Goal-directed Hemodynamic Management and Kidney Injury After Radical Nephrectomy or Nephroureterectomy

Official title

Impact of Goal-directed Hemodynamic Management on Occurrence of Acute and Persistent Kidney Injury After Radical Nephrectomy or Nephroureterectomy: A Randomized Controlled Trial

Overview

Radical nephrectomy and nephroureterectomy are common operations for the treatment of renal cell carcinoma and upper tract urothelial carcinoma, respectively. However, acute kidney injury frequently occurs 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 kidney injury after surgery but requires further demonstration. We hypothesized that goal-directed hemodynamic management combining hydration, inotropes, and forced diuresis to maintain pulse pressure variation \<9%, mean arterial pressure ≥85 mmHg, and urine flow rate \>200 ml/h (3 ml/kg/h) may reduce the incidence of acute kidney injury and improve long-term renal outcome after radical nephrectomy or nephroureterectomy. The purpose of this study is to investigate the effect of goal-directed hemodynamic management on the occurrence of acute and persistent kidney injury in patients following radical nephrectomy and nephroureterectomy.

Detailed 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 for renal cancer of stage T2 or above. For upper tract urothelial carcinoma (UTUC) which includes renal pelvis cancer and ureteral cancer, radical nephroureterectomy is the gold standard treatment. Both procedures involve the removal of one kidney. Acute kidney injury (AKI) is a common complication after radical nephrectomy and nephroureterectomy, with reported incidence from 53.9% to 72.7%. 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, at 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 at 1 to 2 years after surgery.

Taking active measures to reduce the incidence of AKI may improve long-term renal function after radical nephrectomy and nephroureterectomy. 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. However, recent randomized controlled trials showed inconsistent results regarding the effect of tight blood pressure management strategy on kidney outcome. Relevant studies indicated that hydration with forced diuresis and inotropes to maintain cardiac output and blood pressure might improve renal outcome.

In a previous pilot trial of the authors, goal-directed hemodynamic management combining hydration and inotropics 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 combining hydration, inotropics, and forced diuresis can reduce the occurrence of acute and persistent kidney injury in patients undergoing radical nephrectomy and nephroureterectomy.

Interventions

• Other Targeted hemodynamic management
  During anesthesia, hemodynamic managements include active hydration (\>10 ml/kg/h), use of inotropes (dobutamine), and forced diuresis; the targets are to maintain pulse pressure variation \<9%, mean arterial pressure ≥85 mmHg, and urine output \>200 ml/h (3ml/kg/h). During the first 48 hours after surgery, systolic blood pressure is maintained ≥110 mmHg or within 20% of baseline by delaying antihypertensive resumption, providing fluid challenge, and/or vasoactive infusion.
• Other Routine care
  During anesthesia, hemodynamic managements are conducted according to routine practice and usually include fluid infusion at a rate of 6-8 ml/kg/h without inotropics; the targets are to maintain mean arterial pressure ≥60 mmHg and urine output \>0.5 ml/kg/h. During the first 48 hours after surgery, hemodynamic management is performed according to routine practice.

Primary outcome measures

• Incidence of acute kidney injury (early primary outcome) [Time frame: Up to 7 days after surgery]
• Time to new-onset or progression of chronic kidney disease (CKD) (long-term primary outcome). [Time frame: Up to 2 years after surgery]

Secondary outcome measures (6)

• Incidence of myocardial injury after noncardiac surgery (MINS) within 7 days after surgery [Time frame: Up to 7 days after surgery]
• Incidence of delirium within 7 days after surgery [Time frame: Up to 7 days after surgery]
• Incidence of surgical site infection within 30 days after surgery [Time frame: Up to 30 days after surgery]
• Incidence of CKD within 3 months after surgery [Time frame: Up to 3 months after surgery]
• Proportion of various grades of CKD at different timepoints [Time frame: Up to 2 years after surgery]
• Event-free survival [Time frame: Up to 2 years after surgery]

Eligibility criteria

Inclusion criteria

• Age of 18 years or older;
• Scheduled to undergo unilateral radical nephrectomy for renal cancer or unilateral radical nephroureterectomy for upper tract urothelial carcinoma.

Exclusion criteria

• Diagnosed with chronic kidney disease stage 4 or stage 5 (GFR<30 ml/min/1.73m2) before surgery;
• Uncontrolled severe hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg);
• Combined with cardiovascular diseases with Revised Cardiac Risk Index (RCRI) >1 or metabolic equivalents (METs) <4;
• Unable to communicate due to severe dementia, language barrier, or end-stage disease before surgery;
• Other conditions that are considered unsuitable for inclusion (specific reasons should be indicated).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

China · 1 center

• Beijing University First Hospital — Beijing

Publications

• 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. PMID 31912902
• 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. PMID 29713755
• 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. PMID 21406544
• 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. PMID 29063267
• 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. PMID 23591189
• 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. No abstract available. PMID 24988558
• 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. PMID 30473140
• 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. PMID 31929326

Identifiers

NCT: NCT05149196 · 2021-417

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗