Abstract: FR-PO414
APOL1 and suPAR on Time to CKD in Children With Sickle Cell Anemia
Session Information
- Pediatric Nephrology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Zahr, Rima S., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Rashkin, Sara R., St Jude Children's Research Hospital, Memphis, Tennessee, United States
- Elsherif, Laila, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Ataga, Kenneth I., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
- Lebensburger, Jeffrey, The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background
The incidence of CKD increases with time in patients with sickle cell anemia (SCA). Adult SCA patients with high risk APOL1 variants have an increased risk of developing CKD earlier in life, though this finding has not been explored in children. Biomarkers may further aid in predicting kidney injury and disease progression. Elevated levels of the soluble urokinase-type plasminogen activator (suPAR) is linked to the pathogenesis of CKD in APOL1 kidney disease. Elevated podocin, is found in urine of individuals with nephrosis. We aimed to identify the association of elevated suPAR, podocin, and high risk APOL1 on time to develop CKD in pediatric SCA patients.
Methods
Participants <18 years (y) with SCA enrolled in the Sickle Cell Clinical Research and Intervention Program (SCCRIP) participants were examined. Time to CKD (tCKD) was defined as the age at first instance of estimated glomerular filtration rate (eGFR, modified Schwartz formula) <90 ml/min/1.73m2 for patients with > or = 3 consecutive instances. Controls (no instances) were censored at last eGFR. Urine podocin and plasma suPAR were measured using Elisa kits, following manufacturer recommendations. We compared individuals with high biomarker levels (4th quartile) to those with lower levels. High risk APOL1 was defined as homozygous G1 or G2 or double heterozygous. Cox proportional hazards regression was used to test the association of APOL1, podocin, and suPAR with tCKD, adjusted for sex, hydroxyurea use, chronic transfusion use, and five principal components.
Results
We identified 29 cases and 220 controls; 52% of the cohort was female. The mean age at first eGFR assessment was 4.1±3.5y, mean follow-up time of 9.8±3.3y and 26% of children had high risk APOL1. APOL1 was associated with tCKD (hazard ratio (HR)=4.1; P=0.0037). High suPAR was associated with tCKD (HR=2.8; P=0.040), but high podocin was not (HR=1.5; P=0.39). In a joint model, high risk APOL1(HR=4.4; P=0.028) and high suPAR (HR=2.9; P=0.038) were independently associated with tCKD.
Conclusion
High risk APOL1 and elevated suPAR were associated with earlier diagnosis of CKD in children with SCA. Larger prospective studies are needed to assess the clinical utility for APOL1 and suPAR in predicting and monitoring SCA CKD progression throughout the lifespan and if therapeutic interventions can ameliorate disease progression.
Funding
- Other NIH Support