Reduced tubular degradation of glomerular filtered plasma albumin is a common feature in acute and chronic kidney disease.

Abstract

Tubular epithelial cells take up and degrade plasma albumin filtered by the glomerulus. Tubular damage resulting in reduced albumin uptake or degradation has been suggested as one mechanism contributing to albuminuria in kidney disease. This study investigated whether tubular albumin uptake or degradation is altered in acute and chronic glomerular disease. Mouse models of acute glomerular injury (anti-GBM disease and LPS-induced albuminuria) and chronic disease (streptozotocin-induced diabetes and db/db mice) were examined. Mice were injected intravenously with Alexa-albumin plus DQ-albumin and killed 20 minutes later. Tubular uptake of albumin (Alexa-albumin) and albumin degradation (Dye Quenched (DQ)-albumin) was assessed in tissue sections via confocal microscopy. Tubular uptake of Alexa-albumin in the models of diabetic nephropathy was not different to normal mice. However, the fluorescence signal resulting from degradation of DQ-albumin was significantly reduced in db/db mice, and the ratio of degraded to intact albumin was reduced in both models. The ratio of degraded to intact albumin in tubules was also reduced in the anti-GBM model. In the LPS model, both tubular uptake and degradation of albumin were significantly reduced, with a substantial reduction in the ratio of degraded to intact albumin in tubules. LPS stimulation of cultured tubular epithelial cells inhibited albumin uptake, indicating a direct role for LPS in modifying tubular handling of albumin. In conclusion, reduced degradation of filtered albumin in the proximal tubule is a common feature of glomerular diseases. This may be a general mechanism whereby tubular dysfunction contributes to the development of albuminuria.

• Authors: Yingjie Han, Nguyen D K Ly, Greg H Tesch, Philip Poronnik, David J Nikolic-Paterson
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 45 Issue 3 Pg. 241-249 (03 2018) ISSN: 1440-1681 [Electronic] Australia
• PMID: 29124787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 John Wiley & Sons Australia, Ltd.

Chemical References

• Lipopolysaccharides
• Serum Albumin

Topics

• Acute Kidney Injury (metabolism)
• Animals
• Diabetes Mellitus, Experimental (complications)
• Diabetes Mellitus, Type 1
• Diabetes Mellitus, Type 2
• Diabetic Nephropathies (metabolism)
• Kidney Tubules (physiology)
• Lipopolysaccharides
• Mice
• Mice, Inbred NOD
• Renal Insufficiency, Chronic (metabolism)
• Serum Albumin (metabolism)