Effects of continuous hemofiltration on organ perfusion, energy metabolism, oxidative stress, endothelial dysfunction and inflammation

Introduction

Continuous renal replacement therapies (CRRT) are widely used for treatment of acute kidney injury in critically ill patients. Little attention has been paid to the potential adverse effects of CRRT related to extracorporeal circuit bioincompatibility. Limited available evidence suggests that intermittent dialysis may compromise hepatosplanchnic perfusion in acute renal failure patients. By contrast, there are no data on the bio(in)compatibility indices in patients treated by CRRT. To investigate this issue, we utilized a long-term porcine model allowing a broad insight into organ hemodynamic, microvascular, metabolic and other pathways not accessible in human medicine.

Methods

Measurements were performed in 11 healthy instrumented animals. After baseline measurements, animals were randomized to receive either no treatment (n = 6) or continuous venovenous hemofiltration with a polysuphon membrane (CVVH, n = 5). Further data were collected at 6 and 10 hours after the randomization. During each time point the following data related to (1) organ perfusion (hepatosplanchnic and renal blood flows), (2) microcirculation (ileal mucosal and renal cortex laser Doppler flowmetry and sidestream darkfield imaging), (3) energy balance (arterial and regional pH, lactate/pyruvate and ketone body ratios), (4) oxidative/nitrosative stress (thiobarbituric acid reactive species, nitrates + nitrites), (5) inflammation (TNFα, IL-6) and (6) endothelial dysfunction (von Willebrand factor, asymmetric dimethylarginine) were collected.

Results

Hemofiltration affected neither regional organ blood flows nor ileal mucosal and renal cortex microvascular perfusion. No changes in liver and kidney oxygen exchange and energy balance were detected during the 10-hour treatment. Similarly, CVVH did not interfere with surrogate markers of inflammation, oxidative/nitrosative stress and endothelial dysfunction.

Conclusion

In our model CVVH utilizing a modern biocompatible polysulphon membrane did not induce any significant deleterious effects in various biological systems. The importance of our findings lies in the fact that any changes in the studied parameters, if observed in future studies, cannot be attributed to the effects of putative extracorporeal circuit bioincompatibility. Finally, our data support the postulated concept of good biological tolerance of CRRT.