Importance of increased ultrafiltration volume and impact on mortality: sepsis and cytokine story and the role of continuous veno-venous haemofiltration.

While in end-stage renal disease dialysis dose correlates with morbidity and mortality, this correlation is less evident in acute renal failure. In spite of a poor literature in the field, a few recent papers seem to suggest that an increase in treatment dose may result in an improved outcome of critically ill patients affected by acute renal failure. This improvement appears to plateau at a certain level of dialysis dose in the general population while, in septic patients, the correlation between treatment dose and outcome continues linearly. These results suggest that, while the 'renal dose' of renal replacement therapy has a threshold beyond which further improvements cannot be expected, the 'septic dose' of renal replacement therapy is probably higher and may provide benefits beyond simple blood purification from uremic toxins. This approach is in agreement with the recently proposed 'peak concentration hypothesis', which suggests that sepsis may derive from a complete derangement of the immunological response, featuring simultaneous peaks of pro- and anti-inflammatory mediators. This would explain the systemic inflammatory syndrome and the cell hyporesponsiveness of the septic patient and, at the same time, would explain the beneficial effects of new therapies such as high volume hemofiltration, coupled plasmafiltration adsorption and dialysis with hyperpermeable membranes. These therapies could be able to reduce the peaks of the pro- and anti-inflammatory substances circulating during the syndrome, leading to a less severe degree of inflammation and immunodepression.