Abstract
Background
Focal segmental glomerulosclerosis (FSGS) accounts for the majority of new-onset end-stage renal disease (ESRD) during adolescence. FSGS treatment is a great challenge for pediatric nephrologists due to intertwined molecular pathways underlining its complex pathophysiology. There is emerging evidence showing that perturbed lipid metabolism plays a role in the pathophysiology of FSGS.
Methods
We postulate that the nephrotic milieu in FSGS differs from minimal change disease (MCD) and that urinary lipidomics can be used as a tool for early diagnosis of FSGS. We explored the urinary lipid profile of patients with FSGS and MCD using an unbiased metabolomics approach.
Results
We discovered a unique lipid signature characterized by increased concentration of fatty acid (FA) and lysophosphatidylcholines (LPC) and a decrease in urinary concentration of phosphatidylcholine (PC) in patients with FSGS. These findings indicate increased metabolism of membrane phospholipid PC by phospholipase A2 (PLA2), resulting in higher urinary concentrations of LPC and FA.
Conclusions
We propose that increased PC by-products can be used as a biomarker to diagnose FSGS and shed light on the mechanism of tubular and podocyte damage. Validation of identified urinary lipids as a biomarker in predicting the diagnosis and progression of FSGS in a larger patient population is warranted.
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Acknowledgments
We thank Sam Coffey for his technical assistance.
This work was supported by a pilot and feasibility grant (EE) from the NIH (P50 DK096418).
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This study protocol was approved by Cincinnati Children’s Hospital IRB Committee and all human studies were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Signed consent to provide urine for participation in this study was obtained from the parents of the patients and study subjects when appropriate.
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The authors declare there is no conflict of interest.
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Erkan, E., Zhao, X., Setchell, K. et al. Distinct urinary lipid profile in children with focal segmental glomerulosclerosis. Pediatr Nephrol 31, 581–588 (2016). https://doi.org/10.1007/s00467-015-3239-7
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DOI: https://doi.org/10.1007/s00467-015-3239-7