Replenishing Alkali During Hemodialysis: Physiology-Based Approaches

Abstract

The acid-base goal of intermittent hemodialysis is to replenish buffers consumed by endogenous acid production and expansion acidosis in the period between treatments. The amount of bicarbonate needed to achieve this goal has traditionally been determined empirically with a goal of obtaining a reasonable subsequent predialysis blood bicarbonate concentration ([HCO₃ ^- ]). This approach has led to very disparate hemodialysis prescriptions around the world. The bath [HCO₃ ^- ] usually chosen in the United States and Europe causes a rapid increase in blood [HCO₃ ^- ] in the first 1-2 hours of treatment, with little change thereafter. New studies show that this abrupt increase in blood [HCO₃ ^- ] elicits a buffer response that removes more bicarbonate from the extracellular compartment than is added in the second half of treatment, a futile and unnecessary event. We propose that changes in dialysis prescription be studied in an attempt to moderate the initial rate of increase in blood [HCO₃ ^- ] and the magnitude of the body buffer response. These new approaches include either a much lower bath [HCO₃ ^- ] coupled with an increase in the bath acetate concentration or a stepwise increase in the bath [HCO₃ ^- ] during treatment. In a subset of patients with low endogenous acid production, we propose reducing the bath [HCO₃ ^- ] as the sole intervention.

Keywords: Acid-base; acidosis; bicarbonate; hemodialysis; kidney failure.

Figure 1

Contrast between the daily variation in blood bicarbonate concentration ([HCO₃^-]) over the course of 1 week in individuals with normal kidney function and in those on hemodialysis. In those with normal kidney function, the blood [HCO₃^-] varies little from day to day (dashed line), whereas in those receiving hemodialysis, the blood [HCO₃^-] increases abruptly by 6-8 mmol/L during treatment and then gradually decreases in the interval between treatments, creating a “sawtooth” pattern (solid line). The nadir value in the sawtooth occurs after the longest interval between treatments. Adapted from Gennari.

Figure 2

Contrast between the pattern of the blood bicarbonate concentration ([HCO₃^-]) during conventional hemodialysis with the bath [HCO₃^-] maintained at 32 mmol/L throughout treatment and the pattern seen during treatment using a staircase protocol with the initial bath [HCO₃^-] set at 25 mmol/L and ending at 32 mmol/L (see Subsequent Studies Using the Sargent Analytical Model). The triangles in the upper curve are the average measured values in 14 patients and the circles in the lower curve are the average measured values in 20 patients. The curved lines are generated by the best fit using our analytical model. At 90 and 120 minutes, the confidence intervals (not shown) do not overlap. Adapted from Marano et al.

Figure 3

Contrast between the change in the extracellular fluid (ECF) bicarbonate content over the course of a hemodialysis treatment with the bath [HCO₃^-] maintained at 32 mmol/L throughout the treatment and the pattern seen when using a staircase protocol. Both curves were generated from the data obtained from study subjects using the Sargent analytical model. The dashed line represents the change in ECF bicarbonate content plotted against time on dialysis with conventional hemodialysis. The solid line represents the change in ECF bicarbonate content plotted against time on dialysis using the staircase protocol (see Subsequent Studies Using the Sargent Analytical Model). Adapted from Marano et al.

Figure 4

Schematic representation of the Sargent analytic model for alkali addition during hemodialysis. Bicarbonate (Bic) is considered to be confined to extracellular fluid (ECF) water. Three sources of bicarbonate addition from the hemodialysis bath to the ECF are included (left side of figure). The first is the influx of the bicarbonate ion itself, driven by the bath-to-blood water concentration gradient. The second is influx of CO₂, driven by its pressure gradient across the dialysis membrane, and its interaction with blood hemoglobin. The third is the influx of acetate and its metabolism. Any bicarbonate lost into the bath by ultrafiltration is subtracted from the total influx. In addition to the bicarbonate lost by ultrafiltration, bicarbonate exits the ECF because of H⁺ released from body buffers and from organic acid production. The net addition of H⁺ is considered to be directly related to the increase in blood [HCO₃^-] (right side of figure). The key variables of the model are iteratively evaluated during treatment, and the rate of H⁺ addition is determined by a least squares analysis of the measured blood water [HCO₃^-] values minus the model-generated values.