Renal replacement therapy

Renal replacement therapy reduces uremic intoxication and maintains the “internal environment” in a state as close as possible to physiological, without negatively affecting the functions of the patient’s vital organs and systems.

Severe acute renal failure contributes to increased mortality and is associated with a general increase in this indicator to 50-100%. Renal dysfunction most often develops as a consequence of another existing pathology (for example, low cardiac output, infectious and septic complications), which is the cause of death of patients. Extracorporeal therapy methods should be considered as an intermediate treatment, allowing the patient to survive the period until the restoration of the functioning of his own kidneys. In the case of acute renal dysfunction or multiple organ failure syndrome, severe uremia, hyperkalemia or severe metabolic acidosis should not be allowed to develop, since each of these complications can significantly affect the final result of treatment, which necessitates the use of renal replacement therapy methods at earlier stages.

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Indications for renal replacement therapy

With the apparent identity of indications for renal replacement therapy in patients with terminal stage chronic renal failure and in patients with acute renal failure, it is essential to include extracorporeal detoxification methods in complex intensive therapy as early as possible. In intensive care units, extracorporeal blood purification methods are used to a greater extent to maintain the function of the kidneys and other vital organs (heart, lungs, central nervous system) than to replace them. It is necessary to provide optimal treatment with the help of renal replacement therapy without negatively affecting the functions of the patient's organs and systems, without interfering with adequate restoration of renal function.

Indications for renal replacement therapy:

• Non-obstructive oliguria (diuresis <200 ml/12 h).
• Anuria/severe oliguria (diuresis <50 ml/12 h).
• Hyperkalemia (K+>6.5 mmol/l) or rapid increase in plasma K+ levels.
• Severe dysnatremia (115
• Severe acidemia (pH<7.1).
• Azotemia (urea >30 mmol/l).
• Clinically significant swelling of organs and tissues (especially pulmonary edema).
• Hyperthermia (t>39.5 °C).
• Complications of uremia (encephalopathy, pericarditis, neuro- and myopathy).
• Drug overdose.

"Extrarenal" indications (sepsis, congestive heart failure, etc.). There are currently no specific criteria for renal replacement therapy in critically ill patients. The issue of indications for the use of detoxification methods in patients in the intensive care unit should be approached comprehensively, assessing the state of homeostasis and the functions of vital organs as a whole. In patients with acute renal failure, it is preferable to prevent physiological disorders of organs and systems than to subsequently restore their functions. Modern detoxification methods allow for safe and effective blood purification in critically ill patients and provide the opportunity to take a differentiated approach to the choice of renal replacement therapy in order to improve the quality and optimize the results of patient treatment.

Methods of renal replacement therapy

Renal replacement therapy has the following types: hemodialysis, peritoneal dialysis, continuous hemofiltration or hemodiafiltration, "hybrid" methods of renal function replacement. The capabilities of these methods depend on the clearance of substances with different molecular weights, membrane properties, blood flow rate, dialysate and ultrafiltration.

It is known that all substances can be divided into 4 large groups depending on the size of their molecular mass:

• low-molecular substances, with a mass not exceeding 500-1500 D, these include water, ammonia, K Na+, creatinine, urea;
• medium molecular weight - with a mass of up to 15,000 D: inflammation mediators, cytokines, oligopeptides, hormones, fibrin degradation products;
• substances with a relatively large molecular weight - up to 50,000 D: myoglobin, beta2-microglobulins, degradation products of the blood coagulation system, lipoproteins;
• large-molecular substances with a mass exceeding 50,000 D: hemoglobin, albumins, immune complexes, etc.

Hemodialysis uses a diffusion mechanism of mass transfer, in which the osmotic pressure gradient on both sides of the semipermeable membrane is of primary importance. The diffusion mechanism of transport is best suited for filtering low-molecular substances dissolved in large quantities in plasma, and it is less effective with an increase in molecular weight and a decrease in the concentration of the removed substances. The effectiveness of peritoneal dialysis is based on the transport of water and substances dissolved in it through the peritoneum, due to diffusion and ultrafiltration, due to gradients of osmotic and hydrostatic pressures.

Hemofiltration and plasma exchange are based on the principles of ultrafiltration (through a highly permeable membrane) and convection, with the transport of substances being carried out due to the hydrostatic pressure gradient. Hemofiltration is primarily a convective technique, in which the ultrafiltrate is either partially or completely replaced by sterile solutions introduced either before the filter (predilution) or after the filter (postdilution). The most important positive aspect of hemofiltration is the ability to remove the so-called medium molecules involved in the pathogenesis of sepsis and multiple organ failure. These molecules have a fairly high molecular weight and are present in plasma in low concentrations and, therefore, due to the low osmotic gradient, cannot be removed using the diffusion mechanism of mass transfer. In cases where more effective and rapid removal of low-molecular substances is required in patients with hypercatabolism, which is often observed in intensive care units, the principle of combining convection and diffusion is used, for example, during hemodiafiltration. This method is a combination of hemofiltration and hemodialysis, it uses a counter-current of dialysate to the blood flow in the hemofiltration circuit. And finally, hemoperfusion uses the principle of concentration of substances on the surface of the sorbent.

Which method of blood purification and renal replacement therapy is most preferable: intra- or extracorporeal? Continuous or intermittent? Diffusion or convection? It is extremely difficult to answer these questions unambiguously, since the effectiveness of any therapy depends on a complex of components, primarily on the clinical condition of patients, their age and body weight, technical support and equipment for renal replacement therapy in the clinic, as well as the experience and specialization of the clinician (nephrologist or resuscitator) and much more.

Continuous renal replacement therapy is usually given around the clock. This determines the possible side effects.

• The risk of bleeding increases with the constant use of systemic anticoagulation. In patients with a compromised blood coagulation system, especially in the postoperative period, this complication can be fatal.
• The concentration of inotropic drugs, antibiotics and other expensive medications is reduced by constant ultrafiltration or adsorption on the filter membrane.
• Insufficient correction of uremia, especially in patients with hypercatabolism.
• 24-hour renal replacement therapy complicates diagnostic and therapeutic procedures, increases the need for sedatives and limits patient mobility.
• High cost and labor intensity of treatment, especially in cases of severe sepsis and multiple organ failure syndrome, when performing high-volume procedures (ultrafiltration> 6 l/h).

Hybrid technologies of renal replacement therapy

"Hybrid" technologies - slow low-efficiency daily dialysis (SLEDD - Sustained low-efficiency daily diafiltration), preventing the negative impact of intermittent treatment on hemodynamics by removing fluid and substances dissolved in it over a long period of time exceeding 4 hours. This allows avoiding rapid fluctuations in the concentration of dissolved substances and a decrease in intravascular volume. The method allows increasing the dialysis dose in patients with multiple organ dysfunction and high levels of catabolism. An increase in the dose, and therefore the effectiveness of intermittent renal replacement therapy, is possible by extending the procedure time to more than 3-4 hours, as well as increasing the diffusion component of the treatment.

Thus, “hybrid” technologies allow:

• adjust treatment to the patient's condition, combining the therapeutic goals of continuous renal replacement therapy and intermittent hemodialysis;
• ensure a low ultrafiltration rate and achieve stability of hemodynamic parameters;
• to carry out low-efficiency removal of dissolved substances and reduce the risk of developing imbalance syndrome and progression of cerebral edema phenomena;
• increase the duration of the daily procedure to increase the dose and effectiveness of dialysis;
• carry out diagnostic and therapeutic procedures;
• reduce the daily dose of systemic anticoagulation and reduce the overall cost of renal replacement therapy.

To carry out “hybrid” methods, standard dialysis machines (with a mandatory water purification system) are used, using low blood flow rates (100-200 ml/min) and dialysate flow (12-18 l/h).

Treatment should be daily and long-term (more than 6-8 hours), with the possibility of online preparation of replacement solution and dialysate. Depending on the required type of extracorporeal procedure (hemodialysis, hemofiltration or hemodiafiltration), biocompatible, synthetic, highly permeable membranes should be used for SIEDD therapy. Considering the disorders of the blood coagulation system in the postoperative period, the use of "hybrid" technologies allows the use of minimal doses of anticoagulants [2-4 U/kg x h) of heparin] or to carry out procedures without systemic anticoagulation. The use of SLEDD therapy at night allows various diagnostic studies and therapeutic manipulations to be carried out during the day. In addition, nocturnal SLEDD therapy allows hemodialysis to be carried out on the same device for other patients during the day.