Hemodialysis

Hemodialysis (HD) is a therapeutic dialysis procedure used in nephrology, which is based on the principle of blood filtration and is the most common dialysis procedure used in nephrology worldwide.The therapeutic success of hemodialysis is based, among other things, on the use of various buffer substances so that the altered acid-base balance of patients with renal insufficiency can be corrected. Since the acid-base balance cannot be corrected during dialysis by diffusion or convection (transport mechanisms), the supply of buffer substances is essential. Theoretically, bicarbonate, acetate and lactate are suitable for balancing the gradient between acids and bases, but due to various disadvantages of lactate and acetate buffering, hemodialysis treatment in Germany is carried out exclusively using bicarbonate buffering. Bicarbonate is a buffer substance that is chemically a salt of carbonic acid and physiologically has an important function in maintaining the internal environment. In contrast to acetate buffering, the use of bicarbonate in dialysate leads, for example, to greater cardiovascular stability (slight change in the function of the cardiovascular system). Various studies have so far demonstrated that buffering by acetate leads to a cardiodepressant effect (deterioration of cardiac function), so bicarbonate is considered the substance of choice. Hemodialysis represents the most commonly used dialysis procedure in Germany, accounting for 82% of all dialysis procedures performed.

Indications (areas of application)

Acute renal failure (ANV) – as soon as endogenous (the body’s own) renal function is no longer sufficient to clear the blood, an exogenous (non-endogenous) procedure is needed to clear the blood. The clarification of urinary substances is determined on the basis of various parameters. If a laboratory test of the patient’s blood reveals a serum urea value above 200 mg/dl, a serum creatinine value above 10 mg/dl, a serum potassium value above 7 mmol/l or a bicarbonate concentration below 15 mmol/l, a dialysis procedure must be performed quickly. However, it should be noted that not only laboratory values may serve as an indication, but also the clinical presentation (eg, diuretic-resistant hyperhydration with pulmonary edema / water retention in the lungs, heart failure / cardiac insufficiency and incipient cerebral edema / brain swelling; uremic signs such as pericarditis / pericarditis) should be used.
Hyperhydration states (overhydration states) – if conservative therapy (exclusively drug therapy) is not to be considered sufficient from the therapeutic success, hemodialysis is indicated for these difficult to control hyperhydration states in therapy.
Severe hyperphosphatemia (excess phosphate) – an overload of the body with phosphate represents a massive health risk, which is also an indication for the acute use of hemodialysis.
Acute intoxications (poisonings) – Poisonings with dialyzable substances can usually be treated well with hemodialysis.
Uremic serositis – in the presence of an uremic (uremia refers to the presence of urinary substances in the blood above normal levels) inflammatory reaction (examples: Pericarditis / pericarditis, endocarditis / endocarditis), hemodialysis is the drug of choice.

Contraindications

If the criteria for hemodialysis are met, there are no known contraindications to date.

The procedure

Performance of hemodialysis

The basic principle of hemodialysis using a bicarbonate dialysis system is based on the exchange of substances dissolved in fluid and located in one compartment (delimited space) with another compartment. Between these compartments is a semi-permeable membrane.
Through a semipermeable membrane can diffuse (get) only certain substances or molecules that have certain charge and size values. The simplest example of a semipermeable membrane is given when through such a membrane can diffuse the solvent, but not the solute.On the path of diffusion, depending on the molecular size of the substances and the pore size of the semipermeable membrane, substances migrate along the existing concentration gradient (difference in concentration of the substances) from the first compartment with high concentration to the second compartment with lower concentration. This flow reduces to near zero only when equilibrium (balance) of substance concentrations on both sides of the membrane is reached.
Crucial to the function of hemodialysis is the separation of the patient’s blood in the extracorporeal (outside the body) circuit in the dialyzer from the second compartment, which contains the dialysate. This separation of the patients’ blood is accomplished by the dialysis membrane. Of further importance is that such substances as creatinine and urea, for example, which should be largely removed from the blood using hemodialysis, are not contained in the dialysate.
In contrast to the substances to be eliminated (removed from the blood), substances that are not to be completely removed but are to be adjusted to a target range must be added to the dialysis fluid. Depending on the concentration in the blood, substances that need to be adjusted to a target value are thus reduced or added. Examples of such substances or classes of substances include electrolytes (blood salts) such as sodium, potassium, calcium, magnesium, chloride and bicarbonate, but also glucose.
In order to achieve a relevant improvement in transport by diffusion, it is important that the blood and the dialysate are passed through the dialyzer in countercurrent. This can ensure that a concentration gradient from the blood side into the dialysate compartment can be maintained over the entire length of the dialyzer from the inlet leg of the patient’s blood to the blood outlet.
To the function of hemodialysis, however, another operating principle is important. In addition to diffusion through the semipermeable membrane, the mechanism of ultrafiltration also plays a significant role in the operation of the dialysis system. Ultrafiltration enables the removal of water from the blood. The water thus removed is subsequently directed into the compartment containing the dialysate.
The driving force of ultrafiltration is the transmembrane pressure (TMP) at the dialyzer membrane. The transmembrane pressure is composed of two manipulated variables. On the one hand, the transmembrane pressure is influenced by the positive return pressure in the blood compartment; on the other hand, the negative pressure in the dialysate compartment can be cited as a further influencing factor. The positive return pressure is also called the so-called venous pressure, where, on the other hand, the negative pressure in the dialysate compartment represents the so-called suction pressure.
In addition to the transmembrane pressure, the dialysis membrane-specific ultrafiltration coefficient (KUF) determines the ultrafiltrate volume that can be achieved per hour. The various membranes differ primarily in KUF. Low-flux and high-flux membranes can be distinguished as the main groups of these membrane types.
The so-called low-flux membranes have a relatively small pore size. The result is thus a low dialysis membrane-specific ultrafiltration coefficient of 5-15 ml/h/mmHg. In contrast to the low-flux membranes, the high-flux membranes are characterized by larger pores, resulting in significant clearance for medium molecules. An example of these agent molecules is β2-microglobulin, which plays a major role in the defense function of the organism. As a result of these membrane properties, high-flux dialyzers have a higher KUF of 20-70 ml/h/mmHg.
It should be noted, however, that high-flux dialyzers may only be used with modern dialysis machines. As a requirement for these dialysis machines is the control of ultrafiltration by flow or pressure control in the dialysate circuit. It should also be noted that by increasing the pressure in the dialysate compartment, the necessary throttling of ultrafiltration in high-flux dialysis is achieved. The consequence of this throttling is the reversal of direction of the transmembrane pressure. As a result, the ultrafiltration of water from the blood compartment into the dialysate compartment initially decreases sharply and can subsequently lead to the transfer of dialysate into the blood.By means of ultrafiltration, the water as well as the dissolved small-molecule substances are transported through the semi-permeable dialysis membrane in a pressure-dependent manner.
Dialysis membranes with higher “cut-off” (high-cut-off[HCO]- or medium-cut-off[MCO]-membranes) have been developed for the elimination of free light chains in patients with multiple myeloma (plasmocytoma; malignant (malignant) systemic disease belonging to the non-Hodgkin’s lymphomas of B lymphocytes).The high-permeability HCO membranes could also be useful in chronic dialysis patients. Thus, inflammatory mediators could be eliminated.

However, the goal of any procedure must be to achieve high biocompatibility. The term biocompatibility refers to the absence of activation of inflammatory active blood cells and plasma proteins. For the determination of biocompatibility, the activation of the complement system (the body’s own system active in the defense against infection) is considered the most meaningful parameter. The activation of the complement system is accompanied by the production of complement factors C3a and C5a. Using these parameters, it can be concluded that high-flux membranes have superior biocompatibility compared to low-flux membranes. Considering various studies with partly different designs (way of conducting the study), it could be proven that synthetic (artificially produced) high-flux membranes have both a significantly lower complement activation, granulocyte degranulation (activation of special white blood cells, (activation of special white blood cells that play an important role in innate defense function) and cytokine induction (inflammatory factor activation), and despite larger pores, have lower permeability of fever-inducing mediators (substances that promote fever development) than low-flux membranes. Advantages of bicarbonate buffering over acetate buffering:

A key advantage of using bicarbonate as a buffering agent is that bicarbonate is a physiologic buffer. In contrast, acetate represents a non-physiological substance, which thus must first be metabolized to bicarbonate as an indirect buffer substance. Because of this, one hydrogen ion is consumed per molecule of acetate during this metabolization (metabolization) to bicarbonate. However, since the acid-base balance of the patient is disturbed, this time delay can lead to a further deterioration of the balance due to the consumption of hydrogen ions.
As described earlier, acetate buffering represents an uncertainty factor for the cardiovascular system. This uncertainty factor is particularly dependent on the ultrafiltration rate at which dialysis therapy is provided. At high ultrafiltration rates, drops in blood pressure have frequently occurred with the use of acetate dialysis. In contrast, at nearly identical ultrafiltration rates, blood pressure drops have been observed much less frequently with the use of bicarbonate dialysis. This effect is due to the direct vasodilatory effect of acetate, which subsequently leads to a massive drop in blood pressure.
In contrast to acetate dialysis, bicarbonate dialysis also takes place a more rapid return flow of tissue water into the vascular system, so that underfilling of the vascular system can be prevented.
Furthermore, it should be noted that in dialysis using acetate buffering compared to bicarbonate dialysis, blood pressure drops, nausea and cramps occur far more frequently.