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

Not Applicable
Not yet recruiting
Conditions
Nephrectomy
Nephroureterectomy
Hemodynamic Management
Acute Kidney Injury
Chronic Kidney Diseases
Interventions
Other: Targeted hemodynamic management
Other: Routine care
Registration Number
NCT05149196
Lead Sponsor
Peking University First Hospital
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
1724
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Targeted blood pressure managementTargeted hemodynamic managementDuring 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.
Routine careRoutine careDuring anesthesia, hemodynamic managements are conducted according to routine practice and usually include fluids 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
NameTimeMethod
Incidence of acute kidney injury (early primary outcome)Up to 7 days after surgery

Acute kidney injury is diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Acute kidney injury of stage 1 or above is defined as occurrence of acute kidney injury.

Time to new-onset or progression of chronic kidney disease (CKD) (long-term primary outcome).Up to 2 years after surgery

New-onset CKD is defined as a decrease of glomerular filtration rate to \<60 ml/min/1.73 m2 and persists for more than 3 months. Progression of CKD is defined as a decrease of glomerular filtration rate of 40% or more from baseline and persists for more than 3 months.

Secondary Outcome Measures
NameTimeMethod
Incidence of delirium within 7 days after surgeryUp to 7 days after surgery

Delirium is assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM).

Proportion of various grades of CKD at different timepointsUp to 2 years after surgery

CKD is diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Incidence of surgical site infection within 30 days after surgeryUp to 30 days after surgery

Surgical site infection is diagnosed according to predefined definition.

Incidence of CKD within 3 months after surgeryUp to 3 months after surgery

Included new-onset or progression of CKD. New-onset CKD is defined as a decrease of glomerular filtration rate to \<60 ml/min/1.73 m2 and persists for more than 3 months. Progression of CKD is defined as a decrease of glomerular filtration rate of 40% or more from baseline and persists for more than 3 months.

Incidence of myocardial injury after noncardiac surgery (MINS) within 7 days after surgeryUp to 7 days after surgery

MINS is diagnosed according to the Fourth Universal Definition of Myocardial Infarction (2018).

Event-free survivalUp to 2 years after surgery

Time interval from the end of surgery to new-onset or progression of CKD, serious events (required hospitalization or reoperation), or all-cause death, which ever come first. New-onset CKD is defined as a decrease of glomerular filtration rate to \<60 ml/min/1.73 m2 and persists for more than 3 months. Progression of CKD is defined as a decrease of glomerular filtration rate of 40% or more from baseline and persists for more than 3 months.

Trial Locations

Locations (1)

Beijing University First Hospital

🇨🇳

Beijing, Beijing, China

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