title: Biomarkers for early detection of sickle nephropathy.
abstract: Renal complications affect nearly 30-50% of adults with sickle cell anemia (SCA), causing significant morbidity and mortality. Standard renal function tests like serum creatinine and glomerular filtration rate become abnormal in this disease only when renal damage has become extensive and largely irreversible. Moreover, not all patients develop sickle nephropathy (SN). Therefore, noninvasive biomarkers that predict early onset of SN are necessary. We performed a cross-sectional analysis for nephropathy in 116 patients with sickle cell disease, analyzing urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and transforming growth factor-β1 (TGF-β), together with conventional renal biomarkers (urine albumin and osmolality, and serum creatinine and cystatin C estimated GFR) during routine clinic visits when patients were at steady-state/baseline. We observed a distinct biomarker pattern: KIM-1 and NAG emerged as biomarkers with a strong association with albuminuria. Surprisingly, and in contrast to other acute/chronic renal disorders, NGAL, L-FABP, and TGF-β levels did not show any relationship with albuminuria in patients with SCA. Our study identifies potential biomarkers for SN, and suggests longitudinal validation of these biomarkers for early detection of SN, so that therapeutic interventions can be applied before renal damage becomes irreversible.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, University of Cincinnati, Ohio, USA.
authors.forename: Nambirajan
authors.initials: N
authors.lastname: Sundaram
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Jamie
authors.initials: J
authors.lastname: Wilhelm
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: George
authors.initials: G
authors.lastname: Atweh
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Punam
authors.initials: P
authors.lastname: Malik
mesh_terms: D000118:Acetylglucosaminidase / Q000097:blood / Q000652:urine; D000209:Acute-Phase Proteins / Q000652:urine; D000293:Adolescent; D000419:Albuminuria / Q000097:blood / Q000652:urine; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood / Q000652:urine; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood / Q000652:urine; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000209:etiology / Q000652:urine*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000652:urine; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000652:urine; D011991:Receptors, Virus / Q000097:blood
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D003404:Creatinine; D000118:Acetylglucosaminidase