Evaluation of serum and urine fetuin-A levels in children with acute lymphoblastic leukemia during and after high-dose methotrexate therapy: Relation to toxicity.
OBJECTIVE
Fetuin-A is a multifunctional protein with its urine level was considered as a marker of acute kidney injury. We investigated the serum and urine fetuin-A in acute lymphoblastic leukemia (ALL) children during and after high-dose methotrexate (HDMTX).


METHODS
Twenty-two ALL children and 20 matched healthy controls were included. Liver transaminases, serum creatinine, estimated glomular filtration rate (eGFR), creatinine clearance (CrCl), serum β2 microglobulin (B2M), and serum and urine fetuin-A levels were assayed pre and 4 months after the consolidation. Among a subgroup of 15 patients, the investigations were performed 42 hours after the start of the second and the fourth HDMTX infusions.


RESULTS
HDMTX was well tolerated. During HDMTX, there was significant decline in serum fetuin-A together with significant rise of urine fetuin-A and B2M levels compared to the control and to the pre-consolidation levels, changes that persisted 4 months after the consolidation despite recovery of the significantly altered renal functions. The second HDMTX-related serum fetuin-A level directly correlated with eGFR and CrCl (r = 0.86, P < 0.0001 and r = 0.67, P = 0.016, respectively). Four months after consolidation, urine fetuin-A directly correlated with serum creatinine (r = 0.54, P = 0.004) and inversely correlated with the eGFR (r = -0.66, P < 0.0001).


CONCLUSIONS
Significant disturbance in serum and urinary fetuin-A levels, which was related to renal functions, had occurred during HDMTX and persisted for at least 4 months after the consolidation. Serum and urine fetuin-A could be sensitive markers for subtle renal dysfunction in ALL children.
a Department of Pediatrics, Faculty of Medicine , Menoufia University , Naser Street, Shebeen El-koom Menoufia , Egypt.
Seham M
SM
Ragab
b Department of Medical Biochemistry, Faculty of Medicine , Menoufia University , Naser Street, Shebeen El-koom Menoufia , Egypt.
Eman A
EA
Badr
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000652:urine; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000652:urine; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
C556354:AHSG protein, human; D060749:alpha-2-HS-Glycoprotein; D008727:Methotrexate
Acute lymphoblastic leukemia; Fetuin-A; High-dose methotrexate; Nephrotoxicity; Renal biomarkers