Glomerular hyperfiltration and albuminuria in children with sickle cell anemia

Abstract

Early manifestations of sickle nephropathy include glomerular hyperfiltration and proteinuria, typically microalbuminuria. Over time, a subset of patients develops histologic changes, decreased glomerular filtration, and ultimately renal failure. This study was designed to determine the rate of glomerular hyperfiltration and prevalence of albuminuria in a cross-sectional analysis of untreated children with sickle cell anemia (SCA), and to identify correlates of both complications. Measured glomerular filtration rate (GFR) by plasma clearance of 99-technetium diethylenetriaminepentaacetate was compared to GFR estimates calculated from published formulas. Eighty-five children (mean age 9.4 ± 4.8 years) were studied; 76% had glomerular hyperfiltration with mean GFR = 154 ± 37 ml/min/1.73 m(2). GFR declined in teenage years and was significantly correlated with increased serum cystatin C levels and higher systolic blood pressure. Measured GFR had only modest correlations with GFR estimates (Pearson correlation coefficients ≤0.5). Albuminuria, usually microalbuminuria, occurred in 15.9% and was associated with higher diastolic blood pressure and lower white blood cell and absolute neutrophil counts. Cystatin C levels inversely reflect GFR changes and are associated with albuminuria; serial monitoring may provide a sensitive and accurate marker of nephropathy in children with SCA.

Figure 1

Glomerular filtration rate by age group. The measured DTPA GFR values are illustrated in standard box and whisker plots. Boxplots display the minimum, first quartile, median, third quartile, and maximum for each age group. Group means are marked with a cross and connected with a line. The number of patients in each age group is shown in parentheses.

Figure 2

Measured DTPA GFR values versus estimated GFR using the original Schwartz formula (a), modified Schwartz formula (b),and two cystatin C based formulas GFR = −4.32 + (80.35 / cystatin C) (c), and GFR = anti log {1.962 + [1.123*log (1/cystatin C)]} (d).

Figure 3

Measured DTPA GFR values versus serum cystatin C levels (r = −0.40, p = 0.0002).