Advances in proteomic profiling of pediatric kidney diseases

Abstract

Chronic kidney disease (CKD) can progress to kidney failure and require dialysis or transplantation, while early diagnosis can alter the course of disease and lead to better outcomes in both pediatric and adult patients. Significant CKD comorbidities include the manifestation of cardiovascular disease, heart failure, coronary disease, and hypertension. The pathogenesis of chronic kidney diseases can present as subtle and especially difficult to distinguish between different glomerular pathologies. Early detection of adult and pediatric CKD and detailed mechanistic understanding of the kidney damage can be helpful in delaying or curtailing disease progression via precise intervention toward diagnosis and prognosis. Clinically, serum creatinine and albumin levels can be indicative of CKD, but often are a lagging indicator only significantly affected once kidney function has severely diminished. The evolution of proteomics and mass spectrometry technologies has begun to provide a powerful research tool in defining these mechanisms and identifying novel biomarkers of CKD. Many of the same challenges and advances in proteomics apply to adult and pediatric patient populations. Additionally, proteomic analysis of adult CKD patients can be transferred directly toward advancing our knowledge of pediatric CKD as well. In this review, we highlight applications of proteomics that have yielded such biomarkers as PLA2R, SEMA3B, and other markers of membranous nephropathy as well as KIM-1, MCP-1, and NGAL in lupus nephritis among other potential diagnostic and prognostic markers. The potential for improving the clinical toolkit toward better treatment of pediatric kidney diseases is significantly aided by current and future development of proteomic applications.

Keywords: Biomarker; Chronic kidney disease; Mass spectrometry; Pediatric glomerular disease; Proteomics.

Figure 1. Biomarker study design

Candidate biomarker discovery is performed by shotgun proteomics implementing a resolving or separation technique such as gel electrophoresis (2-dimensional differential gel electrophoresis; 2D-DIGE), LC-MS/MS directly into the mass spectrometry platform. Candidate verification can be performed in a different focused absolute quantitative platform such as selected-reaction monitoring or parallel reaction monitoring into a triple-quadrupole mass spectrometer to follow specific signature ions/peptides from known candidates in an independent sample set. Ideally, validation of candidate biomarkers can be performed using specific biochemical assays such as western blot, ELISA or bead-based ligand-antibody assays such as Luminex.