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Acute podocyte injury enhances the susceptibility to blood pressure‐induced injury in rats with underlying ¾ renal mass reduction
Author(s) -
Polichnowski Aaron James,
Picken Maria M.,
Griffin Karen A.,
Bidani Anil K.
Publication year - 2013
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.27.1_supplement.1110.20
Subject(s) - glomerulosclerosis , medicine , endocrinology , proteinuria , blood pressure , podocyte , renal function , kidney disease , kidney , urology
The mechanism by which acute podocyte loss promotes chronic kidney disease (CKD) progression remains poorly understood. We administered a single dose (75 mg/kg i.p.) of puromycin aminonucleoside (PAN, n=14) or saline (sham, n=12) to male Sprague‐Dawley rats 2 weeks after ¾ renal mass reduction via surgical excision. BP was measured continuously every 10 minutes via radiotelemetry (DSI) and 24 hour urine protein excretion was determined weekly for 4 weeks following PAN administration. Two weeks after renal mass reduction and prior to administration of PAN the average systolic BP (125±3 vs. 129±3 mmHg) and 24‐hour proteinuria (8±1 vs. 18±7 mg/day) were similar in the PAN and sham groups, respectively. By contrast, four weeks after PAN administration the average systolic BP (147±4 vs. 135±5 mmHg; p<0.05) and 24 hour proteinuria (255±16 vs 34+8 mg/day; p<0.05) were significantly increased in the PAN vs. sham rats; respectively. Consistent with these findings, glomerulosclerosis (GS, 68±6% vs. 8+3% per 100 glomeruli; p<0.05) and the slope of the relationship between the %GS and average systolic BP (y=1.1x‐87 vs. y=0.4x‐52 %GS/mmHg) was also greater in PAN vs. sham rats; respectively. These data indicate that podocyte loss in the presence of impaired preglomerular autoregulation results in enhanced glomerular susceptibility to hypertensive injury with even modest increases in BP.