Significant changes in pre-dialytic partial pressure of CO2 (pCO2) during a week-long cycle of hemodialysis (HD) can be an effect of the intermittent supplementation of bicarbonate to correct chronic acidosis in patients. Mathematical modeling efforts carried out using the same parameters before each HD session might fail to produce accurate predictions of pCO2 and plasma bicarbonate concentration (CBic) because of this variability. A numerical model describing acid-base equilibrium changes during HD was applied to predict pCO2, pH, and CBic in 24 chronic HD patients, using both fixed parameters for the whole week and estimating a new value of minute ventilation (VE) and net acid generation rate (GH) for each interdialytic interval. Dialysances of bicarbonate and dissolved CO2 were also estimated independently for each HD session. The error of the model compared to the pre-dialytic data of CBic and pCO2 significantly decreased when VE and GH were estimated piecewise throughout the week. To fit the data, VE changed from 3.9 ± 1.0 mL/min before HD1, to 3.8e1 mL/min after HD1, 3.6 ± 1.0 mL/min after HD2, and 3.9 ± 1.1 mL/min after HD3 (p < 0.05). GH changes after each session were not statistically significant. VE values strongly correlated with pre-dialytic pCO2 (Spearman's ρ = -0.97), but GH only weakly correlated with pre-dialytic CBic (ρ = -0.30). Acid-base equilibrium is extremely sensitive to respiratory regulation. When attempting to predict the evolution of pCO2 a CBic during the HD cycle, changes in the respiration parameters must be accounted for by the model, at the risk of a significant loss of prediction accuracy.

Acid-base regulation by the kidneys is largely missing in end-stage renal disease patients undergoing hemodialysis (HD). Bicarbonate is added to the dialysis fluid during HD to replenish the buffers in the body and neutralize interdialytic acid accumulation. Predicting HD outcomes with mathematical models can help select the optimal patient-specific dialysate composition, but the kinetics of bicarbonate are difficult to quantify, because of the many factors involved in the regulation of the bicarbonate buffer in bodily fluids. We implemented a mathematical model of dissolved CO2 and bicarbonate transport that describes the changes in acid-base equilibrium induced by HD to assess the kinetics of bicarbonate, dissolved CO2, and other buffers not only in plasma but also in erythrocytes, interstitial fluid, and tissue cells; the model also includes respiratory control over the partial pressures of CO2 and oxygen. Clinical data were used to fit the model and identify missing parameters used in theoretical simulations. Our results demonstrate the feasibility of the model in describing the changes to acid-base homeostasis typical of HD, and highlight the importance of respiratory regulation during HD.

Despite the significant progress made in understanding chronic kidney disease and uraemic pathophysiology, use of advanced technology and implementation of new strategies in renal replacement therapy, the clinical outcomes of chronic kidney disease 5 dialysis patients remain suboptimal. Considering residual suboptimal medical needs of short intermittent dialysis, it is our medical duty to revisit standards of dialysis practice and propose new therapeutic options for improving the overall effectiveness of dialysis sessions and reduce the burden of stress induced by the therapy. Several themes arise to address the modifiable components of the therapy that are aimed at mitigating some of the cardiovascular risks in patients with end-stage kidney disease. Among them, five are of utmost importance and include: (i) enhancement of treatment efficiency and continuous monitoring of dialysis performances; (ii) prevention of dialysis-induced stress; (iii) precise handling of sodium and fluid balance; (iv) moving towards heparin-free dialysis; and (v) customizing electrolyte prescriptions. In summary, haemodialysis treatment in 2030 will be substantially more personalized to the patient, with a clear focus on cardioprotection, volume management, arrhythmia surveillance, avoidance of anticoagulation and the development of more dynamic systems to align the fluid and electrolyte needs of the patient on the day of the treatment to their particular circumstances.

The large prevalence of respiratory acid-base disorders overlapping metabolic acidosis in hemodialysis population should prompt nephrologists to deal with the partial pressure of carbon dioxide (pCO2) complying with the reduced bicarbonate concentration. What the most suitable formula to compute pCO2 is reviewed. Then, the neglected issue of CO2 content in the dialysis fluid is under the spotlight. In fact, a considerable amount of CO2 comes to patients' bloodstream every hemodialysis treatment and "acidosis by dialysate" may occur if lungs do not properly clear away this burden of CO2. Moreover, vascular access recirculation may be easy diagnosed by detecting CO2 in the arterial line of extracorporeal circuit if CO2-enriched blood from the filter reenters arterial needle.