CD13 Regulation of Albuminuria in Response to Renal Injury

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