Severe renal mass reduction impairs recovery and promotes fibrosis after AKI

Aaron J. Polichnowski, Rongpei Lan, Hui Geng, Karen A. Griffin, Manjeri A. Venkatachalam, Anil K. Bidani

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Preexisting CKD may affect the severity of and/or recovery from AKI. We assessed the impact of prior graded normotensive renal mass reduction on ischemia-reperfusion-induced AKI. Rats underwent 40 minutes of ischemia 2 weeks after right uninephrectomy and surgical excision of both poles of the left kidney (75% reduction of renal mass), right uninephrectomy (50% reduction of renal mass), or sham reduction of renal mass. The severity of AKI was comparable among groups, which was reflected by similarly increased serumcreatinine (SCr; approximately 4.5mg/dl) at 2 days, tubule necrosis at 3 days, and vimentinexpressing regenerating tubules at 7 days postischemia-reperfusion. However, SCr remained elevated compared with preischemia-reperfusion values, and more tubules failed to differentiate during late recovery 4 weeks after ischemia-reperfusion in rats with 75% renal mass reduction relative to other groups. Tubules that failed to differentiate continued to produce vimentin, exhibited vicarious proliferative signaling, and expressed less vascular endothelial growth factor but more profibrotic peptides. The disproportionate failure of regenerating tubules to redifferentiate in rats with 75% renal mass reduction associated with more severe capillary rarefaction and greater tubulointerstitial fibrosis. Furthermore, initially normotensive rats with 75% renal mass reduction developed hypertension and proteinuria, 2-4 weeks postischemia-reperfusion. In summary, severe (>50%) renal mass reduction disproportionately compromised tubule repair, diminished capillary density, and promoted fibrosis with hypertension after ischemia-reperfusion-induced AKI in rats, suggesting that accelerated declines of renal function may occur after AKI in patients with preexisting CKD.

Original languageEnglish (US)
Pages (from-to)1496-1507
Number of pages12
JournalJournal of the American Society of Nephrology
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2014

ASJC Scopus subject areas

  • Nephrology

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