The Nephrology and Hypertension Division at Cincinnati Children’s Hospital Medical Center conducts research to enhance our knowledge to improve the lives of our patients.
Profiling Genes Involved in the Pathogenesis of FSGS
Prasad Devarajan, MD, director of the Division of Nephrology and Hypertension, and S. Steven Potter, PhD, were awarded a grant from the NIH to profile the genes that may be involved in the pathogenesis of focal segmental glomerulosclerosis (FSGS) in both animal models as well as in human kidney biopsies. It is hoped that this unbiased high-throughput approach will lead to the discovery of novel genes and proteins involved in the pathogenesis of FSGS, identify early biomarkers for prediction of disease progression and yield new therapeutic targets.
Using Proteomics to Study Plasma Protein Differences
Devarajan and Megan Lo, a clinical fellow, have initiated a pilot study using proteomics to study plasma protein differences in FSGS transplant patients in an effort to determine who will recur after transplant and who will not. The goal is to establish markers to guide intervention or find causative proteins that can be modified for improved outcomes.
Identifying a Protein Signature
Michael Bennett, PhD, and Devarajan have employed high-throughput urinary proteomic profiling to identify a protein signature that is unique to children with FSGS when compared to minimal change disease and other proteinuric states. They have specifically identified NGAL and alpha-1B-glycoprotein to be markedly overexpressed in FSGS urines, where these markers appear to predict the severity of FSGS as well as response to therapy.
Using Laser-Capture Microarray and Next Generation Sequencing
Kimberly A. Czech, PhD, MD, S. Steven Potter, PhD, and Eric Brunskill, PhD, are looking at molecular pathogenesis of FSGS in glomeruli and the tubulointerstitial compartment using laser-capture microarray and next generation sequencing techniques. One current aim of our group is to develop a technique to look at gene expression patterns in a single glomerulus, and possibly a single cell, to focus in on the molecular pathways involved with disease progression. Based on previous microarray experiments, Czech has initiated a study looking at urine proteins (by ELISA) to determine urinary biomarkers of tissue-remodeling and chronic kidney disease progression in FSGS patients so that we can more accurately titrate treatment therapies to slow the process leading to end-stage kidney disease.
Epidemiological Study: Accurately Determining and Characterizing Trends
In the clinical arena, Elizabeth Abraham, MD, and Jens Goebel, MD, have begun an epidemiologic study to more accurately determine and characterize trends in the incidence and post-transplant recurrence rate of FSGS nationally, and access to two multicenter studies evaluating novel treatment strategies is being made available with Goebel as center principal investigator (PI) at Cincinnati Children’s:
- Tacrolimus and Plasmapheresis in Treatment-Resistant FSGS (Study PI: Tej Mattoo, MD, DCH, FRCP, FAAP, Children’s Hospital of Michigan)
- FONT II (Novel Therapies for Resistant FSGS, study PI: Howard Trachtman, MD, Schneider Children’s Hospital, New York)