Comparative analysis reveals dialysis alters pH through bicarbonate and organic anions in hemodialysis and peritoneal dialysis, indicating different model strengths.
Background: The relative merits of the Henderson–Hasselbalch (HH) versus Stewart frameworks for interpreting dialysis-associated acid–base shifts remain debated. Dialysis alters systemic pH through exogenous bicarbonate delivery, chloride displacement, and removal of organic anions. We compared these approaches across hemodialysis (HD) and peritoneal dialysis (PD). Methods: We studied 53 HD patients with paired pre/post-HD blood gas and chemistry (106 observations) and 41 PD patients cross-sectionally, totaling 147 datasets. Derived variables followed the Figge/Stewart implementation [apparent SID (SIDa), effective SID (SIDe), strong ion gap (SIG), albumin-corrected anion gap (AGc)]. For HD, changes in pH (ΔpH) were modeled using HH predictors (ΔHCO3−, ΔPCO2) and Stewart predictors (ΔSIDa, ΔATOT, ΔPCO2). For cross-sectional data (pre-HD, post-HD, and PD), HH- and Stewart-based level models were fitted. Stewart-predicted pH was also computed using the Figge and the simplified Constable electroneutrality equation. Results: HD increased pH by 0.11, driven by ΔHCO3− = +5.7 mΕq/L, ΔCl− = −2.3 mEq/L, and declines in unmeasured anions (ΔSIG = −3.9; ΔAGc = −3.3). SIDa increased only marginally (+1.3 mEq/L), whereas SIDe rose by +5.3 mEq/L and fully tracked the alkalinization. In Δ-models, HH explained 90% of variance in ΔpH (R2 = 0.903) compared with 51% for Stewart (R2 = 0.514). In level models, HH explained 96% of pH variance versus 36% for Stewart. Bland–Altman analysis showed systematic overestimation of pH by the Figge and Constable approach (bias + 0.111), most pronounced pre-HD. PD patients had consistently higher AGc and SIG values than HD patients, indicating a greater burden of unmeasured anions. Conclusions: Alkalinization during HD is primarily attributable to bicarbonate gain, chloride displacement, and organic-anion clearance. The HH framework provides superior predictive performance for ΔpH, while closed-system Stewart formulations based on SIDa underestimate alkalinization. However, a broader physicochemical interpretation using SIDe and SIG, which incorporate bicarbonate and unmeasured anions, coherently describes the observed physiology. Future applications of the Stewart approach in dialysis should emphasize SIDe and SIG to better reflect the open-system physiology of both HD and PD. Our findings suggest that the HH model remains more predictive of alkalinization, while SIDe and SIG refine the physicochemical understanding.
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Kroustalakis et al. (2025) studied this question.
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