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Effect Of Time-dependent Dialysate Bicarbonate Concentrations On Acid–base And Uremic Solute Kinetics During Hemodialysis Treatments – Scientific Reports – Renal.PlatoHealth.ai

Of the 20 HD patients who participated in this clinical trial, 12 were male; patient age was 65 ± 11 (SD) years. Their height was 169.9 ± 9.8 cm while their body mass index was 25.6 ± 3.1. Predialytic body weight and ultrafiltration volume during the second HD treatment of Week 1 were 75.3 ± 11.3 kg and 1.9 ± 1.0 L, respectively. There were no differences between Group 1 and 2 concerning anthropometric variables and dialysis settings (aside from Treatment protocol). There were no statistically significant differences in blood [HCO3], blood pH, pCO2, urea and creatinine concentrations between treatments with low and high flux hemodialyzers.

HCO3 concentration

Time-dependent changes in blood [HCO3] for Treatments A, B and C are plotted in Fig. 1 and presented in Table 1.

Figure 1
figure 1

Mean values of blood bicarbonate concentration ([HCO3]) during Treatments A, B and C (0–240 min N = 20; 300 min N = 19). *P < 0.05 Treatment B vs Treatment A; #P < 0.05 Treatment C vs Treatment A.

Table 1 Mean ± standard deviations for blood [HCO3], pCO2 and pH as a function of time during different treatment interventions for Group 1 and 2 patients (0–240 min N = 20; 300 min N = 19; *P < 0.05 vs Treatment A).

Statistical analysis showed significant differences in the mean blood [HCO3] between Treatments A and B for each measurement taken during the session (0, 60, 120, 180, 240, 300 min) (P < 0.005). Treatment C differed significantly from Treatment A in terms of mean blood [HCO3] during the first 3 h of HD. There was also a significant effect of time that was independent of the chosen Treatment (P < 0.001).

When the Dbic was held constant at 35 mmol/L (Treatment A), blood [HCO3] increased during the first two to three hours and then remained relatively constant. When the Dbic was 35 mmol/L during the first two hours of HD treatment and then reduced to 30 mmol/L for the remainder of the treatment (Treatment B), the blood [HCO3] increased a lot (similar to Treatment A) during the first two hours of treatment, as expected and then decreased to levels below those in Treatment A. In contrast, when the Dbic was 30 mmol/L during the first two hours of HD treatment, after which it was increased to 35 mmol/L (Treatment C), the blood [HCO3] did not increase as rapidly during the first 2 h as in Treatments A and B, but then increased significantly during the last 2 h of treatment. Thus, as expected during Treatment C, there was a more gradual rise in the intradialytic blood [HCO3] than during Treatment A during the first three hours, and the blood [HCO3] at the end of Treatments C and A were not significantly different. The intradialytic changes in blood [HCO3] shown in Fig. 1 have been previously evaluated quantitatively using the hydrogen ion mobilization model in a separate publication19: the results from that study demonstrated that such changes in blood [HCO3] are those predicted by the model with a mobilization parameter independent of the Dbic profile.

pH

Time-dependent changes in blood pH for Treatments A, B and C are plotted in Fig. 2 and presented in Table 1. There was a significant difference between Treatment B and Treatment A for values measured during 0, 60, 180, 240 and 300 min of HD (P < 0.005). Mean levels of pH differed between Treatment C and Treatment A during the first two hours of HD (P < 0.01).

Figure 2
figure 2

Mean values of blood pH during Treatments A, B, and (0–240 min N = 20; 300 min N = 19). *P < 0.05 Treatment B vs Treatment A; #P < 0.05 Treatment C vs Treatment A.

pCO2

Time-dependent changes in blood pCO2 for Treatments A, B and C are plotted in Fig. 3 and presented in Table 1. There were significant differences between Treatments A and B (P < 0.001) but the interaction term between treatment and time was insignificant. Thus, there was no evidence that the effect of Treatment B changes over time; there was a significant effect of time during the treatment (P < 0.05) but not postdialysis. Hence, there was no evidence that the levels of pCO2 differed pre and post dialysis.

Figure 3
figure 3

Mean values of blood partial pressure of carbon dioxide (pCO2) during Treatments A, B, and C (0–240 min N = 20; 300 min N = 19). *P < 0.05 Treatment B vs Treatment A.

Postdialytic changes in acid–base concentration

Postdialytic changes in blood [HCO3] were observed between the values measured at the end of HD and one hour after in all treatments (P < 0.001). We found significant differences in the percentage change in blood [HCO3] at the end of dialysis and one hour after between Treatments A and B (P = 0.01) with Treatment B lower than Treatment A. There was no significant difference in the percentage changes in postdialytic values between Treatment A and C (P = 0.76).

Postdialytic changes were not observed for blood pH (P = 0.07) and pCO2 (P = 0.12) levels. The percentage changes in these variables after the first hour after dialysis are reported in Table 2.

Table 2 Mean ± standard deviations of percentage post-dialytic changes in serum [HCO3], pH, pCO2 (1 h after the end of HD) for each treatment (N = 19).

Acid–base parameters before HD

The lowest blood [HCO3] before HD was found in Treatment B and this concentration was statistically significant lower in Treatment B than in Treatment A (mean 22.4 ± 2.5 mmol/L vs 23.7 ± 2.01 mmol/L, respectively, P = 0.006). Predialysis blood [HCO3] values for Treatment C did not statistically differ from those before Treatment A.

We found 13 patients, who had blood [HCO3] before HD less than 22 mmol/L in all Treatments: it was 3 patients (15%) in Treatment A, 6 patients (30%) in Treatment B and 4 patients (20%) in Treatment C. The Cochran Q test did not find significant differences in the numbers of patients with blood [HCO3] < 22 mmol/L pre-HD. However, in our study, the fraction of patients with blood [HCO3] < 22 mmol/L pre-HD was the highest in Treatment B.

Both predialytic pH and pCO2 levels differed significantly between Treatment A and B and they levels were significantly lower before HD for Treatment B than Treatment A (both P < 0.01).

HCO3 delivery

Delivery of HCO3 to the patient during Treatments A, B and C were 159 ± 68 (SD) mmol/L, 151 ± 84 mmol/L, and 134 ± 80 mmol/L respectively; these values did not differ statistically (P = 0.27), although the mean delivery in Treatment C was the lowest. As noted above, these calculated values significantly underestimate total alkali delivery to the patient because they omit the contribution from acetate transfer to the patient.

Uremic solute kinetics and small solutes

Time-dependent changes in plasma urea and creatinine concentrations for Treatments A, B and C are plotted in Figs. 4 and 5, respectively. There were no statistically significant differences between Treatment B or C and Treatment A. As expected, the plasma concentration of both solutes decreased significantly during the treatment; these findings were not statistically different for Treatments A, B and C. Further, postdialytic solute concentrations changed to higher levels for the uremic solutes (nonzero postdialytic increase P < 0.001) during all treatments. However, although with mean values numerically similar, creatinine rebound in Treatment C was significantly lower than in Treatment A (P = 0.02).

Figure 4
figure 4

Mean values of urea concentration during Treatments A, B and C (0–240 min N = 20; 300 min N = 19).

Figure 5
figure 5

Mean values of blood creatinine concentration during Treatments A, B and C (0–240 min N = 20; 300 min N = 19).

Values of spKt/V and eKt/V for Treatment A were 1.43 ± 0.22 and 1.23 ± 0.21, respectively; for Treatment B were 1.40 ± 0.19 and 1.21 ± 0.16, respectively; and for Treatment C were 1.40 ± 0.17 and 1.21 ± 0.16, respectively. There were no statistically significant differences in spKt/V and eKt/V between treatments.

The measured concentrations of sodium, chloride and the total osmolarity before and after HD are reported in Table 3.

Table 3 Mean ± standard deviations of sodium and chloride concentrations, and total osmolarity measured with the blood gas analyzer.

Blood pressure, heart rate, saturation

We did not note any statistically significant changes in blood pressure, heart rate and saturation, the patient’s well-being remained good throughout all treatments.