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The Impact of Immunosuppression on Postoperative Graft Function After Graft-Unrelated Surgery

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The Impact of Immunosuppression on Postoperative Graft Function After Graft-Unrelated Surgery Lederer et al. BMC Nephrology (2019) 20:170 https://doi.org/10.1186/s12882-019-1358-2 RESEARCHARTICLE Open Access The impact of immunosuppression on postoperative graft function after graft-unrelated surgery: a retrospective controlled cohort study Ann-Kathrin Lederer1* , Dominic Haffa2, Philipp Felgendreff3,4, Frank Makowiec5, Stefan Fichtner-Feigl2, Roman Huber1 and Lampros Kousoulas2 Abstract Background: Physicians are faced with a growing number of patients after renal transplantation undergoing graft- unrelated surgery. So far, little is known about the postoperative restitution of graft function and the risk factors for a poor outcome. Methods: One hundred one kidney transplant recipients undergoing graft-unrelated surgery between 2005 and 2015 were reviewed retrospectively. A risk analysis was performed and differences in creatinine, GFR and immunosuppressive treatment were evaluated. Additional, a comparison with a case-matched non-transplanted control group were performed. Results: Preoperative creatinine averaged 1.88 mg / dl [0.62–5.22 mg / dl] and increased to 2.49 mg / dl [0.69–8.30 mg / dl] postoperatively. Acute kidney failure occurred in 18 patients and 14 patients had a permanent renal failure. Significant risk factors for the development of postoperative renal dysfunction were female gender, a preoperative creatinine above 2.0 mg / dl as well as a GFR below 40 ml / min and emergency surgery. Patients with tacrolimus and mycophenolate mofetil treatment showed a significant lower risk of renal dysfunction than patients with other immunosuppressants postoperatively. Contrary to that, the risk of patients with cyclosporine treatment was significantly increased. Transplanted patients showed a significantly increased rate of postoperative renal dysfunction. Conclusions: The choice of immunosuppressant might have an impact on graft function and survival of kidney transplant recipients after graft-unrelated surgery. Further investigations are needed. Keywords: Kidney transplantation, Renal failure, Immunosuppression, Graft-unrelated surgery Background which leads to an increased morbidity and mortality of During the past decades, kidney transplantation has be- non-transplanted patients [3] and assumably also of come a safe therapy for end-stage renal disease [1]. The transplanted patients. Besides the risk of acute postoper- growing number of patients living with a transplanted ative renal failure, operating transplanted patients also kidney brings new challenges like the perioperative man- bears the risk of disturbing the sensitive balance of im- agement of graft-unrelated surgery to physicians [2]. A munosuppression. Transplanted patients live under im- typical postoperative complication is acute renal failure, munosuppressive therapy, which has a lot of side effects [4] and interacts with other medical therapies and inter- * Correspondence: [email protected] ventions [5]. The adjustment of immunosuppression 1Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Medical Center – University of Freiburg, Faculty of walks a fine line between graft rejection and nephrotox- Medicine, University of Freiburg, Breisacher Straße 115b, 79106 Freiburg im icity [6]. In addition to steroids, the most common im- Breisgau, Germany munosuppressants for kidney transplant recipients are Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Lederer et al. BMC Nephrology (2019) 20:170 Page 2 of 8 tacrolimus and cyclosporine. While tacrolimus and exclusion of patients were graft-related surgery and cyclosporine differ in their intracellular binding charac- dialysis-depended renal failure). teristics, their immunosuppressive properties result from The meantime since renal transplantation was 15.8 inhibition of calcineurin [6]. Calcineurin dephosphory- years [± 9.3 years, range 2.8–37.6 years]. The vast major- lates a transcription factor of T-lymphocytes and en- ity of patients were transplanted once (mean: 1.29 trans- hances the immune response [7]. Despite a similar plants, maximum of four transplants). The main efficacy of tacrolimus and cyclosporine regarding im- diagnosis that led to transplantation was chronic glomer- munosuppression, tacrolimus has been preferred clinic- ulonephritis (n = 38; 38%), followed by cystic kidney dis- ally because of a better patient outcome [8]. So far, little ease (n = 30; 30%). The mean age of included patients is known about the graft function after graft-unrelated was 59 years [range 41–77 years], two thirds of the pa- surgery and the impact of individual immunosuppres- tients (n = 66; 65%) underwent elective surgery. sion on postoperative graft function. Therefore, we in- Overall, 20 patients out of 101 (20%) died postopera- vestigated the postoperative graft outcome and mortality tively. The leading causes of death were sepsis (n = 14, of kidney-transplanted patients after graft-unrelated 13 with abdominal and one with pulmonary sepsis), in- surgery. tractable hemorrhagic shock (n = 3, one due to a pul- monary embolism and two due to gastrointestinal Methods bleedings), cardiovascular complications (n = 2) and pro- This was a retrospective monocentric and controlled co- gress of neoplastic disease (n = 1). hort study of kidney transplant recipients and healthy controls, reported in line with the STROCSS criteria [9]. Perioperative renal dysfunction Data was obtained as previously described [10]. All kid- Acute kidney failure occurred in 18 of the 101 patients ney transplant recipients with a preserved graft function, (18%). More than 60% of the patients with acute kidney who were treated at the Department for General and failure (n = 11) had demand on acute dialysis. Overall, 14 Visceral Surgery of the University Medical Hospital Frei- patients (14%) developed a permanent renal failure with burg between 2005 and 2015 were screened for eligibility need of long-time dialysis. and, if eligible, compared to a case-matched control of a In the subgroup of patients who died during the post- non-transplanted patient. operative hospital stay (n = 20), 65 % had acute renal fail- GFR was calculated via CKD-EPI equation. The occur- ure, and half of them also required dialysis. rence of renal dysfunction was noted on the basis of the Preoperative creatinine averaged 1.88 mg / dl [0.62– discharge documents. Acute kidney failure was defined 5.22 mg / dl] and increased to 2.49 mg / dl [0.69–8.30 as an increase in creatinine level (reference range 0.51– mg / dl] on the first postoperative day. The calculated 0.95 mg / dl) by more than 0.3 mg / dl in 48 h or as an preoperative GFR averaged 43 ml per minute [8.74– oliguria (< 0.5 ml / kg / h) for more than six hours. 110.30 ml / min] (vs. postoperative GFR 32 ml /min IBM SPSS® (version 23.0) was used for exploratory data [6.50–101.74 ml / min]). The surviving patients (n = 81) analysis. Results were checked for normal distribution. were discharged with an averaged creatinine of 1.70 mg / Evaluation of group differences was carried out by a T-test dl [0.24–6.0 mg / dl] and a GFR of 53.85 ml / min [9.14– as an analysis of two independent groups. A chi-squared 146.38 ml / min]. test was utilized to test for trends and significance and compare groups of categorical data. Differences with a p-value < 0.05 were considered as statistically significant. Risk factors for postoperative renal dysfunction (Table 1) See Additional file 1 for definition of subgroups. Patients whose preoperative creatinine was higher than 2.0 Study was approved by the ethical committee of the mg / dl suffered more frequently from postoperative acute Medical Faculty of the University of Freiburg (EK: 203/ renal failure (p = 0.026). Similar to that, patients with a GFR 17) and was performed according to the principles of lower than 40 ml / min showed significant higher rates of the declaration of Helsinki. It was registered in an ap- acute renal failure postoperatively (p = 0.040). Female pa- proved primary register of the WHO (DRKS00015440). tients suffered more frequently from acute and permanent kidney failure (see Table 1). After emergency surgery (com- Results pared to elective cases) patients suffered more frequently From January 2005 to December 2015 a total of 1535 fromacutekidneyfailure(p = 0.009) and had a higher need kidney transplant recipients were admitted to the De- for dialysis (p = 0.005). We found no influence of the extent partment of General and Visceral Surgery at the Medical of surgery (major vs. minor), localization of operation Center of the University of Freiburg. Out of these, 101 (extra- vs. intra-abdominal), number of transplantations patients underwent abdominal or abdominal wall sur- and time since transplantation on the development of renal gery and were included in our study (main reasons for dysfunction (see Table 1). Lederer et al. BMC Nephrology (2019) 20:170 Page 3 of 8 Table
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