What Exactly Is Dialysis and When Is It Needed?

A frequent reason for inpatient nephrology consultation is either a need for dialysis (in a patient with end-stage renal disease [ESRD] who is hospitalized) or a wish for the nephrologist to consider dialysis (for instance, in a patient with severe chronic kidney disease [CKD] or acute kidney injury [AKI]).

First, let us consider what the term dialysis means. The word comes from a combination of the Greek words dia and lysis, which translate into English as through and splitting, respectively. The word dialysis thus reflects the fact that the procedure involves “splitting” of solutes from blood passing across a semipermeable membrane, the solute diffusing “through” the membrane along its concentration gradient. Diffusion is bidirectional, meaning that a given solute can be either removed or added to the blood. Most of the time, a solute is being removed since its concentration in uremic blood is higher than the concentration in the fluid placed on the other side of the membrane, which is termed dialysate. Examples of such solutes are urea, creatinine, and (usually) potassium. However, in other instances, the solute concentration in dialysate is generally higher than that in the blood, such as with bicarbonate and (often) calcium. Removal of fluid is not achieved by dialysis, but rather by ultrafiltration, which means removal of an ultrafiltrate of plasma (i.e., plasma water containing smaller molecular weight solutes, but not larger molecular weight solutes and proteins). Dialysis results in changes in the plasma concentrations of the solutes either removed or added to the plasma. On the other hand, with ultrafiltration using hemodialysis equipment, a hydrostatic pressure gradient is employed to induce the filtration (or convection) of plasma water across the membrane of the
hemofilter. The frictional force between water and solutes (called solvent drag) results in the convective transport of small-and middle-molecular-weight solutes across the membrane along with the water. An important difference between convection and diffusion is that with convection, solute removal is determined by the pore size of the membrane, whereas with diffusion, efficiency of solute removal is greatest with smaller molecules at any given pore size. When ultrafiltration is performed without dialysis, this is termed isolated ultrafiltration (IUF). With IUF, solutes are present in the ultrafiltrate at the same or similar concentrations to those of the plasma and, as opposed to dialysis, plasma concentration of these solutes will not change due to the procedure.

Many patients and some clinicians are uncertain of the distinction between dialysis and ultrafiltration. Indeed, nephrologists are often requested to “dialyze” patients, when in fact what is desired is fluid removal. Possibly the term “blood purification” (English translation of Chinese term for dialysis) or even “blood cleaning” (pure English!) would be preferable to continuing to speak in Greek. At least this would make clear to patients and practitioners what “dialysis” is really doing.

There are two forms of dialysis: hemodialysis and peritoneal dialysis. Both are effective and widely used for maintenance dialysis, though hemodialysis results in faster solute removal and more predictable fluid removal and is preferred in most acute settings.

WHAT ARE THE INDICATIONS FOR DIALYSIS?

Maintenance Dialysis

The decision to start maintenance dialysis is based upon the presence of ESRD-related signs and symptoms, the estimated glomerular filtration rate (eGFR), the rate of decline of the eGFR, and clinical judgment. Symptoms and signs attributable to kidney failure include serositis (such as pericarditis and pleuritis), acid-base or electrolyte disorders not easily corrected by medical management, dysgeusia (altered taste), severe pruritus, hiccoughs, refractory volume overload, progressive deterioration in nutritional status, or cognitive impairment. In the past, asymptomatic patients with eGFR less than 10 mL/min/1.73 m² were often started on maintenance dialysis even in the absence of symptoms or signs of uremia or fluid overload. This practice has changed somewhat as the result of findings of the Initiating Dialysis Early and Late (IDEAL) study, a randomized clinical trial in which planned early initiation of dialysis in patients with stage 5 CKD was not associated with an improvement in survival or clinical outcomes (Cooper et al., 2010). In this study, 828 patients with an eGFR between 10 and 15 mL/min/1.73 m²
were randomly assigned to dialysis initiation when the eGFR was either 10 to 14 mL/min/1.73 m² or 5 to 7 mL/min/1.73 m². Dialysis was initiated on the basis of the presence of uremic symptoms and volume overload as well as on the eGFR. Since the majority of patients assigned to the late-start arm initiated dialysis when the eGFR was greater than 5 to 7 mL/min/1.73 m², the mean eGFR was 9.8 mL/min/1.73 m² at the start of dialysis for the late-start group versus 12 mL/min/1.73 m² in the early-start arm. On the basis of this study, most nephrologists do not initiate maintenance dialysis in the absence of signs or symptoms of uremia or fluid overload. However, if the eGFR is very low (≤ 5 mL/min/1.73 m²), many nephrologists will start maintenance dialysis even in the absence of symptoms due to risk of complications in seemingly asymptomatic patients. Absolute indications to start dialysis include uremic pericarditis or pleuritis or uremic encephalopathy.

Since eGFR is determined on the basis of population studies, in selected patients, a 24-hour urine for measurement of urea and creatinine clearance may be performed in order to provide a more accurate estimate of the GFR. In the absence of congestive heart failure, the mean of the urea and creatinine clearance is very similar to the GFR measured by inulin clearance in patients with severe CKD (GFR < 20 mL/min) (Lubowitz et al., 1967). In some centers, GFR can be determined by clearance of an exogenous substance that is excreted by glomerular filtration and neither reabsorbed nor secreted by renal tubules (e.g., inulin, iohexol, iothalamate, diethylene triamine pentaacetic acid).

Acute Dialysis

The decision to perform dialysis on a patient with acute renal failure or acute worsening of CKD is based on clinical judgment, as there are no randomized trials for guidance. As opposed to maintenance dialysis, eGFR plays little or no role in the decision process. There is a helpful mnemonic used on rounds—AEIOU.

A—Acidosis (occasionally severe alkalosis)

Dialysis fluid (dialysate) used for hemodialysis contains bicarbonate, usually at a concentration of about 35 mmol/L. Therefore, hemodialysis is very effective at correcting metabolic acidosis. Most dialysis machines can adjust the bicarbonate concentration down to about 28 to 30 mmol/L and up to about 40 mmol/L. Use of the lower bicarbonate concentration can be used to correct severe metabolic alkalosis. Peritoneal dialysate contains lactate, which must be metabolized to produce bicarbonate in the body.

E—Electrolyte disturbance

The most important electrolyte disturbance for which dialysis is performed is hyperkalemia, as severe hyperkalemia can lead to electrocardiographic changes and cardiac arrest. The advisability of rapid correction of hyperkalemia requires clinical judgment and is discussed in Chapter 15. Other electrolyte disturbances occasionally necessitating urgent dialysis are severe hypercalcemia, hyperphosphatemia, and hypermagnesemia. More rapid correction is achieved by hemodialysis than by peritoneal dialysis.

I—Intoxications (when the intoxicant is dialyzable, and enough will be removed to affect patient outcome)

Hemodialysis should be used rather than peritoneal dialysis for intoxications as higher clearance rates can be achieved. In general, dialysis is best used to remove small-molecular-weight toxins that are not bound to plasma proteins (therefore, readily dialyzable) and that have a relatively small volume of distribution (so that a meaningful amount of the total body burden of toxin can be removed). Also, some toxins (such as methanol) exert their most serious toxicity once they are metabolized to other substances (in this case, formic acid and formaldehyde); dialytic removal of the parent compound will prevent conversion to these toxic metabolites. Examples of substances for which dialysis is of clinical benefit for treatment of intoxications are lithium, methanol, ethylene glycol, and salicylate.

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