The loss of podocytes from the glomerular basement membrane (GBM) represents the loss of an irreplaceable component of the glomerular filtration barrier that predisposes regions of bare GBM to form adhesions to the parietal epithelium of Bowman's capsule. These adhesions are the beginnings of synechiae, which progress to the histopathology of focal segmental glomerulosclerosis characteristic of many renal disorders culminating in chronic renal insufficiency (CRI) or end stage renal disease (ESRD). In the adult population, diabetes mellitus accounts for nearly 40% of the cases of ESRD, whereas in the pediatric population, glomerulonephritis accounts for 30% of cases of ESRD. The proposed research will quantitatively demonstrate podocyte loss into the urine utilizing a non-invasive fluorescent reverse-transcriptase quantitative polymerase chain reaction (RT-QPCR). Longitudinally collected urine samples from case patients with glomerulonephropathies and Type I diabetes mellitus will be tested after informed consent has been obtained. Fluorescent RT-QPCR is performed using an intricate series of primers and probes designed for the podocyte-specific protein nephrin. The goals of this project are to longitudinally monitor the case patients' clinical courses and laboratory tests and to correlate these with their quantitative loss of podocytes in the urine. Additionally, the project will quantify urinary podocyte loss before and after initiation of medical therapy, and seek to identify those patients who continue to lose podocytes and are at greatest risk for the development of proteinuria, CRI or ESRD.
| McBryde, Kevin D; Kershaw, David B; Bunchman, Timothy E et al. (2006) Renal replacement therapy in the treatment of confirmed or suspected inborn errors of metabolism. J Pediatr 148:770-8 |
| McBryde, Kevin D; Bunchman, Timothy E; Kudelka, Timothy L et al. (2005) Hyperosmolar solutions in continuous renal replacement therapy for hyperosmolar acute renal failure: a preliminary report. Pediatr Crit Care Med 6:220-5 |
| McBryde, Kevin D; Kudelka, Timothy L; Kershaw, David B et al. (2004) Clearance of amino acids by hemodialysis in argininosuccinate synthetase deficiency. J Pediatr 144:536-40 |
