Clinical trial NCT04420897: The Effect of Intraoperative Arterial Oxygen Pressures on Early Post-Operative Patient and Graft Survival in Living Donor Kidney Transplantation
Official title: The Effect of Intraoperative Arterial Oxygen Pressures on Early Post-Operative Patient and Graft Survival in Living Donor Kidney Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplant; Complications
Hyperoxia
Graft Dysfunction
Lead sponsor: Akdeniz University
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 247
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: We enrolled only 1000 adult living donor kidney transplantations closed files started from 1st of January 2017 to 1st of November 2019. The study conducted at the Department of Anesthesiology and Critical Care with the Department of General and Visceral Surgery Medical Center. All recipient surgical procedure was carried out by the same specialized transplantation surgeons and anesthesiologists after a positive vote of the local ethics committee for transplantation. Recipients with a history of myocardial infarction, chronic respiratory disease (bronchial asthma, COPD) were excluded from the study.

Brief summary: We evaluated the prognostic role of the intraoperative arterial oxygen partial pressures (PaO2) on postoperative patient and graft survival in living donor kidney transplantations.

Detailed description: Undoubtedly, one of the most important elements of life on earth is oxygen. Aerobic organisms adapted to the 20.8% oxygen ratio in the atmosphere have survived even lower than this concentration by developing various defense mechanisms. The real question is whether high levels of oxygen in the blood, which are administered iatrogenically, leads to tissue destruction.

Reactive Oxygen Species (ROS), which is a result of hyperoxia and may be useful even at low levels, may cause tissue loss due to oxidative stress, also called oxygen-free radicals. ROS, whose toxicity is very destructive with its accumulation, may cause damage to macromolecular structures such as lipids, protein, mitochondrial and nuclear DNA. On the organs of the exposed oxidative stress; For lung, asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), cardiovascular system, ischemic heart disease (IHD), hypertension, shock, heart failure, while kidney failure and glomerulonephritis can cause unwanted complications.

The kidneys get for circulation, only 20% of the cardiac output. Since the arterial and venous (AV) structures in the kidneys are anatomically parallel to each other, the oxygen concentration in the renal vein may be relatively higher than the efferent arteriole and cortex because of the oxygen shunt. Thanks to this mechanism, in clinical situations where partial oxygen pressure (Pa02) is high, the oxygen concentration presented to the kidney tissues remains within a certain limit. In fact, AV shunt protects kidney tissue with a structural antioxidant mechanism. Thus, the increase in renal blood flow (RBF) will cause an increase in AV oxygen shunt in parallel, the blood coming to the kidneys participates in the systemic circulation without entering the renal microcirculation. It has been suggested that shunt occurs to protect from hyperoxia at the tissue level by decreasing blood volume in the kidneys. Oxidative stress, which is inevitable as a result, will increase tissue hypoxia paradoxically by increasing the oxygen consumption of the kidneys. It is stated that uremic toxin, especially indoxyl sulfate (IS) accumulation is the cause of the mentioned table. Apart from IS, phenyl sulfate and ρ-cresy sulfate make tubular cells susceptible by reducing glutathione levels. Thus, increased renal hypoxia, renal oxidative stress will result in renal inflammation and fibrosis.

According to recent studies, the antioxidant defense mechanism has been shown not only to be limited to AV shunt. But also the dynamic regulation of intrarenal oxygenation in RBF changes. However, mechanisms developed to prevent hyperoxia have made kidney tissue sensitive to hypoxia. The increase in AV oxygen shunt causes an increase in tissue hypoxia.

Although endogenous antioxidant mechanisms play a major role against free radicals, the postoperative effects of iatrogenic hyperoxia on transplanted kidney grafts and patient survival remain a subject to be investigated. That's why we aim to understand the impact of iatrogenic hyperoxia during the living donor kidney transplantation operations by retrospective data analyzing.

Eligibility criteria: Inclusion Criteria:

* Patients who had living donor kidney transplantation between January 2014 and June 2019 at Akdeniz University Faculty of Medicine Organ Transplant Center.

Exclusion Criteria:

* Patients with missing data
* Patients with a history of chronic heart failure or chronic respiratory disease (bronchial asthma, COPD).
* Presence of cadaveric donor kidney transplantation

Primary outcomes:
measure: Assessment of arterial blood gases with normoxia
timeFrame: Postoperative first following month
measure: Assessment of arterial blood gases with Moderate hyperoxemia
timeFrame: Postoperative first following month
measure: Assessment of arterial blood gases with Severe hyperoxemia
timeFrame: Postoperative first following month
Secondary outcomes:
Other outcomes:
Locations:
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty Department of Anesthesiology and Reanimation
Study officials:
affiliation: Akdeniz University Medical Faculty
name: Bora Di̇nc, MD, Assist. Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dinc B, Yilmaz VT, Aycan IO, Kisaoglu A, Dandin O, Aydinli B, Hadimioglu N, Ertug Z. Effect of post-perfusion hyperoxemia on early graft function in renal transplant recipients: a retrospective observational cohort study. Ir J Med Sci. 2021 Nov;190(4):1539-1545. doi: 10.1007/s11845-020-02499-7. Epub 2021 Jan 4.