Persistent elevation of fetal hemoglobin following chemotherapy in sickle cell disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92111/1/24106_ftp.pd

Transfusional Iron Overload in Sickle Cell Anemia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72471/1/j.1749-6632.1989.tb24225.x.pd

Stability over time of hematological variables in 197 children with sickle cell anemia

One hundred ninety-seven children with sickle cell anemia were followed for 4 years at the Wayne State Comprehensive Sickle Cell Center to evaluate the stability of the hematological variables (Hb, Hct, RBC count, MCV, %HbF and %HBA 2 ) over time. The mean values of the hematological measurements taken during three separate 16-month intervals were used to represent an individual's values. The correlations of the hematological variables between intervals ranged from a low of 0.46 for %HBA 2 to a high of 0.91 for %HbF. Correlations that spanned two intervals (an average of 32 months) were of the same magnitude as those that spanned only one interval (an average of 16 months), suggesting that there was no decrease in the degree of stability of these variables as the time between measurements increased. The stability of the correlations between variables within intervals, and the stability of the coefficients of the first two principal components of the six hematological variables over time suggested that the relationships among variables were also stable. In a recent report [Odenheimer et al, 1983], we used the values of the six hematological variables collected at an individual's first visit to the sickle cell center to identify four hematologically distinct subgroups of children. In the current report, we found that as many as 83% of the individuals remained in the same subgroup in at least two of the three follow-up intervals, suggesting that the factors that contributed to this classification were the result of stable, rather than transient phenomena.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38236/1/1320180316_ftp.pd

Renal medullary carcinoma and sickle cell trait: A systematic review

Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation

Serum Cystatin-C Levels in Infants with Sickle Cell Anemia: Baseline Data from the BABY HUG Trial

Abstract Background: BABY HUG is an NHLBI/NICHD sponsored double-blind placebo-controlled trial (NCT00006400) testing the hypothesis that hydroxyurea therapy (HU), if started early in life, will prevent or postpone organ damage to the spleen and kidney in infants with sickle cell anemia (SCA). All BABY HUG subjects at entry have GFR measured by 99mTc-DTPA radioisotope clearance (DTPA) and estimated using the Schwartz formula, a calculation based on serum creatinine (Cr) and height of the patient (GFR = κ (height)/Cr); κ=0.55 for children age >1 to 13 yr or 0.45 for term infants to age 1 yr. Measurement of GFR in infants is problematic due to difficulties in obtaining urine specimens and venous access. While Cr is a well-established marker for GFR it is not independent of body mass and may be secreted by renal tubules, leading to an overestimate of GFR. Cystatin C (CysC) is a cysteine protease inhibitor produced by all human nucleated cells and freely filtered by the kidney. Serum levels are not affected by muscle mass or gender and stable from age 18 mo to 50 yr, with higher levels in newborns reflecting a lower GFR. CysC offers a more practical and perhaps more accurate measure of GFR than Cr, especially in children with SCA. Normal non-SCA values are 0.5 to 1.4 mg/L. Formulas are published to translate serum levels of CysC to GFR as conventionally reported. Our aim was to determine usual and mean CysC levels in infants with SCA and compare CysC to DTPA and Cr-based assessments of GFR. Methods: Sera obtained and frozen during the eligibility screening phase of BABY HUG were used to determine CysC levels by particle enhanced immune nephelometry. Results: A total of 152 sera from infants age 9–17 mo (mean 13.5) were available. CysC levels ranged from 0.532 to 1.369 mg/L (mean 0.92; median 0.907), approximating the normal range. CysC was strongly and inversely associated with GFR estimated by DTPA (R2=0.086; p=0.001). CysC was also significantly associated with age (inversely, p=0.02), Schwartz GFR (using κ=0.55) (inversely, p=0.007) and Cr (p=0.01), but not with Hb, HbF or WBC count. GFR determined using two CysC-based formulae and the Schwartz formula were compared to GFR by DTPA. GFR Formula GFR* R-square P-value Regression slope *(mean ± SD in ml/min/1.73m2);99mTc-DTPA GFR=123.67±33.72 ml/min/1.73 m2 GFR in non-SS infants age 1–1.5 yr by 51Cr-EDTA clearance: 91.5±17.8 ml/min/1.73 m2 (Piepsz A et al. Eur J Nucl Med Imag2006;33:1477) Schwartz, κ=0.55 191.11±57.85 0.062 0.036 0.141 Schwartz, κ=0.45 154.80 ± 54.06 0.052 0.0123 0.172 CysC (1) 84.45±19.11 0.18 0.0026 0.149 CysC (2) 102.78±25.09 0.16 0.0029 0.196 GFR determined using CysC-based formula 2: GFR = antilog {1.92 + [1.123 × log (1/CysC)]} gave mean values closest to DTPA and similar to published estimates of GFR in non-SCA infants. The Schwartz formula overestimated GFR, especially when the higher κ was used. While correlations are low due to high GFR variability, the four GFR determinations all have a significant association with DTPA. However, because the slopes of the regression lines are not close to 1 (line of equality), measurement agreement with DTPA is poor. Conclusion: The Schwartz formula overestimated GFR in BABY HUG subjects. CysC-based GFR formulae underestimate GFR compared to concurrent DTPA values, but results are similar to published norms. Reports of hyperfiltration, based on creatinine-based determination of GFR, may be exaggerated. The impact of hydroxyurea therapy on CysC levels, if any, will be apparent at completion of the trial in late 2009

Transfusional iron overload in children with sickle cell anemia on chronic transfusion therapy for secondary stroke prevention

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90419/1/22228_ftp.pd

Effect of Hydroxyurea Treatment on Renal Function Parameters: Results from the Multi-Center Placebo-Controlled BABY HUG Clinical Trial for Infants with Sickle Cell Anemia

BACKGROUND: Children with sickle cell anemia (SCA) often develop hyposthenuria and renal hyperfiltration at an early age, possibly contributing to the glomerular injury and renal insufficiency commonly seen later in life. The Phase III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA (BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction by reducing hyperfiltration. PROCEDURE: 193 infants with SCA (mean age 13.8 months) received hydroxyurea 20 mg/kg/day or placebo for 24 months. (99m)Tc diethylenetriaminepentaacetic acid (DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine osmolality after parent-supervised fluid deprivation, and renal ultrasonography were obtained at baseline and at exit to measure treatment effects on renal function. RESULTS: At exit children treated with hydroxyurea had significantly higher urine osmolality (mean 495 mOsm/kg H(2)O compared to 452 in the placebo group, p=0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500 mOsm/kg H(2)O. Moreover, children treated with hydroxyurea had smaller renal volumes (p=0.007). DTPA-derived glomerular filtration rate (GFR) was not significantly different between the two treatment groups, but was significantly higher than published norms. GFR estimated by the Chronic Kidney Disease in Children Schwartz formula was the best non-invasive method to estimate GFR in these children, as it was the closest to the DTPA-derived GFR. CONCLUSION: Treatment with hydroxyurea for 24 months did not influence GFR in young children with SCA. However, hydroxyurea was associated with better urine concentrating ability and less renal enlargement, suggesting some benefit to renal function