Date of Completion

7-22-2016

Embargo Period

7-18-2021

Keywords

CD13 kidney endocytosis inflammation biomarkers

Major Advisor

Linda H. Shapiro

Associate Advisor

Kevin Claffey

Associate Advisor

Guo-Hua Fong

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

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.

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