Evaluation of Renal Function by Glomerular Filtration Rate (GFR) in Infants with Sickle Cell Anemia.

Abstract

Chronic anemia and intraparenchymal sickling within the kidney lead to intravascular volume expansion and an increased glomerular filtration rate (GFR) in sickle cell anemia (SCA). An elevated GFR is considered to be an early indicator of renal damage in SCA, and the pathophysiologic changes leading to sickle nephropathy and elevated GFR likely begin at a young age. The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG), an NHLBI-sponsored multi-center double-blinded placebo-controlled study, compares hydroxyurea versus placebo in infants with SCA, with the primary goal of determining the efficacy of hydroxyurea for the prevention of organ dysfunction in the spleen and kidney. In the Feasibility and Safety Pilot, a primary objective is to assess GFR in infants with SCA between the age of 12 and 18 months by measuring plasma clearance of 99m Tc-DTPA (diethylenetriaminepentaacetic acid) and by estimating GFR using the Schwartz equation. The DTPA GFR was determined following administration of an IV bolus of 25–50 μCi/kg of the radiotracer, with venous blood samples obtained at 1, 2, and 4 hours. GFR was also calculated using the Schwartz equation: 0.55 x body length (cm) ÷ plasma creatinine (mg/dL). For both measurements, a logarithmic transformation was applied to improve linearity between the variables, and to stabilize the variance of the transformed data. To date, 17 infants with SCA (median age 13.2 months) have had GFR measurements, with no complications occurring. The geometric mean of the GFR (± SD) as measured by DTPA plasma clearance was 112 ± 14.6 mL/min/1.73m2 (range 53–178 mL/min/1.73m2). By regression analysis, the GFR was correlated with age, with an increase of approximately 10% per month (univariate p = 0.006, multivariate p = 0.02), and this correlation could not be ascribed to other age-adjusted changes in hemoglobin concentration (p = 0.35), % fetal hemoglobin (HbF, p = 0.67), white blood cell (WBC) count (p = 0.64), or platelet count (p = 0.76). The estimated GFR calculated by the Schwartz equation was not significantly correlated with age (univariate p = 0.12), and adjustments using hemoglobin, %HbF, platelet or WBC counts did not improve the correlation. There was a modest correlation between GFR determined by DTPA and the Schwartz equation (r = 0.44; p = 0.08). These data indicate that (1) GFR measurement using DTPA plasma clearance is feasible in one year-old infants with SCA; (2) renal damage as measured by an elevated DTPA GFR appears to be present early in life and to be increasing with age; (3) preliminary evaluation of the use of the Schwartz formula indicates only a modest level of correlation with results obtained using DTPA measurements; and (4) in the BABY HUG trial, further evaluation of the efficacy of hydroxyurea in preservation of renal function will likely require DTPA GFR measurements rather than GFR estimates using the Schwartz equation.