Development of renal failure in endotoxemic rats: can it be explained by early changes in renal energy metabolism?
Endotoxin shock not only causes renal failure, endotoxemia also leads to metabolic impairment, resulting in energy shortage and loss of cellular integrity; therefore, we tested the hypothesis that early changes in renal metabolism contribute to the development of acute renal failure during endotoxin shock. Endotoxin (Escherichia coli 127B8; 8 mg/kg from t = 0 to 60 min) was infused in three groups of 8 rats, in which renal biopsies were taken at t = 30, 50 and 90 min, respectively; a fourth group (n = 8) served as control. In the biopsies, glucose, lactate, ATP, ADP, AMP and creatine phosphate concentrations were determined. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured from the clearances of 131I-hippurate and 125I-thalamate, respectively. We also assayed urine flow (V; catheter in the bladder), cardiac output (CO), blood pressure (MAP), heart rate (HR) and arterial lactate, glucose and creatinine concentrations. During the first 30 min of endotoxemia, we found no systemic hemodynamic or biochemical changes. From t = 30 to t = 90, CO and MAP decreased to 59 and 70%, respectively, while HR and serum levels rose to 110 and 800%, respectively (p < 0.05), indicating progression of shock. Renal function clearly deteriorated from t = 30; at t = 90 RPF, GFR and V had decreased by 86, 84 and 86%, respectively, plasma creatinine being 193% of the baseline value (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
van Lambalgen
A A
AA
Laboratory for Physiology, Free University, Amsterdam, The Netherlands.
van Kraats
A A
AA
van den Bos
G C
GC
Teerlink
T
T
Stel
H V
HV
Donker
A J
AJ
Thijs
L G
LG
D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D050260:Carbohydrate Metabolism; D004731:Endotoxins / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000150:complications / Q000378:metabolism; D014115:Toxemia / Q000150:complications* / Q000378:metabolism
D004731:Endotoxins; D000255:Adenosine Triphosphate