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

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

Research output: Contribution to journalArticle

90 Citations (Scopus)

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
JournalAmerican Journal of Physiology - Renal Physiology
Volume295
Issue number6
DOIs
StatePublished - Dec 2008

Fingerprint

Microvessels
Acute Kidney Injury
Vascular Endothelial Growth Factor A
Sodium
Kidney
Diet
Chronic Renal Insufficiency
Ischemia
Reperfusion
Creatinine
Albuminuria
Nitric Oxide Synthase Type III
Cardiomegaly
Reperfusion Injury
Serum
Hypertrophy
Blood Vessels
Hypertension
Wounds and Injuries

Keywords

  • Interstitial fibrosis
  • Ischemia
  • Peritubular capillaries
  • Salt sensitivity

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury. / Leonard, Ellen C.; Friedrich, Jessica L.; Basile, David.

In: American Journal of Physiology - Renal Physiology, Vol. 295, No. 6, 12.2008.

Research output: Contribution to journalArticle

@article{271dbe01526a424297424499134b29b6,
title = "VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury",
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.",
keywords = "Interstitial fibrosis, Ischemia, Peritubular capillaries, Salt sensitivity",
author = "Leonard, {Ellen C.} and Friedrich, {Jessica L.} and David Basile",
year = "2008",
month = "12",
doi = "10.1152/ajprenal.00099.2008",
language = "English",
volume = "295",
journal = "American Journal of Physiology - Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - VEGF-121 preserves renal microvessel structure and ameliorates secondary renal disease following acute kidney injury

AU - Leonard, Ellen C.

AU - Friedrich, Jessica L.

AU - Basile, David

PY - 2008/12

Y1 - 2008/12

N2 - 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.

AB - 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.

KW - Interstitial fibrosis

KW - Ischemia

KW - Peritubular capillaries

KW - Salt sensitivity

UR - http://www.scopus.com/inward/record.url?scp=57349093841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57349093841&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00099.2008

DO - 10.1152/ajprenal.00099.2008

M3 - Article

VL - 295

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1931-857X

IS - 6

ER -