Development of Renal Failure in Endotoxemic Rats: Can It Be Explained by Early Changes in Renal Energy Metabolism?

Abstract

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 coli127B8; 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). In the t = 30 biopsies, the only change was an increase in glucose concentration (by 21% vs. control value; p < 0.05), which 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 paralleled that in serum lactate. There were, however, no differences in energy-rich phosphates between the four groups. Thus, our results show that endotoxemia causes early changes in RPF, GFR, V and renal glucose metabolism, but no early decrease in energy status.

Renal Vascular Resistance in Sepsis

“…In addition, to take renal venous pressure or CVP into account, we assessed 22 of the above-mentioned animal studies [22, 31, 33, 41, 45, 47, 48, 61, 73, 74, 85, 95, 103, 105, 111, 124, 125, 126, 135, 136, 138, 139] which measured and reported the CVP and calculated the RVR with CVP and without. There was no difference in the grouping of these studies into decreased, unchanged and increased RVR, when the CVP value was added to the formula used to calculate the RVR.…”

“…We found 56 experiments performed in small animals [20, 24, 26, 27, 39, 42, 43, 44, 55, 57, 58, 59, 62, 63, 64, 67, 68, 72, 77, 79, 81, 82, 87, 88, 89, 90, 93, 94, 96, 97, 99, 100, 103, 104, 105, 110, 116, 120, 121, 122, 129, 132, 133, 134, 137, 138, 139, 141, 142, 143, 147, 148, 149, 150, 151] and 81 performed in large animals [21, 22, 23, 25, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 56, 60, 61, 65, 66, 69, 70, 71, 73, 74, ...…”

“…Of 59 studies using other methods [20, 29, 30, 33, 34, 36, 37, 38, 39, 40, 43, 44, 46, 47, 48, 55, 57, 59, 61, 64, 67, 68, 70, 76, 77, 79, 82, 84, 87, 88, 93, 94, 96, 97, 98, 101, 103, 104, 105, 107, 116, 120, 122, 123, 125, 129, 130, 132, 133, 134, 136, 137, 138, 139, 147, 148, 149, 150, 151], 16 (27.1%) reported a decreased RVR, 5 (8.5%) an unchanged RVR, and 38 (64.4%) an increased RVR (fig. 3; p =0.017).…”

“…Of 108 experiments performed in unconscious animals [21, 22, 23, 24, 25, 26, 27, 28, 37, 38, 39, 40, 41, 42, 43, 45, 49, 50, 52, 56, 57, 58, 59, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 88, 89, 90, 91, 93, 94, 95, 99, 100, 102, 103, 104, 105, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, …”

“…Among 39 ‘short’ experiments [25, 39, 40, 46, 52, 55, 57, 64, 69, 70, 72, 76, 78, 81, 88, 90, 94, 95, 101, 103, 104, 105, 107, 108, 112, 115, 125, 129, 130, 132, 133, 135, 136, 138, 140, 145, 146, 148,] 14 (35.9%) showed a decreased RVR, 4 (10.3%) no change in RVR, and 21 (53.8%) an increase in RVR. Among the 98 ‘long’ observation time studies [20, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 41, 42, 43, 44, 45, 47, 48, 49, 50, 51, 53, 54, 58, 59, 60, 61, 62, 63, 65, 66, 67, 68, 71, 73, 74, 75, 77, 79, 80, 82, 83, 84, 85, 86, …”