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 cell ular integrity; therefore, we tested the hypothesis that early changes in renal metabolism contribute to the development of acute renal fail ure 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 fo urth group (n = 8) served as control. In the biopsies, glucose, lactat e, ATP, ADP, AMP and creatine phosphate concentrations were determined . Renal plasma flow (RPF) and glomerular filtration rate (GFR) were me asured from the clearances of I-131-hippurate and I-125-thalamate, res pectively. We also assayed urine flow (V; catheter in the bladder), ca rdiac output (CO), blood pressure (MAP), heart rate (HR) and arterial lactate, glucose and creatinine concentrations. During the first 30 mi n of endotoxemia, we found no systemic hemodynamic or biochemical chan ges. From t = 30 to t = 90, CO and MAP decreased to 59 and 70%, respec tively, while HR and serum levels rose to 110 and 800%, respectively ( p < 0.05), indicating progression of shock. Renal function clearly det eriorated from t = 30: at t = 90 RPF, GFR and V had decreased by 86, 8 4 and 86%, respectively, plasma creatinine being 193% of the baseline value (p < 0.05). In the t = 30 biopsies, the only change was an incre ase in glucose concentration (by 21% vs. control value; p < 0.05), whi ch peaked at t = 50 (by 63%; p < 0.05), and was still elevated at t = 90 (by 43%; p < 0.05). The rise in renal lactate concentration paralle led that in serum lactate. There were, however, no differences in ener gy-rich phosphates between the four groups. Thus, our results show tha t endotoxemia causes early changes in RPF, GFR, V and renal glucose me tabolism, but no early decrease in energy status.