Hospitalization risks between Renagel phosphate binder treated and non-Renagel treated patients.

AIM: We evaluated 152 sevelamer hydrochloride treated Medicare patients on hemodialysis in a case-controlled study matching 152 randomly selected non-sevelamer hydrochloride treated Medicare patients from the same dialysis facilities and time period. The main outcomes evaluated were the risk of all-cause hospitalization and per-member per-month (PMPM) Medicare expenditures in the follow-up period. PATIENTS AND METHODS: Medicare patients were identified from a total of 195 patients who were included in a long-term safety and efficacy clinical trial evaluating sevelamer hydrochloride [Chertow et al. 1999a]. The average serum calcium-phosphorus product as well as lipid profiles improved in the sevelamer hydrochloride treated group during the trial. Sevelamer treated patients were matched with randomly selected Medicare patients for age, gender, race, diabetic status, and geographic location. Comorbid conditions were characterized and sequential Cox regression models were applied with the outcome being risk of first hospitalization in a 17- month follow-up period. RESULTS: Across all four models, the relative risk of hospitalization was 46% to 54% less in the sevelamer hydrochloride treated group, as compared to the case control group (significant at the p-value 0.03 level). Overall, Medicare expenditures for the control patients per-member per-month were US-$4,745, compared to US-$3,368 in the sevelamer hydrochloride treated patients. CONCLUSION: Sevelamer hydrochloride treated patients had a 50% lower likelihood of hospitalization in the follow-up period after adjustments for the differences in the population. Potential bias may exist between groups because of differences in baseline characteristics that could not be adjusted for within the study design. We feel that to further advance this area, a randomized clinical trial should be performed.

Impact of disease severity and hematocrit level on reuse-associated mortality.

Prior studies on reuse-associated mortality have presented conflicting results and included few adjustments for disease severity or hematocrit levels. To evaluate the impact of patient and provider characteristics on reuse-associated mortality, we developed a period-prevalent model with a 6-month entry period. Five cohorts of Medicare hemodialysis patients surviving from July 1 through December 31 of the entry year (1991, 60,985 patients; 1992, 63,081 patients; 1993, 76,018 patients; 1994, 82,899 patients; 1995, 91,761 patients) were followed up for the next year. Using a basic Cox regression survival model (M-1) including age, sex, race, renal diagnosis, prior end-stage renal disease time, unit age, unit size, water treatment, dialysate, and germicide, results were compared with those using a more inclusive model (M-4) adding dialyzer type (conventional or high efficiency/high flux), unit designation (hospital based or freestanding), unit profit status, comorbidity, disease severity, and hematocrit. The previous association of for-profit units with increased mortality was not present after 1994. Whereas the M-1 analysis showed better survival in reuse units after 1991, the more complete M-4 analysis showed no difference in the risk for mortality between reuse and no-reuse units. We conclude that mortality rates in the United States from 1991 to 1995, when adjusted comprehensively for patient and unit characteristics, were not different in units that practiced reuse and those that did not.

Mortality risks of peritoneal dialysis and hemodialysis.

Studies of outcomes associated with dialysis therapies have yielded conflicting results. Bloembergen et al showed that prevalent patients on continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD) had a 19% higher mortality risk than hemodialysis patients, and Fenton et al, analyzing Canadian incident patients, found a 27% lower risk. Attempting to reconcile these differences, we evaluated incident Medicare patients (99,048 on hemodialysis, 18,110 on CAPD/CCPD) from 1994 through 1996, following up to June 30, 1997. Patients were followed to transplantation, death, loss to follow-up, 60 days after modality change, or end of the study period. For each 3-month survival period, we used an interval Poisson regression to compare death rates, adjusting for age, gender, race, and primary renal diagnosis. A Cox regression was used to evaluate cause-specific mortality, and proportionality was addressed in both regressions by separating diabetic and nondiabetic patients. The Poisson regressions showed CAPD/CCPD to have outcomes comparable with or significantly better than hemodialysis, although results varied over time. The Cox regression found a lower mortality risk in nondiabetic CAPD/CCPD patients (women younger than 55 years: risk ratio [RR] = 0. 61; Cl, 0.59 to 0.66; women age 55 years or older: RR = 0.87; Cl, 0. 84 to 0.91; men younger than 55 years: RR = 0.72; Cl, 0.67 to 0.77; men age 55 years or older: RR = 0.87; Cl, 0.83 to 0.92) and in diabetic CAPD/CCPD patients younger than 55 (women: RR = 0.88; Cl, 0. 82 to 0.94; men: RR = 0.86; Cl, 0.81 to 0.92). The risk of all-cause death for female diabetics 55 years of age and older, in contrast, was 1.21 (Cl, 1.17 to 1.24) for CAPD/CCPD, and in cause-specific analyses, these patients had a significantly higher risk of infectious death. We conclude that, overall, within the first 2 years of therapy, short-term CAPD/CCPD appears to be associated with superior outcomes compared with hemodialysis. It also appears that patients on the two therapies have different mortality patterns over time, a nonproportionality that makes survival analyses vulnerable to the length of follow-up. Further investigation is needed to evaluate both the potential explanations for these findings and the use of more advanced statistical methods in the analysis of mortality rates associated with these dialytic therapies.

Multicenter clinical validation of an on-line monitor of dialysis adequacy.

Quantitation of hemodialysis by measuring changes in blood solute concentration requires careful timing when taking the postdialysis blood sample to avoid errors from postdialysis rebound and from recirculation of blood through the access device. It also requires complex mathematical interpretation to account for solute disequilibrium in the patient. To circumvent these problems, hemodialysis can be quantified and its adequacy assessed by direct measurement of the urea removed in the dialysate. Because total dialysate collection is impractical, an automated method was developed for measuring dialysate urea-nitrogen concentrations at frequent intervals during treatment. A multicenter clinical trial of the dialysate monitoring device, the Biostat 1000 (Baxter Healthcare Corporation, McGaw Park, IL) was conducted to validate the measurements of urea removed, the delivered dialysis dose (Kt/V), and net protein catabolism (PCR). The results were compared with a total dialysate collection in each patient. During 29 dialyses in 29 patients from three centers, the paired analysis of urea removed, as estimated by the dialysate monitor compared with the total dialysate collection, showed no significant difference (14.7 +/- 4.7 g versus 14.8 +/- 5.1 g). Similarly, measurements of Kt/V and PCR showed no significant difference (1.30 +/- 0.18 versus 1.28 +/- 0.19, respectively, for Kt/V and 42.3 +/- 15.7 g/day versus 52.2 +/- 17.4 g/day for PCR). When blood-side measurements during the same dialyses were analyzed with a single-compartment, variable-volume model of urea kinetics, Kt/V was consistently overestimated (1.49 +/- 0.29/dialysis, P < 0.001), most likely because of failure to consider urea disequilibrium. Because urea disequilibrium is difficult to quantitate during each treatment, dialysate measurements have obvious advantages. The dialysate monitor eliminated errors from dialysate bacterial contamination, simplified dialysate measurements, and proved to be a reliable method for quantifying and assuring dialysis adequacy.

Pitfalls of in vivo dialyzer clearance measurement.

Dialyzer small-molecule clearance measurements are commonly made to help identify the cause of inadequate dialysis prescriptions, to determine the efficacy of reuse procedures, or to choose between different types of dialyzers. Clearance measurements can be blood-side- or dialysate-side-based. While blood-side clearance measurement is the classical technique, it suffers from several serious flaws that decrease its accuracy. Chief among these are the inability to accurately measure the blood flow rate and the difficulty in accounting for the presence of nonaqueous components in the blood. Using a dialysate-based clearance measurement technique overcomes these problems for most solutes, provided appropriate guidelines are followed. This article reviews the theory behind both blood- and dialysate-side techniques as well as discussing the practical application of that theory to clearance measurement.

On-line monitoring of the delivery of the hemodialysis prescription.

The BioStat 1000 is a new device which employs dialysate-based urea kinetics to calculate the dose of dialysis (Kt/V) based on a two-pool model and protein catabolic rate (PCR). Previous methods relying on blood sampling techniques were subject to error and difficult to implement. This paper describes the features of the Biostat and the results of the first clinical validation study with an early prototype. The BioStat was found to compare favorably with the reference method of direct dialysate quantification (mDDQ) which had been modified to obtain a "two-pool" Kt/V. In 31 patients no significant difference was found between mean Kt/V from the mDDQ and the mean Kt/V from the BioStat (1.35 +/- 0.33 versus 1.38 +/- 0.36, respectively). The PCR was also not significantly different (53.4 +/- 18.5 g/day versus 51.8 +/- 16 g/day, respectively). The BioStat was demonstrated to be a convenient method producing reliable results.