Albumin contributes to kidney disease progression in alport syndrome

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Abstract

Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb–/–) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb+/– mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3–/–) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3–/–;Alb–/– mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3–/–;Alb+/+ and Col4a3–/–;Alb+/– mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy.

Original languageEnglish
Pages (from-to)F120-F130
JournalAmerican Journal of Physiology - Renal Physiology
Volume311
Issue number1
DOIs
StatePublished - Jul 1 2016

Keywords

  • Albumin
  • Alport syndrome
  • Collagen type IV

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