Distinct effects on long-term function of injured and contralateral kidneys following unilateral renal ischemia-reperfusion

David Basile, Ellen C. Leonard, Deoye Tonade, Jessica L. Friedrich, Shreevrat Goenka

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Salt-sensitive hypertension and chronic kidney disease (CKD) following recovery from acute kidney injury (AKI) may occur secondary to incomplete repair, or by activation of circulating factors stimulated by injury. We created two types of renal injury induced by unilateral ischemia-reperfusion (I/R); in a direct/ipsilateral AKI group, rats were subjected to unilateral I/R and the untouched contralateral kidney was removed by unilateral nephrectomy after 5 wk to isolate effects on the injured kidney. In the remote/contralateral AKI group, the injured kidney was removed after 5 wk to isolate effects on the untouched kidney. When these animals were subsequently challenged with elevated dietary sodium for an additional 4 wk (0.4 to 4%), both remote/contralateral and direct/ ipsilateral AKI rats manifested a significant increase in blood pressure relative to sham-operated controls. Similarly, in acute studies, both ipsilateral and contralateral kidneys had impaired pressure natriuresis and hemodynamic responses. Reductions in vascular density were observed following direct/ipsilateral injury, but were not observed in the remote/contralateral kidney. However, both remote/contralateral and direct/ipsilateral kidneys contained interstitial cells, some of which were identified as activated (low CD62L/CD4+) T lymphocytes. In contrast, only the direct/ipsilateral AKI group demonstrated significant CKD following exposure to elevated salt. This was characterized by a significant reduction in creatinine clearance, an increase in albuminuria, and a dramatic expansion of interstitial inflammation. Taken together, these data suggest that the salt-sensitive features of AKI on hypertension and CKD are segregable such that effects on hemodynamics and hypertension occur independent of direct renal damage. However, prior direct injury to the kidney is required to elicit the full manifestation of CKD induced by elevated sodium intake.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume302
Issue number5
DOIs
StatePublished - Mar 2012

Fingerprint

Reperfusion
Ischemia
Kidney
Acute Kidney Injury
Chronic Renal Insufficiency
Salts
Wounds and Injuries
Hypertension
Hemodynamics
Dietary Sodium
Natriuresis
Albuminuria
Nephrectomy
Blood Vessels
Creatinine
Sodium
Blood Pressure
Inflammation
T-Lymphocytes
Pressure

Keywords

  • Blood pressure
  • Hemodynamics
  • T lymphocytes

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Distinct effects on long-term function of injured and contralateral kidneys following unilateral renal ischemia-reperfusion. / Basile, David; Leonard, Ellen C.; Tonade, Deoye; Friedrich, Jessica L.; Goenka, Shreevrat.

In: American Journal of Physiology - Renal Physiology, Vol. 302, No. 5, 03.2012.

Research output: Contribution to journalArticle

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