Urinary transforming growth factor beta-1 as a marker of renal dysfunction in sickle cell disease.
Renal dysfunction affects 5-18% of patients with sickle cell disease (SCD). To date, no studies have described urinary levels of transforming growth factor β-1 (TGF-β1), a marker of fibrosis, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute/chronic kidney disease, as biomarkers in identifying patients at risk of developing renal disease in SCD. We hypothesized that SCD subjects will have increased urinary excretion of TGF-β1 and NGAL compared with healthy controls (CTR). We examined 51 SCD subjects: 42 HbSS, 8 HbSC, and 1 HbSD. Sixteen out of 42 patients with HbSS were on hydroxyurea (HU). Urinary excretion of TGF-β1 was 26.4 ± 1.5 pg/mgCr in SCD subjects vs 15.0 ± 2.4 pg/mgCr in CTR (p<0.00001). SCD patients with hemoglobin < 9 g/dl had higher urinary TGF-β1 than patients with milder anemia (p=0.002). Urinary TGF-β1 trended lower in HbSS patients treated with HU (23.61 ± 2.6 pg/mgCr), vs patients not on HU (27.69 ± 1.8 pg/mgCr; p=0.055). There was no correlation between urinary TGF-β1 and microalbuminuria or estimated glomerular function. There was no difference in urinary NGAL in SCD patients vs CTR. We suggest that urinary TGF-β1 may serve as a marker of early renal injury in SCD.
Department of Pediatric Nephrology, Albert Einstein College of Medicine, Children's Hospital at Montefiore, 111 East 210th Street, Bronx, NY 10467, USA.
Davoud
D
Mohtat
Rosemary
R
Thomas
Zangfang
Z
Du
Yaa
Y
Boakye
Thomas
T
Moulton
Catherine
C
Driscoll
Robert
R
Woroniecki
D000209:Acute-Phase Proteins / Q000652:urine*; D000293:Adolescent; D000367:Age Factors; D000419:Albuminuria / Q000378:metabolism; D000755:Anemia, Sickle Cell / Q000150:complications*; D015415:Biomarkers / Q000652:urine; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis* / Q000209:etiology / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000652:urine*; D016212:Transforming Growth Factor beta / Q000652:urine*; D055815:Young Adult
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta