Dialysate Composition

Introduction

Patients with end-stage kidney disease (ESKD) depend on dialysis to maintain fluid and electrolyte balance. In hemodialysis, solutes diffuse between blood and dialysate such that, over the course of the procedure, plasma composition is restored toward normal values. The makeup of the dialysate is of paramount importance in accomplishing this goal. Individualizing the dialysate composition is of critical importance in improving tolerance to the procedure, particularly given the number of comorbid conditions typically found in ESKD patients.

Dialysate Sodium

As dialysis has evolved, there has been continued interest in adjusting the dialysate sodium (Na ⁺ ) concentration in an attempt to improve the tolerability of the procedure. In the early days of dialysis, fluid removal was accomplished by a process of osmotic ultrafiltration. High concentrations of glucose were placed in the dialysate in order to create an osmotic driving force for fluid removal since the coil dialyzers used at the time were unable to withstand high transmembrane hydrostatic pressures. In order to prevent the development of hypernatremia as water moved from plasma to dialysate, the Na ⁺ concentration in dialysate was purposely set low, usually in the range of 125–130 mEq/L. With the development of more resilient membranes capable of withstanding high transmembrane pressures, osmotic ultrafiltration was replaced by hydrostatic ultrafiltration. Initially, a low dialysate Na ⁺ concentration continued to be used in order to avoid the problems of chronic volume overload, such as hypertension and heart failure. With the institution of shorter treatment times, volume removal became more rapid, and symptomatic hypotension emerged as a common and often disabling problem during dialysis. It soon became apparent that changes in the serum Na ⁺ concentration, and more specifically changes in serum osmolality, were playing a role in the development of this hemodynamic instability.

The importance of a stable plasma osmolality in maintaining hemodynamic stability was first suggested when the hemodynamic profiles of ultrafiltration were compared to diffusional solute clearance. Ultrafiltration alone (the removal of isoosmolar fluid by exerting a transmembrane pressure across the dialyzer) decreases cardiac output primarily due to a reduction in the stroke volume but is accompanied by an increase in peripheral vascular resistance such that arterial pressure is maintained. By contrast, diffusional dialysis results in a fall in arterial pressure while peripheral vascular resistance remains the same. With conventional dialysis (ultrafiltration and dialysis), less volume removal can be achieved before hypotension occurs as compared to ultrafiltration alone.

In animal studies, both conventional dialysis and sequential ultrafiltration dialysis result in an ultrafiltrate volume that is less than the decrease in extracellular fluid volume, consistent with a shift of fluid into the intracellular compartment. In addition, during sequential ultrafiltration hemodialysis, this shift occurs only during the diffusive phase. In the initial period of dialysis, the extracellular urea concentration rapidly falls, creating an osmotic driving force for water movement into cells due to the higher intracellular urea concentration. With the advent of high-clearance dialyzers and more efficient dialysis techniques, this decline in plasma osmolality becomes more apparent as solute is more rapidly removed. Use of a low dialysate Na ⁺ concentration tends to further augment the intracellular shift of fluid further as plasma tends to become even more hypoosmolar, consequent to the movement of Na ⁺ from plasma to dialysate.

Raising dialysate Na ⁺ to between 139 and 144 mEq/L improves hemodynamic stability and general tolerance to the procedure. A high dialysate Na ⁺ concentration has been shown to be effective in maintaining a relatively constant plasma osmolality, thereby minimizing intracellular water movement during dialysis. By preventing a decrease in plasma osmolality, the higher Na ⁺ dialysate leads to mobilization of fluid from the intracellular space, resulting in better preservation of plasma volume. As the dialysate to plasma Na ⁺ gradient increases, there is a greater contraction of the intracellular fluid compartment. The shift of fluid into the extracellular fluid space increases the hydrostatic pressure of the interstitium, which in turn favors refilling of the vascular space during volume removal. The net effect is a reduced frequency of hypotension and cramps.

The primary concern with use of a higher dialysate Na ⁺ concentration is the potential to stimulate thirst and cause increased weight gain and poor blood pressure control in the interdialytic period. Studies addressing this issue confirmed that a higher dialysate Na ⁺ modestly increased interdialytic weight gain. However, this excess weight was found to be readily removed with improved tolerance to ultrafiltration.

Sodium modeling refers to a strategy of varying the concentration of Na ⁺ in the dialysate during the procedure so as to minimize the potential complications of a high Na ⁺ solution while retaining the beneficial hemodynamic effects. A high dialysate Na ⁺ concentration is used initially with a progressive reduction toward isotonic or hypotonic levels by the end of the procedure. This method allows for a diffusive Na ⁺ influx early in the session to prevent the rapid decline in plasma osmolality resulting from the efflux of urea and other small molecular weight solutes. During the remainder of the procedure, when the reduction in osmolality accompanying urea removal is less abrupt, the lower dialysate Na ⁺ level minimizes the development of hypertonicity and potential for excess thirst, fluid gain, and worsening of hypertension in the interdialytic period. Unfortunately, despite the theoretical predictions of Na ⁺ modeling, the incidence of symptomatic hypotension during dialysis or the degree of interdialytic weight gain between fixed or variable Na ⁺ protocols have been difficult to demonstrate. In fact, the available data suggest that in most chronic dialysis patients, changing the dialysate Na ⁺ during the course of the treatment offers little advantage over a constant dialysate Na ⁺ of between 140 and 145 mEq/L.

In many of the comparative studies, the time-averaged concentration of Na ⁺ has been similar, potentially accounting for the inability to demonstrate a superiority of Na ⁺ modeling. For example, a linear decline in dialysate Na ⁺ from 150 to 140 mEq/L will produce approximately the same postdialysis plasma Na ⁺ as occurs when a fixed dialysate Na ⁺ of 145 mEq/L is used. In addition, the optimal time-averaged Na ⁺ concentration, whether administered in a modeling protocol or with a fixed dialysate concentration, is likely to vary from patient to patient as well as in the same patient during different treatment times. This variability is supported by studies demonstrating wide differences in the month-to-month predialysis Na ⁺ concentration in otherwise stable dialysis patients.

A special report authored by a coalition of dialysis organization leaders emphasizes the need to prevent intradialytic Na ⁺ overload by recommending that the dialysate Na ⁺ should be in the range of 134–138 mEq/L. To minimize the chance of hypotension and ensure adequate volume removal, the expected minimum duration of dialysis should be 4 hours in patients receiving thrice-weekly maintenance dialysis. Lastly, hypertonic saline and Na ⁺ modeling protocols should be avoided.

Despite these recommendations, there are certain situations where Na ⁺ modeling may be considered ( Table 8.1 ). Patients initiating dialysis with marked azotemia are often deliberately dialyzed to decrease the urea concentration slowly over the course of several days to avoid the development of the dialysis disequilibrium syndrome. The use of a high/low-Na ⁺ dialysate in these patients may minimize fluid shifts into the intracellular compartment and decrease the tendency for neurologic complications. A modeling protocol may also be beneficial in patients suffering frequent intradialytic hypotension, cramping, nausea, vomiting, fatigue, or headache. In such patients, Na ⁺ modeling can be individually tailored to minimize increased thirst, weight gain, and hypertension. Combining dialysate Na ⁺ profiling with a varying rate of ultrafiltration may provide additional benefit in particularly symptomatic patients. This combined approach may be of particular benefit in ensuring hemodynamic stability in patients with acute kidney injury in the intensive care unit. Whenever prescribing a Na ⁺ gradient protocol, it is important to monitor the patient for evidence of a progressive increase in total body Na ⁺ manifesting itself as large interdialytic weight gains and/or uncontrolled hypertension ( Table 8.2 ).

Current research is focusing on ways in which the dialysate Na ⁺ concentration can be adjusted to more accurately match intradialytic Na ⁺ removal with interdialytic Na ⁺ intake. The ability to achieve zero Na ⁺ balance would enhance the ability to control hypertension in the interdialytic intervals and minimize the risk of hypotension during the dialysis procedure.

With the increased ability to individualize the dialysate Na ⁺ concentration, one can envision a scenario in which a patient initiated on hemodialysis is initially treated with a dialysate Na ⁺ concentration designed to achieve negative Na ⁺ balance. Once the patient becomes normotensive or requires minimal amounts of antihypertensive medications, the dialysate Na ⁺ can be adjusted on a continual basis to ensure that Na ⁺ balance is maintained. Identifying and delivering an individualized optimal dialysate Na ⁺ are unmet needs in kidney replacement therapy.