Predicting irreparable renal ischemic injury using a real-time marker in the porcine model.
OBJECTIVE
We determined the maximal renal tolerance of warm ischemia using renal cortical interstitial metabolic changes to identify a potential real-time marker of irreparable renal function.


METHODS
Using a single kidney model 3 groups of 5 pigs each underwent 120, 150 and 180 minutes of warm ischemia, respectively. Microdialysis samples were collected before, during and after ischemia. Renal function assessments consisting of serum creatinine and GFR measurements were performed before ischemia and on post-ischemia days 1, 5, 9, 14 and 28. Kidneys exposed and not exposed to ischemia were collected for histological study.


RESULTS
Interstitial glucose and pyruvate concentrations decreased, while lactate concentrations increased to stable levels during ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered, while glycerol increased throughout warm ischemia time. At post-ischemia day 28 renal function returned to pre-ischemia baseline levels in the group with 120 minutes of ischemia but did not recover to baseline in the 150 and 180-minute ischemic groups. Functional data correlated with histological findings. The 120-minute maximal renal tolerance of warm ischemia correlated with a mean +/- SD glycerol concentration of 167 +/- 24 micromol/l.


CONCLUSIONS
Interstitial glycerol is a real-time, renal unit specific, minimally invasive marker of renal function deterioration. Exposure of porcine kidneys to ischemic insults resulting in renal cortical interstitial glycerol concentrations higher than 167 micromol/l is associated with irreparable functional damage in this model.
Weld
Kyle J
KJ
Departments of Urology and Clinical Research, Wilford Hall Medical Center, Lackland Air Force Base, Texas 78236, USA. Kyle.weld@lackland.af.mil
Montiglio
Claudio
C
Bush
Anneke C
AC
Dixon
Patricia S
PS
Schwertner
Harvey A
HA
Hensley
Donna M
DM
Cowart
Jerry R
JR
Cespedes
R Duane
RD
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate; D005990:Glycerol / Q000378:metabolism*; D007668:Kidney / Q000473:pathology*; D007677:Kidney Function Tests; D007773:Lactates / Q000032:analysis; D009392:Nephrectomy / Q000379:methods; D011336:Probability; D011773:Pyruvates / Q000378:metabolism; D011897:Random Allocation; D015427:Reperfusion Injury / Q000473:pathology*; D012680:Sensitivity and Specificity; D013552:Swine; D052096:Warm Ischemia / Q000009:adverse effects* / Q000379:methods
D015415:Biomarkers; D001786:Blood Glucose; D007773:Lactates; D011773:Pyruvates; D005990:Glycerol