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

• Published in: Pediatric nephrology (Berlin, West) West), 2020-05, Vol.35 (5), p.883-889
• Main Authors: Kaspar, Cristin D. W., Beach, Isidora, Newlin, Jennifer, Sisler, India, Feig, Daniel, Smith, Wally
• Format: Article
• Language: English
• Subjects: Adolescent; Age; Albuminuria - blood; Albuminuria - epidemiology; Albuminuria - physiopathology; Anemia, Sickle Cell - blood; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - therapy; Anemia, Sickle Cell - urine; Blood Transfusion; Child; Children; Cohort Studies; Complications and side effects; Cross-Sectional Studies; Diseases; Distribution; Epidermal growth factor receptors; Female; Glomerular filtration rate; Glomerular Filtration Rate - physiology; Gout Suppressants - therapeutic use; Humans; Hyperuricemia; Hyperuricemia - blood; Hyperuricemia - diagnosis; Hyperuricemia - drug therapy; Hyperuricemia - epidemiology; Kidney diseases; Kidney Diseases - blood; Kidney Diseases - etiology; Kidney Diseases - physiopathology; Kidney Diseases - urine; Male; Medicine; Medicine & Public Health; Morbidity; Nephrology; Nephropathy; Original Article; Pediatrics; Prevalence; Renal Elimination - physiology; Renal function; Risk Factors; Sickle cell disease; Therapeutic applications; Uric acid; Uric Acid - blood; Uric Acid - metabolism; Urology
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-019-04432-2

Background 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. Methods 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. Results 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/1.73m 2 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 (R 2 = 0.44, p = 0.0004) and is nonsignificant in normouricemia (R 2 = 0.07, p = 0.0775). Conclusion 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.