Annals of Vascular Surgery
Volume 22, Issue 4 , Pages 520-524, July 2008

Hypothermic Renal Protection Using Cold Histidine–Tryptophan–Ketoglutarate Solution Perfusion in Suprarenal Aortic Surgery

Department of Cardiothoracic and Vascular Surgery, Georg-August-University Goettingen, Germany

published online 06 June 2008.

Article Outline

We examined data of 21 patients who were treated with selective perfusion of both renal arteries with 500 mL of 8°C histidine–tryptophan–ketoglutarate (HTK) solution each for renal protection during aortic surgery. Only the data from aortic surgeries with unavoidable suprarenal aortic cross-clamping for juxtarenal or suprarenal abdominal aortic aneurysms (AAAs) or high Leriche syndrome accompanied with stenosis of renal arteries are presented. Five patients underwent immediate surgery because of perforation of an AAA; the other 16 patients went through elective surgeries. In three cases (14%) stenosis of the renal arteries was diagnosed; nevertheless, implantation of an aortorenal bypass was necessary in seven patients. In total, 14 aortorenal bypasses were implanted (five venous grafts and nine prosthesis grafts). Four (19%) patients needed catecholaminergic support to establish stable circulatory conditions; in two (9%) of these cases additional ischemia of the colon was observed and sigmoidectomy was performed. All of these four patients underwent immediate surgery, and one died after surgery because of severe sepsis. In four cases postsurgical renal insufficiency was observed. Three of these patients were admitted for emergency surgery because of their hemodynamic situation due to perforation of the AAA. None of the patients needed chronic dialysis after surgery. Whereas in all patients who underwent elective surgery the renal function remained stable as judged by postoperative serum creatinine values, in five out of seven patients with aortorenal bypass surgery the renal function improved. Perfusion with cold HTK solution offers an additional procedure to protect renal function in patients undergoing elective surgery with suprarenal cross-clamping of the aorta.

 

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Introduction 

Despite the progress in surgical and anesthetic management, decreased renal function is often observed after abdominal aortic surgery and remains an important intra- and postoperative complication. Renal failure occurs in 1-13% of abdominal aortic reconstructions.1 The rate of renal insufficieny is higher in cases of suprarenal aortic replacement or aortic cross-clamping compared with infrarenal cross-clamping.2 Histidine–tryptophan–ketoglutarate (HTK) solution is routinely used for organ protection in different surgical procedures, e.g., renal, lung, and heart transplantation as well as partial renal tumor enucleation.

Hypothermic renal protection by cold HTK perfusion prolongs the tolerance of renal ischemia.3 Here, we report on our experience with HTK perfusion, focusing on renal function and the incidence of renal failure in 21 patients with abdominal aortic surgery requiring supra-aortic cross-clamping.

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Methods 

Between January 2002 and January 2005, 21 patients underwent aortic surgery for juxtarenal or suprarenal abdominal aortic aneurysm (AAA) or high Leriche syndrome accompanied with stenosis of renal arteries, which required suprarenal cross-clamping. Eighteen patients were male (79 ± 8 years) and three were female (65 ± 6 years). Eight patients (38%) needed surgery because of primary juxta- or suprarenal AAA, and three patients (14%) were operated because of secondary suprarenal aneurysm following aortic replacement. With all three patients it was a matter of true aneurysm. In these cases, the mean latency period was 8 ± 0.5 years. Five patients (24%) were admitted to hospital because of covered or free perforation of a suprarenal AAA. Five patients (24%) underwent surgery because of a high Leriche syndrome. In three cases (14%) an additional stenosis of the renal arteries and in four cases (19%) an aneurysm of the pelvic arteries was observed. Six patients (28%) had baseline renal insufficiency. The baseline renal insufficiency was determined when preoperative serum creatinine (SCr) was more than 1.3 (men) or more than 1.1 (women). Table I summarizes the basic data of the patients. Between February 1999 and May 2005 12 patients underwent aortic surgery for a juxtarenal or suprarenal AAA or high Leriche syndrome, and these patients belonged to the control group, which did not receive HTK solution. Table II summarizes the basic data of the control group. There was no correlation between baseline renal insufficiency and stenosis of the renal arteries. Preoperative imaging included computed tomography (CT) with representation of the renal arteries. In the case of hypertension, which is difficult to regulate, CT angiography of the abdominal aorta by magnetic resonance imaging was performed to determine stenosis of the renal arteries. Both methods tend to overestimate the degree of stenosis. A midline transperitoneal incision was the preferred approach to the abdominal aorta. The retropritoneal approach is used in thoracoabdominal aneurysms. Renal arteries were exposed and entangled with tourniquets. All patients received 5,000 units heparin before suprarenal cross-clamping of the aorta. The HTK dilution was infused in all cases through a catheter with a balloon directly into the kidney arteries. An Angiomed (Karlsruhe, Germany) catheter was used for passive perfusion of 500 mL of 8°C cold Brettschneider HTK solution by gravity to each renal artery. After replacement of the suprarenal aorta, renal perfusion was enabled before completion of the distal aortic anastomosis. In suprarenal AAAs, after perfusion of the renal arteries, at first the proximal anastomosis was made and then the implant was occluded distally and the renal arteries were directly implanted into the prosthesis. Concentration of SCr, electrolytes, coagulation status, blood count, liver enzymes, and urine excretion were monitored every 6 hr for the first 48 hr. Renal insufficiency was defined as an increase in SCr >30% from a preoperative baseline value, any SCr concentration in excess of 2.0 mg/dL, or any need for dialysis. The mean follow-up was 2 ± 0.5 years.

Table I. Baseline characteristics of the study population
Age, years (mean ± SD)
Male (n = 18)79 ± 8
Female (n = 3)65 ± 6
Pre- and intraoperative data
Primary surprarenal aneurysm8 (38%)
Suprarenal aneurysm after aortic replacement3 (14%)
Covered or free perforation of suprarenal AAA5 (24%)
Leriche syndrome5 (24%)
Stenosis of renal arteries3 (14%)
Renal insufficiency6 (28%)
Aneurysm of pelvic arteries4 (19%)
Aortorenal bypass7 (33%)
Aortobifemoral or bi-iliac Y-prosthesis9 (43%)
Interposition of aortic prosthesis12 (57%)
Mean time of cross-clamping21 ± 6 min
ICU treatment2.5 ± 1 days
Intrahospital mortality1 (4.7%)
Table II. Baseline characteristics of control group
Age, years (mean ± SD)
Male (n = 8)71 ± 2
Female (n = 4)68 ± 3
Pre- and intraoperative data
Primary surprarenal aneurysm7 (58%)
Suprarenal aneurysm after aortic replacement3 (25%)
Covered or free perforation of suprarenal AAA2 (16.6%)
Leriche syndrome3 (25%)
Stenosis of renal arteries2 (16.6%)
Renal insufficiency2 (16.6%)
Aneurysm of pelvic arteries2 (16.6%)
Aortorenal bypass4 (33%)
Aortobifemoral or bi-iliac Y-prosthesis4 (33%)
Interposition of aortic prosthesis8 (67%)
Mean time of cross-clamping28 ± 4 min
ICU treatment2.7 ± 1 days
Intrahospital mortality0 (4.7%)

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Results 

Nine (43%) patients received an aortobifemoral or bi-iliac Y-prosthesis; in all other cases (57%) interposition of an aortic prosthesis was sufficient. Three patients (14%) had stenosis of the renal arteries. Four more patients showed operative fibrous degeneration at the entry to the renal arteries, so altogether aortorenal bypasses were necessary in seven cases (33%). Overall, 14 aortorenal bypasses were constructed by use of venous (n = 5) or prosthetic (n = 9) grafts. On reimplanting the renal arteries, both were always implanted into the prosthesis. Mean time of cross-clamping of the aorta was 29 ± 6 min. Mean time of renal artery cold ischemia was 11 + 3 min. All patients were admitted to the intensive care unit (ICU) after surgery. The mean time of treatment at the ICU was 2.5 ± 1 days. In five (24%) patients who underwent emergency surgery because of perforation of AAA hemodynamics had to be stabilized by administration of catecholamines. In two cases (10%) a sigmoidectomy was necessary because of ischemic necrosis of the sigmoid colon. One of these patients died after surgery because of severe sepsis. In one case (5%) postsurgical pneumonia occurred. Revision of one aortorenal bypass (7%) was indicated at the first postoperative day because of occlusion of the bypass. Liver enzymes of all patients showed no pathological alterations.

None of the patients who underwent elective surgery demonstrated an increase in SCr compared to SCr before surgery (Fig. 1). In all patients with preoperative renal insufficiency, a moderate improvement of the SCr was induced by HTK perfusion compared to preoperative data (Fig. 2). All patients who underwent emergency surgery caused by AAA perforation showed a significant increase in SCr values despite the HTK perfusion (Fig. 3). No patient required chronic dialysis. In the control group, four (43%) patients received an aortobifemoral or biiliac Y-prosthesis; in all other cases (57%) interposition of an aortic prosthesis was sufficient. Two (14%) patients had stenosis of the renal arteries; however, aortorenal bypasses were necessary in four cases (33%). Overall, eight aortorenal bypasses were constructed by use of venous (n = 1) or prosthetic (n = 3) grafts. Mean time of cross-clamping of the aorta was 28 ± 4 min. All patients were admitted to the ICU after surgery. Mean time of treatment at the ICU was 2.7 ± 1 days. In two (24%) patients, administration of catecholamines was necessary to reach hemodynamic stabilization. Thirty-day mortality was 0%. Two patients showed preoperative baseline renal insufficiency.

  • View full-size image.
  • Fig. 2 

    In all patients with preoperative renal insufficiency, a moderate improvement in SCr was induced by HTK perfusion compared to preoperative data. ∗Statistically significant (p < .05).

  • View full-size image.
  • Fig. 3 

    All patients who underwent emergency surgery caused by AAA perforation showed a significant increase of SCr values despite HTK perfusion. ∗Statistically significant (p < .05).

Four of the patients who underwent elective surgery, one patient with covered perforation, and one patient with preoperative baseline renal insufficiency demonstrated a significant increase in SCr compared to SCr before surgery (Fig. 4, Fig. 5). Two patients required chronic dialysis.

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Discussion 

Surgical management of supra- and juxtarenal aortic aneurysm and occlusive disease includes supraortic clamping, a procedure that can be complicated by renal, hepatic, and intestinal ischemia. Renal failure occurs in 1–13% of abdominal aortic reconstructions.1 The incidence of renal insufficiency after endovascular repair of AAA is controversial. In a study on 716 patients, El-Sabrout and Reul4 demonstrated that patients requiring suprarenal clamping are older and have a higher incidence of preoperative renal insufficiency. Risk factors for postoperative renal insufficiency are high preoperative creatinine values, hypotension during surgery, and total renal ischemia time.5, 6 Renal protection by perfusion with cold HTK solution is a common procedure in renal transplant surgery.7, 8, 9 Less frequent is the use of HTK solution in renal surgery for oncological reasons.9, 10, 11 Beneficial results were obtained after in situ perfusion with HTK solution.12, 13, 14 Huge advances were made in organ preservation by HTK perfusion in cardiac surgery and particularly in heart transplantation. Additionally, several studies have described sufficient organ preservation of kidney, liver, and pancreas by HTK perfusion.15, 16, 17, 18, 19, 20, 21 HTK contains a high hydrogen ion buffer level that reduces observable acidosis associated with ongoing anaerobic metabolism. The postulated advantages of improved pH buffering with HTK appear to have clinical relevance.21, 22 Additionally, HTK has antioxidative potential to reduce oxidative stress in renal ischemia–reperfusion.22 Schmitz et al.23 indicate that perfusion with HTK improves the results of kidney transplantation, which is reflected by better survival, lower rate of infarction higher cellular energy conservation, and a decrease of free radicals. Other studies on kidney transplantation have shown that machine perfusion with HTK significantly improved cortical microcirculation upon early reperfusion in vivo, as well as maximal serum levels of urea and creatinine.24

The aim of the present study was to report on our experience with renal protection during suprarenal aortic replacement. All patients who underwent surgery with suprarenal cross-clamping of the aorta admitted within one study year were treated with selective perfusion of both renal arteries with 500 mL cold HTK solution on each side. The present data demonstrate that in all patients with suprarenal cross-clamping of the aorta, without concomitant stenosis of the renal arteries, and without any indication for aortorenal bypass perfusion with cold HTK solution conserved stable renal function. In five of seven cases of elevated preoperative SCr and implantation of aortorenal bypass, cold HTK perfusion resulted in decreased levels of SCr.

Suprarenal cross-clamping of the aorta is associated with increased mortality.7 It was demonstrated that the outcome is strongly related to renal function and that preoperative renal failure is associated with higher in-hospital mortality in patients with thoracoabdominal aneurysm repair.23 Diverse intraoperative strategies have been described to protect renal function during surgery, including shortening of renal ischemia time, administration of furosemide, fenoldopam, or dopamine as well as high perfusion pressure.6, 25, 26 Perfusion with cold HTK solution offers an additional procedure to protect renal function in patients who undergo elective surgery with suprarenal cross-clamping of the aorta. The outcome of emergency surgery for perforated AAA crucially relies on short-term surgical procedures and shortening of renal ischemia as well as early use of catecholamines to establish stable hemodynamic conditions and avoid renal insufficiency. Additional modification, e.g., the use of blood cardioplegia, might offer promising perspectives in the surgical treatment of suprarenal aortic replacement.

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References 

  1. Bortolani EM. Suprarenal aortic cross-clamping and renal function. Ann Ital Chir. 2004;75:167–171
  2. Kudo FA, Nishibe T, Miyazaki K, Murashita T, Yasuda K, Ando M. Postoperative renal function after elective abdominal aortic aneurysm repair requiring suprarenal aortic cross-clumping. Surg Today. 2004;34:1010–1013
  3. Kallerhoff M, Blech M, Gotz L, et al. A new method for conservative renal surgery—experimental and first clinical results. Langenbecks Arch Chir. 1990;375:340–346
  4. El-Sabrout RA, Reul GJ. Suprarenal or supraceliac aortic clamping during repair of infrarenal abdominal aortic aneurysms. Tex Heart Inst J. 2001;28:254–264
  5. Wahlberg E, Dimuzio PJ, Stoney RJ. Aortic clamping during elective operations for infrarenal disease: the influence of clamping time on renal function. J Vasc Surg. 2002;336:13–18
  6. Stanic M, Sindjelic R, Neskovic V, Davidivic L, Lotina S. Renal protection during surgical procedures on the infrarenal aorta. Srp Arh Celolk Lek. 2002;130:168–172
  7. Blech M, Hummel G, Kallerhoff M, Ringert RH. Electrolyte equilibration of human kidneys during perfusion with HTK-solution. Urol Res. 1997;25:331–335
  8. de Petriconi R, Gschwend JE, Maier S, Hautmann RE. Continuous in situ cold perfusion with HTK solution in conservative surgery of kidney tumor. Urologe A. 1995;34:449–456
  9. de Petriconi R, Gschwend JE, Maier S, Hautmann RE. New technique of hypothermic renal protection in surgery for tumor of the solitary kidney. J Urol (Paris). 1995;101:125–131
  10. Blech M, Kallerhoff M, Kehrer G, et al. Clinical use of the bretschneider HTK cardioplegic solution for in situ protection of the kidney. Urologe A. 1988;27:44–48
  11. Kallerhoff M, Blech M, Kehrer G, et al. Kidney function parameters following ischemia stress using the Euro-Collins solution or the Bretschneider cardioplegic HTK solution. Urologe A. 1987;26:96–103
  12. Marberger M, Eisenberger F. Regional hypothermia of the kidney: surface or transarterial perfusion cooling? A functional study. J Urol. 1980;124:179–183
  13. Bicknell CD, Cowan AR, Kerle MI, Mansfield AO, Cheshire NJ, Wolfe JH. Renal dysfunction and prolonged visceral ischaemia increase mortality rate after suprarenal aneurysm repair. Br J Surg. 2003;90:1142–1146
  14. Schröder C, Heintz A, Pexa A, Rauen U, Deussen A. Preclinical evaluation of coronary vascular function after cardioplegia with HTK and different antioxidant additives. Eur J Cardiothorac Surg. 2007;31:821–826
  15. Agarwal A, Murdock P, Fridell JA. Comparison of histidine-tryptophan ketoglutarate solution and University of Wisconsin solution in prolonged cold preservation of kidney allografts. Transplantation. 2006;81:480–482
  16. Becker T, Ringe B, Nyibata M, et al. Pancreas transplantation with histidine-tryptophan-ketoglutarate (HTK) solution and University of Wisconsin (UW) solution: is there a difference?. J Pancreas. 2007;8:304–311
  17. Feng L, Zhao N, Yao X, et al. Histidine-tryptophan-ketoglutarate solution vs. University of Wisconsin solution for liver transplantation: a systematic review. Liver Transpl. 2007;13:1125–1136
  18. Kebis A, Kukan M, Grancic P, Jakubovský J. A novel way of liver preservation improves rat liver viability upon reperfusion. J Zhejiang Univ Sci B. 2007;8:289–295
  19. Moray G, Sevmis S, Karakayali FY, Gorur SK, Haberal M. Comparison of histidine-tryptophan-ketoglutarate and University of Wisconsin in living-donor liver transplantation. Transplant Proc. 2006;38:3572–3575
  20. Trushkov S, Bicans J, Shevelev V, Jushinskis J, Suhorukov V, Rozental R. Use of HTK solution in kidney preservation. Transplant Proc. 2003;35:766
  21. Wilson CH, Asher JF, Gupta A, et al. Comparison of HTK and hypertonic citrate to intraarterial cooling in human non-heart-beating kidney donors. Transplant Proc. 2007;39:351–352
  22. Semmelmann A, Neeff H, Sommer O, Thomusch O, Hopt UT, von Dobschuetz E. Evaluation of preservation solutions by ESR-spectroscopy: superior effects of University of Wisconsin over histidine-tryptophan-ketoglutarate in reducing renal reactive oxygen species. Kidney Int. 2007;71:875–881
  23. Schmitz V, Klawitter J, Bendrick-Peart J, et al. Impact of organ preservation using HTK for graft flush and subsequent storage in UW in rat kidney transplantation. Eur Surg Res. 2006;38:388–398
  24. Minor T, Sitzia M, Dombrowski F. Kidney transplantation from non-heart-beating donors after oxygenated low-flow machine perfusion preservation with histidine-tryptophan-ketoglutarate solution. Transpl Int. 2005;17:707–712
  25. Miller Q, Peyton BD, Cohn EJ, et al. The effects of intraoperative fenoldopam on renal blood flow and tubular function following suprarenal aortic cross-clamping. Ann Vasc Surg. 2003;17:656–662
  26. Wahlberg E, Dimuzio PJ, Stoney RJ. Aortic clamping during elective operations for infrarenal disease: the influence of clamping time on renal function. J Vasc Surg. 2002;36:13–18

PII: S0890-5096(08)00083-6

doi:10.1016/j.avsg.2008.02.008

Annals of Vascular Surgery
Volume 22, Issue 4 , Pages 520-524, July 2008