Reversibility of structural and functional damage in a model of advanced
diabetic nephropathy.
Authors Pichaiwong W, Hudkins KL, Wietecha T, Nguyen TQ, Tachaudomdach C, Li W, Askari
B, Kobayashi T, O'Brien KD, Pippin JW, Shankland SJ, Alpers CE
Submitted By Charles Alpers on 10/29/2013
Status Published
Journal Journal of the American Society of Nephrology : JASN
Year 2013
Date Published 6/1/2013
Volume : Pages 24 : 1088 - 1102
PubMed Reference 23641056
Abstract The reversibility of diabetic nephropathy remains controversial. Here, we tested
whether replacing leptin could reverse the advanced diabetic nephropathy modeled
by the leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition
of the renin-angiotensin-aldosterone system (RAAS), resulted in near-complete
reversal of both structural (mesangial matrix expansion, mesangiolysis, basement
membrane thickening, podocyte loss) and functional (proteinuria, accumulation of
reactive oxygen species) measures of advanced diabetic nephropathy.
Immunohistochemical labeling with the podocyte markers Wilms tumor 1 and p57
identified parietal epithelial cells as a possible source of regenerating
podocytes. Thus, the leptin-deficient BTBR ob/ob mouse provides a model of
advanced but reversible diabetic nephropathy for further study. These results
also suggest that restoration of lost podocytes is possible but is not induced
by RAAS inhibition, possibly explaining the limited efficacy of RAAS inhibitors
in promoting repair of diabetic nephropathy.

Investigators with authorship
Charles AlpersUniversity of Washington
Kevin O'BrienUniversity of Washington