Adult: Aorta: Clinical Trial
Renal perfusion with histidine-tryptophan-ketoglutarate compared with Ringer's solution in patients undergoing thoracoabdominal aortic open repair

https://doi.org/10.1016/j.jtcvs.2021.02.090Get rights and content

Abstract

Objective

The objective of this study was to compare the efficacy of renal perfusion with Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) versus enriched Ringer's solution for renal protection in patients undergoing open thoracoabdominal aortic aneurysm (TAAA) repair.

Methods

Ninety consecutive patients scheduled for elective open TAAA repair were enrolled between 2015 and 2017 in a single-center, phase IV, prospective, parallel, randomized, double-blind trial (the CUstodiol versus RInger: whaT Is the Best Agent [CURITIBA] trial), and randomized to renal arteries perfusion with 4°C Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany; n = 45) or 4°C lactated Ringer's solution (n = 45). The incidence of acute kidney injury (AKI) in patients undergoing TAAA open surgery using Custodiol renal perfusion versus an enriched Ringer's solution was the primary end point.

Results

Ninety patients completed the study (45 patients in each group). The incidence of postoperative AKI was significantly lower in the Custodiol group (48.9% vs 75.6%; P = .02). In the multivariable model, only the use of Custodiol solution resulted as protective from the occurrence of any AKI (odds ratio, 0.230; 95% confidence interval, 0.086-0.614; P = .003), whereas TAAA type II extent was associated with the development of severe AKI (odds ratio, 4.277; 95% confidence interval, 1.239-14.762; P = .02). At 1-year follow-up, serum creatinine was not significantly different from the preoperative values in both groups.

Conclusions

The use of Custodiol during open TAAA repair was safe and resulted in significantly lower rates of postoperative AKI compared with Ringer's solution. These findings support safety and efficacy of Custodiol in this specific setting, which is currently off-label.

Graphical abstract

Results of a single-center, prospective, randomized study comparing the efficacy of Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) renal perfusion on perioperative acute kidney injury (AKI) in patients undergoing thoracoabdominal aortic open repair. This image summarizes outcomes of renal perfusion with Custodiol compared with lactated Ringer's solution for renal protection in patients undergoing open thoracoabdominal aortic aneurysm repair. What emerged from this trial was that patients in the Custodiol group showed significantly less AKI than those in the Ringer's group (49% vs 76%; P = .02) and that the use of Custodiol resulted as protective from the occurrence of any AKI in multivariable analysis (P = .003). TAAA, Thoracoabdominal aortic aneurysm.

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Section snippets

Trial Design and Eligibility Criteria

“CUstodiol Versus RInger: whaT Is the Best Agent? A Randomized Double Blind Trial” (CURITIBA) study is a prospective, single-center, randomized, double-blind, controlled, parallel trial on AKI in patients undergoing TAAA open repair using Custodiol renal perfusion versus an enriched Ringer's solution. The trial protocol (version 4.0, dated March 4, 2015) follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Statement for protocols of clinical trials.

The

Results

In the study period, 113 patients were admitted at the Department of Vascular Surgery of San Raffaele Scientific Institute with a diagnosis of thoraco-abdominal aortic aneurysm, with indication to open surgical repair; 96 patients were considered eligible for enrollment in the CURITIBA trial after review of inclusion/exclusion criteria. Among these, 6 refused to sign or withdrew informed consent from the trial. Finally, 90 patients underwent randomization for intention-to-treat analysis (45

Discussion

Renal injury is a well known serious complication of TAAA surgical repair. Patients who present with renal dysfunction, especially when hemodialysis or hemofiltration is required, are at high risk for the development of additional perioperative complications, including respiratory failure, cardiac events, hemodynamic instability, and spinal cord ischemia.21

Many techniques have been proposed with the aim to improve intraoperative organ protection, including different methods of renal perfusion.

Conclusions

The results of this trial support the use of cold Custodiol solution for perfusion of the renal arteries during open TAAA repair. It showed safety and efficacy in reducing postoperative renal dysfunction compared with standard crystalloid solutions. These findings corroborate the use of Custodiol not only in TAAA patients, but also in other cases that require suprarenal clamping, including juxtarenal and pararenal aneurysms, or in further cases of renal surgery.

References (26)

  • S. Chatterjee et al.

    Early-stage acute kidney injury adversely affects thoracoabdominal aortic aneurysm repair outcomes

    Ann Thorac Surg

    (2019)
  • M.M. Marrocco-Trischitta et al.

    Chronic kidney disease classification stratifies mortality risk after elective stent graft repair of the thoracic aorta

    J Vasc Surg

    (2009)
  • P.P. Goodney et al.

    Survival after open versus endovascular thoracic aortic aneurysm repair in an observational study of the Medicare population

    Circulation

    (2011)
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      Citation Excerpt :

      Similarly, this study reported a significantly increased rate of renal failure in the SA group (21.1%) if compared with the NSA group (5.3%) (P = .013).6 Among the 12 patients who experienced renal failure in the SA group, four showed postoperative kidney embolization at postoperative CTA; despite acute kidney injury after TAAA OSR being influenced by different factors, such as the baseline renal function and the intraoperative perfusion strategy, the presence of SA was shown to have an impact on postoperative renal failure in this series, and embolization may be one of the causes.13,24 The composite outcome “any embolization” was also significantly increased in patients with SA (P = .008), underling the impact of diffuse aortic wall thrombosis as major cause of end-organ embolization.

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    This research received an unconditional grant from Dr Franz Köhler Chemie GmbH, Werner-von-Siemens-Straße 22-28 64625 Bensheim, Germany.

    Drs Andrea Kahlberg and Yamume Tshomba contributed equally to this work.

    CURITIBA Investigators: Yamume Tshomba (Principal Investigator), Luca Apruzzi, Domenico Baccellieri, Luca Bertoglio, Samuele Bossi, Renata Castellano, Barbara Catenaccio, Roberto Chiesa, Elisa Colombo, Angela Maria Ferrante, Andrea Kahlberg, Giovanni Landoni, Rosalba Lembo, Germano Melissano, Pasquale Nardelli, Laura Pasin, Enrico Rinaldi, Elisa Simonini, and Massimo Venturini.

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