Clinical trial NCT05149196: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Nephrectomy
Nephroureterectomy
Hemodynamic Management
Acute Kidney Injury
Chronic Kidney Diseases
Keywords: Nephrectomy
Nephroureterectomy
Hemodynamic Management
Acute Kidney Injury
Chronic Kidney Diseases
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2021-12-08
Enrollment: 1724
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Eligibility criteria: Inclusion criteria:

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

Exclusion criteria

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

Primary outcomes:
measure: Incidence of acute kidney injury (early primary outcome)
timeFrame: Up to 7 days after surgery
measure: Time to new-onset or progression of chronic kidney disease (CKD) (long-term primary outcome).
timeFrame: Up to 2 years after surgery
Secondary outcomes:
measure: Incidence of myocardial injury after noncardiac surgery (MINS) within 7 days after surgery
timeFrame: Up to 7 days after surgery
measure: Incidence of delirium within 7 days after surgery
timeFrame: Up to 7 days after surgery
measure: Incidence of surgical site infection within 30 days after surgery
timeFrame: Up to 30 days after surgery
measure: Incidence of CKD within 3 months after surgery
timeFrame: Up to 3 months after surgery
measure: Proportion of various grades of CKD at different timepoints
timeFrame: Up to 2 years after surgery
measure: Event-free survival
timeFrame: Up to 2 years after surgery
Other outcomes:
measure: AKI stage within 7 days after surgery
timeFrame: Up to 7 days after surgery
measure: Proportion of patients admitted in intensive care unit after surgery
timeFrame: Up to 30 days after surgery
measure: Incidence of other major postoperative complications
timeFrame: Up to 30 days after surgery
measure: Length of hospital stay after surgery
timeFrame: Up to 30 days after surgery
measure: Prevalence of neurocognitive disorder at 6 months and 1 year after surgery
timeFrame: At 6 months and 1 year after surgery
measure: Quality of life at 6 months and 1 year after surgery
timeFrame: At 6 months and 1 year after surgery
measure: Overall survival time
timeFrame: Up to 2 years after surgery
Locations:
city: Beijing
country: China
facility: Beijing University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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