The role of mineral metabolism and inflammation on dialysis vascular access failure.

Thrombosis of arteriovenous fistula (AVF) is the leading cause of vascular access (VA) loss usually due to silent stenosis. Therefore, assessment of relevant risk factors of VA monitoring may provide insight into potential therapeutic targets for stenosis and thrombosis. The aim of this study was to evaluate the influence of cardiovascular risk factors (including inflammation and mineral metabolism dysfunctions) on the failure of internal AVF in HD patients. 128 HD patients with internal AVF were included in the study and followed up for two years. At baseline, VA morphology and function were followed by Doppler ultrasonography and serum albumin, prealbumine, C-reactive protein, orosomucoid, calcium, phosphorus, parathyroid hormone, bone-type alkaline phosphatase, osteoprotegerin and receptor activator of nuclear factor ê ê B ligand were measured. At baseline, 50 stenoses were detected but none of them required any intervention. Age and biological parameters did not significantly differ between patients with or without VA stenosis. Over the two year- follow up, VA thrombosis occurred in 19 patients. Preexisting stenosis of VA was present in 9/19 patients (47.3% of cases) (chi-square = 3.708, p = 0.0538). Despite the low rate of events, phosphorus [1.75 (0.95-2.77) vs 1.42 (0.47-3.22) mmol/L, p = 0.0416], Calcium x Phosphorus product [4.00 (2.00-5.90) vs 3.40 (1.10-6.80) mmol(2)/L(2), p = 0.0676] and parathyroid hormone [165.00 (1.00-944.00) vs 79.50 (1.00-846.60) ng/L, p = 0.0814) levels were higher in the 19 thrombotic patients whereas all other biological parameters did not significantly differ. These results, which confirm that VA thrombosis occurs more frequently upon preexisting stenosis, also demonstrate that mineral metabolism disorders, compared to inflammation, may contribute to VA dysfunction leading to thrombosis.

Dialock: a new vascular access device for extracorporeal renal replacement therapy. Preliminary clinical results.

BACKGROUND: Vascular access, a vital tool for end-stage renal disease patients, remains a weak component of extracorporeal renal replacement therapy (RRT) and the first cause of morbidity. Permanent catheters proposed as an alternative to permanent AV fistulae are associated with a significant risk of infection. A subcutaneously implantable chamber connected to permanent catheter appears highly desirable to reduce such hazards. METHODS: Dialock, a metallic port-like valve device connected to permanent silicone twin catheters has been developed (Biolink Corp, Middleboro, MA, USA). After being implanted subcutaneously below the clavicle, Dialock provides a linear flow passage to two Silastic catheters placed in the right atrium via the right internal jugular vein. The valve is accessed percutaneously each dialysis session with needle cannulae that functionally convert the device into twin catheters. Interdialytic patency of the catheters is ensured by antithrombotic lock (heparin or low-molecular-weight heparin). RESULTS: Dialock was implanted in 10 ESRD patients (64+/-12 years) under general anaesthesia, with almost immediate use for HD. RRT consisted of three HD sessions per week lasting 4 h; 699 HD sessions were performed. Average duration of use was 5.7 patient-months (1.3-9.6 months). Patient satisfaction was evident in all cases. Three episodes of bacteraemia occurring in the early phase of the study were cured by appropriate antibiotics. No device was removed because of infection. Skin condition at the puncture sites has remained satisfactory in all patients. Nurse training for cannulating was brief (2-3 x). Effective blood flow was 307+/-3.3 ml/min, with a venous pressure of 195+/-39 mmHg and a recirculation rate of 6.7+/-0.8%. Effective Kt/V dp delivered was 1.36+/-0.03 with a nPCR of 1.20+/-0.005 g/kg/day. Haematoma and a small amount of bleeding of the skin puncture sites observed in the initial period of the study were effectively prevented by reducing heparin lock volume. CONCLUSIONS: The Dialock device offers a new and interesting vascular access alternative for haemodialysis bridging the 'gap' between permanent catheters and arteriovenous fistulae. Dialock's place in the vascular access strategy for haemodialysis patients deserves further long-term clinical studies.

Precise quantification of dialysis using continuous sampling of spent dialysate and total dialysate volume measurement.

The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.

Protein catabolic rate determination from a single measurement of dialyzed urea.

Protein catabolic rate (PCR, in g protein/kg/day) for anuric patients can be accurately determined without blood sampling by equating urea generation over 7 days to the urea dialyzed in the three dialyses of this period as measured by partial dialysate collection (PDC) or with a urea monitor. The feasibility of determining the week's dialyzed urea from measurement of urea dialyzed in a single session, obviating the need to monitor three consecutive dialyses, was examined in a steady-state simulation of 540 anuric patients spanning the full range of dialysis parameters. It was found that the first, midweek, and last dialyses account for nearly constant fractions (37.9, 32.1, and 30.0%, respectively) of the week's urea removal, leading to equations of the form: PCR = CU/BW + 0.17 where U is the grams of urea dialyzed in the first, midweek, or final dialysis of the week, C = 2.45, 2.89, or 3.10, respectively, and BW is the patient's dry weight in kilograms. These equations were tested on 1312 weeks of PDC data gathered in 42 dialysis patients. Using the midweek U resulted in a mean absolute error in PCR < 0.05 g/kg/day when compared to PCR determined using all three of the week's U values.

Creatinine kinetic modelling: a simple and reliable tool for the assessment of protein nutritional status in haemodialysis patients.

While the mathematical modelling of urea kinetics is in wide use for evaluating treatment adequacy and protein nutrition in dialysis patients, the kinetics of creatinine generation in dialysis patients has been relatively unexplored. In this study creatinine kinetic modelling as a clinical tool was investigated in a group of 90 patients treated by haemodialysis (n = 20), haemodiafiltration (60), haemofiltration (7), or biofiltration (3) over a 6-36-month period. A single pool model of creatinine kinetics was employed to obtain monthly values of creatinine distribution space and creatinine appearance rate. Extrarenal creatinine degradation rate, estimated using a clearance of 0.038 l/kg/24 h as suggested by Mitch and co-workers, was added to creatinine appearance rate in urine and dialysate to calculate a corrected creatinine index (CI). Extrarenal degradation accounted for 12 +/- 2% of CI. CI was higher in males (22.4 +/- 4.5 mg/kg/24 h) than females (19.8 +/- 4.8) and decreased with age, falling off more sharply for the female group (CI = 29.9-0.185.age, R = 0.72) than the males (CI = 24.1-0.030.age, R = 0.31). CI was found to correlate strongly with protein catabolic rate determined by urea kinetic modelling (CI = 8.84 +/- 10.91.PCR). Low or reduced CI was associated in this study group with severe malnutrition status and high mortality rate. CI is suggested as a strong predictor of patient morbidity and mortality.

Calcium kinetics and the long-term effects of lowering dialysate calcium concentration.

The optimal dialysate calcium (Ca) content for hemodialysis has been classically fixed at 1.75 mM. However, this dialysate Ca concentration (dCa) with its positive intradialytic Ca balance combined with the use of CaCO3 as a phosphate binder may result in hypercalcemia. To prevent or treat hypercalcemia, a decrease in dCa has been proposed. In the present study both the acute and the long-term effects of lowering dCa were assessed. Additionally, given the results obtained after one year with low dCa the effectiveness of i.v. 1 alpha vitamin D3 in lowering PTH serum levels in two groups of patients dialyzed with different dCa was also studied. (a) Ca kinetics during hemodialysis (HD) and on line hemodiafiltration (HDF) were studied in a group of nine stable patients who were sequentially treated with 1.75, 1.5 and 1.25 mM dCa. Dialysate was the same but for the dCa which was lowered stepwise. Na, K, tCa, ionized Ca (iCa), proteins, phosphate and pH were measured from blood inlet and outlet and dialysate outlet at the start, one hour, two hours and after the treatments. At the same time weight, blood pressure and heart rate were recorded. The sieving of iCa was significantly different in HDF versus HD (F = 6.73; P < 0.01); intravenous infusion of 18 liters of filtered ultrapure dialysate compensated the Ca loss due to the convective component of HDF, as iCa was similar at the blood inlet in HD and HDF in the three dCa tested (F = 2.59; NS). Intradialytic iCa kinetics measured in the blood inlet were significantly different with different dCa (P < 0.001 for 1.75 mM vs. 1.5 mm and P < 0.001 for 1.5 mM vs. 1.25 mM). A significant increase in post-dialysis iCa was observed with dCa of 1.75 and 1.5 while no modification was observed with 1.25 mM dCa. (b) Regarding long-term effects of lowering dCa, seven of the nine patients acutely studied were followed for a one year period after changing from dCa = 1.5 to dCa = 1.25 mM. A control group of six patients was maintained with dCa = 1.5 for the same period of time and with the same treatment schedule but for dCa. Total Ca, phosphate and alkaline phosphatase were assessed monthly, and phosphate binders and oral vitamin D derivative doses were adapted accordingly. Intact PTH was determined quarterly. CaCO3 oral intake was more than doubled in the low dCa group. Total Ca, phosphate and ALP were similar in both groups over the assessed year.(ABSTRACT TRUNCATED AT 400 WORDS)

Accuracy of Kt/V estimations in high-flux haemodiafiltration using per cent reduction of urea: incorporation of urea rebound.

The estimation of Kt/V by utilization of the pre- and postdialysis urea concentrations (per cent reduction in urea and In(Upre/Upost)) provides a simple, quick technique that can be applied at the bedside. However, the accuracy of such techniques has been questioned. One possible reason for this inaccuracy may be the frequently observed postdialysis rebound in serum urea. We assessed the urea rebound at 30 min postdialysis in 34 haemodiafiltered patients and compared the calculation of Kt/V using this urea concentration with that using the immediate postdialysis concentration. These results were then compared to the Kt/V calculated by urea kinetic modelling (UKM), also utilizing the delayed serum urea concentration. The degree of urea rebound observed was large, 21.4%, being a reflection of the short-duration, rapid-flux dialysis. The formulae for calculation of Kt/V all significantly correlated with Kt/V by UKM but all gave results significantly different from Kt/V by UKM (P < 0.001 by paired t test). For assessment of Kt/V by these formulae or by UKM, the urea rebound is too large to ignore in the setting of short-duration, rapid-flux dialysis.

The effects of reprocessing high-flux polysulfone dialyzers with peroxyacetic acid on beta 2-microglobulin removal in hemodiafiltration.

The reuse of dialyzers is widely practiced, especially in the United States. Despite this, the effects of reuse on the efficacy of removal of solutes and more recently proteins such as beta 2-microglobulin (beta 2M) are the subject of much debate. There is considerable evidence to suggest that reuse after cleansing and sterilizing with formalin, with or without bleach, maintains dialyzer performance. In this study, we have examined peroxyacetic acid use as the cleansing and sterilizing agent using Renatron machines. We analyzed reuse in 24 patients using polysulfone membranes in a hemodiafiltration (HDF) unit over a 2-year period. The mean maximum number of uses achieved was 20.1 +/- 0.5. Several factors considered clinically to influence the number of reuses achievable (hemoglobin, white blood cell, and platelet levels, erythrocyte sedimentation rate [ESR], and fibrinogen and total protein levels) were found not to influence the maximum number of uses obtainable. We then assessed prospectively the performance of 26 polysulfone dialyzers after peroxyacetic acid reprocessing up to 20 times, particularly with regard to their ability to remove beta 2M. We report that this combination of polysulfone membranes reprocessed with peroxyacetic acid used for HDF up to 20 times exhibits a maintained high level removal of compounds beyond a molecular weight (MW) of 12,000. Any secondary membrane formation that occurs appears not to influence the subsequent removal of beta 2M. Thus, we would recommend the use of peroxyacetic acid for reprocessing dialyzers in a safe and efficacious manner.

Comparison of hemodialysis and hemodiafiltration: a long-term longitudinal study.

Although hemodiafiltration is purported to provide better cardiovascular stability for dialysis patients; other possible benefits of this therapy have not been well defined. We have compared treatment with hemodialysis (HD) and hemodiafiltration (HDF) in 20 stable patients over a period of 18 months. Dialysis parameters (dialysate composition and flow, duration, dialyzer) were the same in the two periods except for the added convection of HDF and a higher tolerated blood flow in HDF. Cardiovascular parameters were remarkably similar in the two treatment periods, indicating that stable patients do not benefit further from this therapy in terms of these factors. The clearance of urea was significantly improved with HDF, which was reflected in a higher Kt/V and lower TACurea. We observed a significant correlation between Kt/V and PRU in both HD and HDF modes. This correlation was linear and the regression line was similar in both modes. The clearance of beta 2-microglobulin was also significantly improved by HDF compared to HD. Thus the benefit of HDF in stable dialysis patients is the improved clearance of small molecules and beta 2-microglobulin without increasing dialysis time. Further clinical benefits due to the improved clearance may only become apparent with longer follow-up.

Measurement of vascular access recirculation without contralateral venous puncture.

The rate of recirculation is an important variable in calculating the correct dose of dialysis delivered to a patient. Traditionally it is calculated using blood results obtained from the arterial and venous lines and from venous puncture of the opposite arm. To avoid this venipuncture, cessation of the blood pump for 1 or 2 min was attempted to mimic the systemic circulation. This technique underestimated recirculation but was statistically correlated with the result obtained by the classical method, thus it is possible to derive a formula to obtain the recirculation value without contralateral venipuncture.

Effect of reuse on dialyzer efficacy.

The effect of reuse on dialyzer efficacy was examined by measuring blood compartment volume and dialyzer mass transfer coefficient (maximum dialyzer clearance) as a function of dialyzer use number. The 102 polysulfone dialyzers tested (F60 and HF80, Fresenius) were reprocessed on Renatron machines using peroxyacetic acid as the dual cleansing and sterilizing agent. Each dialyzer was used an average of 14.4 +/- 5.7SD times and was tested once (twice for 13/102 dialyzers) during a routine dialysis session at an arbitrary use number (7.6 +/- 5.3; range 1 to 24). The parameters tested were found to decrease only marginally with reuse, corresponding to a blood compartment volume loss of approximately 1% (R = 0.04) over a 5-week/15-use period and a decrease in dialyzer mass transfer coefficient of approximately 3% (R = 0.07 and 0.06) over the same period for urea and creatinine, respectively. It was concluded that the loss in dialyzer efficacy is negligible over the average use period of almost 5 weeks per dialyzer.

Beta-2 microglobulin serum levels in maintenance dialysis. What does it mean?

beta-2 Microglobulin levels (beta-2M) were analyzed at four month intervals in sera of 237 patients on various forms of dialysis over a 2 year period; twelve patients volunteered to participate in short-term kinetics studies. Duplicate beta-2M measurements in biologic fluids were performed using an RIA kit. The data presented confirm elevated serum beta-2M in dialyzed patients whatever the dialysis method used and give an overview on various factors affecting circulating serum beta-2M. Intraindividual beta-2M variations were 13% in stable ESRD patients. Unusually high values (greater than 2 SE) were observed in patients presenting with severe intercurrent disease (e.g., cancer). The only significant difference observed between groups of patients, HD (46 +/- 1 mg/L) and PD (IPD: 33 +/- 3, CAPD: 37 +/- 2 mg/L), was due to the residual renal function preserved in a higher percentage of PD patients. No significant difference was noted in HF (40 +/- 2 mg/L) and HDF (38 +/- 5 mg/L) patients, despite a higher beta-2M removal rate. beta-2M membrane permeability differs greatly among filters. It is high for AN69 and Polysulfone, intermediate for Polyamide, low for Polyacrylonitrile and none for Cuprophane. Peritoneal membrane is highly permeable to beta-2M with beta-2M dialysate/serum levels of 0.20 at the end of a 6 hr exchange. In conclusion, beta-2M determination in uremic patients is useful in assessing material permeability and biocompatibility. However, it is too early to determine the impact or the beneficial effects of using highly permeable membrane to prevent beta-2M-amyloidosis related nonarticular complications.

[What does circulating beta 2 microglobulin signify in uremic patients on maintenance dialysis?]. / Que signifie la beta 2 microglobuline circulante chez les urémiques en traitement de suppléance?

The authors report a 2 years prospective study on s beta 2M variations observed in a large uremic population (237 patients, 159 M, 78 F, age: 51.1 +/- 5.9 y.o.). The study consisted in two parts. A long term follow-up of s beta 2M in patients regularly treated with various dialysis modalities; hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), intermittent peritoneal dialysis (IPD) and continuous ambulatory peritoneal dialysis (CAPD). s beta 2M was found elevated in the overall population (41.4 +/- 10.2 mg/l) with a 12.5% variation over time observation in stable patients, not influenced by sex, causal nephropathy, and dialysis mode in anuric patients, beta 2M was inversely correlated with residual diuresis. Residual kidney function preserved longer and in a higher proportion of PD patients was the only significant fact explaining for the difference observed in s beta 2M levels between HD (46 +/- 5) and PD (33 +/- 3) patients. Intercurrent inflammatory and tumoral states increased significantly s beta 2M level in uremic patients. The short term study showed that highly permeable membranes (AN69, polysulphone) used either in HD, HF or HDF were able to decrease s beta 2M from 50 to 60%, and to remove 150 to 200 mg per session, while on the opposite HD/cuprophane increased s beta 2M from 10 to 15%. beta 2M dialysate/plasma equilibrium ratio for peritoneal membrane after a 6 hour dwelling time was 0.20, permitting a net removal of 45 +/- 4 mg/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

A bedside micromethod for the determination of total carbon dioxide in biological fluids.

The quality control of bicarbonate hemodialysis requires the determination of TCO2, either in blood or in dialysate. The use of the M + D TCO2 kit, a bedside micromethod, gave the authors an economical and reliable solution to this problem.