The association of the sodium "setpoint" to interdialytic weight gain and blood pressure in hemodialysis patients.

INTRODUCTION: Hemodialysis patients lack the normal mechanisms to regulate body water volume and osmolality. The dialysis treatment is expected to adequately regulate both body water volume and body Na+ content, which is the primary action determining body water osmolality. Data in subjects with normal renal function indicate that an individual has a specific osmolality value above which thirst is generated and fluid will be ingested. This specific osmolality value or "setpoint" varies among individuals, but is quite reproducible within an individual. It was postulated that hemodialysis patients also may have a Na+ 'setpoint', which if increased by the use of higher dialysate Na+ concentration, might be associated with increased interdialytic weight gain and blood pressure. METHODS: Monthly laboratory and treatment data were abstracted on 58 hemodialysis patients and included pre- and post-dialysis serum Na+ concentrations, interdialytic weight gain and blood pressure over 9 to 16 months. The Na+ concentrations were averaged to determine the individual Na+ 'setpoint' and the Na+ gradient (Dialysis Na+ concentration - mean Na+ concentration) was determined for each patient. RESULTS: Linear regression analyses showed that there was a statistically significant association between the magnitude of the Na+ gradient and interdialytic weight gain and blood pressure. CONCLUSIONS: These data suggest that interdialytic weight gain in individual patients may be associated with the use of dialysate Na+ concentration in excess of the patient's desired Na+ 'setpoint'. More individualization of dialysate Na+ concentration may be indicated.

Whither goest Kt/V?

Uremia is characterized by gross contamination of body water with a wide spectrum of retained solutes normally excreted by the kidney. The rationale for dialysis therapy is that these retained solutes have concentration-dependent toxicity, which can be ameliorated through removal by dialysis. Apart from the well-established clinical consequences of abnormalities in fluid, electrolyte, acid base metabolism, and retained beta 2-microglobulin (beta 2 m), there is very little understanding of solute-specific uremic toxicity. Evidence is reviewed to demonstrate the following: (1) Many aspects of the uremic syndrome are controlled by adequate dialysis of low molecular weight solutes. (2) Urea can serve as a generic molecule to quantitate the fractional clearance of body water by dialysis (Kt/V) of retained low molecular weight solutes. (3) Urea has no concentration-dependent toxicity, and the generation rate of putative toxic low molecular weight solutes is not proportional to urea generation. The major clinical consequences and controversies stemming from these interrelationships are reviewed. Kinetic approaches to determine Kt/V dose equivalency between intermittent and continuous dialysis therapy are reviewed. We conclude that Kt/V can and will be generalized to describe the kinetics of other solutes such as beta2m as our knowledge of uremic toxicity grows, and hence, it is predicted that it will goeth and goeth and goeth.

Hemoglobin and hematocrit: an analysis of clinical accuracy. Case study of the anemic patient.

Hemoglobin (Hgb) and hematocrit (Hct) are often used interchangeably to evaluate anemia in dialysis patients. Hgb is the preferred method in most European countries, while Hct is generally used by clinicians in the United States. This article examines the comparative accuracy of these two values, including a same-patient assessment of laboratory samples. These data illustrate that Hgb is a more accurate method of assessing anemia. Using Hgb may help nurses and patients by: (a) decreasing variability in laboratory assessment, (b) avoiding ongoing errors in anemia measurement, (c) decreasing the nursing time spent on anemia management, and (d) increasing the potential for patients remaining in the recommended DOQI target Hgb range of 11 g/dL to 12 g/dL.

The incident patient cohort study design with uncontrolled dose. Substantial over-estimation of mortality as a function of peritoneal dialysis dose?

In the Canada-USA (CANUSA) Study, the dialysis dose was neither randomized nor held constant, was measured at 6 month intervals, and the relative risk of mortality (R) was found to correlate linearly to mean values of weekly peritoneal plus renal urea clearance normalized to volume, (KprT/ V)m, ranging from 1.5 to 2.3. A risk/dose (R/D) function was derived for continuous ambulatory peritoneal dialysis from kinetic criteria for dose equivalency in hemodialysis (HD) and peritoneal dialysis (PD) and the HD R/D function. This PD R/D function was nonlinear with breakpoint from steep to shallow slope at (KprT/V)ud = 2.00, where ud refers to uniform single doses in contrast to mean doses with wide variances on the mean. The predicted decrease in renal urea clearance KrT/V per 6 months of CANUSA follow-up was computed from serial measured KrT/V in the Randomized Dialysis Prescription and Clinical Outcomes Study and showed it to be 0.21 +/- 0.34. The CANUSA (KprT/V)m values were corrected for the distributed values of 3 months decrements in KrT/V, and the population mortality risk at each (KprT/V)m dose level reported in CANUSA was computed from summation of the product of the R/D curve and fractional distribution of (KprT/V)ud values. From these calculations, the authors conclude that maximum (KprT/V)ud level achieved in CANUSA was 2.00, and the study does not define R/D response above this level.

Computerized urea kinetic modeling to prescribe and monitor delivered Kt/V (pKt/V, dKt/V) in peritoneal dialysis. Fresenius Randomized Dialysis Prescriptions and Clinical Outcome Study (RDP/CO).

A computerized urea kinetic model of peritoneal urea transport (PACK-PD) has been developed and used to calculate prescription parameters which would result in the prescribed weekly peritoneal urea clearance (pKpt/V) required to achieve levels of weekly summed renal + peritoneal urea clearance (pKprt/ V) targeted at 1.75 and 2.16. Baseline kinetic data were obtained and analyzed with PACK-PD on 88 patients, and the program then used these data to calculate the required pKpt/V and subsequently the delivered Kpt/V (dKpt/V) from the dialysate collections. A total of 108 prescriptions were written and compared to dKpt/V measured over one to 24 months in the 88 patients. Both continuous ambulatory peritoneal dialysis and automated peritoneal dialysis (APD) were studied (APD consisted of PD+ with one or two diurnal and two to four nocturnal cycler exchanges). The correlation of dKpt/V to pKpt/V showed r = 0.93 with 95% confidence limits (CL) on agreement of +/-20% over a range of pKpt/V 0.52-2.55. The 95% CL on (dKpt/V-pKpt/V) were +/-0.30. We concluded: (1) that the prescription can be modeled as reliably in peritoneal dialysis as in hemodialysis (HD) where dKt/V and pKt/V agree to +/-25%, (2) that any individual weekly dKpt/V may vary as much as 0.3-0.4 from pKpt/V, and (3) that frequent measurement of dKpt/V and adjustment of pKpt/V as needed are required (as in HD) to control mean dKpt/V to within +/-10% of mean pKpt/V.

Epoetin alfa--focus on dialyzability. Case study of the anemic patient.

Epoetin alfa therapy has typically been administered at the end of dialysis. A recently completed in vivo study with a small patient population strengthens previous study findings and suggests that this protein can be safely administered during high-flux dialysis without fear of membrane adsorption. Data indicate that successful use of this technique depends on a variety of factors, including the site of administration. If confirmed, these findings could benefit both patients and clinicians.

Case management of the anemic patient. Epoetin alfa: focus on kinetic dosing.

Epoetin alfa (EPOGEN, recombinant human erythropoietin) has proven to be a major therapeutic advance in treating the chronic refractory anemia associated with end-stage renal disease (ESRD). As with many medications, the dose of Epoetin alfa must be individualized for each patient. In order to elicit a consistent production of red cells from the bone marrow, it is desirable that dose modifications be made as infrequently as possible. Gotch and Uehlinger have developed a kinetic model that can limit dose modifications by predicting the optimal dose of Epoetin alfa for each patient. Termed the Erythrokinetic Model, it compares individual patient response to Epoetin alfa to the life cycle of a red blood cell. This article describes the Gotch/Uehlinger Erythrokinetic Model and uses it to gauge the clinical response of 2 patients to Epoetin alfa.

An analysis of thermal regulation in hemodialysis with one and three compartment models.

A one compartment model of heat kinetics in hemodialysis (HD) was formulated, solved for the body surface heat transfer coefficient, and used to analyze reported clinical data. The analysis showed a linear relationship between percent change in body surface (y) and fractional dialyzer (x) heat loss, such that y = -25 - 44X, p less than 0.001. Thus, when X = 0, surface heat loss decreases 25% and core temperature (T) rises, and X must equal 45% of heat production to stabilize core T during HD. A three compartment model predicts that skin clothing insulation will have to increase 2.5 times to avoid thermal discomfort when X = 45% of heat production. A theoretic mechanism for decreased symptomatic hypotension resulting from stabilization of core T is proposed.

Hydrogen ion balance in dialysis therapy.

A model to describe hydrogen ion balance (H+B) in acetate and bicarbonate dialysis therapy was developed based on measurement of metabolic addition of hydrogen ion (H+) to the body between and during dialyses and measurement of net buffer repletion during dialysis. Metabolic H+ generation was shown to be equal to 0.77 times the protein catabolic rate plus the total net removal of lactate and beta-hydroxybutyrate ions during dialysis. Buffer repletion was calculated from total net flux of acetate and bicarbonate during dialysis. The model was used for eight paired studies of H+B on one week each of acetate and bicarbonate dialysis and showed that cumulative H+B with acetate was -7 +/- 28 (M +/- SEM) mmol/week compared to -175 +/- 45 mmol/week with bicarbonate (P less than 0.001). It is concluded that there is an initial, strongly negative H+B when patients on acetate dialysis are converted to bicarbonate. The possible physiologic significance of this is discussed.