HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/5/F1136    most recent 00541.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kramer, A. B. Articles by Navis, G. Search for Related Content PubMed PubMed Citation Articles by Kramer, A. B. Articles by Navis, G.

Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time

Departments of ¹Pathology and Laboratory Medicine, ²Nephrology, and ³Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and ⁴Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Submitted 15 November 2007 ; accepted in final form 11 February 2009

Tubulointerstitial lesions are important in the progression of proteinuric renal disease. Tubular kidney injury molecule-1 (Kim-1) is induced in acute renal injury and reversible as a natural course. Kim-1 is also present in chronic renal damage; however, the dynamics of Kim-1 in chronic renal damage and effects of antiproteinuric treatment on Kim-1 are unknown. We studied Kim-1 in adriamycin nephrosis (AN) before and after renin-angiotensin system blockade. A renal biopsy was taken 6 wk after adriamycin injection to study renal damage and Kim-1 expression. Subsequently, ACE inhibition (ACEi; n = 23), angiotensin II antagonist (AT_1A; n = 23), or vehicle (n = 10) was given for 6 wk; healthy rats served as controls (CON; n = 8). In AN, renal Kim-1 mRNA was induced 26-fold vs. CON at week 6, with further increase in vehicle to week 12 (40-fold) but was reduced by ACEi and AT_1A to 10- and 12-fold vs. CON (P < 0.05 vs. week 6). Kim-1 protein was undetectable in CON; in AN, it was present in brush border of dilated tubules in areas with adjacent interstitial lesions. Renal Kim-1 protein levels increased from weeks 6–12 in vehicle and decreased in ACEi- and AT_1A-treated groups (P < 0.05). In vehicle, urinary Kim-1 was increased (P < 0.05 vs. CON), with a reduction by ACEi and AT_1A (P < 0.05 vs. vehicle). Renal and urinary Kim-1 correlated with proteinuria and interstitial damage cross-sectionally. Reductions in proteinuria and renal Kim-1 correlated, which was not associated by corresponding changes in tubulointerstitial fibrosis. In conclusion, on longitudinal follow-up during antiproteinuric treatment increased renal Kim-1 expression is reversible in proportion to proteinuria reduction, likely reflecting reversibility of early tubular injury, supporting its potential as a biomarker for tubulointerstitial processes of damage and repair.

ACE inhibitors; chronic kidney disease; fibrosis; proximal tubule; proteinuria