Longitudinal study of renal phenotype in mouse model of sickle cell trait

Background: Sickle cell disease (SCD) is an autosomal recessive blood disorder caused by mutations in the β-globin gene, resulting in hemoglobin S (HbS) polymerization and red blood sickling. SCD patients carry two copies of the mutant HbS (HbSS) and develop anemia, iron overload and to end-organ damage. Heterozygous carriers (AS) are said to have sickle cell trait (SCT). While not associated with shortened life expectancy, individuals with SCT are at increased risk for a limited number of complications, including chronic kidney disease (CKD) that has yet to be fully elucidated. Our objective was to examine if mouse model of SCT is associated with worsening kidney function over time, mimicking an increased risk of CKD in SCT. Methods: We used male humanized sickle cell trait (HbAS) and age-matched genetic control (HbAA) mice (n=18). Analysis of urinary renal biomarkers (albuminuria, proteinuria, kidney injury marker 1 (KIM-1), osmolality) and time course of kidney function (determined via transcutaneous measurement of glomerular filtration rate (GFR)) were conducted in 4-week intervals from 12 to 40 weeks of age. Results: At 8 weeks of age, HbAS mice exhibited no differences in GFR, or proteinuria compared to HbAA controls. Significant increase in GFR, but not proteinuria, was observed in HbAS at 16 weeks of age compared to HbAA mice (241.6±5.3 ul/min vs 218.2±5 ul/min, respectively, p ˂0.05). Importantly, significant loss of kidney function measured by GFR (200 ± 3 vs 217.9 ± 3.2 ul/min, p Funding: NHLBI–R00HL144817 and NHLBI-R01 HL157441 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.