Hyperfiltration During Early Childhood Precedes Albuminuria in Pediatric Sickle Cell Nephropathy

Abstract

In patients with diabetes mellitus, hyperfiltration precedes the development of albuminuria. Pediatric sickle cell anemia (SCA) patients have a high prevalence of hyperfiltration and albuminuria during early childhood and adolescence. We tested the hypothesis that hyperfiltration precedes the development of albuminuria in a longitudinal pediatric SCA cohort.

Methods:

We identified 91 participants with HbSS or SB0 thalassemia 5–21 years of age enrolled in a longitudinal sickle cell nephropathy cohort study who had a cystatin C measured during early childhood (4–10 years of age). Early hyperfiltration was defined as a mean eGFR >180 ml/min/1.73m ² using cystatin C obtained from 4–10 years of age. Persistent albuminuria was defined as an albumin to creatinine ratio >30mg/g on two of three untimed urine specimens. Time to event analysis estimated survival curves for participants with and without hyperfiltration using Kaplan-Meier curves and used logrank test for categorical variables to assess the association with time to development of the first episode persistent albuminuria.

Results:

Persistent albuminuria occurred more often and at an earlier age in participants with early hyperfiltration compared to those without early hyperfiltration (log-rank, p=0.004). Participants who developed albuminuria have a significant increase in their eGFR during childhood (p=0.003) as compared to participants who have not yet progressed to albuminuria (p=0.26). For every one g/dL increase in hemoglobin, the hazard ratio for developing persistent proteinuria decreased by 0.56 (95% CI: 0.3, 1.06, p=0.07).

Conclusion:

Hyperfiltration precedes the development of persistent proteinuria in pediatric SCA patients. Intervention strategies should target lowering eGFR during early childhood.