Impact of Renal Replacement Therapy on Metabolism and Nutrient Requirements in the Critically Ill Patient

Metabolic Effects of Hemodialysis Modalities

All iRRTs obviously are not specific types of therapy that eliminate uremic toxins only from the bloodstream, but also all other substances that are water soluble and have a low molecular weight ( Box 73.1 ). Thus iRRT modalities are associated with relevant losses of various nutrients and electrolytes.

Amino acids with a mean molecular weight of about 145 D are eliminated effectively during hemodialysis (HD). Amino acid loss is affected by the type of membrane used, the treatment modality (HD vs. hemodiafiltration [HDF]), and blood flow. However, a general rule is to assume a loss of about 2 g/hr of treatment, which may be increased by about 30% with the use of modern high-flux membranes. Furthermore, the loss of about 4 g amino acids, which is associated with the elimination of small peptides must be added. During SLED an amino acid loss of about 1 g/hr of treatment has been reported.

Depending on the transmembrane pressure and the use of membranes with higher molecular cutoffs (and especially with “super-flux” membranes), a relevant elimination of albumin can occur. Filter clotting and the obligatory residual blood remaining in the extracorporeal circuit after termination of intermittent hemodialysis (iHD) treatment can result in additional losses of proteins (and blood).

During iHD relevant amounts of water-soluble vitamins are eliminated. As has been shown for vitamin C, in addition to diffusive losses during iHDF, convective losses contribute to the elimination of vitamins.

This is especially relevant for ICU patients with preexisting malnutrition and reduced vitamin stores. Thiamine presents a crucial factor in energy metabolism, and iHD-induced losses can cause serious and even life-threatening complications, such as lactic acidosis and neurologic injury (see below, Metabolic Effects of Continuous Renal Replacement Therapy Modalities). Carnitine also is eliminated during iHD, the relevance of which has not been assessed in acutely ill patients with AKI.

Most dialysate solutions for HD are designed for the therapy of chronic iHD patients and thus are phosphate free. Patients with AKI are at risk of developing hypophosphatemia, and this is augmented during iHD. Patients with AKI who develop hypophosphatemia during iHD may develop serious complications, such as weaning failure, and have a worse prognosis.

Metabolic side effects during HD, however, are caused not only by the loss of various substances. Originally shown in investigations with sham HD treatments, the extracorporeal HD circuit induces—depending on the biocompatibility of the membrane used—an activation of protein catabolism. This is mediated mainly by the induction of an inflammatory reaction and the release of inflammatory mediators. This activation of protein catabolism persists several hours after termination of HD treatment. Intracellular mRNA of cytokines in skeletal muscle is upregulated also for several hours. Thus, iHD therapy induces an inflammatory reaction and is a catabolic event.

In addition, it was demonstrated that during iHD there is an increased formation of reactive oxygen species (ROS). This is caused not only by the losses of nutritive antioxidants, such as vitamin C, but also by generation of ROS by the bioincompatibility of the extracorporeal circuit and the interaction of blood and artificial surfaces and in the bubble trap.

In critically ill patients with AKI a profound depression of the antioxidant system is present, which is implicated as a leading mechanism in the pathophysiology of tissue injury and organ dysfunction. iHD can contribute to this pro-oxidative state. The loss/increased metabolic use of antioxidants increases nutrition requirements of antioxidative compounds.

Taken together, many of the untoward side effects of iHD are present also when using modern, more biocompatible membranes and tubing systems and can be attributed to the obligatory phenomena of bioincompatibility. iHD induces an inflammatory reaction, which, together with the hemodynamic stress induced by iHD and its consequences for microcirculation, is associated with the induction of protein catabolism and the cardiopulmonary side effects and potential tissue injury. Last, this increases the risk of developing infections by impairment of immunocompetence. Whether anticoagulation with heparin may contribute to this pattern of side effects and whether this potentially can be mitigated by the use of citrate anticoagulation remains to be shown (below, Metabolic Effects of Continuous Renal Replacement Therapy Modalities).

Therapeutic Implications

The most important implication of this broad spectrum of side effects of iHD concerns nutrition therapy. Therapy-associated losses have to be considered when designing a nutrition program and be compensated by an increased intake.

Amino acid intake should be increased by 0.2 g/kgBW. The intake of water-soluble vitamins should be increased to twice the recommended daily allowance (RDA) (i.e., 2 ampoules of a multivitamin preparation/day).

Plasma phosphate must be monitored during therapy, and phosphate must be substituted as required. In patients not on nutrition support, intradialytic parenteral nutrition may be considered to improve nutrition state. Intradialytic nutrition can reverse the catabolic event hemodialysis into an anabolic situation.

However, also from a metabolic perspective, the practice of iHD has to be adapted to the ICU patient, to minimize hemodynamic instability and hemodynamic microcirculatory stress and to improve biocompatibility (potentially also by the modification of anticoagulation).

Heat Loss

Modern machines for CRRT have integrated heating systems by which the temperature of substitution fluid /dialysate can be adapted as required and heat balance can be modified. But also the use of those modern systems for CRRT is associated with heat loss, depending on the dose of therapy and filtration volume. Thus, during CRRT, body temperature is usually reduced.

This therapy-induced hypothermia can be desired (in the case of high fever, multiple organ dysfunction syndrome [MODS], and hemodynamic instability) and induce beneficial effects (i.e., reduction of oxygen consumption, improvement of hemodynamics, reduction of protein catabolism, mitigation of inflammation and tissue injury). However, this hypothermia potentially also can induce untoward effects, such as a disturbance of immunocompetence and increase in infections and impairment of wound healing.