Acute Kidney Injury, Chronic Kidney Diseases, Hemodynamic Management, Nephrectomy, Nephroureterectomy
Conditions
Keywords
Nephrectomy, Nephroureterectomy, Hemodynamic Management, Acute Kidney Injury, Chronic Kidney Diseases
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.
Interventions
OTHERTargeted 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.
OTHERRoutine 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.
Sponsors
Peking University First Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Incidence of myocardial injury after noncardiac surgery (MINS) within 7 days after surgery | Up to 7 days after surgery | MINS is diagnosed according to the Fourth Universal Definition of Myocardial Infarction (2018). |
| Incidence of delirium within 7 days after surgery | Up 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). |
| Incidence of surgical site infection within 30 days after surgery | Up to 30 days after surgery | Surgical site infection is diagnosed according to predefined definition. |
| Incidence of CKD within 3 months after surgery | Up 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. |
| Proportion of various grades of CKD at different timepoints | Up to 2 years after surgery | CKD is diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. |
| Event-free survival | Up 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients admitted in intensive care unit after surgery | Up to 30 days after surgery | Proportion of patients admitted in intensive care unit after surgery. |
| Incidence of other major postoperative complications | Up to 30 days after surgery | Major 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. |
| Length of hospital stay after surgery | Up to 30 days after surgery | Length of hospital stay after surgery |
| Prevalence of neurocognitive disorder at 6 months and 1 year after surgery | At 6 months and 1 year after surgery | Neurocognitive disorder is defined as a decrease of neurocognitive function score of 1 standard deviation (SD) or more from baseline. Neurocognitive function is assessed with the Montreal Cognitive Assessment-telephone version (T-MoCA; score ranges from 0 to 22, with higher score indicating better cognitive function). |
| Quality of life at 6 months and 1 year after surgery | At 6 months and 1 year after surgery | Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF), 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. |
| Overall survival time | Up to 2 years after surgery | Time interval from the end of surgery to all-cause death. |
| AKI stage within 7 days after surgery | Up to 7 days after surgery | Acute kidney injury is diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. |
Countries
China
Contacts
Primary ContactDong-Xin Wang, MD,PhD
Backup ContactQiongfang Wu, MD
Outcome results
None listed