VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury

Ellen C. Leonard, Jessica L. Friedrich, David P. Basile

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

Acute kidney injury induced by renal ischemia-reperfusion (I/R) compromises microvascular density and predisposes to chronic kidney disease (CKD) and sodium-dependent hypertension. VEGF-121 was administered to rats fed a standard (0.4%) sodium diet at various times following recovery from I/R injury for up to 35 days. VEGF-121 had no effect on the initial loss of renal function, as indicated by serum creatinine levels measured 24 h after injury. Serum creatinine levels declined thereafter, indicative of renal repair. Rats were then switched to an elevated (4.0%) sodium diet for an additional 28 days to induce CKD. The 4.0% sodium diet enhanced renal hypertrophy, interstitial volume, albuminuria, and cardiac hypertrophy relative to postischemic animals maintained on the 0.4% sodium diet. Administration of VEGF-121 from day 0 to 14, day 0 to 35, or day 3 to 35 after I/R suppressed the effects of sodium diet on CKD development, while delayed administration of VEGF-121 from day 21 to 35 had no effect. Endothelial nitric oxide synthase protein levels were upregulated in postischemic animals, and this effect was significantly increased by the 4.0% sodium diet but was not influenced by prior treatment with VEGF. Conversely, microvascular density was preserved in postischemic animals treated with VEGF-121 relative to vehicle-treated postischemic animals. These data suggest that early, but not delayed, treatment with VEGF-121 can preserve vascular structure after ischemia and influence chronic renal function in response to elevated sodium intake.

Original languageEnglish (US)
Pages (from-to)F1648-F1657
JournalAmerican Journal of Physiology - Renal Physiology
Volume295
Issue number6
DOIs
StatePublished - Dec 1 2008

Keywords

  • Interstitial fibrosis
  • Ischemia
  • Peritubular capillaries
  • Salt sensitivity

ASJC Scopus subject areas

  • Physiology
  • Urology

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