Water permeability of high-flux dialyzer membranes after Renalin reprocessing.

Dialysis with high-flux membranes is widely used, in part, because they are thought to increase the removal of middle molecules when compared with low-flux membranes. Dialyzer reprocessing; however, is thought to alter middle molecule clearance. Renalin, a mixture of germicidal agents, has widespread use in dialyzer reprocessing. We determined the effect of Renalin reprocessing on the water permeability of three different dialyzers of Fresenius (F80A and 200A) and Gambro (17R) manufacture using the dead-end filtration method. Two hundred and seventeen, predominantly used but some new, dialyzers were evaluated. Water permeability of the used, but not the new, dialyzers fell abruptly and dramatically with reprocessing. The permeability fell almost 70% in the F80A dialyzer after three reprocessing procedures with similar, but somewhat slower declines, seen in the other two dialyzers. We conclude that there is a decline in water permeability seen in Renalin reprocessed dialyzers. This factor and the associated change in solute clearance and ultrafiltration characteristics should be considered in assessing the effectiveness of dialyzer reprocessing.

Measuring total body water in peritoneal dialysis patients using an ethanol dilution technique.

UNLABELLED: Measuring total body water in peritoneal dialysis patients using an ethanol dilution technique. BACKGROUND: The accuracy with which total body water (TBW) is estimated is a direct determinant of the reliability of Kt/V urea measurements in peritoneal dialysis (PD) patients. Ethanol dilution has been previously shown to be a reliable measure of TBW. Advances in breath alcohol technology make this a feasible clinical tool. METHODS: We gave 19 fasting chronic PD patients 0.3 g/kg of ethanol (EtOH) orally on two separate occasions. Breath alcohol concentrations (BrACs), determined by dual-beam infrared analysis, were recorded at baseline and periodically thereafter until BrACs were less than 0.01%. The TBW was then determined by standard pharmacokinetic techniques. RESULTS: TBW measurements were reproducible, with a mean between-run difference of -0.004 liter/kg (95% limits of agreement -0.040 to 0. 032 by Bland-Altman). The Watson equations tended to underestimate TBW, with a mean difference (EtOH - Watson) of +3.0 liters (SD 4.0 liters, P = 0.004) and a mean absolute difference of 4.1 liters (SD 2.7 liters, range -4.4 to 9.5 liters). Kt/V was calculated from dialysate and urine collection, using V as determined from TBW estimates from EtOH and Watson. The mean Kt/V(EtOH) was 2.31 (SD 0. 50) compared with 2.46 (SD 0.52) using Watson. The mean absolute difference between the two Kt/V estimates was 0.26 (SD 0.20, range -0.87 to 0.57), with Kt/V overestimated by Watson in 14 patients. EtOH was well tolerated, and the procedure was completed in about four hours. CONCLUSIONS: Measuring V by the BrAC technique does not require blood sampling, is reliable, and is reproducible. It is a potentially useful method for a periodic determination of volume that may allow for more accurate Kt/V measurement in PD patients.

Effects of erythropoietin, angiotensin II, and angiotensin-converting enzyme inhibitor on erythroid precursors in patients with posttransplantation erythrocytosis.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) have become the treatment of choice for posttransplantation erythrocytosis (PTE). Yet the pathogenesis of PTE and the mechanisms of action of ACEI remain unclear. Therefore, we studied the dose response to erythropoietin (Ep), angiotensin II (AII), and the ACEI enalaprilat on the in vitro proliferation of erythroid progenitors in patients with PTE and in controls. We also evaluated ACE polymorphism in the two groups. METHODS: Twelve patients with PTE and 12 renal transplant patients without PTE were studied. Erythroid burst-forming units (BFU-E) were isolated from peripheral blood using standard methods. Ep sensitivity was determined for four patients with PTE and three control patients, using 0-3 U/ml Ep. AII dose response was studied in four patients with PTE and five control patients, using AII concentrations of 0-1000 nM. The effect of enalaprilat was studied in eight patients with PTE and eight control patients, using drug concentrations of 0-10 ng/ml. ACE gene insertion/deletion polymorphism was determined by polymerase chain reaction. RESULTS: PTE patients showed a significant shift of the Ep response curve to the left compared with controls, with 50% maximal growth occurring at a lower Ep concentration (0.3 U/ml vs. 0.95 U/ml, P<0.025.) However, there was no difference in the number of BFU-E colonies between PTE patients and controls. AII added to the growth medium produced only minor stimulation in both groups. PTE patients showed significant inhibition of BFU-E growth with 10 ng/ml enalaprilat, but controls showed no inhibition of BFU-E growth with ACEI. There was no difference in ACE polymorphism between PTE and controls. CONCLUSIONS: Our data suggest that PTE is associated with increased erythroid progenitor sensitivity to Ep. The effect of ACEI to decrease hematocrit in patients with PTE may be due to inhibition of red cell precursor growth.

Comparison of clinical features and liver histology in hepatitis C-positive dialysis patients and renal transplant recipients.

OBJECTIVE: Liver biopsies in hepatitis C virus (HCV)-positive end stage renal disease (ESRD) patients before or after renal transplantation were compared to study the effect of transplant-related immunosuppression. METHODS: In this prospective study all patients on the active transplant list and all patients with functioning renal transplants at our hospital were tested for HCV antibody (ELISA-2) over a 30-month period. HCV infection was confirmed by polymerase chain reaction in most patients. All HCV-positive patients were asked to undergo liver biopsy without regard to serum transaminase levels. Patients were interviewed, examined, and had detailed chart review. By protocol, liver histology was evaluated according to stage and inflammatory activity in a blinded fashion. RESULTS: There were 129 HCV-antibody-positive patients, of 795 tested. Sixty-seven agreed to liver biopsy. Of these, 22 patients had never been transplanted and 45 had received transplants. Mean transplant duration before biopsy was 41.2 months (range, 1-204 months). Transplant patients had significantly longer duration of ESRD and estimated duration of HCV infection than patients not transplanted. Dialysis patients had significantly more portal inflammatory activity and lymphoid follicles on biopsy whereas transplant patients had more piecemeal necrosis and steatosis. However, the total histological activity score and stage were similar between groups. Multivariate analysis confirmed the association between transplant and steatosis. But independent variables including transplant duration, HCV infection duration, and ESRD duration were not correlated with histological findings. CONCLUSION: Renal transplantation may not be associated with an increased risk of progressive liver disease in HCV-positive patients, compared with ESRD patients receiving chronic dialysis. Long-term studies with serial liver biopsies are needed to resolve this issue.

Pharmacokinetics of vancomycin when administered during high flux hemodialysis.

This study was undertaken to evaluate the pharmacokinetics of relatively high-dose vancomycin when administered during high-flux hemodialysis using a polysulfone membrane (F-80, Fresenius). Five noninfected, anuric patients received a single dose of 25 mg/kg of vancomycin infused during hemodialysis at a rate of one gram per hour and timed such that the end of the infusion coincided with the end of dialysis. Blood samples were drawn during the infusion, up to six hours after the end of dialysis and then prior to the next three dialysis treatments. Spent dialysate was collected during the infusion. Samples were analyzed using the EMIT assay. The percent of vancomycin lost during the first dialysis session ranged from 39.1 to 55.1% (mean, 45.7+/-6.4). The concentration of vancomycin at 6 hours after hemodialysis ranged from 18.2 to 45.1 mg/L (mean, 29.6+/-10.0 mg/l). Dialysis clearance ranged from 96.1 to 158.1 ml/min (mean, 130.7 +/-30.0 ml/min). One week after dosing, serum concentrations ranged from 8.14 mg/l to 10.1 mg/l (mean, 9.0+/-1.0 mg/l). This study suggests than an initial dose of 25 mg/kg of vancomycin, given during high-flux dialysis, may provide adequate serum concentrations in anuric hemodialysis patients for up to seven days. This dosing scheme reduces inconvenience to the patient and staff, and potentially can reduce nursing costs associated with post-dialysis administration; its cost is minimal. At this point, subsequent dosing is best determined by therapeutic drug monitoring.

Simplified measurement of intra-access pressure.

The measurement of intra-access pressure (P[IA]) normalized by mean arterial BP (MAP) helps detect venous outlet stenosis and correlates with access blood flow. However, general use of P(IA)/MAP is limited by time and special equipment costs. Bernoulli's equation relates differences between P(IA) (recorded by an external transducer as PT) and the venous drip chamber pressure, PDC; at zero flow, the difference in height (deltaH) between the measuring sites and fluid density determines the pressure deltaPH = P(IA) - P(DC) Therefore, P(DC) and PT measurements were correlated at six different dialysis units, each using one of three different dialysis delivery systems machines. Both dynamic (i.e., with blood flow) and static pressures were measured. Changes in mean BP, zero calibration errors, and hydrostatic height between the transducer and drip chamber accounted for 90% of the variance in P(DC), with deltaPH = -1.6 + 0.74 deltaH (r = 0.88, P < 0.001). The major determinants of static P(IA)/MAP were access type and venous outflow abnormalities. In grafts, flow averaged 555 +/- 45 ml/min for P(IA)/MAP > 0.5 and 1229 +/- 112 ml/min for P(IA)/MAP < 0.5. DeltaPH varied from 9.4 to 17.4 mmHg among the six centers and was related to deltaH between the drip chamber and the armrest of the dialysis chair. Concordance between values of P(IA)/MAP calculated from PT and from P(DC) + deltaPH was excellent. It is concluded that static P(DC) measurements corrected by an appropriate deltaPH can be used to prospectively monitor hemodialysis access grafts for stenosis.

Pharmacokinetics of intraperitoneal fluconazole during continuous cycling peritoneal dialysis.

OBJECTIVE: To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD). DESIGN: Prospective, nonrandomized, single-dose, open-label study. PARTICIPANTS: Five noninfected volunteer CCPD patients. INTERVENTIONS: Patients received a single dose of intraperitoneal fluconazole 200 mg during their long daytime dwell. Blood samples were collected before and 1, 3, 6, 12 (end of first dwell), 24 (after overnight cycling), 48, 72, 96, and 120 hours after dosing. Used dialysate was collected throughout the study. Unless the patient was anuric, urine was collected for the first 48 hours. MAIN OUTCOME MEASURE: Fluconazole concentrations were assayed by gas-liquid chromatography. Pharmacokinetic parameters were calculated using standard noncompartmental techniques. RESULTS: The bioavailability of intraperitoneal fluconazole was 96% +/- 2% over a 12-hour dwell, absorption half-life was 2.5 +/- 1.2 hours, serum elimination half-life was 71.65 +/- 12.76 hours, and volume of distribution was 0.66 +/- 0.13 L/kg. Peritoneal clearance was 5.96 +/- 0.93 mL/min and proportional to total dialysate volume. Renal clearance was proportional to renal creatinine clearance. CONCLUSIONS: Current treatment guidelines for fungal peritonitis suggest fluconazole 200 mg intraperitoneally every 24 hours. Our data suggest that this dose, administered every 48 hours, is more than sufficient to maintain serum and peritoneal concentrations above the minimum inhibitory concentration for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.

Validation of a revised slow-stop flow recirculation method.

Slow flow/stop flow methods have replaced the three needle technique as methods of choice for measuring recirculation. However, the time delay after reducing blood flow may affect the BUN in the systemic (slow flow/stop flow arterial line) sample and therefore limit the accuracy of this methodology. It has been observed that recirculation does not occur in a properly cannulated access unless the access blood flow rate is less than the dialyzer blood flow rate (BFR). This suggests that the systemic sample could be obtained at a higher than usual blood pump rate. We studied 50 patients and compared a revised slow-stop flow (S/SF) recirculation technique in which the systemic sample was drawn after the blood pump rate was reduced to 120 ml/min for 10 seconds and then stopped, to a non-urea based method that utilized indicator velocity dilution (IVDM). Seven patients were found to have recirculation by IVDM; all had recirculation by S/SF of more than 10% (minimum 16.7%) and an access BFR that was less than the dialyzer BFR. In the 43 patients without recirculation by IVDM, the mean recirculation by S/SF was 1.9 +/- 3.2% (mean +/- SD). Five patients without recirculation by IVDM had more than 5% recirculation by S/SF (range, 5.9 to 8.3%). Although there was a small systematic tendency to overestimate recirculation, this modified urea based method was still able to detect recirculation with good reliability. Single values above 10% are highly likely to indicate the presence of true recirculation. Repeated values over 5%, are also likely to be significant, indicating the presence of true recirculation and its clinical correlate, marginal access blood flow.

A brief history of vascular access for hemodialysis: an unfinished story.

Progress in the development of permanent vascular access for hemodialysis has been much slower than progress in other areas of end-stage renal disease (ESRD) patient care. This article provides a brief historical overview of the major means used for vascular access since the start of chronic hemodialysis. These access modalities include external shunts, arteriovenous fistulae, prosthetic arteriovenous grafts, needle-less access devices, and tunneled central venous catheters. Despite the evolution of access methodology, vascular access complications remain a major impediment to the full rehabilitation of the chronic hemodialysis patient.

Recirculation, urea disequilibrium, and dialysis efficiency: peripheral arteriovenous versus central venovenous vascular access.

When accurate, non-urea-based methods of measuring recirculation are used, recirculation is usually absent in arteriovenous (AV) accesses. When urea-based methods are used to measure recirculation in AV accesses, falsely elevated recirculation rates are common. These errors are due to AV and venovenous disequilibrium (peripheral vein method), delayed systemic sampling (two-needle methods), and errors in urea measurement (all methods). The literature suggests that recirculation in central venovenous (CV) catheters is approximately 5%. The methods used for these determinations have all been urea based. However, there are few theoretical problems in using urea-based measurements for measuring recirculation in this setting, making it more likely that these values are accurate. When hemodialysis via CV and AV accesses are compared, equilibrated Kt/V values differ significantly for the same single-pool Kt/V when 15-second postdialysis blood urea nitrogen values are used for modeling, but differ minimally when 2-minute postdialysis samples are used. The impact of transient retrograde blood flow in the superior vena cava on recirculation and whether dialysis efficiency is influenced by the exact site of CV catheter placement (superior vena cava v right atrium) is uncertain.