Mass Spectrometry of Urine Proteins for Early Detection of Renal Complications in Sickle Cell Disease

PURPOSE: Sickle cell disease (SCD) is an autosomal recessive genetic disorder caused by a single G6V mutation in the β-globin gene. SCD patients have various complications including chronic renal failure and nephrotic syndrome which can develop in 30-50% of sickle cell patients. Currently there are no reliable methods to identify the risk for renal complications in the early stages for the subset of people who will develop renal failure. It is essential that new noninvasive prognostic biomarkers be discovered to help assess patients for risk of renal failure which may lead to early intentions and greater survival rates among SCD patients.

METHODS: Urine samples were collected from 25SCD patients and 6 healthy controls. Trypsin digests of urine proteins were analyzed by nano LC coupled in-line to LTQ Orbitrap XL tandem mass spectrometer. Proteins identified with Proteome Discoverer software were further quantified using SIEVE 2.1 (Thermo).

RESULTS: About 80 proteins were detected in urine. Among those, about 10 proteins were found at higher levels in SCD patients, including seruloplasmin, transferring and alpha-1-acid glycoprotein precursor.

CONCLUSION: Several of the detected proteins may cause early changes in glomerular permeability and be a potential biomarker for early renal manifestations in SCD. Further studies are needed to form a more conclusive relationship between renal complications and the proteins present in urine of SCD patients.

SUPPORT: NIH Research Grants 8G12MD007597 and P50HL118006-01.