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Delayed Onset of Proteinuria by Selected Renal Cells in a Canine Model of Early Stage CKD
Author(s) -
Guthrie Kelly Isley,
Brands Michael,
Rivera Elias,
Genheimer Christopher,
Sangha Namrata,
Bravo Mike,
Jayo Manuel,
Jain Deepak,
Bertram Timothy A.,
Ludlow John W.,
Presnell Sharon,
Kelley Rusty
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1121.4
Subject(s) - nephron , proteinuria , renal function , urology , medicine , nephrectomy , kidney disease , stage (stratigraphy) , endocrinology , kidney , biology , paleontology
Surgical reduction of kidney mass (RKM) models have been used to study cardiovascular ramifications of early CKD, however long‐term features of the model have not been well defined. This study characterized a canine RKM model and its use in evaluating efficacy of autologous selected renal cells (SRC) through one‐year post‐nephrectomy by monitoring renal specific, whole animal, and terminal histological parameters. SRC preserve tubular and glomerular functions in rodent nephrectomy models. Dogs underwent 2‐step nephrectomy (RKM) and hemi‐nephrectomized dogs served as controls. Using International Renal Interest Society guidelines, 15 weeks post‐nephrectomy RKM dogs were in late Stage I/early Stage II CKD as defined by sCre (1.6), systolic BP (144–157) and mild proteinuria (UPC 0.2). SRC were then delivered to 4 RKM dogs. All animals demonstrated improving sCre values indicating sufficient nephron mass remained for increased singlular nephron GFR to compensate for RKM and maintain eGFR, thus limiting the sensitivity in detecting filtration related treatment effects. SRC therapy significantly reduced proteinuria and evidence of interstitial tubular disease and juxtamedullary glomerular degeneration. Analysis of urine proteins supports the presence of specific treatment benefit to the tubulointerstitial renal compartment. Since proteinuria is considered to be an early indicator of and a contributor to progression of human and canine CKD, this model may provide a useful approach to evaluate potential therapeutics for CKD and supports continued effort toward developing regenerative medicine products containing SRC.