Perioperative Dexmedetomidine Improves Outcomes of Kidney Transplant

Graft function is crucial for successful kidney transplantation. Many factors may affect graft function or cause delayed graft function (DGF), which decreases the prognosis for graft survival. This study was designed to evaluate whether the perioperative use of dexmedetomidine (Dex) could improve the incidence of function of graft kidney and complications after kidney transplantation. A total of 780 patients underwent kidney transplantations, 315 received intravenous Dex infusion during surgery, and 465 did not. Data were adjusted with propensity scores and multivariate logistic regression was used. The primary outcomes are major adverse complications, including DGF and acute rejection in the early post‐transplantation phase. The secondary outcomes included length of hospital stay (LOS), infection, overall complication, graft functional status, post‐transplantation serum creatinine values, and estimated glomerular filtration rate (eGFR). Dex use significantly decreased DGF (19.37% vs. 23.66%; adjusted odds ratio, 0.744; 95% confidence interval, 0.564–0.981; P = 0.036), risk of infection, risk of acute rejection in the early post‐transplantation phase, the risk of overall complications, and LOS. However, there were no statistical differences in 90‐day graft functional status or 7‐day, 30‐day, and 90‐day eGFR. Perioperative Dex use reduced incidence of DGF, risk of infection, risk of acute rejection, overall complications, and LOS in patients who underwent kidney transplantation.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

☑ Graft function is crucial for successful kidney transplantation. Dexmedetomidine (Dex) has been shown to have renal protective effect in preclinical and other surgeries.

• WHAT QUESTION DID THIS STUDY ADDRESS?

☑ The objective of this study was to evaluate whether the perioperative Dex administration was associated with improved graft kidney function or decreased complications after kidney transplantation.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

☑ This study demonstrated that perioperative Dex administration was associated with improved kidney function and outcomes in patients who underwent kidney transplantation.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

☑ The results from this study suggest perioperative Dex administration could be beneficial to donor kidney grafts.

The cost to care for patients with chronic kidney disease and endstage renal disease (ESRD) is significant with total spending over US $120 billion for Medicare beneficiaries alone representing 33.8% of total Medicare fee‐for‐service spending according to the United States Renal Data System 2019 annual data report. ¹ There were nearly 500,000 patients receiving maintenance dialysis treatments and well over 200,000 living with a kidney transplant in the United States by the end of 2015. ² Thus, ESRD is a major public health problem due to its high morbidity and mortality as well as social and financial implications. ³ Treatment outcomes vary depending on different modalities like hemodialysis, peritoneal dialysis, and renal transplantation. Renal transplantation has an obvious survival advantage over dialysis treatments for patients with ESRD along with better quality of life. ⁴ , ⁵ , ⁶ However, the 5‐year graft survival rate was 74.4% in deceased‐donor transplants and 85.6% in living‐donor transplants. ⁷ The etiology of graft kidney dysfunction is multifactorial and involves immunologic factors, surgical techniques, hemodynamic alterations, inflammatory mechanisms, apoptosis, and ischemia/reperfusion (I/R) injury. ⁸ Although advances in immunosuppressive therapy and treatment of hypertension and hyperlipidemia have improved outcomes following kidney transplantation, poor initial graft function occurs in up to 5% of living donor recipients and up to 20% of deceased donor recipients. Infection occurs in up to 30% of renal transplant recipients during the first 3 months post‐transplantation. ⁹ , ¹⁰ The transplant population has expanded to older and sicker patients, and only about 7.3% candidates on the US kidney transplant waiting list received deceased donor kidney transplantations. ¹¹ Approximately 15% of procured kidneys were discarded despite long waiting lists. ¹¹ At the same time, graft rejection episodes occur in about 20% of low‐risk transplant recipients within the first 26 weeks post‐transplantation. ⁹ The probability of first‐year all‐cause graft failure (return to dialysis, repeat transplantation, or death with a functioning transplant) for deceased donor kidney transplant recipients was about 7.7%. ³ , ¹² , ¹³ It is important to identify factors responsible for decreased graft function and find appropriate interventions.It is well known that renal function is closely associated with hemodynamic performance, sympathetic activity, inflammatory responses, and I/R injury. The hemodynamic stabilizing and sympatholytic effects produced by alpha₂ agonists have been shown to prevent the deterioration of renal function after cardiac surgery. ¹² , ¹⁴ , ¹⁵ The mechanisms could be inhibition of renin release, increased glomerular filtration, and increased excretion of sodium and water via the kidneys. ¹⁶ Dexmedetomidine (Dex) is a short‐acting selective alpha₂ agonist in comparison to clonidine and has an alpha₂ to alpha₁ selectivity ratio of 1,600:1. ¹⁷ Dex has a stabilizing effect on hemodynamics mediated by reducing sympathetic tone, decreasing inflammatory response, alleviating I/R injury, inhibiting renin release, increasing glomerular filtration rate, increasing secretion of sodium and water by the kidneys, and decreasing insulin secretion. ¹⁸ , ¹⁹ Although Dex has been shown to alleviate acute kidney injury (AKI) in other surgeries, ¹⁴ , ¹⁵ no study has demonstrated the benefit of Dex on graft function in renal transplantation. Thus, this study was designed to determine whether the perioperative use of Dex is associated with improved graft kidney function and decreased incidence of complications after renal transplantation.