Influence of convection on small molecule clearances in online hemodiafiltration.

BACKGROUND: Dialysis efficacy is mostly influenced by dialyzer clearance. Urea clearance may be estimated in vitro by total ion clearance, which can be obtained by conductivity measurements. We have previously used this approach to assess in vitro clearances in a system mimicking predilutional and postdilutional online hemodiafiltration with a wide range of QD, QB, and ultrafiltration rates. Our current study elaborates on a formula that allows the prediction of the influence of ultrafiltration on small molecule clearances, and validates the mathematical approach both experimentally in vitro and clinically in vivo data. METHODS: Two conductivimeters in the dialysate side of an E-2008 Fresenius machine were used. HF80 and HF40 polysulfone dialyzers were used; reverse osmosis water and dialysate were used for blood and dialysate compartments, respectively. Study conditions included QB of 300 and 400 mL/min and QD of 500 and 590 mL/min, with a range of ultrafiltration rate from 0 to 400 mL/min in postdilutional hemodiafiltration and to 590 mL/min in predilutional hemodiafiltration. Urea clearances were determined in the in vivo studies, which included 0, 50, 100, and 150 mL/min ultrafiltration rates. RESULTS: The ultrafiltration rate and clearance were significantly correlated (R > 0.9, P < 0.001) and fitted a linear model (P < 0.001) in all of the experimental conditions. The following formula fitted the experimental points with an error <2% for both postdilutional and predilutional online diafiltration in vitro, respectively. K = K0 + [(QB - K0)/(QB)] x ultrafiltration rateK = K0 + [((QD x QB)/(QB + QD) - K0)/QD] x ultrafiltration rate where K is the clearance; K0 is the clearance with nil ultrafiltration rate; QD is the total dialysate produced (in commercial HDF, QD = QDi + Qinf). Since weight loss was maintained at 0, ultrafiltration rate = infusion flow. QB is the "blood" line flow. The formula was also verified in vivo in clinical postdilutional hemodiafiltration with a QB taking into account the cellular and water compartments. DISCUSSION: In vitro, by simply determining the clearance in conventional dialysis, the total clearance for any ultrafiltration rate may be estimated in both predilutional and postdilutional online diafiltration with an error of less than 2%. The same applies to in vivo postdilutional hemodiafiltration when the formula takes into account the cellular and water composition of blood.

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.

Calcium balance and intact PTH variations during haemodiafiltration.

BACKGROUND: Recent approaches to prevent and treat secondary hyperparathyroidism in dialysis patients include decreasing dialysate Ca content from 1.75 to 1.5 mM or lower. We have recently observed that by decreasing dialysate Ca to 1.25 mM a rise in intact parathormone serum levels occurs despite adequately controlled predialysis Ca and phosphate serum levels. In that study complementary treatment with high-dose 1 alpha(OH) vitamin D3 was required to suppress the parathormone. In the present study we aimed to assess the total Ca balance as well as the modifications in parathormone induced by the dialysis session in order to understand the reasons for which the rise in parathormone was induced. METHODS: Fourteen HD patients treated with haemodiafiltration three times/week gave their informed consent for the study. They were distributed in two groups with identical treatment but for the dialysate Ca content which was 1.5 and 1.25 mM respectively and for the amount of oral CaCO3 received. Total and ionized Ca, phosphate, pH, and albumin as well as parathormone were measured in serum before and after dialysis and in the spent dialysate during two dialysis sessions. RESULTS: Serum ionized Ca (normalized to pH 7.4) did not change during 1.25 mM dialysate Ca and significantly increased with 1.5 mM (P < 0.001). The end-dialysis values being 1.25 +/- 0.02 and 1.38 +/- 0.02 mM respectively. Total Ca significantly decreased with 1.25 mM dialysate Ca (P < 0.04) and increased with 1.5 mM (P < 0.003), the end-dialysis values being 2.51 +/- 0.03 and 2.75 +/- 0.04 mM respectively. In the dialysate the difference in ionized Ca concentrations, fresh minus spent dialysate was -1.78 +/- 1.12 mmol/l (NS) and 4.26 +/- 1.47 mmol/l (P < 0.02) respectively for 1.25 and 1.5 mM dialysate Ca. The difference in total Ca concentrations, fresh minus spent dialysate was -0.1 +/- 0.01 mmol/l (P < 0.05) and -0.002 +/- 0.01 mmol/l (NS) respectively. Phosphate removal was higher in 1.25 mM dialysate-Ca-treated patients (40.4 +/- 1.75 mmol/session versus 34 +/- 1.3 mmol/session respectively, P < 0.015). The use of 1.25 mM dialysate Ca did not result in a change in serum parathormone, while the use of 1.5 mM resulted in a decrease of 43 +/- 15% (P < 0.02) in patients with marked hyperparathyroidism. CONCLUSIONS: Our data remind us of the difficulty in assessing Ca balances and identifies the phosphate content as one of the factors influencing the amount of ionized Ca in the dialysate. Although the long-term parathormone increase we observed using 1.25 mM dialysate Ca may well not be explained only by the acute intradialytic modifications, the negative Ca balance identified here (which was missed with the analysis of ionized Ca alone), and the lack of parathormone inhibition may participate in the relapse of hyperparathyroidism.

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.

Serum alpha 2-macroglobulin in haemodialysis patients: baseline and kinetic studies.

The pathogenesis of dialysis related amyloidosis remains unresolved despite the identification of beta 2-microglobulin (beta 2M) as the major protein constituent, as well as other proteins being present in the deposits. Among the latter we have assessed the serum concentrations of alpha 2-macroglobulin (alpha 2M) both in the baseline stage and during the haemodialysis (HD) procedure. We have also assessed the influence of the membrane on alpha 2M kinetics. Fifteen HD patients with histologically proven dialysis-related amyloidosis (DRA group) and 15 HD patients clinically and radiologically considered dialysis-related amyloidosis free (control group) were included in the baseline study. Blood was sampled the day before the second dialysis of the week and alpha 2M, beta 2M and alpha 1 antitrypsin were determined along with the routine biological analysis of these patients. Serum alpha 2M was greater in dialysis-related amyloidosis than in control patients (t = 2.35; P < 0.026). Serum beta 2M was similar in both groups. The serum alpha 2M and beta 2M correlated in patients with dialysis-related amyloidosis (r = 0.64; P < 0.01), while no correlation was found in controls (r = 0.17; NS). Stepwise analysis taking the presence of dialysis-related amyloidosis as the dependent variable retained the serum alpha 2M concentration as the first variable in the model (F = 4.4; partial r = 0.38; P < 0.046).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Recovery of renal function in patients with accelerated malignant nephrosclerosis on maintenance dialysis with management of blood pressure by captopril.

Recovery of renal function to a self-sustaining level was observed in 4 patients with accelerated malignant hypertension who required chronic hemodialysis therapy. Excellent blood pressure control was achieved in all the patients on captopril therapy. Hemodialysis could be discontinued after 2-9 months of captopril therapy; on recovery of renal function levels of creatinine clearance became stable ranging from 28 to 56 ml/min within 5-15 months of captopril treatment, and remained at this level during 21-64 months of observation. The management of hypertension and the inhibition of the renin-angiotensin system afforded by chronic angiotensin-converting enzyme inhibition is very promising as a means of reversing the process of malignant nephrosclerosis.

Standard methods for the microbiological assessment of electrolyte solution prepared on line for haemofiltration.

The preparation of large volumes of intravenous solution at the bedside (on-line preparation) requires bacteriological monitoring and pyrogen control before final sterilisation. We tested the sensitivity of microbiological methods and their applicability in routine clinical conditions during haemofiltration. In vitro, the 0.22 micron membrane filter technique (MF) showed a better or equal bacterial recovery with two test organisms. Parallel tests of 0.22 and 0.45 micron MF under simulated haemofiltration conditions showed no significant difference in the number of detected bacteria. Routine MF with 0.22 micron membranes offers a simple and reliable way to monitor the bacterial content of on-line prepared electrolyte solution in clinical conditions.

The natriuretic response to acute saline loading in normotensive and hypertensive renal transplant recipients.

The response to acute isotonic saline loading (1800 ml in 3 h) was assessed in 12 normotensive and 11 hypertensive renal transplant recipients. Both groups had similar renal function, daily urinary excretion of sodium and doses of steroids. The natriuretic response to saline was not affected in hypertensive transplants and changes in blood pressure, renin and aldosterone were identical in both groups. Similar correlations between presaline fractional excretion of sodium (FENa+) and the FENa+ obtained during saline were found in normotensive and hypertensive patients. These results demonstrate that recipients of renal transplants who are hypertensive do not show an exaggerated natriuresis in response to saline, thus suggesting that normal kidneys carry their characteristics when transplanted in a new environment. The role of renal denervation remains unclear.

Effect of acetate on ketogenesis during hemodialysis.

The concentration of plasma acetate, glucose, and ketone bodies were determined for both venous and arterial blood before and at the end of dialysis with an acetate-containing dialysate. We also determined lactate and pyruvate levels in arterial plasma. The results obtained in the same patients were compared when dialysis were done with or without glucose and discussed in terms of hormonal changes (insulin, glucagon). Arterial plasma acetate (p less than 0.001) and ketone body levels (p less than 0.05) increased significantly during dialysis both with glucose and without glucose (p less than 0.001 in both cases). Higher end-dialysis arterial levels were found for the latter set of glucose-free dialysis (p less than 0.05 and p less than 0.001, respectively, for acetate and ketone bodies), and a correlation was established between end-dialysis arterial concentrations of acetate and ketone bodies. This suggests high consumption of both endogenous and exogenous acetate to feed ketogenesis. This is concurrent with decreased insulin and high glucagon levels. Under these conditions, plasma accumulation of ketone bodies would facilitate an indirect elimination of acetate by the dialyzer (about 10% of the acetate load). Our results suggest that hormone variations during glucose-free dialysis which promote fatty acid oxidation and ketogenesis from acetyl groups hinder acetate-dependent lipogenesis.