Hemodialysis using a low bicarbonate dialysis bath: Implications for acid-base homeostasis.

The low bath bicarbonate concentration ([ HCO3- ]) used by a nephrology group in Japan (25.5 mEq/L), coupled with a bath [acetate] of 8 mEq/L, provided an opportunity to study the acid-base events occurring during hemodialysis when HCO3- flux is from the patient to the bath. We used an analytic tool that allows calculation of HCO3- delivery during hemodialysis and the physiological response to it in 17 Japanese outpatients with an average pre-dialysis blood [ HCO3- ] of 25 mEq/L. Our analysis demonstrates that HCO3- addition is markedly reduced and that all of it comes from acetate metabolism. The HCO3- added to the extracellular fluid during treatment (19.5 mEq) was completely consumed by H+ mobilization from body buffers. In contrast to patients dialyzing with higher bath [ HCO3- ] values in the US and Europe, organic acid production was suppressed rather than stimulated. Dietary analysis indicates that these patients are in acid balance due to the alkaline nature of their diet. In a larger group of patients using the same bath solution, pre-dialysis blood [ HCO3- ] was lower, 22.2 mEq/L, but still in an acceptable range. Our studies indicate that a low bath [ HCO3- ] is well tolerated and can prevent stimulation of organic acid production.

Changing dialysate composition to optimize acid-base therapy.

In response to rapid alkali delivery during hemodialysis, hydrogen ions (H+ ) are mobilized from body buffers and from stimulation of organic acid production in amounts sufficient to convert most of the delivered bicarbonate to CO2 and water. Release of H+ from nonbicarbonate buffers serves to back-titrate them to a more alkaline state, readying them to buffer acids that accumulate in the interval between treatments. By contrast, stimulation of organic acid production only serves to remove added bicarbonate (HCO3 - ) from the body; the organic anions produced by this process are lost into the dialysate, irreversibly acidifying the patient as well as diverting metabolic activity from normal homeostasis. We have developed an analytic tool to quantify these acid-base events, which has shown that almost two-thirds of the H+ mobilized during hemodialysis comes from organic acid production when bath bicarbonate concentration ([HCO3 - ]) is 32 mEq/L or higher. Using data from the hemodialysis patients we studied with our analytical model, we have simulated the effect of changing bath solute on estimated organic acid production. Our simulations demonstrate that reducing bath [HCO3 - ] should decrease organic acid production, a change we propose as beneficial to the patient. They also highlight the differential effects of variations in bath acetate concentration, as compared to [HCO3 - ], on the amount and rate of alkali delivery. Our results suggest that transferring HCO3 - delivery from direct influx to acetate influx and metabolism provides a more stable and predictable rate of HCO3 - addition to the patient receiving bicarbonate-based hemodialysis. Our simulations provide the groundwork for the clinical studies needed to verify these conclusions.

Acid-base homeostasis during hemodialysis: New insights into the mystery of bicarbonate disappearance during treatment.

In patients receiving hemodialysis, it has long been recognized that much more bicarbonate is delivered during treatment than ultimately appears in the blood. To gain insight into this mystery, we developed a model that allows a quantitative analysis of the patient's response to rapid alkalinization during hemodialysis. Our model is unique in that it is based on the distribution of bicarbonate in the extracellular fluid and assesses its removal from this compartment by mobilization of protons (H+ ) from buffers and other sources. The model was used to analyze the pattern of rise in blood bicarbonate concentration ([HCO3- ]), calculated from measurements of pH and PCO2 , in patients receiving standard bicarbonate hemodialysis. Model analysis demonstrated two striking findings: (1) 35% of the bicarbonate added during hemodialysis was due to influx and metabolism of acetate, despite its low concentration in the bath solution, because of the rapidly collapsing gradient for bicarbonate influx. (2) Almost 90% of the bicarbonate delivered to the patients was neutralized by H+ generation. Virtually all the new H+ came from intracellular sources and included both buffering and organic acid production. The small amount of added bicarbonate retained in the extracellular fluid increased blood [HCO3- ], on average, by 6 mEq/L in our patients. Almost all this rise occurred during the first 2 hours. Thereafter, blood [HCO3- ] changed minimally and always remained less than bath [HCO3- ]. This lack of equilibrium was due to the continued production of organic acid. Release of H+ from buffers is a reversible physiological response, restoring body alkali stores. By contrast, organic acid production is an irreversible process during hemodialysis and is metabolically inefficient and potentially catabolic. Our analysis underscores the need to develop new approaches for alkali repletion during hemodialysis that minimize organic acid production.

Conservation of Mass: An Important Tool in Renal Research.

The dialytic treatment of end-stage renal disease (ESRD) patients is based on control of solute concentrations and management of fluid volume. The application of the principal of conservation of mass, or mass balance, is fundamental to the study of such treatment and can be extended to chronic kidney disease (CKD) in general. This review discusses the development and use of mass conservation and transport concepts, incorporated into mathematical models. These concepts, which can be applied to a wide range of solutes of interest, represent a powerful tool for quantitatively guided studies of dialysis issues currently and into the future. Incorporating these quantitative concepts in future investigations is key to achieving positive control of known solutes, and in the analysis of such studies; to relate future research to known results of prior studies; and to help in the understanding of the obligatory physiological perturbations that result from dialysis therapy.

A cluster randomized controlled trial of child-focused psychiatric consultation and a school systems-focused intervention to reduce aggression.

BACKGROUND: While school-based anti-bullying programs are widely used, there have been few controlled trials of effectiveness. This study compared the effect of manualized School Psychiatric Consultation (SPC), CAPSLE (a systems and mentalization focused whole school intervention), and treatment-as-usual (TAU) in reducing aggression and victimization among elementary school children. METHOD: Participants were 1,345 third to fifth graders in nine elementary schools in a medium-sized Midwestern city who took part in a cluster-level randomized controlled trial with stratified restricted allocation, to assess efficacy after two years of active intervention and effectiveness after one year of minimal input maintenance intervention. Outcome measures included peer and self-reports of bullying, bystanding, and mentalizing behavior and classroom behavioral observations of disruptive and off-task behavior. RESULTS: CAPSLE moderated the developmental trend of increasing peer-reported victimization (p < .01), aggression (p < .05), self-reported aggression (p < .05) and aggressive bystanding (p < .05), compared to TAU schools. CAPSLE also moderated a decline in empathy and an increase in the percent of children victimized compared to SPC (p < .01) and TAU conditions (p < .01). Results for self-reported victimization, helpful bystanding, and beliefs in the legitimacy of aggression did not suggest significantly different changes among the study conditions over time. CAPSLE produced a significant decrease in off-task (p < .001) and disruptive classroom behaviors (p < .01), while behavioral change was not observed in SPC and TAU schools. Superiority with respect to TAU for victimization (p < .05), aggression (p < .01), and helpful (p < .05) and aggressive bystanding (p < .01) were maintained in the follow-up year. CONCLUSIONS: A teacher-implemented school-wide intervention that does not focus on disturbed children substantially reduced aggression and improved classroom behavior.

Analyzing the true cost of delivering medications.

Reimbursement to providers for delivering medications in the dialysis field is a subject of current concern, with some payors limiting payment to an amount equaling the provider's acquisition cost. At the same time, some providers arbitrarily mark up medications by a large factor. For dialysis, as well as for the general medical field, an objective approach is required for both providers and payors to fairly set prices and reimbursement levels. This analysis evaluated all cost elements involved in the delivery of medications and determined that an increase over the acquisition cost is appropriate for pricing and reimbursement. The increase has 2 parts: a fixed cost associated with resources required for a medication irrespective of its cost and a markup on the acquisition price. The conclusion of this analysis is that an increase over acquisition cost in reimbursement of providers for delivering medications is required to fairly compensate them for their actual costs and avoid compelling them to either incur a loss or cost shift by overcharging some payors to compensate for underpayment by others. Planned adjustments in Medicare reimbursement for dialysis may not recognize this reality.

Iron requirements in hemodialysis.

The correction of anemia in dialysis patients with erythropoietin (EPO) can be frustrated by insufficient iron. To address this effect, we preloaded candidate EPO patients with intravenous iron in the early 1990s. Preloading with 900-1,525 mg of iron yielded the following results: 70% of patients had increasing hematocrits (HCTs) without EPO, and 40% of patients had HCTs greater than 30%. Apparent lack of iron led to blood loss studies. Routes evaluated were blood sampling, dialyzer clotting, blood in the dialyzer circuit and postdialysis bleeding. Projected annual losses were between 2,516 and 5,126 ml, depending on circuit and posttreatment losses. In terms of red cell loss, the results are comparable to those in the early days of dialysis before the introduction of current technology. Extension of these studies to daily dialysis predicts possible losses with this 6 times a week therapy of between 4,663 and 9,884 ml per year.

Identifying the value of computers in dialysis.

Dialysis providers use computers to automate complicated tasks, ease staff burden, and develop knowledge or understanding to improve operations and patient care. Some applications are successful, others are not. Success can be economically quantified. Business--billing and accounts receivable computerization--can yield over $5.00 for $1.00 invested. The clinical case is more complex and difficult to economically justify. Computerization of clinical information for charge capture is the simplest application (< $1.00/treatment) yielding the greatest benefit. Economic benefits for improving quality of care through electronic medical records are more problematic. Provider benefit of clinical computing is strictly the net income from more dialysis treatments. Greater complexity--e.g., total electronic records--means more expensive systems and increased staff effort. Many systems cost in the $5.00 + range which must be paid by increasing provider overhead. Dialysis providers must determine the point where computerization no longer decreases operational costs as computing cost increases. This is a classical optimization problem; its solution is crucial to the economic health of the dialysis enterprise.