The benefits of EDA regarding pain control, ICU stay, intestinal motility and early mobilization are frequently reported 17–22. 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 23,24. 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 25–28. DGF predisposes for chronic rejection, chronic allograft nephropathy and seems to be causal for increased rates of graft failure and mortality 29,30.
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 questionable. Even when looking at the decline of the serum creatinine levels over the first two days postoperatively there can be found no significant or clinically relevant difference. The recipients of the no-EDA group start at a slightly higher level of serum creatinine which should be taken in 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 31,32. 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 33–35. It is reported that up to 25% of the living kidney donors after open surgical technique nephrectomy suffer from chronification of postoperative pain 36. A reduction of somatic pain within the first six postoperative weeks is associated with improved mental health of kidney donors 32. 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 if 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 37. 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 events38,39. 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 stimulus40. Due to inhibition of nociceptive and non-nociceptive pathways of sympathetic innervation of the adrenal glands, EDA with local anesthetics leads to a perioperative sympathicolysis41. It is also reported that EDA modulates postoperative hypercoagulability by normalizing antithrombin III- activity and decreasing of platelet aggregation 42–44. This could be one of the reasons that we found a significantly increased rate of DGF in the group of patients who refused perioperative EDA.
The present study has several severe 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 trusting of their physicians and therefore had less anxiety or stress levels which may have influenced DGF of their donated kidney. 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 were 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 45,46. 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 were fully aware that correlation does not proof causality. Especially in such a multifactorial context like living kidney transplantations, larger numbers of prospectively randomized assigned patients are needed to provide stronger evidence.