Goal-directed Hemodynamic Management and Acute Kidney Injury After Radical Nephrectomy

Acute Kidney Injury Clinical Trial

Official title:

Impact of Goal-directed Hemodynamic Management on the Incidence of Acute Kidney Injury and Long-term Outcomes in Patients Undergoing Radical Nephrectomy: A Randomized Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05149196
• Other study ID #: 2021-417
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 2022
• Est. completion date: October 2028

Study information

• Verified date: April 2022
• Source: Peking University First Hospital
• Contact: Dong-Xin Wang, MD,PhD
• Phone: 86 10 83572784
• Email: wangdongxin[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Radical nephrectomy is a standard operation for the treatment of renal cell carcinoma. However, acute kidney injury frequently occur after surgery. And the occurrence of acute kidney injury is associated with an increased risk of chronic kidney disease. Intraoperative hypotension is identified as an important risk factor of postoperative acute kidney injury. Preliminary studies showed that goal-directed hemodynamic management may reduce organ injury after surgery but requires further demonstration. We hypothesized that goal-directed hemodynamic therapy achieved by combining liquid therapy and vasopressors can reduce the incidence of acute kidney injury after radical nephrectomy. The purpose of this study was to investigate the effect of goal-directed hemodynamic management on the incidence of acute kidney injury in patients following radical nephrectomy.

Description:

Renal cancer accounts for 20.3% of urinary system tumors, and the incidence is still increasing. Surgical resection is the main treatment of renal cancer; radical nephrectomy is the standard operation. Acute kidney injury (AKI) is a common complication after radical nephrectomy, with an incidence of up to 53.9%. AKI is associated with the development of chronic kidney disease (CKD) and is an independent risk factor of new onset CKD in patients without underlying kidney disease. A meta-analysis showed that one year after surgery, patients with AKI had a 2.7-fold increased risk of new onset or progression of CKD and a 4.8-fold increased risk of end-stage renal disease. Moreover, even mild AKI is associated with renal insufficiency 1-2 years after surgery. Taking active measures to reduce the incidence of AKI may improve long-term renal function after radical nephrectomy. Many clinical studies show that intraoperative hypotension is an important risk factor of postoperative kidney injury. For example, a study found that intraoperative mean arterial pressure (MAP) <65 mmHg or a decrease of more than 20% from baseline was associated with an increased risk of postoperative AKI; the risk of AKI increased alone with prolonged duration of hypotension. A recent randomized controlled trial showed that, compared with routine intraoperative blood pressure management, goal-directed hemodynamic management reduced the incidence of organ injury from 63.4% to 46.3% within 30 days after surgery. A meta-analysis included 65 randomized controlled trials with 9308 patients and observed the effect of goal-directed hemodynamic management on postoperative AKI. The results showed that a combination of fluid therapy with vasopressors reduced the incidence of AKI in high-risk patients following major abdominal or orthopedic surgery. In a previous pilot trial of the authors, goal-directed hemodynamic management reduced the incidence of AKI by about 40% in patients following partial nephrectomy. However, the difference was not statistically significant due to insufficient sample size. The purpose of this trial is to investigate whether goal-directed intraoperative hemodynamic management can reduce the incidence of acute kidney injury in patients undergoing radical nephrectomy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 788
• Est. completion date: October 2028
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Age of 18 years or older;

2. Scheduled to undergo radical nephrectomy for renal cancer. Exclusion criteria

1. Refused to participate;

2. Diagnosed with chronic kidney disease (stage 3 or higher) before surgery;

3. Uncontrolled severe hypertension (systolic blood pressure =180 mmHg or diastolic blood pressure =110 mmHg);

4. Unable to communicate due to severe dementia, language barrier, or end-stage disease before surgery;

5. Enrolled in other trials;

6. Other conditions that are considered unsuitable for inclusion (specific reasons should be indicated).

Related Conditions & MeSH terms

• Acute Kidney Injury
• Carcinoma, Renal Cell
• Chronic Kidney Diseases
• Hemodynamic Management
• Kidney Diseases
• Nephrectomy
• Renal Cell Carcinoma
• Renal Insufficiency, Chronic
• Wounds and Injuries

Intervention

Other:
• Targeted blood pressure management
During anesthesia, mean blood pressure is maintained =85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; For patients admitted to intensive care unit after surgery, mean blood pressure is maintained =85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; In the general ward, systolic blood pressure is maintained =110 mmHg or within 10% of baseline by delaying antihypertensive resumption, providing fluid challenge, and/or norepinephrine infusion.
• Routine care
In the general ward, management is performed according to routine practice.

Locations

Country	Name	City	State
China	Beijing University First Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (26)

Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014 Jul 3;371(1):58-66. doi: 10.1056/NEJMra1214243. Review. — View Citation

Cho A, Lee JE, Kwon GY, Huh W, Lee HM, Kim YG, Kim DJ, Oh HY, Choi HY. Post-operative acute kidney injury in patients with renal cell carcinoma is a potent risk factor for new-onset chronic kidney disease after radical nephrectomy. Nephrol Dial Transplant. 2011 Nov;26(11):3496-501. doi: 10.1093/ndt/gfr094. Epub 2011 Mar 15. — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. — View Citation

Ficarra V, Novara G, Secco S, Macchi V, Porzionato A, De Caro R, Artibani W. Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates for nephron-sparing surgery. Eur Urol. 2009 Nov;56(5):786-93. doi: 10.1016/j.eururo.2009.07.040. Epub 2009 Aug 4. — View Citation

Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172. — View Citation

Garofalo C, Liberti ME, Russo D, Russo L, Fuiano G, Cianfrone P, Conte G, De Nicola L, Minutolo R, Borrelli S. Effect of post-nephrectomy acute kidney injury on renal outcome: a retrospective long-term study. World J Urol. 2018 Jan;36(1):59-63. doi: 10.1007/s00345-017-2104-7. Epub 2017 Oct 23. — View Citation

Giglio M, Dalfino L, Puntillo F, Brienza N. Hemodynamic goal-directed therapy and postoperative kidney injury: an updated meta-analysis with trial sequential analysis. Crit Care. 2019 Jun 26;23(1):232. doi: 10.1186/s13054-019-2516-4. — View Citation

Kellum JA, Ronco C, Mehta RL. Fluid management in acute kidney injury. Int J Artif Organs. 2008 Feb;31(2):94-5. — View Citation

Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84. doi: 10.1159/000339789. Epub 2012 Aug 7. — View Citation

Kim WH, Shin KW, Ji SH, Jang YE, Lee JH, Jeong CW, Kwak C, Lim YJ. Robust Association between Acute Kidney Injury after Radical Nephrectomy and Long-term Renal Function. J Clin Med. 2020 Feb 25;9(3). pii: E619. doi: 10.3390/jcm9030619. — View Citation

Klatte T, Rossi SH, Stewart GD. Prognostic factors and prognostic models for renal cell carcinoma: a literature review. World J Urol. 2018 Dec;36(12):1943-1952. doi: 10.1007/s00345-018-2309-4. Epub 2018 Apr 30. Review. — View Citation

Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. Erratum in: Ann Intern Med. 2011 Sep 20;155(6):408. — View Citation

Monk TG, Bronsert MR, Henderson WG, Mangione MP, Sum-Ping ST, Bentt DR, Nguyen JD, Richman JS, Meguid RA, Hammermeister KE. Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery. Anesthesiology. 2015 Aug;123(2):307-19. doi: 10.1097/ALN.0000000000000756. Erratum in: Anesthesiology. 2016 Mar;124(3):741-2. — View Citation

Myles PS, McIlroy DR, Bellomo R, Wallace S. Importance of intraoperative oliguria during major abdominal surgery: findings of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery trial. Br J Anaesth. 2019 Jun;122(6):726-733. doi: 10.1016/j.bja.2019.01.010. Epub 2019 Feb 16. — View Citation

Pancaro C, Shah N, Pasma W, Saager L, Cassidy R, van Klei W, Kooij F, Vittali D, Hollmann MW, Kheterpal S, Lirk P. Risk of Major Complications After Perioperative Norepinephrine Infusion Through Peripheral Intravenous Lines in a Multicenter Study. Anesth Analg. 2020 Oct;131(4):1060-1065. doi: 10.1213/ANE.0000000000004445. — View Citation

Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65. — View Citation

See EJ, Jayasinghe K, Glassford N, Bailey M, Johnson DW, Polkinghorne KR, Toussaint ND, Bellomo R. Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure. Kidney Int. 2019 Jan;95(1):160-172. doi: 10.1016/j.kint.2018.08.036. Epub 2018 Nov 23. — View Citation

Shin CH, Long DR, McLean D, Grabitz SD, Ladha K, Timm FP, Thevathasan T, Pieretti A, Ferrone C, Hoeft A, Scheeren TWL, Thompson BT, Kurth T, Eikermann M. Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study. Ann Surg. 2018 Jun;267(6):1084-1092. doi: 10.1097/SLA.0000000000002220. — View Citation

Shin S, Han Y, Park H, Chung YS, Ahn H, Kim CS, Cho YP, Kwon TW. Risk factors for acute kidney injury after radical nephrectomy and inferior vena cava thrombectomy for renal cell carcinoma. J Vasc Surg. 2013 Oct;58(4):1021-7. doi: 10.1016/j.jvs.2013.02.247. Epub 2013 Apr 13. — View Citation

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8. — View Citation

Sun LY, Wijeysundera DN, Tait GA, Beattie WS. Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery. Anesthesiology. 2015 Sep;123(3):515-23. doi: 10.1097/ALN.0000000000000765. — View Citation

Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264. doi: 10.1016/j.jacc.2018.08.1038. Epub 2018 Aug 25. Review. — View Citation

Turan A, Cohen B, Adegboye J, Makarova N, Liu L, Mascha EJ, Qiu Y, Irefin S, Wakefield BJ, Ruetzler K, Sessler DI. Mild Acute Kidney Injury after Noncardiac Surgery Is Associated with Long-term Renal Dysfunction: A Retrospective Cohort Study. Anesthesiology. 2020 May;132(5):1053-1061. doi: 10.1097/ALN.0000000000003109. — View Citation

Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26. — View Citation

Wesselink EM, Kappen TH, Torn HM, Slooter AJC, van Klei WA. Intraoperative hypotension and the risk of postoperative adverse outcomes: a systematic review. Br J Anaesth. 2018 Oct;121(4):706-721. doi: 10.1016/j.bja.2018.04.036. Epub 2018 Jun 20. — View Citation

Wu QF, Kong H, Xu ZZ, Li HJ, Mu DL, Wang DX. Impact of goal-directed hemodynamic management on the incidence of acute kidney injury in patients undergoing partial nephrectomy: a pilot randomized controlled trial. BMC Anesthesiol. 2021 Mar 3;21(1):67. doi: 10.1186/s12871-021-01288-8. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of life of survivors at 1, 2, and 3 years after surgery	Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF). This is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.	Up to 3 years after surgery
Other	Proportion of intensive care unit admission with endotracheal intubation	Proportion of intensive care unit admission with endotracheal intubation	Up to 30 days after surgery
Other	Length of stay in intensive care unit after surgery	Length of stay in intensive care unit after surgery	Up to 30 days after surgery
Other	Pain severity after surgery	Pain severity is assessed with the numeric rating scale. This is a 11-point scale with 0= no pain and 10=the worst pain.	UP to 3 days after surgery
Primary	Incidence of acute kidney injury	Acute kidney injury is diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.	Up to 3 days after surgery
Secondary	Classification of acute kidney injury	Classification of acute kidney injury is diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.	Up to 3 days after surgery
Secondary	Proportion of intensive care unit after surgery	Proportion of intensive care unit after surgery	Up to 30 days after surgery
Secondary	Incidence of postoperative complications	Postoperative complications are defined as new-onset medical conditions that are harmful to patients' recovery and required therapeutic intervention, i.e., grade 2 or higher on the Clavien-Dindo classification.	Up to 30 days after surgery
Secondary	Length of hospital stay after surgery	Length of hospital stay after surgery	Up to 30 days after surgery
Secondary	Chronic kidney disease free survival time	Time interval from the end of surgery to new onset of chronic kidney disease (stage 3 or above) or all-cause death, which ever come first. Chronic kidney disease is defined as glomerular filtration rate <60 ml/min/1.73 m2.	Up to 3 years after surgery
Secondary	Event free survival	Time interval from the end of surgery to new-onset chronic kidney disease (stage 3 or above), serious events (required hospitalization or reoperation), or all-cause death, which ever come first.	Up to 3 years after surgery
Secondary	Overall survival time	Time interval from the end of surgery to all-cause death.	Up to 3 years after surgery