoperatively no significant or clinically relevant difference can be found. The recipients of the no-EDA group start at a slightly higher level of serum creatinine which should be taken into account. Further baseline characteristics of donors and recipients showed no statistically significant difference or clinically relevant imbalance between the donors and recipients of both groups. An increased intraoperative fluid and vasopressor consumption in the EDA group could be associated with the EDA mediated inhibition of the sympatho- adrenal response with consecutive vasodilatation. However, neither intraoperative fluid nor vasopressor consumption showed a statistically significant difference in our study.\u003c/p\u003e\n\u003cp\u003eThe standard surgical technique for donor nephrectomy in our institution is an open anterior extraperitoneal minimal incision laparotomy. Open surgical technique for donor nephrectomy is associated with inferior cosmetic result, longer hospitalization and more intra- and postoperative pain with consecutively increased need for pain medication [36, 37]. However, the open surgical approach showed superior results in terms of warm ischemia period, surgical costs, length of operation, intraperitoneal complications, recovery of graft function, recipient anastomosis difficulties and incidence of acute tubulus necrosis [38–40]. It is reported that up to 25% of living kidney donors after open surgical technique nephrectomy suffer from chronification of postoperative pain [41]. A reduction of somatic pain within the first six postoperative weeks is associated with improved mental health of kidney donors [37]. These findings underline the need for EDA from the donors’ perspective. The described clinical benefits of EDA for the donor might lose their relevance and have to be reconsidered in case the surgical approach in our institution changes to laparoscopic technique. \u003c/p\u003e\n\u003cp\u003eThe reasons why kidney grafts fail to function immediately after transplantation when acute rejection, urological or vascular reasons are ruled out are associated with the transplanted kidney. DGF is modulated and caused by complex mechanisms of hypoxic and ischemic injuries and insufficient repair mechanisms [42]. These cascades seem to be induced by the operative trauma and the corresponding physiological stress response during donor nephrectomy. It is known that surgical procedures and the physiological stress response are associated with intra- and postoperative hypercoagulability which results in postoperative thromboembolic and vaso-occlusive events[43, 44]. Increased levels of tissue factor, tissue plasminogen activator, plasminogen activator inhibitor-1, and von Willebrand factor which all contribute to hypercoagulability are reported to be found proximately after surgical stimulus[45]. Due to inhibition of nociceptive and non-nociceptive pathways of sympathetic innervation of the adrenal glands, EDA with local anesthetics leads to a perioperative sympathicolysis[46]. Experimental reports on rats showed a significantly improved microcirculation in the areas of EDA mediated sympathetic blockage[47]. In an ovine model with artificially administered pulmonary embolism therapeutic EDA improved macrohemodynamic parameters[48]. It is also reported that EDA modulates postoperative hypercoagulability by normalizing antithrombin III- activity and a decrease of platelet aggregation [49–51]. We hypothesize that a decreased risk of thrombotic and vasoocclusive events which is mediated by therapeutic EDA could be one of the reasons that we found a significantly increased rate of DGF in the non-EDA group. \u003c/p\u003e\n\u003cp\u003e\u003ca name=\"_Hlk535959084\"/\u003e\u003ca name=\"_Hlk535959054\"/\u003eThe potential benefit of EDA performed for the transplantation could not be investigated by our study group. In our institution the transplantation itself is performed without EDA due to the mandatory immune suppressive therapy and the high incidence of platelet dysfunction in patients suffering from end stage renal disease[52, 53]. Hadimioglu and colleagues found improved clinical results and an attenuated stress response in kidney transplantations performed with EDA and general anesthesia compared to general anesthesia alone[54]. Against the background of these results and the results of our study, we will reconsider our previous approach with regard to the use of EDA in kidney transplants. \u003c/p\u003e\n\u003cp\u003eThe present study has several distinct limitations. \u003c/p\u003e\n\u003cp\u003eFirst, the retrospective and non-randomized design implies that a study protocol which addresses randomization on who receives EDA is missing. It is speculative why patients opted for or against EDA, possibly the way whether EDA was offered by the visiting anesthesiologist or rather recommended plays an important role. Perhaps patients who opted for EDA were more trustful of their physicians and therefore had less anxiety or stress levels which may have influenced DGF of their donated kidney. The way EDA was offered to the donors might have been changed throughout the years. We have seen that EDA is more frequently performed in the last years of the program compared to the very early years of the observation period. However, this imbalance of EDA rates throughout the observational period was not associated with an accumulation of RRTs or DGF in the early or the late years of the observation. RRT was initiated by visiting nephrology specialists and the request of the attending ICU physician when patients were threatened by volume overload or increased serum potassium levels. We are fully aware that living donor kidney transplantation is a highly complex procedure. The outcome quality is affected by various confounding variables for which we have not adjusted in our study due to the limited number of cases with DGF. \u003c/p\u003e\n\u003cp\u003eThere are also several slightly different definitions on delayed graft function in literature. In our study DGF was defined as any renal replacement therapy in the first postoperative week, when hyperacute rejection, vascular and urinary tract complications were ruled out. More than 22 different definitions of DGF are described, the most common definition refers to any RRT within the first posttransplantational week [55, 56]. Due to the manageable size of our cohort we could screen every case of RRT for the underlying reasons. Knowing these reasons leading to RRT for every patient, we decided to choose a more specific definition of delayed graft function. Beyond the discussion about the definition we have to state, that in the EDA group none of the patients who received RRT showed graft associated reasons leading to RRT. In no case of the EDA group, graft perfusion deficits or insufficient otherwise unexplainable graft dysfunction led to RRT. Finally, we can report of an association between EDA for donor nephrectomy and a lower rate of DGF in our study. However, we are fully aware that correlation does not proof causality. Especially in a multifactorial context such as living kidney transplantations, larger numbers of prospectively randomized assigned patients are needed to provide stronger evidence. \u003cb\u003e \u003c/b\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this retrospective cohort study, we found an association between epidural analgesia for living kidney donors and significantly less delayed graft function in the corresponding kidney recipients. These results favor not only the beneficial analgesic effect of epidural analgesia for donors, but also show significant beneficial effects for kidney recipients. As our analysis depends on the authors' experience, derived from a very low level of evidence with consecutive relevant shortcoming in terms of study design, number of index cases and adjustment of confounding variables, our findings have to be confirmed by prospective randomized trials. \u003cb\u003e \u003c/b\u003e\u003c/p\u003e"},{"header":"List of abbreviations","content":"\u003cp\u003eDGF – delayed graft function\u003c/p\u003e\n\u003cp\u003eEDA – epidural analgesia\u003c/p\u003e\n\u003cp\u003eGA – general anesthesia\u003c/p\u003e\n\u003cp\u003eRRT – renal replacement therapy\u003c/p\u003e\n\u003cp\u003eSOP – standard operating procedure\u003c/p\u003e\n\u003cp\u003eSTROBE – Strengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cb\u003eAvailability of data and materials\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due institutional restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eAuthors contributions:\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eSH initiated the study, performed statistically processing, contributed to the writing of the manuscript, UG developed the study design, contributed to data collection and proofread the manuscript, HB advised the study design, is responsible for the anesthesia SOPs and proof read the manuscript, BJ operated most of the patients is responsible for the postoperative care of the patients and contributed to data collection, KK contributed to data collection and writing of the manuscript, WB contributed to data collection and wrote the manuscript. All authors contributed substantially to this work and all of them revised and agreed to the final version of the manuscript with full access to all data.\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eEthics approval and consent to participate\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe local ethics committee approved the analysis and publication of the data and confirmed that no specific patient´s consent was necessary because of the anonymous and observational design of the study (approval number EK 555/17).\u003c/p\u003e\n\u003cp\u003eEthics Committee University of Freiburg, Germany Engelberger Straße 21 79106 Freiburg\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eConsent for publication\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eAcknowledgements\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eCompeting interests\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eFunding\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe article processing charge was funded by the German Research Foundation (DFG) and the University of Freiburg in the funding program Open Access Publishing. The funding body had no influence on study design, data collection, analysis, interpretation and writing the manuscript. \u003c/p\u003e"},{"header":"References ","content":"\u003cp class=\"bibliography\"\u003e\u003cb/\u003e1. Lionaki S, Kapsia H, Makropoulos I, Metsini A, Skalioti C, Gakiopoulou H, et al. Kidney transplantation outcomes from expanded criteria donors, standard criteria donors or living donors older than 60 years. Ren Fail. 2014;36:526–33.\u003c/p\u003e\n\u003cp class=\"bibliography\"\u003e2. Axelrod DA, Schnitzler MA, Xiao H, Irish W, Tuttle-Newhall E, Chang S-H, et al. An economic assessment of contemporary kidney transplant practice. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2018;18:1168–76.\u003c/p\u003e\n\u003cp class=\"bibliography\"\u003e3. Guimarães J, Araújo AM, Santos F, Nunes CS, Casal M. Living-donor and Deceased-donor Renal Transplantation: Differences in Early Outcome--A Single-center Experience. 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A Single-Center Comparison of 22 Competing Definitions of Delayed Graft Function After Kidney Transplantation. Ann Transplant. 2016;21:152–9.\u003c/p\u003e\n\u003cp class=\"bibliography\"\u003e56. Yarlagadda SG, Coca SG, Garg AX, Doshi M, Poggio E, Marcus RJ, et al. Marked variation in the definition and diagnosis of delayed graft function: a systematic review. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2008;23:2995–3003.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cb\u003eTable 1: \u003c/b\u003e\u003c/p\u003e\n\u003ctable\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eYear\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eNumber of patients\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eWith EDA (n/%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eRRT within 7 days (n/%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eDGF (n/%)\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2008\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2009\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1/3%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2010\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1/3%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1/3%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2011\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6/18%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3/9%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3/9%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2012\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e15/43%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3/9%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1/3%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2013\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e14/44%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2014\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e35\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8/23%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2/6%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1/3%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e14/45%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2/6%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2/6%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2016\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e25/83%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2/7%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1/3%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e23\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e16/70%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1/4%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0/0%\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp\u003e\u003cb\u003eTable 1:\u003c/b\u003e Distribution of patients, rate of EDA, incidence of RRT and DGF throughout the observation period. \u003c/p\u003e\n\u003cp/\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003e \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eTable 2\u003c/b\u003e\u003c/p\u003e\n\u003ctable\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ewithout EDA (n=192)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ewith EDA (n=99)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003esignificance\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDonor and nephrectomy data\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDonor male sex [n/(%)]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e71 (37%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e32 (32%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.469\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDonor BMI [kg/m²]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e25.7 ± 4.1\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e25.5 ± 3.5\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.165\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDonor age [years]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e52\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.416\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDonor preoperative hemoglobin [g/dl]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e14.1 ± 1.2\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e14.1 ± 1.2\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.919\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eCrystalloid fluid for nephrectomy [ml]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1813 ± 907\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2191 ± 1113\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.053\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eMax. dose of noradrenaline after cut [µg/kg/min]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.03 ± 0.04\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.06 ± 0.05\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.300\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eNephrectomy time (cut – suture) [min]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e135 ± 38\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e144 ± 48\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient and transplantation data\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient BMI [kg/m²]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e24.8 ± 3.9\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e25.6 ± 4.2\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.168\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient male sex [n/(%)]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e121 (62%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e61 (62%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.899\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient age [years]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e44 ± 13\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e47 ± 13\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.853\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient rest diuresis [ml]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1098 ± 907\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1134 ± 858\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.062\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient preoperative creatinine [mg/dl]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8.0 ± 2.8\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e7.6 ± 2.8\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.744\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDuration of transplantation [min]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e161 ± 55\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e145 ± 41\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.129\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eWarm ischemic period [min]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e29 ± 9\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e26 ±7\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.138\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eMAP for anastomosis [mmHg]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e93 ± 11\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e88 ± 16\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.165\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eFluid intake during transplantation [ml]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2782 ± 1366\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3477 ± 1233\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.559\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePosttransplantation data\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDiuresis first hour [ml]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e425 ± 430\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e383 ± 390\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.358\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDiuresis 24 hours [ml]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e9947 ± 5313\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e10871 ± 6419\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.062\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient creatinine 12-24 hours postoperative [mg/dl]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4.37 ± 2.2\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4.09 ± 1.8\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.189\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient creatinine 36-48 hours postoperative[mg/dl]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3.15 ± 2.1\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3.04 ± 1.7\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.404\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRecipient creatinine 7 days postoperative [mg/dl]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2.17 ± 1.6\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2.04 ± 1.1\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003e0.036\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eMax. recipient serum potassium level within 7d \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e5.15 ± 0.6\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e5.11 ± 0.4\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRenal replacement therapy first postoperative week [n/(%)]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e11 (6%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3 (3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.312\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDelayed graft function [n/(%)]\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e9 (4.6%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003e0.031\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eTable 2:\u003c/b\u003e Main results of the study. Continuous variables are given as mean ± standard deviation, categorical variables are given as absolute number and percentage. \u003c/p\u003e\n\u003cp/\u003e\n\u003cp/\u003e\n\u003cp/\u003e\n\u003cp/\u003e\n\u003cp/\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eTable 3: \u003c/b\u003e\u003c/p\u003e\n\u003ctable\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eCase Number\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eYear\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eEDA\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eUnderlying reason leading to RRT within 7 days\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eDGF\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e507\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2010\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003egraft perfusion deficit\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e581\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2011\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003einsufficient graft function, later sepsis\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e588\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2011\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ecritical potassium levels, good graft function later on\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e624\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2011\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eacute tubules necrosis\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e666\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2012\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ehumoral rejection\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e692\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2012\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ebleeding complication, needed operative revision\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e701\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2012\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003einsufficient graft function\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e829\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2014\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ehumoral rejection\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e859\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2014\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003egraft perfusion deficit\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e888\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003einsufficient graft function, critical potassium levels \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e935\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2015\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003einsufficient graft function\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e1017\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2016\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003einsufficient graft function\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e1023\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2016\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ehumoral rejection\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e1089\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2017\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eyes\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003ethrombosis of recipients iliac vessel\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eno\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp/\u003e\n\u003cp\u003e\u003cb\u003eTable 3: \u003c/b\u003eUnderlying reasons for renal replacement therapy (RRT) and met definition of delayed graft function (DGF).\u003cb\u003e \u003c/b\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"kidney transplantation, delayed graft function, epidural analgesia, donor nephrectomy","lastPublishedDoi":"10.21203/rs.2.101/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.101/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background The beneficial effects of epidural analgesia (EDA) in terms of pain control and postoperative convalescence are widely known and led to a frequent use for patients who underwent living donor kidney nephrectomy. The objective of this study was to determine whether general anesthesia (GA) plus EDA compared to GA only, administered for living donor nephrectomy has effects on postoperative graft function in recipients.\nMethods In this monocentric, retrospective cohort analysis we analyzed the closed files of all consecutive donor- recipient pairs who underwent living donor kidney transplantations from 2008 to 2017. The outcome variable was delayed graft function (DGF), defined as at least one hemodialysis within seven days postoperatively, once hyperacute rejection, vascular or urinary tract complications were ruled out. Statistical analyses of continuous variables were calculated using the two-tail Student’s t test and Fisher exact test for categorical variables with a significance level of p\u003c0.05, respectively.\nResults The study enclosed 291 consecutive living donor kidney transplantations. 99 kidney donors received epidural analgesia whereas 192 had no epidural analgesia. The groups showed balanced pretransplantational characteristics and comparable donors´ and recipients’ risk factors. 9 out of all 291 recipients needed renal replacement therapy (RRT) during the first 7 days due to delayed graft function; none of these donors received EDA. The observed rate of DGF in recipients whose kidney donors received epidural analgesia was significantly lower (0% vs. 4.6%; p=0.031).\nConclusions In our cohort we observed a significantly lower rate of DGF when epidural analgesia for donor nephrectomy was administered. Due to restrictions of the study design this observation needs further confirmation by prospective studies.","manuscriptTitle":"Lower rate of delayed graft function is observed when epidural analgesia for living donor nephrectomy is administered.","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2019-03-11 22:28:13","doi":"10.21203/rs.2.101/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2019-03-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-03-08T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-03-08T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2018-12-09T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2019-02-19 18:34:01","doi":"10.21203/rs.2.101/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-03-04T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-12T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-02-12T12:00:00+00:00","index":2,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **Not relevant to this manuscript**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\n"},{"type":"editorInvitedReview","content":"","date":"2019-02-12T12:00:00+00:00","index":1,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n\nComments to Author:\n---\nI have no other comment about the manuscript.\nAfter the first revision process, the Authors properly addressed all the issues raised.\n\n"},{"type":"reviewersInvited","content":"","date":"2019-02-11T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-02-11T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvited","content":"","date":"2019-01-29T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-01-29T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2018-12-09T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2018-12-13 01:21:58","doi":"10.21203/rs.2.101/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2019-01-17T12:00:00+00:00","index":2,"fulltext":"Form responses:\r\n---\r\n* Are the methods appropriate and well described? **Yes**\r\n* Does the work include the necessary controls? **Yes**\r\n* Are the conclusions drawn adequately supported by the data shown? **No**\r\n* Statistical review: **I am able to assess the statistics**\r\n* Quality of written English: **Needs some language corrections before being published**\r\n* Declaration of competing interests: **I declare that I have no competing interests**\r\n\r\nComments to Author:\r\n---\r\n\r\nI commend with the authors for this hypothesis generating study.\r\nThey performed a single-center retrospective evaluation of their consecutive donor-recipient pairs who underwent living donor kidney transplantations from 2008 to 2017.\r\nThe aim of the study was to determine whether general anesthesia plus epidural analgesia compared to general anesthesia alone has a positive impact on postoperative graft function in recipients.\r\nThe outcome evaluated was delayed graft function, defined as at least one hemodialysis within 7 days postoperatively, once hyperacute rejection, vascular or urinary tract complications were ruled out.\r\n291 consecutive living donor kidney transplantations were extracted. 99 kidney donors received epidural analgesia and were compared vs a cohort of 192 patients who denied epidural analgesia.\r\nAt baseline, groups were balanced.\r\nThe authors found 9 out of all 291 recipients who needed renal replacement therapy during the first 7 days due to delayed graft function; all of them received no epidural analgesia.\r\nThus the authors concluded that a significantly (p = 0.03) lower rate of delayed graft function is observed when epidural analgesia for donor nephrectomy is administered.\r\n\r\nI have some comments about the paper.\r\n1. The authors stated in the introduction that \"The primary intent of providing perioperative epidural anesthesia for donor nephrectomy are the beneficial effects for the donor. These effects are mostly mediated by perioperative sympathicolysis which probably may have effects on the kidney intended for transplantation\". Such statement should be better referenced.\r\n2. I would suggest a Language revision to improve the quality of the study.\r\n3. It is unclear to me why p-value for rate of delayed graft function is \u003c than 0.03...That is a Fisher test...I would say it is = 0.03...Moreover, it is curious the fact that the occurrence of the event is 0 vs 9. As the group without events has a lower sample size, maybe the authors want to disclose it. With a larger sample size some events could have been observed.\r\n4. The study is biased by the self-selection of patients. The authors should better clarify this in the discussion. Moreover, one population is twice the challenger. There is no statistical balance between some covariates. The authors were lucky to have comparable baseline variables between the groups, but renal function is a complex outcome that could be modified by many factors.\r\n5. One outcome only was used to test the eventual differences between the groups. This seems to be forced. Maybe including other outcomes would improve the value of the study.\r\n6. I would soften the conclusions of the study, stating that this is the authors' experience, derived from a very low level of evidence analysis.\r\n7. I would change the title of the manuscript i.e. \"lower rate of delayed graft function is observed when epidural analgesia for donor nephrectomy is administered\"\r\n"},{"type":"decision","content":"Revise","date":"2019-01-17T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-01-16T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-01-16T12:00:00+00:00","index":1,"fulltext":"Form responses:\r\n---\r\n* Are the methods appropriate and well described? **No**\r\n* Does the work include the necessary controls? **Yes**\r\n* Are the conclusions drawn adequately supported by the data shown? **No**\r\n* Statistical review: **I recommend additional statistical review**\r\n* Quality of written English: **Needs some language corrections before being published**\r\n* Declaration of competing interests: **I have no competing interests**\r\n\r\nComments to Author:\r\n---\r\n\r\nPlease include all comments for the authors in this box rather than uploading your report as an attachment. Please only upload as attachments annotated versions of manuscripts, graphs, supporting materials or other aspects of your report which cannot be included in a text format.\r\nPlease overwrite this text when adding your comments to the authors.\r\n\r\nThis paper studied the efficacy of epidural analgesia (EDA) on living donor nephrectomy for possible better early graft function in recipients after transplantation. The study results suggest epidural analgesia applied on living donors has a positive impact on early graft function for kidney transplant recipients. This is a retrospective analysis and after reviewing the manuscript, the study provides some interesting findings. However, there are some issues that need to be addressed prior to its publication.\r\n\r\n1)\tThere is no flow chart or information detailing how the two groups of patients were recruited: were kidney transplants performed without EDA in the early years or was the EDA technique only adopted in recent years. Were a similar percentage of patients collected in corresponding years for the two groups?\r\n2)\tThere is no information provided on how many anesthesiologists were involved in the transplantation, were there different techniques between the two groups?\r\n3)\tThe authors found that the serum creatinine level as well as the maximum serum potassium level within 7 days were statistically significant (EDA versus GA: only 2.04 vs 2.17 mg/dl and 5.11 vs 5.15 mmol/l) between the two groups. However, what is the clinical significance of these findings?\r\n4)\tIn the discussion section, the author failed to provide an adequate potential mechanism of why the EDA patient group may have better early graft function on transplant recipients.\r\n5)\tHave the authors thought about performing EDA on transplant recipients? Does such application have any impact on early graft functions?\r\n6)\tThe biggest flaw of this study is that the authors did not adjust many confounding variables.\r\n7)\tThere are some typo issues in the manuscript as well."},{"type":"reviewerAgreed","content":"","date":"2019-01-14T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-01-09T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2018-12-09T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2018-12-09T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"81052057-6869-4d31-82d0-8eebfda366f6","owner":[],"postedDate":"March 11th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":774,"name":"Internal Medicine Specialties"}],"tags":[],"updatedAt":"","versionOfRecord":{"articleIdentity":"rs-101","link":"https://doi.org/10.1186/s12871-019-0713-y","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2019-03-18 12:00:00","publishedOnDateReadable":"March 18th, 2019"},"versionCreatedAt":"2019-03-11 22:28:13","video":"","vorDoi":"10.1186/s12871-019-0713-y","vorDoiUrl":"https://doi.org/10.1186/s12871-019-0713-y","workflowStages":[]},"version":"v3","identity":"rs-101","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-101","version":["v3"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}