Elevation of urinary alpha-1-antitrypsin and transferrin excretion in children of patients with nephrolithiasis.

Background: Children of patients with nephrolithiasis (NL) are highly susceptible to stone development. Abnormal urinary mineral excretion and elevated protein/albumin excretion rates have been reported in disease-free children of patients with NL. Increased protein excretion in these children could be associated with the risk of stone formation. Objective: Explore the urinary proteomic profiles in children with NL who are highly susceptible to stone development. The suspected urinary proteins were further validated in the urine of children with and without a family history of stone formation. Methods: Twenty-eight patients with NL (N), 40 volunteers (V), 46 children of patients with NL (NC) and 33 children of volunteer subjects (VC) were enrolled. The 24-hour urine of the participants was collected. Thirty urine samples were randomly selected from each children's group (NC and VC) to investigate proteins with abnormal excretion. Quantitative proteomic analysis was conducted using tandem mass spectrometry. The levels of bikunin (AMBP), alpha-1-antitrypsin (AAT), transferrin (TF), alpha-2-HS-glycoprotein (fetuin-A), and adiponectin levels were measured in all samples using enzyme-linked immunosorbent assay. Results: Total urinary protein excretion was increased in both N and NC. Urinary excretion rates for 26 proteins increased and 2 proteins decreased in the NC group compared to the VC group. The urinary excretion rates of AMBP, AAT, and TF in patients with NL and their children were higher than those of control and normal children while fetuin-A was increased only in the NC group. Elevation of urinary AAT and TF was dependent on urinary supersaturation. Conclusion: Children of patients with calcium oxalate had increased urinary protein excretion, including AAT, TF, AMBP, and fetuin-A, considering the consequences of abnormal urine compositions. Increased excretion of these proteins may impact stone formation in these high-risk childhood members by regulation of renal inflammation, oxidation, crystallization, and crystal growth. We propose that AAT and TF excretion rates are potentially used as indicators for urinary supersaturation in high-risk populations.