Browsing by Author "Gardner, D. S."

Now showing 1 - 4 of 4
  • Thumbnail Image
    ItemOpen Access
    Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.
    (Federation of American Societies for Experimental Biology (FASEB), 2014) Dunford, L. J.; Sinclair, K. D.; Kwong, W. Y.; Sturrock, C.; Clifford, B. L.; Giles, T. C.; Gardner, D. S.
  • Thumbnail Image
    ItemOpen Access
    Protein‐energy malnutrition during early gestation in sheep blunts fetal renal vascular and nephron development and compromises adult renal function.
    (Blackwell Publishing, 2011-12-15) Lloyd, L. J.; Foster, T.; Rhodes, P.; Rhind, S. M.; Gardner, D. S.
    A poor diet during pregnancy has been linked to long-term health outcomes for the baby, such as an increased risk of diseases of the heart and kidney. We show in an experimental model that recreates a poor diet during pregnancy, i.e. a diet low in protein with adequate energy, that kidney development in the baby is affected in such a way as to reduce the potential for new blood vessels to form. This results in a greater number of important, functional kidney cells spontaneously dying. Later in life, these effects in the kidney manifest as permanently reduced kidney function, especially if the baby subsequently becomes overweight as an adult. The research reinforces advice to pregnant mothers about the importance of eating a nutritionally balanced diet during pregnancy.
  • No Thumbnail Available
    ItemMetadata only
    Remote conditioning or erythropoietin before surgery primes kidneys to clear ischemia-reperfusion-damaged cells: a renoprotective mechanism?
    (American Physiological Society, 2014) Gardner, D. S.; Welham, S. J. M.; Dunford, L. J.; McCulloch, T. A.; Hodi, Z.; Sleeman, P.; O'Sullivan, S.; Devonald, M. A. J.
    Acute kidney injury is common, serious with no specific treatment. Ischemia-reperfusion is a common cause of acute kidney injury (AKI). Clinical trials suggest that preoperative erythropoietin (EPO) or remote ischemic preconditioning may have a renoprotective effect. Using a porcine model of warm ischemia-reperfusion-induced AKI (40-min bilateral cross-clamping of renal arteries, 48-h reperfusion), we examined the renoprotective efficacy of EPO (1,000 iu/kg iv.) or remote ischemic preconditioning (3 cycles, 5-min inflation/deflation to 200 mmHg of a hindlimb sphygmomanometer cuff). Ischemia-reperfusion induced significant kidney injury at 24 and 48 h (χ2, 1 degree of freedom, >10 for 6/7 histopathological features). At 2 h, a panel of biomarkers including plasma creatinine, neutrophil gelatinase-associated lipocalin, and IL-1β, and urinary albumin:creatinine could be used to predict histopathological injury. Ischemia-reperfusion increased cell proliferation and apoptosis in the renal cortex but, for pretreated groups, the apoptotic cells were predominantly intratubular rather than interstitial. At 48-h reperfusion, plasma IL-1β and the number of subcapsular cells in G2-M arrest were reduced after preoperative EPO, but not after remote ischemic preconditioning. These data suggest an intrarenal mechanism acting within cortical cells that may underpin a renoprotective function for preoperative EPO and, to a limited extent, remote ischemic preconditioning. Despite equivocal longer-term outcomes in clinical studies investigating EPO as a renoprotective agent in AKI, optimal clinical dosing and administration have not been established. Our data suggest further clinical studies on the potential renoprotective effect of EPO and remote ischemic preconditioning are justified.
  • Thumbnail Image
    ItemEmbargo
    Remote effects of acute kidney injury in a porcine model.
    (American Physiology Society, 2015-02-15) Gardner, D. S.; De Brot, S.; Dunford, L. J.; Roma, L. G.; Welham, S. J. M.; Fallman, R.; O'Sullivan, S. E.; Oh, W.; Devonald, M. A. J.
    Background: Acute Kidney Injury (AKI) is a common and serious with no specific treatment. An episode of AKI may affect organs distant to the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross-talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we test the hypothesis that early effects of AKI on distant organs is by immune cell infiltration leading to inflammatory cytokine production, extravasation and edema. Study Design: In 29 pigs exposed to either sham-surgery or renal ischemia-reperfusion (control, n=12; AKI, n=17) we assessed remote organ (liver, lung, brain) effects in the short-(from 2 to 48h reperfusion) and longer-term (5 weeks later) using immunofluorescence (for leucocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (electrolytes), blood hematology and chemistry (e.g. liver enzymes) and PCR (for inflammatory markers). Results: AKI elicited significant, short-term (~24h) increments in enzymes indicative of acute liver damage (e.g. AST:ALT ratio; P=0.02) and influenced tissue biochemistry in some remote organs (e.g. lung tissue [Ca++] increased; P=0.04). These effects largely resolved after 48h and no further histopathology, edema, apoptosis or immune cell infiltration was noted in liver, lung or hippocampus in the short- and longer-term. Conclusions: AKI has subtle biochemical effects on remote organs in the short-term including a transient increment in markers of acute liver damage. These effects resolved by 48h and no further remote organ histopathology, apoptosis, edema or immune cell infiltration was noted.