Hyperuricemia is associated with a lower glomerular filtration rate in pediatric sickle cell disease patients.

Abstract

Sickle cell nephropathy (SCN) is a progressive disease that contributes significant morbidity and mortality in sickle cell disease (SCD), yet it remains poorly understood. Hyperuricemia negatively impacts renal function in the non-sickle cell population but is understudied in SCD. We performed a cross-sectional analysis of the first 78 pediatric SCD patients enrolled in a cohort study. The mechanism of development of hyperuricemia (defined, serum uric acid (UA) ≥ 5.5 mg/dL) was characterized as a result of either UA overproduction or inefficient renal excretion by the Simkin index and fractional clearance of urate (FCU) equations. Associations between hyperuricemia and albuminuria or estimated glomerular filtration rate (eGFR) were determined by linear regression. The prevalence of hyperuricemia in this young population (mean age 11.6 ± 3.77 years) was 34.2%. Only 1 hyperuricemic participant overproduced UA by Simkin index, while 62.5% were inefficient renal excretors of UA (FCU < 4%). Hyperuricemia was associated with a significant decrease in average eGFR, -27 ml/min/1.73m2 below normouricemia (mean eGFR 151.6 ± 40.32), p = 0.0122. Notably, the previously accepted association between decline of eGFR with age is significantly modified by hyperuricemia stratification, where hyperuricemia explains 44% of the variance in eGFR by age (R2 = 0.44, p = 0.0004) and is nonsignificant in normouricemia (R2 = 0.07, p = 0.0775). These findings indicate that hyperuricemia may be associated with early eGFR decline in SCN. This association must be further characterized in prospective cohort studies in SCN, and hyperuricemia must be investigated as a potential therapeutic target for SCN.