A multinational clinical validation study of PD ADEQUEST 2.0. PD ADEQUEST International Study Group.

OBJECTIVE: To clinically validate the use of the newly released kinetic modeling program, PD ADEQUEST 2.0 for Windows (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), by assessing the level of agreement between measured and modeled values of urea and creatinine clearances (CCr), glucose absorption, total drain volumes, and net ultrafiltration for all forms of peritoneal dialysis. DESIGN: A nonrandomized, multinational, prospective longitudinal study. PATIENTS: The study involved 104 adult patients [41 on continuous ambulatory peritoneal dialysis (CAPD), 63 on automated peritoneal dialysis (APD)] from 16 centers in 7 countries. All patients underwent a 4-hour peritoneal equilibration test (PET) but with varying percentage dextrose concentrations (1.5% or 2.5% dextrose) and varying fill volumes (range 1.5 - 2.5 L). Patients with a residual renal function greater than 10 mL/min were excluded, as were patients who had peritonitis within 6 weeks prior to baseline. MAIN OUTCOME MEASURES: Correlation coefficients and Bland-Altman limits of agreement were used to assess the level of agreement between measured and modeled values of weekly peritoneal urea Kt/V (pKt/V) and total Kt/V, weekly peritoneal creatinine clearance (pCCr, L/week/1.73 m2) and total CCr (L/week/1.73 m2), daily drain volume (L/day), net ultrafiltration (UF, L/day), daily peritoneal urea and creatinine mass removal (g/day), and daily peritoneal glucose absorption (g/day). Measured values were obtained from three repeat 24-hour urine and dialysate collections per patient, while modeled values were calculated using the Baxter PD ADEQUEST 2.0 program in conjunction with kinetic parameters estimated from a 4-hour PET and long-dwell exchange independent of the 24-hour collections. RESULTS: The results show there is excellent agreement between measured and modeled urea Kt/V and CCr with concordance correlation coefficients ranging from 0.83 to 0.97 among CAPD and APD patients. There was also excellent agreement between measured and modeled values of glucose absorption and total drain volumes (concordance correlations of 0.90 and 0.98, respectively). This level of agreement was further supported by a Bland-Altman analysis of individual differences, including differences between measured and modeled net UF (coefficient of clinical agreement ranged from 0.66 to 0.92). CONCLUSIONS: Data from a carefully performed PET and overnight exchange can, in combination with a scientifically and clinically validated kinetic model, provide clinicians with a powerful mathematical tool for use in CAPD and APD prescription management. Although not intended to replace actual measurements, kinetic modeling can prove useful as a means for quickly estimating approximate levels of clearance for a wide variety of alternative prescriptions. This, in turn, should speed up the process by which a physician can optimize the dose of dialysis suitable for a given patient and his/her lifestyle.

Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).

Glutathione is a major cellular antioxidant that protects protein thiols and inhibits cellular damage due to oxygen free radicals. It has been reported previously that patients undergoing dialysis have low levels of blood glutathione, which may lead to increased susceptibility to oxidant stress. L-2-oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises cellular glutathione levels by increasing delivery of cysteine, the rate-limiting substrate for glutathione synthesis. This study investigates the effect of OTZ on blood glutathione in a blinded, placebo-controlled study of patients with chronic renal failure treated by peritoneal dialysis. Twenty patients were randomly selected to receive OTZ (0.5 g three times a day orally with meals) or placebo for 14 d. Patients visited the clinic for predose blood collection and safety evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose [follow-up]). Glutathione concentrations were determined in whole blood by HPLC. OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/- 129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139 mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo group at any patient visit, and levels in the OTZ-treated group returned to baseline at follow-up. There were no serious adverse events attributable to OTZ, and the drug appeared to be well tolerated by patients with renal failure treated by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases blood glutathione levels, which may improve antioxidant status in dialysis patients.

Inline fluid dynamics in piggyback and manifold drug delivery systems.

Inline mixing characteristics of primary and secondary i.v. solutions were evaluated for the piggyback and manifold systems. Dextrose (5%) and sodium chloride (0.9%) were used as markers for the primary and secondary solutions, respectively. With a 120-mL/hr flow rate, samples (up to 180) were collected over 36 minutes to quantify the change in concentration of each marker when the primary solution was changed to the secondary solution (phase 1) and when the secondary solution was changed to the primary solution (phase 2). The relative concentration data for each marker were fitted to a Weibull mathematical model to describe the disappearance and appearance of the two solutions over time. These data were then used to calculate the volume of secondary solution that was mixed with the primary solution in phases 1 and 2. With the piggyback system, the total mixing volume was 13.5 mL, with 11.1 mL contributed by the secondary solution (phase 1). In phase 2, the total mixing volume decreased to 6.6 mL, with 2.0 mL contributed by the secondary solution. The mixing volumes for the manifold system were markedly reduced; 5.8 mL of the secondary solution became mixed with 1.9 mL of the primary solution. The total mixing volume during phase 1 was reduced from 13.5 to 5.6 mL. The mixing volumes for the primary, secondary, and total solutions in phase 2 were comparable to those with the piggyback system. The use of manual clamps or automated line closures as part of a manifold system can substantially reduce the mixing of solutions inline, compared with a piggyback system.

Effect of silver oxide/trichloroisocyanuric acid antimicrobial urinary drainage system on catheter-associated bacteriuria.

We assessed the efficacy of silver oxide coating of the indwelling urethral catheter and catheter adapter, and instillation of trichloroisocyanuric acid into the urinary drainage bag in the prevention of catheter-associated bacteriuria in a prospective and randomized study of 74 patients. Bacteriuria was documented in 29 of the 74 patients (39 per cent). There was a significant difference between the attack rates, with 11 of 41 patients (27 per cent) in the test group and 18 of 33 (55 per cent) in the control group having bacteriuria (p equals 0.02) after a median time to bacteriuria of 36 and 8 days, respectively (p equals 0.01). Urethral meatal colonization was implicated as the source of bladder bacteriuria in 12 of 18 patients (67 per cent) in the control group and 5 of 11 (45 per cent) in the test group. Trichloroisocyanuric acid significantly reduced drainage bag contamination but bag contamination with the same microorganism responsible for bacteriuria preceded infection in only 2 of the 29 patients (7 per cent), 1 in each group. Patients who received systemic antimicrobial agents acquired bacteriuria less frequently than those who did not. The apparent protective effect of systemic antimicrobials was strongest during the first 4 days of catheterization. The data indicate that episodes of bacteriuria arising from the urethral meatus are common among catheterized patients and that the antimicrobial catheter is effective in reducing the incidence of catheter-associated bacteriuria.