Date of Completion
CD13 kidney endocytosis inflammation biomarkers
Linda H. Shapiro
Field of Study
Doctor of Philosophy
Diabetes is a serious public health threat that leads to a variety of complications
including diabetic nephropathy. Initiated by elevated blood glucose levels,
glomerular and proximal tubule damage promotes progressive nephron deterioration
leading to end stage renal failure. A common indicator of impending kidney failure is
an increase in urinary albumin levels. Urinary proteins are efficiently reabsorbed via
receptor-mediated endocytosis in the epithelial cells of the renal proximal tubules by
endocytic proteins megalin and cubilin. CD13 has been previously identified as a
negative regulator of receptor-mediated endocytosis of numerous cell types. Urinary
albumin levels were significantly decreased in CD13KO animals compared to wild
type animals in models of diabetic nephropathy and albumin overload. CD13
negatively regulates receptor-mediated endocytosis of albumin in proximal tubules.
Currently, there are limited reliable biomarkers that accurately detect renal injury and
its progression. Single-pass, apically expressed proximal tubule brush border
proteins (CD10, CD13 and CD26) were easily shed into the urine predicting renal
obstruction in patients with ureteropelvic junction obstruction. Targeting reliable
noninvasive biomarkers of renal injury is critical to diagnosing patients at risk.
Gerber, Claire, "CD13 Regulation of Albuminuria in Response to Renal Injury" (2016). Doctoral Dissertations. 1139.