Abstract: PO0065
Angiotensin 1-7 as a Novel Biomarker of AKI in Pediatric Kidney Transplant Recipients
Session Information
- AKI Clinical, Outcomes, and Trials - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Ehrhardt-Humbert, Lauren, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
- Chen, Ashton, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
- South, Andrew M., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
Background
While graft survival rates of pediatric kidney transplant recipients have improved dramatically, acute kidney injury (AKI) accounts for up to 21% of graft failure in pediatric patients and prompt diagnosis of AKI is difficult. AKI activates the renin-angiotensin system (RAS), leading to increased angiotensin (Ang) II-induced inflammation and fibrosis. The ACE2/Ang-(1-7) pathway mitigates these effects but may be downregulated in AKI. The objective was to investigate Ang II and Ang-(1-7) as biomarkers to predict AKI in pediatric kidney transplant recipients. We hypothesized that changes in Ang II and Ang-(1-7) over time would predict biopsy-proven AKI in the first 6 months post-transplant.
Methods
This was a prospective cohort study of children recruited from a kidney transplant evaluation clinic. Blood and urine were collected pre-transplant and post-transplant at several time points. Ang II and Ang-(1-7) were measured with radioimmunoassays. Participants underwent for-cause or surveillance biopsies and histologic findings were recorded. We applied directed acyclic graph-informed Cox proportional hazards regression analysis with robust standard errors adjusted for age to estimate the association of time-varying Ang II and Ang-(1-7) with AKI.
Results
Of the 27 participants, mean age was 11.7 +6.1 years, 63% were male, and 44% were Caucasian. The most common cause of kidney failure was congenital anomalies of the kidney and urinary tract (30%) and 74% received a deceased-donor transplant. Ten patients (37%) had AKI, most commonly due to tacrolimus toxicity (19%). In the urine, a 1-unit increase per day in Ang II (HR 0.97, 95% CI 0.93-1.0), Ang-(1-7) (0.99, 0.98-0.999), and Ang II:Ang-(1-7) (0.56, 0.28-1.11) over time predicted AKI, while blood levels did not.
Conclusion
Among pediatric kidney transplant recipients, changes in urinary Ang II and Ang-(1-7) over time predicted biopsy-proven AKI in the first 6 months post-transplant. Conversely, our findings suggest that for every 1-unit per day decrease in urine Ang-(1-7)[AMSM1] , AKI risk increases by 1%. Our findings support the notion that both pathways of the renin-angiotensin system are involved in transplant AKI. Larger studies are needed to confirm the utility of measuring Ang II and Ang-(1-7) as biomarkers to detect transplant AKI and inform its pathophysiology.